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JAMA_Chen2024

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https://jamanetwork.com/journals/jamaoncology/fullarticle/2653898

A woman in her 50s presented to the emergency department with acute, severe, left flank pain. There was no medical history of trauma, fever, or hematuria. She was receiving therapy for mantle cell lymphoma and had previously undergone 1 cycle of the Nordic protocol (comprising cyclophosphamide, doxorubicin, vincristine, prednisolone, cytarabine, and rituximab).1 However, this resulted in tumor lysis syndrome and neutropenic sepsis. The patient was reluctant to undergo further infusional therapy and was switched to ibrutinib, 560 mg, once daily. During the 2-month period that she was receiving ibrutinib therapy, there were no concurrent administrations of anticoagulants. At presentation, she was hypotensive (blood pressure, 79/45 mm Hg) with conjunctival pallor and left renal angle tenderness. The patient’s hemoglobin count was low (7.6 g/dL; reference range, 12-16 g/dL; to convert to g/L, multiply by 10.0), which represented a significant decrease from the baseline (10.6 g/dL) measured 1 month before presentation. She was also found to have acute-onset thrombocytopenia (40×109/L; reference range, 140-400×109/L) and leukocytosis (12.75×109/L, reference range, 4-10×109/L). Her coagulation profile (prothrombin time) was normal. A computed tomographic (CT) scan of the abdomen and pelvis was performed (Figure 1A) and compared with a similar scan performed 4 months prior (Figure 1B). A, Findings from computed tomographic scan at presentation. B, Previous findings from computed tomographic scan. What Is Your Diagnosis?

Abdominal aortic aneurysm rupture

Spontaneous perinephric hematoma

Splenic rupture

Pyelonephritis

B. Spontaneous perinephric hematoma

B

Spontaneous perinephric hematoma

The CT scan revealed an acute large left perinephric hematoma with multiple foci of active hemorrhage (Figure 1A). The spleen was mildly enlarged, and was without evidence of rupture. The abdominal aorta was well visualized without evidence of aneurysm dilatation or rupture. The patient underwent left renal arterial embolization, following hemodynamic stabilization with a transfusion of 3 units of packed red blood cells and 1 unit of platelets (Figure 2).A, Bleeding demonstrated at the lower pole vascular of the left kidney. B, Postembolisation angiogram showing hemostasis (coils introduced into lower pole artery). A 3.5 × 2.7-cm Bosniak I cyst was initially demonstrated in the left kidney at the initial CT scan2 (Figure 1B). We postulate that a spontaneous cyst rupture occurred, and the concurrent administration of ibrutinib contributed to a bleeding diathesis that led to development of a large perinephric hematoma.3Following these events, treatment with ibrutinib was stopped, and the patient was started on rituximab and bortezomib. There were no further episodes of bleeding from the left kidney, and she did not require additional blood transfusions. The platelet and white blood cell counts normalized, and the patient was discharged 8 days later.Ibrutinib is a Bruton tyrosine kinase inhibitor indicated in the treatment of mantle cell lymphoma, and has been associated with a good tolerability profile.4 It is also effective therapy against chronic lymphocytic leukemia,5 small lymphocytic lymphoma,6 and Waldenstrom macroglobulinemia.7 Spontaneous bleeding has been reported with ibrutinib, and is most commonly related to grade 1 and grade 2 hemorrhagic adverse events in the cutaneous system (petechiae, ecchymoses). The incidence of these events have been reported in up to 50% of patients, especially those requiring concurrent antiplatelet or anticoagulation therapy. However, up to 3% of patients may experience major bleeding in the viscera (≥grade 3), especially after trauma.4 In a phase III trial comparing ofatumumab and ibrutinib for the treatment of chronic lymphoid leukemia, there was 1 case of a grade 3 and grade 4 hemorrhage (subdural hematoma), respectively.8 This trial had excluded patients who required warfarin but not other forms of anticoagulation.The bleeding diathesis associated with ibrutinib is likely to be related to selective inhibition of platelet signaling and function necessary for collagen-induced platelet aggregation and activation. It also decreases firm platelet adhesion on von Willebrand factor under physiological arterial blood flow, thereby leading to accentuated bleeding in specific conditions, such as trauma.3,9 The thrombocytopenia observed at clinical presentation is likely to be related to consumption from bleeding. This is supported by the subsequent normalization of the platelet counts with angiographic hemostasis.To our knowledge, this is the first report of a perinephric hematoma arising from a rupture of a simple renal cyst and leading to a grade 4 hemorrhagic adverse event. According to current guidelines, interruption of ibrutinib monotherapy is recommended if grade 3 or higher nonhematologic toxic effects, grade 3 or higher neutropenia with infection or fever, or grade 4 hematologic toxic effects occur.10Spontaneous perinephric hematomas are rare, and are usually caused by benign renal tumors (angiomyolipomas), vascular abnormalities, or other disorders, such as a rupture of a renal artery aneurysm. The clinical symptoms can range from mild flank and/or abdominal pain in minor cases to acute cardiovascular collapse in major bleeding episodes. A strong clinical judgement is required so that early axial imaging with CT can facilitate a prompt and precise diagnosis of a potentially life-threatening condition. The options for definitive treatment include renal arterial embolization, or surgical intervention (nephrectomy).

Oncology

A woman in her 50s presented to the emergency department with acute, severe, left flank pain. There was no medical history of trauma, fever, or hematuria. She was receiving therapy for mantle cell lymphoma and had previously undergone 1 cycle of the Nordic protocol (comprising cyclophosphamide, doxorubicin, vincristine, prednisolone, cytarabine, and rituximab).1 However, this resulted in tumor lysis syndrome and neutropenic sepsis. The patient was reluctant to undergo further infusional therapy and was switched to ibrutinib, 560 mg, once daily. During the 2-month period that she was receiving ibrutinib therapy, there were no concurrent administrations of anticoagulants. At presentation, she was hypotensive (blood pressure, 79/45 mm Hg) with conjunctival pallor and left renal angle tenderness. The patient’s hemoglobin count was low (7.6 g/dL; reference range, 12-16 g/dL; to convert to g/L, multiply by 10.0), which represented a significant decrease from the baseline (10.6 g/dL) measured 1 month before presentation. She was also found to have acute-onset thrombocytopenia (40×109/L; reference range, 140-400×109/L) and leukocytosis (12.75×109/L, reference range, 4-10×109/L). Her coagulation profile (prothrombin time) was normal. A computed tomographic (CT) scan of the abdomen and pelvis was performed (Figure 1A) and compared with a similar scan performed 4 months prior (Figure 1B). A, Findings from computed tomographic scan at presentation. B, Previous findings from computed tomographic scan.

what is your diagnosis?

What is your diagnosis?

Abdominal aortic aneurysm rupture

Pyelonephritis

Spontaneous perinephric hematoma

Splenic rupture

c

female

51-60

original

https://jamanetwork.com/journals/jamacardiology/fullarticle/2661812

A 75-year-old woman recently diagnosed as having stage IV lung adenocarcinoma was admitted for dyspnea and weakness. There was no history of illicit drug use, autoimmune disease, or cardiopulmonary disease. Physical examination was remarkable only for asthenia. Cardiac examination was normal. Chest computed tomography (CT) demonstrated multiple pulmonary nodules, a spiculated mass in the right medial upper lobe, vertebral metastases, and small bilateral subsegmental pulmonary emboli. Cranial CT showed scattered subacute embolic cortical infarcts and dural metastases. Serum troponin was 2.6 ng/mL (type 2 myocardial infarction) with nonspecific electrocardiographic changes. Transthoracic echocardiogram showed normal biventricular function with normal wall motion and shaggy, bulky masses on the tips of both mitral valve leaflets (Figure) (Video 1). A saline contrast bubble study was negative for an intracardiac shunt, and commercial intravenous contrast showed no clot. Transesophageal echocardiogram showed large, 1.4 × 0.5-cm, frondlike, mobile masses on the atrial surface of the mitral leaflets with mild mitral regurgitation. In addition, a large 1.1  × 1.6-cm multilobulated, mobile mass was seen on the subvalvular chordae of the tricuspid valve, with trace tricuspid regurgitation. Gated cardiac CT angiogram confirmed mobile hypoattenuating masses on the mitral valve leaflets that prolapsed to the left atrium during systole (Video 2). No myocardial, pulmonary vein, or pericardial involvement was seen.Transthoracic echocardiogram. A, Parasternal long axis showing masses on the tips of both mitral valve leaflets (arrowheads). B, Parasternal long axis view showing mild mitral regurgitation. C, Right ventricular inflow view demonstrating an echogenic mass on the tricuspid valve chordae (arrowhead). D, Right ventricular inflow view showing mild tricuspid regurgitation. What Would You Do Next?

Initiate broad-spectrum antibiotics

Refer for surgical valve replacement

Treat with full-dose anticoagulation

Initiate chemotherapy (erlotinib)

Nonbacterial thrombotic endocarditis

C

Treat with full-dose anticoagulation

Results of blood cultures and serologies were normal, and the patient stayed afebrile. Antibiotics were not initiated because infective endocarditis (IE) was not suspected. The observed masses were felt to be vegetations from nonbacterial thrombotic endocarditis (NBTE), and low-molecular-weight heparin was initiated.Also known as marantic or Libman-Sacks endocarditis, NBTE is a rare condition characterized by the deposition of thrombi on previously undamaged heart valves in the absence of an infection and an increased frequency of arterial embolic events. It normally occurs in the setting of advanced malignancy, such as adenocarcinomas, in hypercoagulable states, or in rheumatological conditions, such as lupus.1 The most commonly affected valves are the aortic and mitral, though involvement of right-sided heart valves has infrequently been reported.1 Vegetations typically present on the atrial surface of the atrioventricular valves and the ventricular surface of the semilunar valves. The sterile vegetations consist of degenerating platelets interwoven with strands of fibrin and vary in size from microscopic to large, with a tendency to detach and cause infarction more readily than vegetations seen in IE.2 Tumor necrosis factor and interleukins are released secondary to an interaction between macrophages and malignant cells; this causes endothelial damage and sloughing, creating a thrombogenic valvular surface.3 Platelets and clotting factors may also be activated by this interaction, further facilitating thrombosis.3Nonbacterial thrombotic endocarditis is often unsuspected until the occurrence of embolic events. Echocardiography is often the first tool for the diagnosis of NBTE. Transesophageal echocardiogram can provide important information about vegetation size and location and can help rule out IE, which often has valve destruction, leaflet perforation, regurgitation, and abscess formation, features typically absent in NBTE. As in this patient, the presence of both left- and right-sided vegetations is more consistent with NBTE than IE. Vegetations in NBTE are easily dislodged due to little inflammatory reaction at the site of attachment. Systemic emboli occur in nearly 50% of patients with NBTE, with the cerebral, coronary, renal, and mesenteric circulation being the usual sites.1 This patient had evidence of systemic embolization to the brain and coronary circulation, which likely caused her myocardial infarction. Coronary CT angiography showed no evidence of coronary artery disease. The subsegmental pulmonary emboli were likely embolic events from tricuspid valve involvement.In addition to managing the underlying malignancy, indefinite anticoagulation with heparin is the mainstay of therapy for NBTE.1 Vitamin K antagonists and novel oral anticoagulants do not appear to be as efficacious.4 The case for anticoagulant therapy is further strengthened by the observation that in malignancies, both Trousseau syndrome and NBTE have a prothrombotic etiology in common.4 Because anticoagulation is relatively contraindicated in IE owing to the risk of cerebral embolization and hemorrhagic transformation, the clinical decision making regarding this can be challenging. In this patient, the rapid development of large vegetations and lack of fevers and valve regurgitation and the clinical context of lung malignancy as well as embolic events favored the initiation of heparin.Surgery is indicated in the presence of severe valvular dysfunction, recurrence of embolic events despite adequate anticoagulation, and uncertainty regarding diagnosis.1 As this patient had asymptomatic, mild mitral regurgitation, valve surgery was not indicated. She was discharged home and prescribed enoxaparin.At 3 months, the patient remained afebrile without symptoms and was responding well to erlotinib and enoxaparin with reduction in tumor burden and had no further embolic events. A follow-up echocardiogram performed 2 weeks later showed a decrease in the size of the vegetations.

Cardiology

A 75-year-old woman recently diagnosed as having stage IV lung adenocarcinoma was admitted for dyspnea and weakness. There was no history of illicit drug use, autoimmune disease, or cardiopulmonary disease. Physical examination was remarkable only for asthenia. Cardiac examination was normal. Chest computed tomography (CT) demonstrated multiple pulmonary nodules, a spiculated mass in the right medial upper lobe, vertebral metastases, and small bilateral subsegmental pulmonary emboli. Cranial CT showed scattered subacute embolic cortical infarcts and dural metastases. Serum troponin was 2.6 ng/mL (type 2 myocardial infarction) with nonspecific electrocardiographic changes. Transthoracic echocardiogram showed normal biventricular function with normal wall motion and shaggy, bulky masses on the tips of both mitral valve leaflets (Figure) (Video 1). A saline contrast bubble study was negative for an intracardiac shunt, and commercial intravenous contrast showed no clot. Transesophageal echocardiogram showed large, 1.4 × 0.5-cm, frondlike, mobile masses on the atrial surface of the mitral leaflets with mild mitral regurgitation. In addition, a large 1.1  × 1.6-cm multilobulated, mobile mass was seen on the subvalvular chordae of the tricuspid valve, with trace tricuspid regurgitation. Gated cardiac CT angiogram confirmed mobile hypoattenuating masses on the mitral valve leaflets that prolapsed to the left atrium during systole (Video 2). No myocardial, pulmonary vein, or pericardial involvement was seen.Transthoracic echocardiogram. A, Parasternal long axis showing masses on the tips of both mitral valve leaflets (arrowheads). B, Parasternal long axis view showing mild mitral regurgitation. C, Right ventricular inflow view demonstrating an echogenic mass on the tricuspid valve chordae (arrowhead). D, Right ventricular inflow view showing mild tricuspid regurgitation.

what would you do next?

What would you do next?

Initiate broad-spectrum antibiotics

Initiate chemotherapy (erlotinib)

Treat with full-dose anticoagulation

Refer for surgical valve replacement

c

female

71-80

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2656340

A woman in her 30s presented with a 7-month history of right-sided nasal obstruction. She had been treated with several courses of oral antibiotics and intranasal steroids without improvement of symptoms. She had no history of sinus infections or allergic rhinitis. Nasal obstruction was constant and associated with right paranasal pressure. Results from a head and neck examination, including cranial nerve, were normal, except for the results from nasal endoscopy, which showed a deviated septum and a soft-tissue mass emanating from the right middle meatus inferior to the middle turbinate that seemed to have a polypoid appearance superiorly and a papillomatous appearance inferiorly. A computed tomographic (CT) scan of the sinuses without contrast showed complete opacification of the right paranasal sinuses with mass effect on the medial maxillary wall with mild hyperostosis posterolaterally. The patient underwent an endoscopic right sinonasal mass biopsy. Intraoperatively, further excision of the mass was aborted owing to an unusual appearance of the mass as well as clear fluid exuding from the mass during microdebridement. Pathologic analysis of the biopsied tissue revealed a uniform spindle cell tumor comprised of cellular fascicles and tumor cells with bland nuclei (Figure, A and B). A magnetic resonance image (MRI) of the face with contrast was obtained postoperatively to further delineate the mass and evaluate for intracranial extension. Initial histologic stains showed the tumor to be positive for S-100 and actin (Figure, C and D) and negative for GFAP, CD34, and cytokeratin. Additional immunostains showed the tumor to be negative for SOX-10 and B-catenin.Histopathologic images. A and B, Hematoxylin-eosin. C, S-100 immunohistochemical stain. D, Smooth muscle actin immunohistochemical stain. What Is Your Diagnosis?

Biphenotypic sinonasal sarcoma

Solitary fibrous tumor

Malignant peripheral nerve sheath tumor

Synovial sarcoma

A. Biphenotypic sinonasal sarcoma

A

Biphenotypic sinonasal sarcoma

Biphenotypic sinonasal sarcoma (BSNS) is a low-grade malignant sinonasal tumor that exhibits both neural and myogenic differentiation, first described by Lewis et al.1 BSNS is an indolent tumor that occurs more commonly in middle-aged women (male to female ratio, 1:3; mean age at presentation, 52 years).1,2 Typical presenting symptoms are nonspecific, such as nasal obstruction, facial pressure, and congestion.1In patients who present with unilateral nasal mass, evaluation should include a detailed medical history; head and neck examination, including cranial nerve examination; nasal endoscopy; and a CT scan of the sinuses. In cases with neurologic abnormalities or suspicion for encephalocele, or if there are CT findings of bony erosion in the lateral sinonasal walls or skull base, or intracranial or orbital involvement MRI should be obtained.3,4In a case series of 28 patients reported by Lewis et al,1 the nasal cavity (54%) and the ethmoid sinuses (57%) were the most common locations. Seven (25%) tumors with orbital extension, 3 tumors (11%) with cribriform plate involvement, and 1 tumor with intracranial extension (4%) were reported. There was also 1 tumor accompanied by osteitis (4%), which implies a slow-growing, expansile lesion. There were no known regional or distant metastases, and no patient died from this disease.Histologically, BSNS is poorly circumscribed and unencapsulated with a highly cellular spindle cell proliferation. The cells have elongated, hypochromatic nuclei and are arranged in fascicles, sometimes demonstrating an alternating “herringbone” pattern. BSNS is considered histologically low-grade, as it lacks high mitotic rates or necrosis. It is almost always positive for smooth muscle actin and S-100 proteins.2 Ninety-six percent of cases of BSNS have genetic rearrangements of the PAX3 gene, which plays a role in melanocytic, neuronal and skeletal muscle differentiation.5 Three such gene rearrangements of PAX3 have been found in BSNS: the PAX3-MAML3 fusion gene (55%-79% of cases),5,6 the PAX3-FOX01 fusion (7%),6,7 and the PAX3-NCOA1 fusion (2%)6,8; 11% to 21% have no identifiable PAX3 fusion gene.6,7The S-100 positivity of BSNS may suggest schwannoma or malignant peripheral nerve sheath tumor (MPNST). Up to 30% of MPNSTs have S-100 and SOX-10 expression. BSNS is generally not as diffusely S-100 positive as schwannoma or MPNST. BSNS is consistently negative for SOX-10, which also helps with differentiation. The presence of smooth muscle differentiation also argues against schwannoma or MPNST. Malignant peripheral nerve sheath tumors also differ from BSNS in that they are usually much higher grade, with necrosis and a high mitotic rate.2 However, sometimes BSNS may also show rhabdomyoblastic differentiation by morphologic or immunohistochemical analysis (MyoD1), and there are limited data suggesting these may be associated with NCOA1 and FOX01 fusion partners.7 At least 70% of MPNSTs have mutations in EED1 or SUZ12, with subsequent PRC2 inactivation leading to loss of H3K27me3 on immunohistochemical staining, which has been shown as a specific diagnostic marker for MPNST.9There is substantial immunophenotypic overlap between BSNS and synovial sarcoma, as up to 30% of synovial sarcoma cases express S-100. However, epithelial differentiation and immunophenotypic positivity for EMA, TLE, and SSX gene rearrangements in synovial sarcoma are not identified concurrently in BSNS.7 Other immunohistochemical markers consistently positive in BNSN include calponin, B-catenin, and factor XIIIa.8 BSNS is also occasionally positive for desmin, myogenin, cytokeratins, and EMA.10 When these immunohistochemical markers are tested as a panel, the diagnosis of BNSN could be separated from its mimickers.10In this patient’s case, the tumor histologically showed dense fascicles of bland, uniform spindle cells with areas showing a herringbone architecture. The tumor showed patchy positivity for S-100 and actin, and was negative for SOX-10, cytokeratin, and B-catenin. Using both histologic analysis and immunochemical markers, the diagnosis of BSNS was determined.

General

A woman in her 30s presented with a 7-month history of right-sided nasal obstruction. She had been treated with several courses of oral antibiotics and intranasal steroids without improvement of symptoms. She had no history of sinus infections or allergic rhinitis. Nasal obstruction was constant and associated with right paranasal pressure. Results from a head and neck examination, including cranial nerve, were normal, except for the results from nasal endoscopy, which showed a deviated septum and a soft-tissue mass emanating from the right middle meatus inferior to the middle turbinate that seemed to have a polypoid appearance superiorly and a papillomatous appearance inferiorly. A computed tomographic (CT) scan of the sinuses without contrast showed complete opacification of the right paranasal sinuses with mass effect on the medial maxillary wall with mild hyperostosis posterolaterally. The patient underwent an endoscopic right sinonasal mass biopsy. Intraoperatively, further excision of the mass was aborted owing to an unusual appearance of the mass as well as clear fluid exuding from the mass during microdebridement. Pathologic analysis of the biopsied tissue revealed a uniform spindle cell tumor comprised of cellular fascicles and tumor cells with bland nuclei (Figure, A and B). A magnetic resonance image (MRI) of the face with contrast was obtained postoperatively to further delineate the mass and evaluate for intracranial extension. Initial histologic stains showed the tumor to be positive for S-100 and actin (Figure, C and D) and negative for GFAP, CD34, and cytokeratin. Additional immunostains showed the tumor to be negative for SOX-10 and B-catenin.Histopathologic images. A and B, Hematoxylin-eosin. C, S-100 immunohistochemical stain. D, Smooth muscle actin immunohistochemical stain.

what is your diagnosis?

What is your diagnosis?

Biphenotypic sinonasal sarcoma

Solitary fibrous tumor

Synovial sarcoma

Malignant peripheral nerve sheath tumor

a

female

31-40

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2657611

A young boy presented with a 4-week history of an enlarging right facial mass, which had not responded to a course of azithromycin prescribed by his pediatrician. He had a history of asthma, chronic otitis media with effusion, and obstructive sleep apnea and had undergone 3 sets of tympanostomy tubes and an adenotonsillectomy. He had no history of fevers or other constitutional symptoms. Physical examination demonstrated a 3-cm firm and tender right parotid mass. Clear saliva could be expressed from the Stensen duct. A computed tomographic (CT) scan was performed, showing a discrete 2 × 2-cm necrotic mass in the right parotid gland (Figure, A). A fine-needle aspirate (FNA) yielded a cellular sample with spindloid features, suggesting a neoplasm of uncertain subtype. A broad differential diagnosis was raised, including both benign and malignant salivary neoplasms. Per recommendation of the head and neck multidisciplinary tumor board, the patient underwent total parotidectomy and neck dissection because the mass was grossly infiltrative of the parotid, and several enlarged level IB and II lymph nodes were observed at the time of surgery. The mass was shaved off the marginal mandibular branch of the facial nerve because it was adherent to it. Permanent histopathologic images showed normal parotid gland architecture effaced by confluent granulomata with Langhans-type giant cells and central necrosis (Figure, B). Additional studies, including flow cytometry and tissue cultures, were obtained.A, Coronal computed tomographic (CT) image demonstrating right parotid mass and level II adenopathy. B, The normal parotid gland architecture is effaced by confluent granulomata with necrosis (hematoxylin-eosin, original magnification ×200). What Is the Diagnosis?

Mucoepidermoid carcinoma

Infectious pseudotumor

Histiocytic necrotizing lymphadenitis

Granulomatosis with polyangiitis

B. Infectious pseudotumor

B

Infectious pseudotumor

Findings from a intraoperative frozen section were consistent with a granulomatous or infectious process with reactive adenopathy despite its clinical appearance. The patient was found to have a fungal abscess of the parotid gland due to Scopulariopsis species, which grew in 2 sets of fungal cultures. All other bacterial and viral cultures and polymerase chain reaction results were negative for organisms. Additional special staining, Grocott methenamine silver and periodic acid–Schiff, were performed on the tissue samples, but results were negative. To date, he has been followed for 36 months, and there has been no evidence of recurrence. He experienced a mild case of Frey syndrome, which he has managed with intermittent use of topical antiperspirants.Parotid masses in the pediatric patient are uncommon and present a diagnostic challenge. Most masses have an infectious or benign etiology; however, upward of 16% of parotid masses may harbor a malignant neoplasm.1 Thus, although parotid masses are less common in pediatric than adult patients, there is a higher incidence of cancer. Workup, including FNA, should be attempted if the patient is cooperative, and imaging, including ultrasonography and/or CT, should be obtained if surgical intervention is being considered.2 Compared with adults, infectious pseudotumors are a more common in the pediatric population and thus actively considered in the differential diagnosis. In this case, the preoperative imaging was especially concerning for a malignant process, but a culture could have been considered in addition to cytology.The parotid gland is the most likely salivary gland to become infected. Usual pathogens of parotid infections include Streptococcus aureus, Streptococcus species, and rarely, gram-negative bacteria.3 Fungal etiologies are exceedingly rare, and Scopulariopsis species have never been previously reported as the pathogenic agent of a parotid abscess. Scopulariopsis is a common saprophytic, filamentous fungi found in the environment in soil and organic wastes. This mold has a wide geographic distribution and is a common cause of noninvasive infections, including onychomycosis, keratitis, and otomycosis.4,5 Rarely does this organism cause invasive disease, but it has been shown to affect both immunocompetent and immunocompromised patients. Previously documented locations have included the sinuses, endocardium, brain, lungs, skin, and deep cutaneous tissues.6 It was postulated that the patient’s respiratory disease predisposed him to this unusual infection, but results from an exhaustive immunologic and rheumatologic workup were negative for any immunodeficiency or autoimmune disease. Infectious disease specialists did not recommend antifungal therapy as by the time the cultures resulted, the patient had no signs of persistent infection or wound complications.Our case involved aggressive radiographic and intraoperative features with nondiagnostic cytology that increased the concern for malignancy. Jaryszak et al2 formulated an algorithm for an approach of solid (nonvascular) pediatric parotid gland lesions where surgery is recommended in cases of nondiagnostic biopsies or in uncooperative patients for whom a biopsy is unable to be performed. The use of intraoperative frozen section can help guide the extent of surgery; however, the lesion in this case wrapped around the marginal mandibular nerve intraoperatively, requiring extensive dissection to separate the mass from the surrounding structures. These findings led to a complete neck dissection owing to continued suspicion of malignant neoplasm despite the nonneoplastic frozen section. Without such concerning gross findings, decision whether to perform a neck dissection can await final pathologic analysis.This is the first reported case of Scopulariopsis species infection within the parotid gland. This unusual and unique clinical entity demonstrates some of the challenges encountered when treating pediatric parotid masses. While the ultimate diagnosis was atypical, potential infectious or immunologic etiologies should be carefully considered in other similar clinical situations.

General

A young boy presented with a 4-week history of an enlarging right facial mass, which had not responded to a course of azithromycin prescribed by his pediatrician. He had a history of asthma, chronic otitis media with effusion, and obstructive sleep apnea and had undergone 3 sets of tympanostomy tubes and an adenotonsillectomy. He had no history of fevers or other constitutional symptoms. Physical examination demonstrated a 3-cm firm and tender right parotid mass. Clear saliva could be expressed from the Stensen duct. A computed tomographic (CT) scan was performed, showing a discrete 2 × 2-cm necrotic mass in the right parotid gland (Figure, A). A fine-needle aspirate (FNA) yielded a cellular sample with spindloid features, suggesting a neoplasm of uncertain subtype. A broad differential diagnosis was raised, including both benign and malignant salivary neoplasms. Per recommendation of the head and neck multidisciplinary tumor board, the patient underwent total parotidectomy and neck dissection because the mass was grossly infiltrative of the parotid, and several enlarged level IB and II lymph nodes were observed at the time of surgery. The mass was shaved off the marginal mandibular branch of the facial nerve because it was adherent to it. Permanent histopathologic images showed normal parotid gland architecture effaced by confluent granulomata with Langhans-type giant cells and central necrosis (Figure, B). Additional studies, including flow cytometry and tissue cultures, were obtained.A, Coronal computed tomographic (CT) image demonstrating right parotid mass and level II adenopathy. B, The normal parotid gland architecture is effaced by confluent granulomata with necrosis (hematoxylin-eosin, original magnification ×200).

what is the diagnosis?

What is your diagnosis?

Mucoepidermoid carcinoma

Infectious pseudotumor

Histiocytic necrotizing lymphadenitis

Granulomatosis with polyangiitis

b

male

11-20

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2664071

A 7-month-old infant presented to the otolaryngology clinic for noisy breathing. His noisy breathing had been present since birth, constant, exacerbated with feeding, sleeping, and supine positioning. He fed poorly from the bottle with frequent choking, grunting, and irritability, and had minimal weight gain with 1 cyanotic event while feeding. His medical history was significant for prematurity, born at 26 weeks, and a 60-day intubation during a 99-day neonatal intensive care unit stay. The physical examination was remarkable only for biphasic stridor and a weak cry. Nasopharyngolaryngoscopy showed no laryngomalacia, laryngeal lesions, or cord paralysis.Shortly after this visit, the patient presented to the emergency department with increased work of breathing, tachypnea, retractions, weak cry, and stridor. Examination was significant for subcostal retractions, and biphasic stridor. Due to a lack of response to racemic epinephrine, albuterol, and steroids, he was admitted to the intensive care unit for heliox and intravenous steroids, resulting in mild improvements. A viral panel was positive for rhinovirus. A few days later he was taken to the operating room for direct laryngoscopy and bronchoscopy.During sedation, a prolonged expiratory phase with quick chest wall rise on inspiration and slow fall with expiration was observed. Capnography showed a restrictive “shark fin” waveform (Figure, A). The direct laryngoscopy and bronchoscopy were performed (Figure, C and D).Images show the (A) preintervention and (B) postintervention capnography wave form as seen on the anesthesia monitor. Endoscopy images on (C) expiration and (D) inspiration. What Is Your Diagnosis?

Laryngotracheitis (croup)

Subglottic cyst

Subglottic stenosis

Subglottic hemangioma

B. Subglottic cyst

B

Subglottic cyst

Subglottic cysts (SC) are rare causes of airway obstruction in pediatric patients with an estimated incidence of 1.9 for 100 000 living births.1 Subglottic cysts are most commonly found in patients born preterm with studies citing a prematurity incidence of 93% to 100%2; SC are commonly misdiagnosed and can be difficult to treat in neonates presenting with complex comorbidities.The pathogenesis is unclear but hypothesized to be due to mucosal damage to the subglottis resulting in fibrosis causing blockage of the subepithelial secretory mucous glands.3 Histologically, the mucosal secretory glands are most prominent in the subglottis. Endotracheal intubation is the most common mechanism causing mucosal damage.4 Subglottic cysts occur mostly commonly along the left lateral subglottis and are hypothesized to be secondary to intubations occurring from the right side of the mouth by right-handed operators resulting left-sided subglottis mucosal damage.5Patients often present with biphasic stridor, with expiratory stridor more pronounced than inspiratory stridor owing to the ball-valve effect. Dysphonia, apneic episodes, and history of respiratory distress secondary to recurrent respiratory infections are also common.Treatment of SC consists of cyst marsupialization with a cold technique, coblation, or lasers. For this patient, the SC were lanced with a sickle knife, and a microdebrider was used to remove the remaining cyst wall. Recurrences of SC are frequent with a reported recurrent incidence of 25% to 73%.2,6,7 For this reason, careful follow-up with repeat endoscopies is recommended in a 1-month to 6-month interval until cysts have fully resolved. This patient was taken for repeat direct laryngoscopy and bronchoscopy at 1 month and SC had not recurred. The patient has been followed clinically and has not exhibited any symptoms prompting return to the operating room.Capnography is the monitoring of carbon dioxide concentration. The waveform represents the amount of carbon dioxide during ventilation which can help diagnose the cause of respiratory distress. The normal waveform is a rectangular shape, starting with exhalation and a sharp spike with exhaled air, followed by a plateau, and then a sharp downward spike during inhalation. In the case of airway obstruction, such as a ball-valving subglottic lesion, air is trapped creating a curve in the initial spike and plateau or “shark fin” appearance (Figure, A).8 Capnography is able to provide real-time feedback on how well the intervention is working, as in this case, once the cyst was removed, the capnography instantly returned to a normal rectangular shape (Figure, B).The typical differential diagnosis of biphasic stridor in an infant is laryngomalacia, subglottic stenosis, subglottic hemangioma, and laryngotracheitis. In the presence of intubation history, a high suspicion for subglottic pathology is key. Initially, this patient was thought to have laryngotracheitis owing to the acute onset of symptoms; however, the lack of response to medical therapy and endoscopy findings were not consistent with this pathology. The laryngotracheitis endoscopic finding is subglottic erythema and edema resulting in the double-cord sign.9 The clinical presentation for a subglottic hemangioma is rapid onset of respiratory difficulty usually by 4 months of age, an endoscopic finding of a submucosal lesion, with 29% having a cutaneous hemangioma in the beard distribution.10 Subglottic stenosis has a similar clinical presentation as this patient. Subglottic cysts and subglottic stenosis can be associated and can be seen as discrete lesions on endoscopy. Subglottic cysts can be buried beneath the mucosa giving the appearance of a soft subglottic stenosis.6The presence of subglottic cysts should be considered in a child with upper airway symptoms and history of prematurity and intubation. Diagnosis and therapeutic intervention is made with endoscopy. An expiratory restrictive pattern on capnography can be a suggestive of a ball-valving cyst. A high recurrence rate necessitates follow-up endoscopy and prolonged observation.

General

A 7-month-old infant presented to the otolaryngology clinic for noisy breathing. His noisy breathing had been present since birth, constant, exacerbated with feeding, sleeping, and supine positioning. He fed poorly from the bottle with frequent choking, grunting, and irritability, and had minimal weight gain with 1 cyanotic event while feeding. His medical history was significant for prematurity, born at 26 weeks, and a 60-day intubation during a 99-day neonatal intensive care unit stay. The physical examination was remarkable only for biphasic stridor and a weak cry. Nasopharyngolaryngoscopy showed no laryngomalacia, laryngeal lesions, or cord paralysis.Shortly after this visit, the patient presented to the emergency department with increased work of breathing, tachypnea, retractions, weak cry, and stridor. Examination was significant for subcostal retractions, and biphasic stridor. Due to a lack of response to racemic epinephrine, albuterol, and steroids, he was admitted to the intensive care unit for heliox and intravenous steroids, resulting in mild improvements. A viral panel was positive for rhinovirus. A few days later he was taken to the operating room for direct laryngoscopy and bronchoscopy.During sedation, a prolonged expiratory phase with quick chest wall rise on inspiration and slow fall with expiration was observed. Capnography showed a restrictive “shark fin” waveform (Figure, A). The direct laryngoscopy and bronchoscopy were performed (Figure, C and D).Images show the (A) preintervention and (B) postintervention capnography wave form as seen on the anesthesia monitor. Endoscopy images on (C) expiration and (D) inspiration.

what is your diagnosis?

What is your diagnosis?

Laryngotracheitis (croup)

Subglottic cyst

Subglottic stenosis

Subglottic hemangioma

b

male

0-10

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2644959

A man in his 60s presented with a 3-month history of intertrigo involving his groin that he had been treating with a combination of clotrimazole cream, 1%, and hydrocortisone cream, 1%. His intertrigo improved, but he then developed bright red, burning and painful nodules around his scrotum (Figure 1). His medical history included prostate cancer, hypertension, anxiety disorder, hyperlipidemia, gastroesophageal reflux disease, and diverticulosis. His medications included omeprazole, alprazolam, amlodipine besylate, atenolol, simvastatin, and valsartan. On physical examination, there were 2 symmetrical solitary erythematous nodules in the right and left inguinal folds adjacent to the scrotum.Clinical image of well-demarcated erythematous solitary papule in the right inguinal fold. What Is Your Diagnosis?

Deep fungal infection

Cutaneous malakoplakia

Granular cell tumor

Metastatic prostate cancer

B. Cutaneous malakoplakia

B

Cutaneous malakoplakia

Histopathological findings included epidermal ulceration overlying a diffuse dermal proliferation composed of sheets of histiocytes with eosinophilic granular cytoplasm. Intracytoplasmic Michaelis-Gutmann bodies were present appearing as basophilic, somewhat laminated intracytoplasmic inclusion bodies measuring 5 to 8 μm in diameter. The bodies were highlighted with iron (Prussian blue) and calcium (Von Kossa) stains. A background population of many plasma cells and a few neutrophils was also noted (Figure 2 and Figure 3).Excisional biopsy pathologic analysis showing ulcerated nodule with sheeted dermal proliferation and histiocytes with pink granular cytoplasm focally containing laminated slightly basophilic inclusions (Michaelis-Gutmann bodies) (arrowheads) with background plasma cells and neutrophils (hematoxylin-eosin, original magnification ×400).A, Prussian blue, and B, Von Kossa stains highlight Michaelis-Gutmann bodies (original magnification ×400).Malakoplakia is a granulomatous disease that is thought to be caused by inadequate destruction of bacteria by macrophages. It can be seen in internal organs, most often the genitourinary tract; but rare cutaneous cases have been described.1-4 In the rare cutaneous cases in the literature, it is most often reported in the perianal/genital area, but other cutaneous sites may also be affected.1 It is more commonly seen in immunocompromised individuals, specifically in patients with a history of organ transplant, human immunodeficiency virus infection, and diabetes mellitus.2 Clinical presentation of malakoplakia is variable, and diagnosis is made with skin biopsy and histological detection of Michaelis-Gutmann bodies within the eosinophilic granular cytoplasm of histiocytes (von Hansemann cells). Michaelis-Gutmann bodies are basophilic cytoplasmic inclusions that may be highlighted by periodic acid–Schiff, Prussian blue, or Von Kossa stains. Michaelis-Gutmann bodies are thought to represent iron and calcium deposits of residual bacteria. Culture of the lesions can yield bacteria, most commonly coliform bacilli such as Escherichia coli. There are many reports of successful treatment with prolonged antibiotic therapy (>30 days) appropriate for gram-negative bacterial organisms using fluoroquinolones, trimethoprim-sulfamethoxazole, clofazimine, or bethanechol chloride in addition to surgical excision.1,2 There have been no reports of malignant transformation.4Our patient was a healthy individual with no history of immunosuppression or diabetes. Tissue culture for fungus and atypical mycobacteria had negative results; however, tissue culture for bacteria did grow E coli. Our patient was given a 2-week course of ciprofloxacin, and on 3-week follow-up the lesions had resolved, leaving behind postinflammatory hyperpigmentation; therefore, antibiotic therapy was not continued for longer than 2 weeks. At 2-month follow-up, the patient was still clear of cutaneous malakoplakia lesions. The nodule involving the left groin was also excised, which has served as a successful treatment.

Dermatology

A man in his 60s presented with a 3-month history of intertrigo involving his groin that he had been treating with a combination of clotrimazole cream, 1%, and hydrocortisone cream, 1%. His intertrigo improved, but he then developed bright red, burning and painful nodules around his scrotum (Figure 1). His medical history included prostate cancer, hypertension, anxiety disorder, hyperlipidemia, gastroesophageal reflux disease, and diverticulosis. His medications included omeprazole, alprazolam, amlodipine besylate, atenolol, simvastatin, and valsartan. On physical examination, there were 2 symmetrical solitary erythematous nodules in the right and left inguinal folds adjacent to the scrotum.Clinical image of well-demarcated erythematous solitary papule in the right inguinal fold.

what is your diagnosis?

What is your diagnosis?

Cutaneous malakoplakia

Metastatic prostate cancer

Granular cell tumor

Deep fungal infection

a

male

61-70

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2648076

A previously healthy man in his 30s was referred to our department for evaluation of asymptomatic cutaneous lesions that had been present for 4 months. He had been treated with a course of high-potency topical corticosteroids without any improvement. Physical examination revealed annular red plaques with scale and superficial erosions over the trunk and extremities. Strikingly, plaques on both arms showed a corymbiform pattern, with a central and multiple satellite lesions (Figure, A). On the lower limbs, infiltrated plaques with prominent crusts were seen (Figure, B). Also, there were papulosquamous lesions on the left sole, but the palms were spared. The genital area was not involved. There was neither regional lymph node enlargement nor systemic involvement. Two biopsy specimens from both types of lesions were obtained for histopathologic evaluation, showing an identical histologic pattern (Figure, C and D). What Is Your Diagnosis?

Psoriasis

Lupus erythematosus

Secondary syphilis

T-cell lymphoma

C. Secondary syphilis

C

Secondary syphilis

Histological examination showed parakeratosis, epidermal hyperplasia, and a diffuse and dense lymphoid proliferation through the papillar and reticular dermis (Figure, C). This proliferation was composed of atypical lymphoid cells, which showed epidermotropism, and, after immunohistochemical staining, were positive for CD3 and CD8 (Figure, D). Although these findings initially oriented to a diagnosis of cutaneous T-cell lymphoma, the presence of a mixed psoriasiform and lichenoid pattern and a sparse number of plasma cells represented a clue for suspected syphilis infection. Finally, a specific immunohistochemical stain for Treponema pallidum showed several treponemas in reticular dermis.Results from rapid plasma reagin (RPR) serology were positive (titer of 1:128) as well as the more specific T pallidum hemagglutination assay and fluorescent treponemal antibody absorption test. An extended serological workup also revealed a previously undiagnosed human immunodeficiency virus (HIV) infection, with a 247 CD4 cell count and 175 000 viral copies/mL. Cerebrospinal fluid examination obtained from a lumbar puncture revealed normal cell count and protein levels with negative results from a venereal disease research laboratory test, ruling out underlying neurosyphilis. Ophthalmologic evaluation did not reveal abnormalities. The patient started treatment for syphilis infection with 3 doses of benzathine penicillin G, and antiretroviral therapy was initiated after the first dose. Six months later, the RPR titer had declined to 1:8 and the HIV viral load was undetectable. Cutaneous lesions resolved with residual postinflammatory hyperpigmentation within 1 month.Syphilis is an infectious disease caused by T pallidum with protean cutaneous manifestations. The increase in the incidence of this disease has been unstoppable in the past 2 decades, particularly among HIV-infected individuals and certain groups, such as men who have sex with men.1The natural history of this disease is well known; if not treated it goes through 4 stages: primary, secondary, latent, and tertiary. Especially during the secondary period, it can present with atypical manifestations or with manifestations that, although typical, are very infrequent. Patients who are positive for HIV infection are more likely to manifest unusual presentations, such as overlap of the stages. This fact has been attributed to immune dysregulation, more of a qualitative rather than a quantitative type.2For all these reasons, syphilis is called “the great imitator” or “the great mimicker.” There are several reports on the literature of syphilis mimicking cutaneous lymphomas or pseudolymphomas.3,4 A diffuse and dense lymphocytic infiltrate in papillary dermis can lead to a histological diagnosis of lymphoma. In this patient, an inverted CD4/CD8 peripheral blood immunophenotype, due to a very low CD4+ lymphocyte count, made the infiltrate almost exclusively composed of CD8+ atypical lymphocytes. Based on this fact, along with atypical, eroded, rapidly progressing and widely distributed cutaneous lesions, a T-cell lymphoma was suspected. The initial differential diagnosis included CD8+ T-cell lymphoma mycosis fungoides type, and a diagnosis of primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma was initially made, and for this reason, the patient was initially referred to our lymphoma unit. However, the absence of monoclonal T-cell receptor rearrangement and the “corymbiform morphology” of the lesions caused us to suspect a syphilitic infection. Also, a combined psoriasiform and lichenoid dermatitis with a mixed inflammatory infiltrate that included plasma cells is a common histopathological pattern of secondary syphilis.Corymbose syphilis is a historical term derived from the Greek, describing a cluster of fruit or flowers; it reflects morphologic characteristics consisting of a central plaque surrounded by discrete papules along the periphery, resembling an explosion. Corymbose lesions have been described as a sign of relapse of reinfection.5 In the literature, most of the cases reporting syphilis mimicking T-cell lymphomas correspond to HIV-positive patients with fever, lymph node enlargement, and ulceronecrotic lesions in the context of malignant syphilis.6 Unlike these cases, our patient showed an excellent overall condition.The current increase in new cases of syphilis, especially among particular groups, is leading to the reemergence of forgotten old scenarios, which physicians should bear in mind within the differential diagnosis of their daily practice.

Dermatology

A previously healthy man in his 30s was referred to our department for evaluation of asymptomatic cutaneous lesions that had been present for 4 months. He had been treated with a course of high-potency topical corticosteroids without any improvement. Physical examination revealed annular red plaques with scale and superficial erosions over the trunk and extremities. Strikingly, plaques on both arms showed a corymbiform pattern, with a central and multiple satellite lesions (Figure, A). On the lower limbs, infiltrated plaques with prominent crusts were seen (Figure, B). Also, there were papulosquamous lesions on the left sole, but the palms were spared. The genital area was not involved. There was neither regional lymph node enlargement nor systemic involvement. Two biopsy specimens from both types of lesions were obtained for histopathologic evaluation, showing an identical histologic pattern (Figure, C and D).

what is your diagnosis?

What is your diagnosis?

Lupus erythematosus

Secondary syphilis

T-cell lymphoma

Psoriasis

b

male

31-40

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2648856

A 40-year-old man of Scandinavian descent presented with enlarging, nonpainful upper extremity nodules developing over the preceding 9 months (Figure, A). He was renovating a commercial cannabis grow-house in California at time of onset. He described the construction site as being filled with intoxicating mold. He reported shortness of breath and a 20-pound weight loss. He denied recent travel or aquarium exposure. Most concerning was the inability to use his right upper extremity. Also, he developed a pathological fracture of his right foot (Figure, B). Clinical examination of his forearms revealed several yam-size (4-6 cm), nontender, nonulcerated, boggy subcutaneous nodules in a sporotrichoid pattern and large nodules scattered on his trunk and abdomen. There was no palpable lymphadenopathy or lower extremity lesions. His medical history is significant for diabetes mellitus type 2 and hypothyroidism. Medications included glipizide, metformin, and levothyroxine.A, Nodules are 4 to 6 cm in diameter on the right upper extremity. B, A pathological fracture on the fifth metatarsal on the right foot is indicated by the white arrowhead. C, Histopathology shows pale, nodular aggregations of inflammatory cells in the deep dermis, extending into the fibrotic subcutis, as well as (D) aggregations composed of epitheliod histiocytes with few other inflammatory cells, so called “naked granulomas.”The patient’s laboratory tests showed fasting glucose of 122.0 mg/dL (reference range, 65.0-115.0 mg/dL); total calcium, 10.2 mg/dL (reference range, 8.5-10.5 mg/dL); blood urea nitrogen, 16.0 mg/dL (reference range, 10.0-24.0 mg/dL); creatinine, 1.30 mg/dL (reference range, 0.6-1.3 mg/dL); hemoglobin A1c, 6.7 (reference range, 4.0-6.0); 1,25-OH vitamin D 70, ng/mL (reference range, 15.9-55.6).Liver enzymes were within normal limits along with a negative purified protein derivative and quantiferon test results. A culture from a cutaneous nodule with microbial stains for bacteria, fungal culture, and acid-fast bacilli was negative. Computed tomography of the chest revealed hilar lymphadenopathy. An incisional biopsy of a nodule on the right wrist was obtained, which showed nodular aggregations of epithelioid histiocytes with sparse peripheral lymphocytes, extending from the deep dermis into the subcutis (Figure C and D). Periodic acid–Schiff diastase and Fite stains were negative for fungal and mycobacterial organisms, respectively. What Is Your Diagnosis?

Sporotrichosis

Subcutaneous sarcoidosis

Tumoral calcinosis

Erythema nodosum

B. Subcutaneous sarcoidosis

B

Subcutaneous sarcoidosis

Analysis of the biopsy specimen showed deep dermal sarcoidal granulomas extending into the subcutis and no evidence of infection, which in combination with his clinical presentation, is consistent with sarcoidosis with cutaneous, pulmonary, metabolic, and bone involvement. He was started on 40 mg of prednisone daily, methotrexate 15mg/week, and hydroxychloroquine 200 mg twice daily. After 12 weeks of therapy, the lesions resolved and he was able to return back to work with full mobility. His pulmonary function improved throughout the course of therapy.Darier-Roussy sarcoidosis is a rare subcutaneous manifestation of sarcoidosis, affecting approximately 1% to 4% of patients with sarcoidosis. It was originally described in 1904 by the French dermatologist Ferdinand-Jean Darier and the Swiss-French pathologist Gustave Roussy.1 They believed mycobacteria was the inciting microbe. Darier-Roussy sarcoidosis has been associated with systemic and subcutaneous involvement.2 Clinically, it is characterized by multiple asymptomatic to slightly tender flesh colored nodules commonly located on the extremities. In contrast with erythema nodosum, which is typically seen on the anterior lower extremities, the lesions of subcutaneous sarcoidosis are flesh colored, not tender, and are generally free of lymphocytic infiltrate.2,3Tumoral calcinosis is generally characterized by hypercalcemia with calcium salt deposits occurring in the hip and shoulder joints. Histologically, these masses are comprised of calcium phosphate and calcium hydroxyapatite.4 Sporotrichosis, an agricultural pathogen caused by the fungus Sporothrix schenckii, can manifest as linear subcutaneous nodules that may also show granulomatous inflammation; however, the organism can usually be identified through stains and by culture.5Sarcoidosis is often referred to as the “great imitator” and can have multiple presentations. Although it can involve multiple organ systems, cutaneous lesions are present in about 25% of patients. Common locations affected include the skin, lungs, lymph nodes, eyes, and heart.6 Skin lesions are heterogeneous and may be specific including facial granulomatous plaques, or present with nonspecific reactive findings, such as erythema nodosum. Biopsy can be beneficial by demonstrating epithelioid granulomatous inflammation.5Dysregulation of calcium metabolism is a complication of sarcoidosis. This results in hypercalcemia, hypercalciuria, and reduced bone density. The most common bones affected in sarcoidosis are the small bones of the hands and feet.7 Pathological fractures can occur and are attributed to abnormal calcium metabolism, often seen in patients with extensive cutaneous disease.7 Extra renal synthesis of calcitriol is central to the pathogenesis of abnormal calcium homeostasis. Calcitriol also has known immunosuppressive properties which may be an adaptive response allowing the inciting antigen or microbe to go unnoticed by the immune system.8Environmental, occupational exposure, and Scandinavian descent may have been multifactorial in this patient’s development of this rare variant of sarcoidosis. Positive associations of sarcoidal granulomatous development have been demonstrated in patients exposed to mold, mildew, musty odors, and pesticides.9 Worldwide, the highest incidence of sarcoidosis is in individuals of Nordic heritage.5The majority of microorganisms associated with marijuana are plant pathogens and may affect immunocompetent humans. There is a subgroup of opportunistic plant pathogens associated with postharvest and/or storage decay of marijuana, which may have been the case here. These include several Aspergillus species (including Aspergillus Mucor), Pseudomonas aeruginosa, Clostridium botulinum, and toxigenic Escherichia coli.10 Additionally, opportunistic organisms on cannabis plants can produce dangerous toxins or can elicit allergic reactions when inhaled.10 Perhaps bronchioalveolar lavage may be another way to further elucidate etiological factors in systemic sarcoidosis.Despite significant advances in characterizing features of sarcoidosis, the underlying pathophysiological cause remains unclear. As marijuana is becoming a more accepted form of medical therapy for patients, education in its procurement and dissemination is vital for the public’s health.

Dermatology

A 40-year-old man of Scandinavian descent presented with enlarging, nonpainful upper extremity nodules developing over the preceding 9 months (Figure, A). He was renovating a commercial cannabis grow-house in California at time of onset. He described the construction site as being filled with intoxicating mold. He reported shortness of breath and a 20-pound weight loss. He denied recent travel or aquarium exposure. Most concerning was the inability to use his right upper extremity. Also, he developed a pathological fracture of his right foot (Figure, B). Clinical examination of his forearms revealed several yam-size (4-6 cm), nontender, nonulcerated, boggy subcutaneous nodules in a sporotrichoid pattern and large nodules scattered on his trunk and abdomen. There was no palpable lymphadenopathy or lower extremity lesions. His medical history is significant for diabetes mellitus type 2 and hypothyroidism. Medications included glipizide, metformin, and levothyroxine.A, Nodules are 4 to 6 cm in diameter on the right upper extremity. B, A pathological fracture on the fifth metatarsal on the right foot is indicated by the white arrowhead. C, Histopathology shows pale, nodular aggregations of inflammatory cells in the deep dermis, extending into the fibrotic subcutis, as well as (D) aggregations composed of epitheliod histiocytes with few other inflammatory cells, so called “naked granulomas.”The patient’s laboratory tests showed fasting glucose of 122.0 mg/dL (reference range, 65.0-115.0 mg/dL); total calcium, 10.2 mg/dL (reference range, 8.5-10.5 mg/dL); blood urea nitrogen, 16.0 mg/dL (reference range, 10.0-24.0 mg/dL); creatinine, 1.30 mg/dL (reference range, 0.6-1.3 mg/dL); hemoglobin A1c, 6.7 (reference range, 4.0-6.0); 1,25-OH vitamin D 70, ng/mL (reference range, 15.9-55.6).Liver enzymes were within normal limits along with a negative purified protein derivative and quantiferon test results. A culture from a cutaneous nodule with microbial stains for bacteria, fungal culture, and acid-fast bacilli was negative. Computed tomography of the chest revealed hilar lymphadenopathy. An incisional biopsy of a nodule on the right wrist was obtained, which showed nodular aggregations of epithelioid histiocytes with sparse peripheral lymphocytes, extending from the deep dermis into the subcutis (Figure C and D). Periodic acid–Schiff diastase and Fite stains were negative for fungal and mycobacterial organisms, respectively.

what is your diagnosis?

What is your diagnosis?

Sporotrichosis

Tumoral calcinosis

Subcutaneous sarcoidosis

Erythema nodosum

c

male

31-40

White

original

https://jamanetwork.com/journals/jamapediatrics/fullarticle/2654882

An 11-year-old boy of East-Asian descent presented to the hospital with an 8-month history of progressive vision loss, night blindness, and light sensitivity. He also had a long-standing complaint of dry eyes. His medical history included diagnoses of eczema and multiple food allergies. Owing to concerns about food triggers of his eczema, the child had a restrictive diet consisting solely of potato, pork, lamb, apples, cucumber, and Cheerios. There was no history of redness, discharge, or trauma to the eyes. The vision loss was not associated with pain, headache, fever, or photopsias (flashes of light). On examination, the child’s visual acuity was limited to detecting hand motion at 30 cm. His conjunctiva had dry, keratinized patches with foamy appearance (Figure 1A). The cornea showed areas of marked epitheliopathy with opacity (Figure 1B). His pupils were equal and reactive to light with no relative afferent pupillary defect. His funduscopic examination showed mild optic nerve pallor. He had normal extraocular movements.A, Photograph of the patient’s eye before treatment. Arrowheads indicate dry keratinized patches (Bitot spots). B, Photograph of the patient’s eye before treatment demonstrating marked corneal epitheliopathy with opacity. What Is Your Diagnosis?

Glaucoma

Vitamin A deficiency

Sjögren syndrome

Bilateral cataracts

B. Vitamin A deficiency

B

Vitamin A deficiency

This patient’s diagnosis was made based on a history of a limited diet and classic findings of xerophthalmia (severe dry eye) and Bitot spots on ophthalmologic examination. His vitamin A level (drawn on presentation) was 14.33 μg/dL (normal range, 25.79-48.71; to convert to micromoles per liter, multiply by 0.0349).Typical food sources for vitamin A include various plant/animal sources, such as carrots, sweet potatoes, dark leafy green vegetables, fish, liver, and butter/margarine.1 Vitamin A deficiency is generally a result of poor dietary intake and represents a major cause of preventable childhood blindness. Vitamin A deficiency is generally thought of as a disease that primarily affects people in low-resource environments, such as countries in the developing world, where food choices are limited and malnutrition is endemic.2 Current guidelines recommend regular supplementation at various doses based on age in populations at risk for vitamin A deficiency. These steps have been shown in clinical trials to decrease all-cause and diarrhea-related mortality as well as morbidity associated with measles infections.3 Xerophthalmia describes the conjunctival xerosis (dryness), keratinization, and heaping of material, with the creation of Bitot spots, characteristic of vitamin A deficiency (Figure 1A). These findings are the natural response to exposure of the conjunctiva to dry conditions. This can be a result of various conditions associated with abnormal eyelid closure or lacrimal gland dysfunction (eg, vitamin A deficiency or Sjögren syndrome). Nonocular manifestations of vitamin A deficiency include growth restriction and relative immune deficiency.Vitamin A is also essential for vision by allowing normal functioning of photoreceptors. Vitamin A is particularly important for the function of rhodopsin (the photosensitive pigment in rod cells). As such, visual impairment predominantly affects night vision. However, as this patient demonstrates, cone photoreceptors may also become affected in severe deficiencies with loss of normal vision. Vitamin A, in the form of retinol, undergoes a series of biochemical changes, which results in the conduction of nerve impulses along the optic nerve, affecting the perception of light and color. In general, a serum retinol level less than 20.06 μg/dL is considered low; however, clinical correlates are essential.1The patient started receiving megadoses of vitamin A, consisting of 200 000 IU daily for 2 days followed by a third dose 2 weeks later based on the findings of xerophthalmia and vision loss, along with his limited intake of foods rich in vitamin A. This is the standard of care presented by the World Health Organization for treatment of vitamin A deficiency associated with xerophthalmia.4 Follow-up examination 6 weeks after vitamin A supplementation showed major improvements. Visual acuity improved to 20/800 bilaterally, and the xerophthalmia with Bitot spots resolved (Figure 2). Vision loss associated with vitamin A deficiency can be reversible; however, in cases with established optic atrophy, as was the case in this patient, a degree of vision loss is likely permanent.5 This patient illustrates the importance of considering micronutrient deficiencies in high-resource settings, particularly in persons for which a diet rich in various food sources is not evident, such as children with highly restrictive diets. Vitamin A deficiency is an important consideration when such patients present with severe dry eyes or vision loss.

Pediatrics

An 11-year-old boy of East-Asian descent presented to the hospital with an 8-month history of progressive vision loss, night blindness, and light sensitivity. He also had a long-standing complaint of dry eyes. His medical history included diagnoses of eczema and multiple food allergies. Owing to concerns about food triggers of his eczema, the child had a restrictive diet consisting solely of potato, pork, lamb, apples, cucumber, and Cheerios. There was no history of redness, discharge, or trauma to the eyes. The vision loss was not associated with pain, headache, fever, or photopsias (flashes of light). On examination, the child’s visual acuity was limited to detecting hand motion at 30 cm. His conjunctiva had dry, keratinized patches with foamy appearance (Figure 1A). The cornea showed areas of marked epitheliopathy with opacity (Figure 1B). His pupils were equal and reactive to light with no relative afferent pupillary defect. His funduscopic examination showed mild optic nerve pallor. He had normal extraocular movements.A, Photograph of the patient’s eye before treatment. Arrowheads indicate dry keratinized patches (Bitot spots). B, Photograph of the patient’s eye before treatment demonstrating marked corneal epitheliopathy with opacity.

what is your diagnosis?

What is your diagnosis?

Glaucoma

Vitamin A deficiency

Bilateral cataracts

Sjögren syndrome

b

male

11-20

Asian

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2656355

A 48-year-old man presented to the emergency department with a 1-week history of worsening right lower quadrant tenderness and fullness. This was associated with diarrhea, vomiting, fevers, and chills. He reported some relief of symptoms with loperamide. He denied any history of weight loss, melena, or hematochezia. Other than a previous open hemorrhoidectomy, the patient had no significant medical history. Of note, he had no family history of intestinal disease.On examination, he had a fever with a temperature of 39°C and tachycardia with a heart rate of 102 beats per minute. On abdominal examination, there was localized tenderness with guarding and fullness in the right lower quadrant. Results from his blood laboratory investigations demonstrated leukocytosis, with white blood cell count of 17 000/µL (to convert to ×109/L, multiple by 0.001) and a C-reactive protein level of 205 mg/L (to convert to nmol/L, multiple by 9.524). However, given the clinical history, the patient underwent a computed tomographic (CT) scan of the abdomen and pelvis with intravenous contrast (Figure 1). He then underwent an exploratory laparotomy. Transverse computed tomographic scan indicated a large right-sided inflammatory phlegmon measuring 7.5 cm in transverse diameter in a 48-year-old man. What Is Your Diagnosis?

Desmoid tumor

Acute appendicitis

Lymphoma

Carcinoid tumor

B. Acute appendicitis

B

Acute appendicitis

The CT scan demonstrated a right sided 7.5-cm inflammatory mass with fluid and air, as well as a calcified density consistent with an appendicolith. At the surgical procedure, the patient had a perforated retrocecal appendix. There was a phlegmon with a confluent mesenteric ulcer extending from the small bowel mesentery into the right mesocolon. Based on these findings, an ilecolic resection was conducted, rather than a simple appendectomy. The affected region of mesentery was included as part of the resection.Appendicitis is the most common cause of an acute abdomen. Inflammation of the appendix can be categorized as simple or complicated, and CT imaging can differentiate between both. Clinically, a palpable mass is often present. This is confirmed by an inflammatory phlegmon or circumscribed abscess on CT imaging. Management of complicated appendicitis remains controversial, and the most common approach involves initial conservative therapy with interval appendectomy thereafter.1Classic illustrations of the mesentery by Leonardo da Vinci, Andreas Vesalius, and Bartolomeo Eustachius depicted a continuous structure. By contrast, 19th-century depictions described multiple separate mesenteries. This teaching was dogmatically indoctrinated in all text during the 20th century.2,3 In 2014, investigation of the mesentery demonstrated continuity between the small intestinal and right mesocolon (as well as more distal regions).4-6 Continuity has implications for multiple disease processes, including complicated retrocecal appendicitis.The mesentery maintains connectivity between the intestine and systems of the body.7 However, this is a 2-edged sword as it means the mesentery is susceptible to diseases involving associated structures.8 Conditions involving mesentery can be divided to primary and secondary mesenteropathies. The latter arises from direct or systematic spread of a disease process such as intestinal malignancy or inflammation.9,10 The present case involves the secondary development of a large mesenteric ulcer as part of a phlegmon complicating retrocecal appendicitis. Mesenteric ulceration can occur in the setting of severe local inflammation, infection, or as part of a neoplastic process. On this basis, an ileocolic resection including the intervening and affected mesentery was conducted. During laparotomy, the patient’s ascending colon, ascending mesocolon, terminal ileum, and its mesentery were detached by separating components of the mesofascial plane (ie, the mesentery and fascia) (Figure 2). Histology confirmed a gangrenous appendix with a purulent inflammatory reaction involving the small- and large-bowel margins. No feature of chronic inflammatory bowel disease or malignancy was seen. This patient recovered well, was discharged on postoperative day 5, and required no further treatment.Intraoperative findings included extensive mesenteric ulceration of the undersurface of the mesentery that is normally flattened against the posterior abdominal wall.

Surgery

A 48-year-old man presented to the emergency department with a 1-week history of worsening right lower quadrant tenderness and fullness. This was associated with diarrhea, vomiting, fevers, and chills. He reported some relief of symptoms with loperamide. He denied any history of weight loss, melena, or hematochezia. Other than a previous open hemorrhoidectomy, the patient had no significant medical history. Of note, he had no family history of intestinal disease.On examination, he had a fever with a temperature of 39°C and tachycardia with a heart rate of 102 beats per minute. On abdominal examination, there was localized tenderness with guarding and fullness in the right lower quadrant. Results from his blood laboratory investigations demonstrated leukocytosis, with white blood cell count of 17 000/µL (to convert to ×109/L, multiple by 0.001) and a C-reactive protein level of 205 mg/L (to convert to nmol/L, multiple by 9.524). However, given the clinical history, the patient underwent a computed tomographic (CT) scan of the abdomen and pelvis with intravenous contrast (Figure 1). He then underwent an exploratory laparotomy. Transverse computed tomographic scan indicated a large right-sided inflammatory phlegmon measuring 7.5 cm in transverse diameter in a 48-year-old man.

what is your diagnosis?

What is your diagnosis?

Carcinoid tumor

Acute appendicitis

Desmoid tumor

Lymphoma

b

male

41-50

White

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2657534

A woman in her 50s with a history of systemic lupus erythematosus, congestive heart failure, and type 2 diabetes presented to the emergency department with worsening abdominal pain 1 day after discharge from an admission for similar abdominal pain. The patient described a 4-day history of progressively worsening abdominal pain and diarrhea and denied fevers, chills, diaphoresis, or any previous similar episodes. Her abdomen was distended and mildly tender, and her pain was disproportionate to the findings of her physical examination. There were no abnormal laboratory test findings. The abdominal computed tomography (CT) scan from her initial admission (Figure, A) and the abdominal CT angiogram on readmission (Figure, B) showed dramatic progression of her disease.A, Coronal view of computed tomography (CT) scan from 3 days prior to readmission demonstrating isolated duodenal thickening; B, coronal view of CT angiography scan on readmission demonstrating thickened small bowel and free fluid. What Is Your Diagnosis?

Mesenteric ischemia

Superior mesenteric venous thrombosis

Lupus enteritis

Superior mesenteric artery embolism

C. Lupus enteritis

C

Lupus enteritis

The patient was admitted to the medical intensive care unit. A rheumatology consultation was obtained, and she was given intravenous methyprednisolone, 1000 mg daily, for 4 days. The patient’s abdominal pain improved within 8 hours of methyprednisolone administration, and by hospital day 2, she was tolerating a diet of solid food.Systemic lupus erythematosus is an autoimmune-mediated chronic inflammatory disease with the potential to affect every organ system.1 Systemic lupus erythematosus affects the hematologic, renal, and central nervous systems most commonly, and presentations can be variable.1 Enteritis is a relatively rare sequela of systemic lupus erythematosus, typically presenting with signs and symptoms similar to those of mesenteric ischemia, with pain out of proportion to the findings on physical examination.2 In some studies, lupus enteritis is referred to as the most frequent possible cause of abdominal pain in patients with systemic lupus erythematosus2; alternatively, in other studies, lupus enteritis is cited as a relatively rare cause of abdominal pains, illustrating our lack of knowledge about this disease secondary to its relative rarity.3 Laboratory test findings are nonspecific and usually positive only for inflammatory markers.4 Computed tomography scans demonstrate severe bowel wall thickening (ie, target sign). Mesenteric fat stranding and engorged mesenteric vessels are also commonly observed.5 Bladder wall thickening is frequently found on CT scans. The patient also presented with a moderate degree of ascites.Given the grave findings on CT scans, lupus enteritis can appear on cursory glance to resemble mesenteric ischemia but is lacking the large vessel thrombosis and/or occlusion seen in that disease.5 Prompt recognition of lupus enteritis is key to preventing the sequelae of perforation, obstruction, or necrosis.Management of lupus enteritis consists of prompt administration of immunologic suppression, usually consisting of pulse doses of corticosteroids.4 Several practitioners have reported positive outcomes using alternative methods of immunosuppression such as cyclophosphamide. These are considered second-line therapies in cases in which corticosteroids have failed or are contraindicated.4,6 Patients usually respond well to immunosuppression, as was seen in our case, with complete resolution of abdominal pain within hours.Vigilant surgical attention is warranted for early recognition of clinical deterioration. Despite the relative paucity of literature on lupus enteritis, the pendulum has shifted from early surgical intervention toward medical management in the absence of absolute indications for surgical intervention such as bowel necrosis or perforation.There have been reports of the recurrence of lupus enteritis being associated with the degree of initial bowel wall thickening or the involvement of the urinary tract.7,8 Lymphopenia, elevated amylase, and hypoalbuminemia are reported to be associated with poorer outcomes.9In conclusion, lupus enteritis, while relatively rare, is an important diagnosis to consider for patients with systemic lupus erythematosus presenting with severe abdominal pain. Given the profound findings on CT scans, it is often the consultant surgeon determining the treatment for these patients. With appropriate immunosuppressive therapy, potentially morbid diagnostic operations can be avoided.9

Surgery

A woman in her 50s with a history of systemic lupus erythematosus, congestive heart failure, and type 2 diabetes presented to the emergency department with worsening abdominal pain 1 day after discharge from an admission for similar abdominal pain. The patient described a 4-day history of progressively worsening abdominal pain and diarrhea and denied fevers, chills, diaphoresis, or any previous similar episodes. Her abdomen was distended and mildly tender, and her pain was disproportionate to the findings of her physical examination. There were no abnormal laboratory test findings. The abdominal computed tomography (CT) scan from her initial admission (Figure, A) and the abdominal CT angiogram on readmission (Figure, B) showed dramatic progression of her disease.A, Coronal view of computed tomography (CT) scan from 3 days prior to readmission demonstrating isolated duodenal thickening; B, coronal view of CT angiography scan on readmission demonstrating thickened small bowel and free fluid.

what is your diagnosis?

What is your diagnosis?

Lupus enteritis

Superior mesenteric venous thrombosis

Superior mesenteric artery embolism

Mesenteric ischemia

a

female

51-60

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2650805

A 43-year-old construction worker experienced bilateral lower extremity crush injuries after a large heavy object fell onto his thighs, traumatically amputating his right leg. He also had a left leg degloving injury, distal femur fracture, and posterior knee dislocation with bleeding through the open fractures and wounds. He was profoundly hypotensive (blood pressure, 70/40 mm Hg) and anemic (hemoglobin level, 5.6 g/dL [to convert to grams per liter, multiply by 10]) from extensive blood loss. He was urgently transfused and taken to the operating room for bilateral lower extremity irrigation and drainage and reconstruction of the left leg. Unfortunately, postoperative infection necessitated a left leg above-knee amputation.The patient was admitted to the intensive care unit, intubated, and sedated for 1 month. On awakening, he reported that he was unable to see out of each eye. Bedside examination revealed no light perception vision with 7-mm pupils that were nonreactive bilaterally. Extraocular movements were full and there was no ptosis. Slitlamp examination findings were normal, and fundus photographs of the posterior pole in each eye are presented in the Figure. Magnetic resonance imaging of the brain performed earlier in the hospitalization was normal. The patient was previously healthy and did not take any medications.Appearance of the optic nerves in fundus photographs taken 4 weeks after the patient’s injury at work. The optic discs are characterized by diffuse pallor, with no evidence of edema or hemorrhages. The remainder of the posterior pole, including macula and vessels, appear normal bilaterally.Counsel the patient on the prognosis of his condition What Would You Do Next?

Test patient with optokinetic nystagmus drum

Repeat magnetic resonance imaging of the brain

Counsel the patient on the prognosis of his condition

Test pupils with dilute pilocarpine

Bilateral posterior ischemic optic neuropathy secondary to severe hypotension

C

Counsel the patient on the prognosis of his condition

In patients with severely reduced vision and significant blood loss, the main differential includes bilateral ischemic optic neuropathy (ION) and bilateral occipital infarcts. Acutely, both can produce normal-appearing optic discs, but the pupillary responses differ. In diseases causing no light perception vision by affecting the visual pathway anterior to the lateral geniculate nucleus, the pupils should be nonreactive or minimally reactive. With vision loss due to occipital infarcts, the pupils should remain briskly reactive. Axons providing input to the pupillary pathway leave the optic tract to enter the brachium of the superior colliculus and synapse in the pretectal nucleus of the midbrain. These axons bypass the visual cortex and thus are unaffected by occipital lesions.In this patient, fundus examination findings revealed diffuse optic disc pallor suggestive of bilateral optic atrophy (Figure). Optic disc pallor reflects axonal degeneration caused by pathology in the anterior visual pathway between the optic nerve and lateral geniculate nucleus, where retinal ganglion cells first synapse. The pattern of optic atrophy can further localize pathology. Optic tract lesions cause bow-tie atrophy of the contralateral optic disc, while chiasmal lesions produce bilateral bow-tie atrophy. Optic neuropathies preferentially affecting the papillomacular bundle (ie, hereditary and toxic etiologies) may produce temporal pallor. Acquired visual cortex lesions do not typically cause optic atrophy, as this would require trans-synaptic axonal degeneration. Although recent research suggests that retrograde trans-synaptic axonal degeneration may occur in occipital ischemia,1 the time course has not been clearly defined and likely takes longer than 4 to 6 weeks to manifest.In the context of severe anemia and hypotension, the most likely diagnosis was ION. Ischemic optic neuropathy can be characterized as anterior, presenting with optic disc edema, or posterior, which primarily affects the retrobulbar optic nerve, producing a normal-appearing optic disc in the acute setting.2 In both, disc pallor is seen after 4 to 6 weeks.2 We hypothesize that the orbital portions of the optic nerves were the primary site of injury in this patient, who did not have preexisting vascular risk factors. In otherwise healthy patients with severe hypotension and anemia, infarction is thought to occur in the orbital portion of the optic nerves, where thin pial blood vessels can be compressed by hypoxia-induced optic nerve edema.3 In patients with hypotension and preexisting arterioscleroses, exacerbation of baseline hypoperfusion from atherosclerotic hyalinosis of terminal juxtalaminar ciliary vessels may result in optic nerve infarction clinically indistinguishable from anterior ION.3 Hypotensive patients with neither anemia nor arteriosclerosis are more likely to experience visual loss from watershed infarcts in the parietal and occipital lobes, rather than ION.3 Unfortunately, because no ophthalmic examination was performed within 1 month after the trauma, we could not confirm the location of optic nerve infarction in this patient.To rule out functional visual loss, an optokinetic nystagmus drum (option 1) could have been used. A positive optokinetic nystagmus response approximates visual acuity to be 20/200 or better.4 Patients with functional vision loss have normal pupillary responses and optic disc appearance. In this patient, nonreactive mydriatic pupils and optic disc pallor reflected loss of pupillary pathway input. Repeating magnetic resonance imaging of the brain (option 2) would provide no further localizing value. Testing with pilocarpine (option 4) to rule out other causes of nonreactive mydriatic pupils was also unnecessary.Approximately 50% of patients with ION from severe blood loss experience some visual recovery, the degree of which is likely proportional to the severity and duration of hypotension and anemia.5 Unfortunately, there is no established treatment, and few patients fully recover vision. This patient was reevaluated 6 months later; visual acuity remained no light perception, and the ocular examination was unchanged.

Ophthalmology

A 43-year-old construction worker experienced bilateral lower extremity crush injuries after a large heavy object fell onto his thighs, traumatically amputating his right leg. He also had a left leg degloving injury, distal femur fracture, and posterior knee dislocation with bleeding through the open fractures and wounds. He was profoundly hypotensive (blood pressure, 70/40 mm Hg) and anemic (hemoglobin level, 5.6 g/dL [to convert to grams per liter, multiply by 10]) from extensive blood loss. He was urgently transfused and taken to the operating room for bilateral lower extremity irrigation and drainage and reconstruction of the left leg. Unfortunately, postoperative infection necessitated a left leg above-knee amputation.The patient was admitted to the intensive care unit, intubated, and sedated for 1 month. On awakening, he reported that he was unable to see out of each eye. Bedside examination revealed no light perception vision with 7-mm pupils that were nonreactive bilaterally. Extraocular movements were full and there was no ptosis. Slitlamp examination findings were normal, and fundus photographs of the posterior pole in each eye are presented in the Figure. Magnetic resonance imaging of the brain performed earlier in the hospitalization was normal. The patient was previously healthy and did not take any medications.Appearance of the optic nerves in fundus photographs taken 4 weeks after the patient’s injury at work. The optic discs are characterized by diffuse pallor, with no evidence of edema or hemorrhages. The remainder of the posterior pole, including macula and vessels, appear normal bilaterally.Counsel the patient on the prognosis of his condition

what would you do next?

What would you do next?

Test pupils with dilute pilocarpine

Counsel the patient on the prognosis of his condition

Repeat magnetic resonance imaging of the brain

Test patient with optokinetic nystagmus drum

b

male

41-50

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2652886

A man in his 60s presented to the emergency department with a 3-week history of numbness of the right side of the forehead and cheek and severe right-sided ocular discomfort that was relentless and kept him awake at night. He had been seen 2 weeks previously with similar symptoms and was diagnosed as having blepharitis and discharged with instructions for eyelid hygiene. His symptoms failed to improve, and he visited his family physician the following week. His physician prescribed a course of amoxicillin and clavulanate potassium, but the symptoms remained.The patient had no other ocular history or history of facial surgery. His medical history included ischemic heart disease and hypercholesterolemia, and he was an ex-smoker of 20 pack-years.Examination revealed unaided visual acuity of 20/20 OD and 20/20 OS. He had no evidence of proptosis, no relative afferent pupillary defect, and a full range of extraocular eye movement. Slitlamp examination demonstrated moderate bilateral blepharitis and extensive punctate keratopathy of the right eye. Findings from posterior segment examination were unremarkable. Examination of the cranial nerves demonstrated reduced sensation in the distribution of the ophthalmic and maxillary branches of the right trigeminal nerve, including complete corneal anesthesia. All other cranial nerve functions remained normal.Order computed tomography of the brain with angiographyPrescribe analgesia to treat atypical trigeminal neuralgia and refer the patient to a neurologistOrder contrast-enhanced magnetic resonance imaging of the brain What Would You Do Next?

Order computed tomography of the brain with angiography

Prescribe analgesia to treat atypical trigeminal neuralgia and refer the patient to a neurologist

Order contrast-enhanced magnetic resonance imaging of the brain

Continue treatment for blepharitis

Space-occupying lesion of the right Meckel cave

C

Order contrast-enhanced magnetic resonance imaging of the brain

The patient’s unilateral neurologic signs indicated a pathologic process centered on the right trigeminal nerve, and the involvement of the ophthalmic and maxillary nerves, but not the mandibular nerve, localized the lesion to the Meckel cave (MC). The MC is a mouth-shaped cavity at the anterior aspect of the middle cranial fossa. It houses the trigeminal nerve root ganglion and ophthalmic (V1), maxillary (V2), and mandibular (V3) branches until their exit at separate foramina.1 Lesions within the MC may present with pain, paresthesia, or motor dysfunction of the trigeminal nerve or its individual branches.2Contrast-enhanced magnetic resonance imaging of the brain revealed an enhancing mass centered within the MC, extending along the right trigeminal nerve (Figure 1A). The scan also identified 6 ring-enhancing lesions up to 4 mm in diameter within the cerebellar hemispheres (Figure 1A). There was a mass in the right frontal lobe (Figure 1B).Magnetic resonance image of the brain demonstrating an enhancing mass centered within the Meckel cave and extending along the right trigeminal nerve (A, white arrowhead), 6 ring-enhancing lesions up to 4 mm within the cerebellar hemispheres (A, yellow arrowhead), and an enhancing mass in the right frontal lobe (B, arrowhead). Both, axial view. A indicates anterior; L, left; P, posterior; and R, right.Owing to the presence of pain and the loss of function of the involved anatomical structures, the diagnosis is likely an infiltrative process, not blepharitis or atypical trigeminal neuralgia. Magnetic resonance imaging of the brain was the correct next step because the lesion was clinically localized to the MC. Computed tomography is unlikely to reveal soft-tissue masses on the skull base unless reactive or destructive bony changes are present or the lesion is particularly large.Because the brain lesions were suspected to be metastases, the patient was referred to the oncology department, and computed tomography (CT) of the chest, abdomen, and pelvis revealed a large, ill-defined mass in the superior lobe of the right lung with multiple abdominal metastases (Figure 2). Examination of a liver biopsy specimen revealed secondary small cell lung carcinoma.Computed tomographic scan of the chest revealing a large, ill-defined mass in the superior lobe of the right lung (arrowhead) with adjacent satellite nodules and associated with enlarged mediastinal and right hilar lymph nodes.Differential diagnoses of isolated dysfunction of unilateral ophthalmic and maxillary branches of the trigeminal nerve include trigeminal neuralgia, which may be subdivided into classic and symptomatic. In symptomatic trigeminal neuralgia, extrinsic lesions cause neuropathy.3 Causes of rare presentations of symptomatic trigeminal neuralgia include neurosarcoidosis, hematoma, and meningocele.4,5 These differential diagnoses overlap with more ominous space-occupying lesions, which should always be excluded. Differential diagnoses for MC tumors include meningiomas, schwannomas, and rarer secondary lesions from distal primary tumors or perineural extension of local tumors.2The intracranial lesions were initially reported as likely representing 3 different histologic types of schwannoma, meningioma, and metastases on radiologic examination; however, it is likely that all were secondary lung metastases. Cerase et al6 described a similar case of a presumed benign schwannoma of the MC in a patient who presented with sensory loss and paresthesia of the right cheek. An adenocarcinoma of the lung was detected incidentally on chest radiography performed before general anesthesia.Appropriate workup of patients with unfavorable signs is critical.2 Paresthesia, trigeminal motor deficits, and age older than 50 years at presentation (within the context of pain) have been reported as more typical of malignant tumors.2The patient was treated by the oncology department but declined further treatment after diagnosis. He was referred to palliative care and died 3 months after his first presentation.

Ophthalmology

A man in his 60s presented to the emergency department with a 3-week history of numbness of the right side of the forehead and cheek and severe right-sided ocular discomfort that was relentless and kept him awake at night. He had been seen 2 weeks previously with similar symptoms and was diagnosed as having blepharitis and discharged with instructions for eyelid hygiene. His symptoms failed to improve, and he visited his family physician the following week. His physician prescribed a course of amoxicillin and clavulanate potassium, but the symptoms remained.The patient had no other ocular history or history of facial surgery. His medical history included ischemic heart disease and hypercholesterolemia, and he was an ex-smoker of 20 pack-years.Examination revealed unaided visual acuity of 20/20 OD and 20/20 OS. He had no evidence of proptosis, no relative afferent pupillary defect, and a full range of extraocular eye movement. Slitlamp examination demonstrated moderate bilateral blepharitis and extensive punctate keratopathy of the right eye. Findings from posterior segment examination were unremarkable. Examination of the cranial nerves demonstrated reduced sensation in the distribution of the ophthalmic and maxillary branches of the right trigeminal nerve, including complete corneal anesthesia. All other cranial nerve functions remained normal.Order computed tomography of the brain with angiographyPrescribe analgesia to treat atypical trigeminal neuralgia and refer the patient to a neurologistOrder contrast-enhanced magnetic resonance imaging of the brain

what would you do next?

What would you do next?

Continue treatment for blepharitis

Order computed tomography of the brain with angiography

Prescribe analgesia to treat atypical trigeminal neuralgia and refer the patient to a neurologist

Order contrast-enhanced magnetic resonance imaging of the brain

d

male

61-70

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2653290

A 5-year-old girl was referred for evaluation of blepharoptosis of the left eye present since birth (Figure). Her mother reported that, since infancy, the child’s left eye has twitched during feeding and mealtimes. The patient was born at term; had an unremarkable delivery; and had no history of developmental delay, trauma, or systemic illness. Her ocular history was significant only for bilateral mixed astigmatism (−0.25 + 0.75 × 145 OD and −0.25 + 1.00 × 005 OS). There was no family history of strabismus, amblyopia, or congenital ptosis. Her best-corrected visual acuity was 20/30 OD and 20/40 OS. Pupils were reactive to light bilaterally, and there was neither an afferent pupillary defect nor anisocoria. Extraocular motility was full. There was notable asymmetry in the following eyelid measurements: palpebral fissure height (10 mm OD; 5-6 mm OS) and margin reflex distance 1 (3.5 mm OD; 0.5-1.5 mm OS). In addition, elevation of the left upper eyelid was observed with lateral jaw thrust but not with anterior-posterior jaw movements or with mouth opening and closing. The levator function was 14 mm OU, and the margin crease distances were 5 mm OD and 6 mm OS. The remainder of the anterior and posterior segment slitlamp examination was unremarkable.External photographs of blepharoptosis of the left eye in the neutral jaw position (A) and the left upper eyelid elevated with rightward jaw thrust (B).Discuss carefully observing vs surgical repair of the ptosis What Would You Do Next?

Conduct genetic testing

Perform urgent neuroimaging

Start oral corticosteroids

Discuss carefully observing vs surgical repair of the ptosis

Marcus Gunn syndrome (congenital trigemino-oculomotor synkinesis)

D

Discuss carefully observing vs surgical repair of the ptosis

This patient had Marcus Gunn syndrome, a congenital synkinesis characterized by unilateral blepharoptosis with elevation of the ptotic eyelid during mouth or jaw movements. First described by Robert Marcus Gunn in 1883, this condition is thought to arise from aberrant connections between the oculomotor nerve and the mandibular branch of the trigeminal nerve.1,2 It is also known as congenital trigemino-oculomotor synkinesis because there is simultaneous involuntary contraction of the levator palpebrae superioris with contraction of the ipsilateral external pterygoid muscle or, less commonly, the internal pterygoid muscle. Winking movements of the ptotic eyelid may be elicited by mouth opening, anterior jaw movement, contralateral jaw thrust, chewing, sucking, or nursing.Among patients presenting for evaluation of congenital ptosis, the prevalence of Marcus Gunn syndrome may be as high as 5%.3 Common associated findings include strabismus in nearly 60% of cases, double elevator palsy in 8% to 25% of cases, and amblyopia in an estimated 23% to 59% of affected individuals.3,4 Amblyopia in affected individuals is most commonly secondary to concurrent strabismus or anisometropia.3 Marcus Gunn syndrome is almost always unilateral, with less than 5% of patients affected bilaterally.5It is essential to distinguish Marcus Gunn syndrome from other causes of congenital and acquired ptosis, including masses of the upper eyelid, Horner syndrome, oculomotor nerve palsy, congenital myasthenic syndrome, blepharophimosis-ptosis-epicanthus inversus syndrome, and congenital fibrosis of extraocular muscles. The astute clinician must be watchful for the systemic and ocular abnormalities that occur in each of these conditions. It is also important to test ocular motility and alignment, assess refractive error, and evaluate for amblyopia. Palpebral fissure heights, margin reflex distances, margin crease distances, and levator function should be measured in each eye at rest and with jaw movements.Marcus Gunn syndrome is a clinical diagnosis. Although rare familial cases and associated genetic anomalies have been reported, most cases of this syndrome are thought to occur sporadically, and genetic testing is not routinely performed (choice A).6,7 The precise neuroanatomical mechanisms underlying Marcus Gunn syndrome have not yet been elucidated. Neuroradiological investigations are unnecessary and may be unrevealing for isolated cases (choice B). The administration of oral corticosteroids is not recommended and has not been investigated for the treatment of Marcus Gunn syndrome (choice C). Not all cases require treatment, but surgical correction of ptosis may be considered for cosmesis, obstruction of the visual axis, amblyopia, or abnormal head positioning (choice D). It is appropriate to discuss that surgery may improve the functional or cosmetic problems caused by ptosis. It should also be emphasized that affected children require monitoring for amblyopia.Some sources report that Marcus Gunn syndrome improves with age, whereas others speculate that patients, over time, learn to mask the ptosis and winking.3 Bilateral frontalis suspension after levator excision is commonly performed when surgery is indicated, but the optimal surgical approach is case dependent.4,8,9 If surgery is pursued, anesthesiologists should be alerted because individuals with Marcus Gunn syndrome may have robust oculocardiac reflexes and an increased risk of intraoperative arrhythmia.10Surgical repair or conservative management with close follow-up examinations were options discussed with the child’s parents. The parents deferred surgery at this time and elected instead to return for regular follow-up examinations.

Ophthalmology

A 5-year-old girl was referred for evaluation of blepharoptosis of the left eye present since birth (Figure). Her mother reported that, since infancy, the child’s left eye has twitched during feeding and mealtimes. The patient was born at term; had an unremarkable delivery; and had no history of developmental delay, trauma, or systemic illness. Her ocular history was significant only for bilateral mixed astigmatism (−0.25 + 0.75 × 145 OD and −0.25 + 1.00 × 005 OS). There was no family history of strabismus, amblyopia, or congenital ptosis. Her best-corrected visual acuity was 20/30 OD and 20/40 OS. Pupils were reactive to light bilaterally, and there was neither an afferent pupillary defect nor anisocoria. Extraocular motility was full. There was notable asymmetry in the following eyelid measurements: palpebral fissure height (10 mm OD; 5-6 mm OS) and margin reflex distance 1 (3.5 mm OD; 0.5-1.5 mm OS). In addition, elevation of the left upper eyelid was observed with lateral jaw thrust but not with anterior-posterior jaw movements or with mouth opening and closing. The levator function was 14 mm OU, and the margin crease distances were 5 mm OD and 6 mm OS. The remainder of the anterior and posterior segment slitlamp examination was unremarkable.External photographs of blepharoptosis of the left eye in the neutral jaw position (A) and the left upper eyelid elevated with rightward jaw thrust (B).Discuss carefully observing vs surgical repair of the ptosis

what would you do next?

What would you do next?

Discuss carefully observing vs surgical repair of the ptosis

Start oral corticosteroids

Perform urgent neuroimaging

Conduct genetic testing

a

female

0-10

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2654131

A woman in her 60s presented to the ophthalmology clinic with 10 months of blurred vision in her left eye. More recently, she noted that her left eye “drifts out at times.” She also reported drooping of the left upper eyelid and binocular, variable horizontal or vertical diplopia at distance. She also complained of itchy eyes but denied any pain or headaches. Her medical history includes breast cancer, diagnosed in 2000 and treated with lumpectomy and radiotherapy. A mammogram, completed 4 months before her ophthalmology visit, was reported as stable. On presentation, her visual acuity was 20/20 OD and 20/40 OS. She had slightly decreased color vision (8/10 Ishihara plates) of the left eye and there was no relative afferent pupillary defect. Confrontation visual fields were full. External examination revealed mild left proptosis and severely limited adduction of the left eye. Both optic nerves appeared normal on retinal examination. Magnetic resonance imaging of the brain (Figure 1) showed a 2.3-cm intraconal mass inseparable from the left lateral rectus muscle. The mass medially deviated the left optic nerve and conformed to the shape of the orbital globe with mild bony remodeling of the lateral orbital wall.T1-weighted magnetic resonance imaging of the brain shows a 2.3-cm intraconal mass (black asterisk) molding to the left orbital globe with medial deviation of the optic nerve (blue asterisk). What Would You Do Next?

Excisional biopsy

Begin chemotherapy

Incisional biopsy

Begin corticosteroid treatment

Adenocarcinoma consistent with metastatic breast carcinoma

A

Excisional biopsy

Intraoperative pathologic results revealed adenocarcinoma consistent with metastatic breast carcinoma (Figure 2). Immunohistochemical staining results showed estrogen-receptor positive cells consistent with metastatic breast carcinoma. This patient’s history of breast cancer and the presentation of a slow-growing, painless, restrictive lesion that molded to the shape of the left orbital globe was concerning for several serious medical conditions, including metastasis, lymphoma, or an inflammatory mass. Her examination showed a slight worsening of visual acuity and color vision that may have been related to a compressive effect of the tumor on the optic nerve.Histologic image of left lateral rectus muscle cells showing fibrous tissue with invasion of adenocarcinoma cells (hematoxylin-eosin, original magnification ×200). Cells stain estrogen-receptor positive by immunohistochemistry, consistent with metastatic breast carcinoma.The most prevalent orbital neoplasms in patients older than 60 years are lymphoproliferative lesions. Malignant orbital lymphoma accounts for 67% to 90% of lymphoproliferative lesions.1 These lesions present with a slow, painless onset; progression can be associated with a palpable mass, ocular restriction, or proptosis.2 On imaging, these lesions appear as an irregular mass molding to the orbital bones or globe. An incisional biopsy is necessary to confirm the diagnosis.Metastatic disease accounts for 1% to 13% of orbital tumors.1 Metastatic breast cancer accounts for 48% to 53% of all orbital metastases in women.3,4 These metastatic lesions typically occur 4.5 to 6.5 years after the diagnosis of the primary breast carcinoma and commonly affect the orbital fat or extraocular muscles.5 On imaging, orbital metastases are difficult to differentiate from other neoplasms or nonneoplastic infiltrative processes; thus, an incisional biopsy (choice C) is necessary to confirm the diagnosis. An excisional biopsy (choice A) can be performed for a well-circumscribed lesion when metastatic disease is not suspected; however, a metastatic process is possible given this patient’s history and symptoms. If metastasis is confirmed, an excisional biopsy will no longer be curative for the patient, and the patient should be evaluated to characterize the full extent of the disease. For patients with confirmed metastasis, examination by an oncologist is necessary and treatment often requires radiotherapy and/or chemotherapy (choice B).Nonspecific orbital inflammation (NSOI) is the third most common cause of orbital disease after thyroid eye disease and lymphoproliferative disease.6 Although a common disease, NSOI is a diagnosis of exclusion. Typically, NSOI is unilateral and presents with proptosis, motility deficits, and pain.6 Nonspecific orbital inflammation involving the extraocular muscles typically presents with unilateral thickening of one or two muscles and the surrounding fat, tendon, and myotendinous junction. Because NSOI is a diagnosis of exclusion, corticosteroid treatment (choice D) to reduce inflammation should not begin if the physician suspects other diagnoses, such as lymphoma or metastasis.6After incisional biopsy, further imaging revealed metastatic disease involving the sternum, anterior second and third ribs, pulmonary region, and lymph nodes. She completed a 2-week course of external beam radiotherapy targeting the left orbit, and her oncologist began treatment with oral exemestane. On examination at a subsequent ophthalmology visit, she had enophthalmos of the left eye with slight improvement in exotropia; visual acuity was stable. The patient will continue radiotherapy and follow-up with her oncologist, radiation oncologist, and ophthalmologist.

Ophthalmology

A woman in her 60s presented to the ophthalmology clinic with 10 months of blurred vision in her left eye. More recently, she noted that her left eye “drifts out at times.” She also reported drooping of the left upper eyelid and binocular, variable horizontal or vertical diplopia at distance. She also complained of itchy eyes but denied any pain or headaches. Her medical history includes breast cancer, diagnosed in 2000 and treated with lumpectomy and radiotherapy. A mammogram, completed 4 months before her ophthalmology visit, was reported as stable. On presentation, her visual acuity was 20/20 OD and 20/40 OS. She had slightly decreased color vision (8/10 Ishihara plates) of the left eye and there was no relative afferent pupillary defect. Confrontation visual fields were full. External examination revealed mild left proptosis and severely limited adduction of the left eye. Both optic nerves appeared normal on retinal examination. Magnetic resonance imaging of the brain (Figure 1) showed a 2.3-cm intraconal mass inseparable from the left lateral rectus muscle. The mass medially deviated the left optic nerve and conformed to the shape of the orbital globe with mild bony remodeling of the lateral orbital wall.T1-weighted magnetic resonance imaging of the brain shows a 2.3-cm intraconal mass (black asterisk) molding to the left orbital globe with medial deviation of the optic nerve (blue asterisk).

what would you do next?

What would you do next?

Begin chemotherapy

Excisional biopsy

Begin corticosteroid treatment

Incisional biopsy

b

female

61-70

Black

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2652903

A 73-year-old man was diagnosed as having multiple myeloma (MM), with serum protein electrophoresis (SPEP) and immunofixation (IF) showing a monoclonal (M) IgA κ at 0.3 g/dL and serum free κ/λ ratio skewed at 257. A computed tomographic scan showed lytic lesions, and bone marrow biopsy findings revealed 30% κ-restricted plasma cells. He was assigned to the bortezimib-lenalidomide-dexamethasone–elotuzumab (VRD-E) arm of a phase 3 trial. Three weeks after therapy initiation, follow-up SPEP-IF demonstrated an M-IgA κ at 0.1 g/dL. Two months later, SPEP-IF demonstrated a new M-IgG κ band in the same electrophoretic position as the M-IgA κ, with the 2 distinguishable only by IF and measured at 0.1 g/dL. Three months later, SPEP-IF demonstrated only the M-IgG κ, with the original M-IgA κ not detected. Over the next 8 months, the patient received maintenance therapy with VRD-E, and monthly SPEP-IF consistently showed M-IgG κ at 0.1 g/dL, with the original M-IgA κ consistently not detected. The serum free κ/λ ratio gradually decreased to 4.86 one year later. The Table summarizes assay data.Clonal evolution of myeloma cells to both IgG- and IgA-secreting cells.Immune dysregulation from multiagent therapy resulting in a new M-protein.New MGUS or B-cell lymphoproliferative disorder, such as monoclonal B lymphocytosis.Therapeutic monoclonal antibody at serum concentration detectable by SPEP-IF. How Do You Interpret These Test Results?

Clonal evolution of myeloma cells to both IgG- and IgA-secreting cells.

Immune dysregulation from multiagent therapy resulting in a new M-protein.

New MGUS or B-cell lymphoproliferative disorder, such as monoclonal B lymphocytosis.

Therapeutic monoclonal antibody at serum concentration detectable by SPEP-IF.

D

Therapeutic monoclonal antibody at serum concentration detectable by SPEP-IF.

Serum protein electrophoresis separates serum proteins into the fractions albumin, α-, β-, and γ-globulins. It is used to detect monoclonal gammopathy in suspect cases of plasma cell dyscrasia or B-cell lymphoproliferative disorder (eg, Waldenstrom macroglobulinemia). Normal serum immunoglobulins form a polyclonal or Gaussian distribution in the γ-globulin region, while a monoclonal protein typically appears as a discrete single peak in the γ- or β-regions, the characteristic “M-spike.” When an M-spike is detected, IF is performed; this test uses anti–heavy chain and anti–light chain antisera to identify the M-protein isotype. The concentration and isotype of the M-protein can help distinguish MGUS (typically <3 g/dL) from overt MM (usually >3 g/dL) or B-cell lymphoma (usually IgM type). The sensitivity of SPEP for M-protein detection in MM is 87.6%,1 with 98.6% specificity for any monoclonal gammopathy (compared with IF).2 National Comprehensive Cancer Network guidelines for MM include SPEP and IF in diagnostic workup.3 Averaging $19.91 and $41.42, respectively, these tests are relatively inexpensive for disease monitoring.4Serum protein electrophoresis is used to monitor response to therapy in patients with MM because M-protein levels reflect malignant plasma cell burden. The typical limit of detection for SPEP is 0.1 g/dL and for IF is 0.02 g/dL; these limits can be lower with hypogammaglobulinemia.5 Exogenous therapeutic monoclonal antibody (t-mAb), for example, newly approved MM therapies daratumumab and elotuzumab (both IgG κ), have therapeutic serum concentrations in this range.6 When spiked into normal sera, both appear on SPEP-IF with characteristic migration, and both are reported detectable by SPEP-IF in treated patients7. We have noted t-mAbs up to 0.1 g/dL in more than 90% of t-mAb–treated patients with MM. The t-mAb band is especially problematic if it has the same migration and/or isotype as the disease M-protein, with potential for a false-positive result in patients actually in complete remission (defined as no detectable M-protein). In patients with relapsed or refractory MM with significant disease M-protein, interference by t-mAbs is less of a clinical issue, although the appearance of an additional low-level band may cause confusion when interpreting assay results.In this case, IF showed a new IgG κ distinct from the patient’s M-IgA κ, that although migrating in the same position, was consistent with history of elotuzumab therapy.The serum free light chain assay measures unbound light chains and should not be affected by t-mAbs. However, this assay does not definitively identify an M-protein.Techniques using anti-idiotypic antibodies against t-mAbs (eg, the daratumumab IFE reflex assay), are under investigation. The anti-idiotype changes daratumumab’s electrophoretic migration, allowing for evaluation of disease M-protein. This approach adds considerable time and cost and is not yet approved by the US Food and Drug Administration. Also, the anti-idiotype technique warrants a separate assay for each t-mAb. Strategies using mass spectroscopy for M-protein identification may ultimately be more practical.5Because the M-IgG κ was explained by elotuzumab therapy, the clinical treatment was not altered. However, reporting of SPEP-IF results by the clinical laboratory has been revised to indicate potential presence of t-mAb, when such conclusions can be made from patient history or laboratory notification. Education regarding potential interference of SPEP-IF by t-mAbs has been instituted. Physicians are advised to notify the laboratory of t-mAb therapy in appropriate patients and to correlate results with therapy history.T-mAbs, such as elotuzumab and daratumumab, are detectable by SPEP-IF and may confound assay interpretation with extraneous or false-positive results.Oncologists should correlate SPEP-IF results with t-mAb therapy and are advised to alert the laboratory of therapy in appropriate patients, so that a more accurate test interpretation can be rendered by the laboratory.For patients with low-level disease M-proteins indistinguishable from t-mAb on SPEP-IF, the serum free light chain assay may be more useful for monitoring disease.Pathologists should be aware of this phenomenon when interpreting SPEP-IF, so that the presence of t-mAb may be accurately noted.

Diagnostic

A 73-year-old man was diagnosed as having multiple myeloma (MM), with serum protein electrophoresis (SPEP) and immunofixation (IF) showing a monoclonal (M) IgA κ at 0.3 g/dL and serum free κ/λ ratio skewed at 257. A computed tomographic scan showed lytic lesions, and bone marrow biopsy findings revealed 30% κ-restricted plasma cells. He was assigned to the bortezimib-lenalidomide-dexamethasone–elotuzumab (VRD-E) arm of a phase 3 trial. Three weeks after therapy initiation, follow-up SPEP-IF demonstrated an M-IgA κ at 0.1 g/dL. Two months later, SPEP-IF demonstrated a new M-IgG κ band in the same electrophoretic position as the M-IgA κ, with the 2 distinguishable only by IF and measured at 0.1 g/dL. Three months later, SPEP-IF demonstrated only the M-IgG κ, with the original M-IgA κ not detected. Over the next 8 months, the patient received maintenance therapy with VRD-E, and monthly SPEP-IF consistently showed M-IgG κ at 0.1 g/dL, with the original M-IgA κ consistently not detected. The serum free κ/λ ratio gradually decreased to 4.86 one year later. The Table summarizes assay data.Clonal evolution of myeloma cells to both IgG- and IgA-secreting cells.Immune dysregulation from multiagent therapy resulting in a new M-protein.New MGUS or B-cell lymphoproliferative disorder, such as monoclonal B lymphocytosis.Therapeutic monoclonal antibody at serum concentration detectable by SPEP-IF.

how do you interpret these test results?

How do you interpret these results?

New MGUS or B-cell lymphoproliferative disorder, such as monoclonal B lymphocytosis.

Therapeutic monoclonal antibody at serum concentration detectable by SPEP-IF.

Immune dysregulation from multiagent therapy resulting in a new M-protein.

Clonal evolution of myeloma cells to both IgG- and IgA-secreting cells.

b

male

71-80

original

https://jamanetwork.com/journals/jamacardiology/fullarticle/2657543

A 52-year-old man with mild asthma presented to the hospital after an episode of unheralded syncope while walking. On arrival, he was afebrile, with a blood pressure of 120/80 mm Hg, heart rate of 35/min, respiratory rate of 16/min, and pulse oximetry of 98% on ambient air. His examination revealed regular bradycardia without cannon A waves, clear lung fields to auscultation, and warm extremities. Chest radiography revealed hilar adenopathy. Electrocardiography showed sinus bradycardia, first-degree atrioventricular block, left posterior fascicle, and right bundle branch blocks (Figure 1A). Transthoracic echocardiography revealed an ejection fraction of 50% without regional variation. On exercise stress single-photon emission computed tomography, the patient completed 9 minutes of a standard Bruce protocol and developed transient high-grade atrioventricular block but had no ischemic ST-segment changes or defects on perfusion imaging. Cardiac magnetic resonance imaging (cMRI) with gadolinium contrast-enhanced first-pass myocardial perfusion imaging at rest and contrast-enhanced late gadolinium enhancement imaging revealed low-normal left ventricular systolic function but no other abnormalities (Figure 1B). What Would You Do Next?

Order invasive electrophysiologic testing

Order coronary angiography

Order 30-day event monitoring

Order cardiac fluorodeoxyglucose positron emission tomography

Cardiac (and systemic) sarcoidosis

D

Order cardiac fluorodeoxyglucose positron emission tomography

Sarcoidosis is an inflammatory, granulomatous disease of unclear origin that affects multiple organs. Clinically evident cardiac involvement occurs in 5% of patients with sarcoidosis, although the estimated prevalence of clinically silent cardiac involvement in patients with systemic or pulmonary disease is higher (25%).1 Recognition of cardiac involvement in sarcoidosis is important because its presence portends a poor prognosis.2Clinical manifestations of cardiac sarcoidosis (CS) depend on the location and extent of disease and include conduction abnormalities, ventricular arrhythmias, heart failure, and sudden death. The 2014 Heart Rhythm Society Guidelines provide a diagnostic framework for CS and recommend that patients with biopsy-proven extra-CS be screened for cardiac symptoms and with 12-lead electrocardiography.3 In the presence of symptoms or abnormal electrocardiography and/or echocardiography results, advanced cardiac imaging (cMRI and/or FDG-PET) should be performed. In adults younger than 60 years without established sarcoidosis, the presence of unexplained Mobitz II or complete heart block should prompt further evaluation with chest computed tomography or other advanced imaging, such as PET. If the results of 1 or more of these modalities are positive, a biopsy should be performed.3 Lymph node or lung biopsy is preferred because of higher sensitivity and lower procedural risk. Otherwise, endomyocardial biopsy may be performed with electrophysiologic or image guidance because of the focal nature of the disease.3Because cardiac biopsy may be limited by diagnostic yield, feasibility, and procedural risk, cMRI and FDG-PET are important tools for the diagnosis of CS. Both provide high sensitivity (>75%) for detecting CS, although FDG-PET has a higher sensitivity and cMRI a higher specificity.4 Thus, PET may lead to the diagnosis of CS when cMRI findings are negative or inconclusive. Imaging findings suggestive of CS on both modalities have strong prognostic implications.5,6Corticosteroids are the first-line medical treatment for CS. Observational data suggest that corticosteroid therapy in CS may be associated with improved atrioventricular conduction and lower rates of adverse cardiovascular events, although there is a paucity of high-quality data that demonstrate survival benefit.7 Despite this, most experts recommend treatment of CS with corticosteroid therapy.1 More recent investigations suggest that corticosteroid therapy can reduce myocardial inflammation, as assessed by FDG-PET, and may be associated with improvement in ejection fraction.8 Consequently, FDG-PET may be used serially to assess response to therapy and guide further management.4Beyond medical therapy, device guidelines apply to patients with CS and advanced heart block. Patients with CS also have a substrate for ventricular arrhythmias and should undergo risk stratification and consideration for implantable cardioverter-defibrillator placement. Implantable cardioverter-defibrillator therapy is recommended for patients with sustained ventricular arrhythmias, including prior cardiac arrest and/or left ventricular ejection fraction of 35% or less despite optimal medical therapy and immunosuppression. Implantable cardioverter-defibrillator therapy may also be useful in patients with CS who have an indication for permanent pacemaker placement, unexplained syncope believed to be arrhythmic in origin, and/or inducible sustained arrhythmias.3Although the patient’s cMRI findings were unremarkable, cardiac FDG-PET results revealed myocardial inflammation in the basal inferoseptal wall (Figure 2A). Fused whole-body PET computed tomography revealed multifocal FDG-avid mediastinal, hilar, supraclavicular, and upper abdominal lymphadenopathy (Figure 2B). Endobronchial ultrasonography-guided lymph node biopsy revealed noncaseating granulomas consistent with sarcoidosis. The patient was started on a regimen of prednisone, 40 mg daily. During the hospitalization, he also developed complete heart block and underwent placement of a dual-chamber pacemaker defibrillator. Four months after discharge, interval FDG-PET revealed resolution of myocardial inflammation with small residual perfusion defect in the basal inferior wall and reduction in FDG uptake of lymphadenopathy.Patient outcome. A, Technetium Tc 99m sestamibi resting myocardial perfusion single-photon emission computed tomographic (CT) (top rows) and fluorodeoxyglucose positron emission tomographic (FDG-PETs) scans (bottom rows) showing focal, intense FDG uptake of the basal inferoseptal wall (arrowheads). B, Fused whole-body PET-CT scan showing multifocal FDG-avid lymph nodes.

Cardiology

A 52-year-old man with mild asthma presented to the hospital after an episode of unheralded syncope while walking. On arrival, he was afebrile, with a blood pressure of 120/80 mm Hg, heart rate of 35/min, respiratory rate of 16/min, and pulse oximetry of 98% on ambient air. His examination revealed regular bradycardia without cannon A waves, clear lung fields to auscultation, and warm extremities. Chest radiography revealed hilar adenopathy. Electrocardiography showed sinus bradycardia, first-degree atrioventricular block, left posterior fascicle, and right bundle branch blocks (Figure 1A). Transthoracic echocardiography revealed an ejection fraction of 50% without regional variation. On exercise stress single-photon emission computed tomography, the patient completed 9 minutes of a standard Bruce protocol and developed transient high-grade atrioventricular block but had no ischemic ST-segment changes or defects on perfusion imaging. Cardiac magnetic resonance imaging (cMRI) with gadolinium contrast-enhanced first-pass myocardial perfusion imaging at rest and contrast-enhanced late gadolinium enhancement imaging revealed low-normal left ventricular systolic function but no other abnormalities (Figure 1B).

what would you do next?

What would you do next?

Order 30-day event monitoring

Order cardiac fluorodeoxyglucose positron emission tomography

Order invasive electrophysiologic testing

Order coronary angiography

b

male

51-60

original

https://jamanetwork.com/journals/jama/fullarticle/2662870

A 66-year-old man with newly diagnosed multiple myeloma underwent autologous hematopoietic stem cell transplantation (HSCT). On posttransplant day 10, he developed fever (38.4°C). He was started on empirical treatment with cefepime; however, his fevers persisted despite antibiotic therapy. On posttransplant day 14 he developed new-onset pruritic, confluent, erythematous, blanching morbilliform macules and papules on his trunk and extremities (Figure, left). Review of systems was notable for diarrhea and a 6-pound weight gain since transplantation and negative for headache, cough, shortness of breath, or abdominal pain.Left, Macules and papules on the trunk of the patient. Right, Axial chest computed tomography of the patient.On examination, there was no lymphadenopathy or hepatosplenomegaly. The patient’s heart rate was 100/min, blood pressure was 106/68 mm Hg, and he occasionally experienced mild hypoxia to 94% on ambient air. Results of a basic metabolic panel were normal, with a blood urea nitrogen level of 10 mg/dL (3.57 mmol/L) and creatinine level of 0.7 mg/dL (61.88 μmol/L). White blood cell (WBC) count was 7300/μL, and absolute neutrophil count (ANC) was 5480/μL. Neutrophil recovery occurred beginning on posttransplant day 10, with WBC count of 700/μL and ANC of 532/μL on posttransplant day 10, correlating with the onset of the patient’s fevers. Platelet count was 48 × 103/μL, and hemoglobin was 8.2 g/dL. Results of liver function tests were normal. Blood, urine, sputum, and respiratory viral cultures were negative. Tests for cytomegalovirus, Epstein-Barr virus, human herpesvirus-6, adenovirus, parvovirus, cryptococcal antigen, aspergillus galactomannan antigen, β-glucan, and Clostridium difficile were negative. Chest computed tomography demonstrated multifocal ground-glass and consolidative pulmonary opacities (Figure, right). Computed tomography of the abdomen was unremarkable. A skin punch biopsy demonstrated subtle vacuolar change; rare epidermal dyskeratosis, including within a hair follicle; and superficial perivascular mononuclear cell infiltrate with occasional eosinophils.Perform bronchoscopy and biopsy of the pulmonary lesions What Would You Do Next?

Initiate empirical antiviral and antifungal therapy

Discontinue antibiotic therapy and consider systemic corticosteroids

Obtain ferritin and soluble IL2Rα testing

Perform bronchoscopy and biopsy of the pulmonary lesions

Engraftment syndrome

B

Discontinue antibiotic therapy and consider systemic corticosteroids

The key to the correct diagnosis is the onset of noninfectious fever and rash during, and sometimes prior to, the neutrophil recovery phase (engraftment) after HSCT. Complications of engraftment syndrome can include pulmonary, hepatic, renal, and central nervous system dysfunction. Patients with mild engraftment syndrome who do not have end-organ damage or respiratory compromise may be safely treated with supportive care.Empirical antiviral and antifungal therapy is unnecessary, given the patient’s clinical stability, the low suspicion for infection, and negative findings on viral and fungal testing. Ferritin and soluble IL2Rα are used in the diagnosis of hemophagocytic lymphohistiocytosis (HLH), an inflammatory syndrome that can result in multiple-organ failure and death. However, the patient did not have hepatosplenomegaly, and his cytopenias were attributable to his recent HSCT, making the diagnosis of HLH unlikely. Although bronchoscopy may be considered in the workup for new pulmonary infiltrates, it is unnecessary for diagnosis of engraftment syndrome.Engraftment syndrome describes a collection of systemic findings arising during the engraftment period after autologous HSCT and, less commonly, after allogeneic, syngeneic, or umbilical cord blood transplantation.1 During engraftment, neutrophil levels reach 0.5 × 109/L or greater for more than 3 sequential days, an early sign that the graft is capable of immune system reconstitution. Typically observed to occur within 4 to 22 days after transplantation,2 engraftment syndrome can also begin in the days before neutrophil recovery is observed. The condition has been reported in patients receiving autologous HSCT for both malignant and nonmalignant conditions.According to the Spitzer criteria and Maiolino criteria, diagnostic features include fever, erythematous rash, and manifestations of noncardiogenic pulmonary edema, such as pulmonary infiltrates.3,4 Renal dysfunction, hepatic dysfunction, diarrhea, weight gain, and transient encephalopathy can also result.3,4 Reported incidences of the syndrome after autologous HSCT vary from 7% to 59% based on the diagnostic criteria used3; among patients with multiple myeloma after HSCT, incidences vary from 10% to 29%.5,6 The pathogenesis remains poorly understood. It is thought that a proinflammatory state during the neutrophil recovery period causes activation of leukocytes and cytokines, such as IL-1, TNF-α, and IFN-γ. Subsequently, vascular leak and organ dysfunction result in hallmark symptoms.1The primary differential diagnosis for the symptoms observed in engraftment syndrome includes morbilliform drug rash, viral exanthem, and acute graft-vs-host disease (GVHD).1 Exanthematous drug rashes are generally asymptomatic and do not present with systemic findings. Symptoms of engraftment syndrome can resemble those of acute GVHD, which manifests with erythematous morbilliform rash, hepatic dysfunction, and diarrhea. However, acute GVHD typically develops after allogeneic transplant, whereas engraftment syndrome is more commonly associated with autologous transplant. Furthermore, pulmonary interstitial infiltrates and respiratory symptoms are not characteristic of acute GVHD. Radiologic features of engraftment syndrome are variable but include ground-glass or consolidative pulmonary opacities, interstitial pulmonary edema, and pleural effusions.7 The histologic features of engraftment syndrome are nonspecific and include interface vacuolar change and superficial perivascular infiltration. These findings can overlap with those seen in acute GVHD and a subset of drug rashes. However, prominent eosinophils, which were not observed in this patient, are more suggestive of drug rash. According to one study, features that favor engraftment syndrome over acute GVHD include a predominance of CD4+ T cells and decreased CD1a+ cells, but this has yet to be replicated in additional studies.8 Thus, although certain histologic clues may point to a diagnosis of engraftment syndrome, engraftment syndrome is a clinical diagnosis that does not require biopsy.Approximately one-third of patients with engraftment syndrome require no specific therapy.9 Supportive measures such as topical steroids, antipyretics, supplemental oxygen, and diuretics are beneficial in mild cases. Systemic treatment with corticosteroids may be considered in cases of clinically significant pulmonary edema, respiratory compromise, or persistent fevers lasting beyond 72 hours.1 Administration of methylprednisolone at 1 to 1.5 mg/kg per day will generally yield improvement within a few days, after which corticosteroids can be gradually tapered, with symptoms resolving within a week.1 Rapid improvement with short courses of corticosteroids is characteristic of engraftment syndrome and allows for differentiation from acute GVHD, which typically requires a more sustained course of treatment.10Antibiotics were discontinued, and the patient’s rash was managed with topical clobetasol (0.05% ointment) and antihistamines for pruritus. Interval chest computed tomography in 4 days revealed improvement of the pulmonary infiltrates. The fevers resolved within a few days, and the rash resolved within 1 week. The patient was discharged home on posttransplant day 20.

General

A 66-year-old man with newly diagnosed multiple myeloma underwent autologous hematopoietic stem cell transplantation (HSCT). On posttransplant day 10, he developed fever (38.4°C). He was started on empirical treatment with cefepime; however, his fevers persisted despite antibiotic therapy. On posttransplant day 14 he developed new-onset pruritic, confluent, erythematous, blanching morbilliform macules and papules on his trunk and extremities (Figure, left). Review of systems was notable for diarrhea and a 6-pound weight gain since transplantation and negative for headache, cough, shortness of breath, or abdominal pain.Left, Macules and papules on the trunk of the patient. Right, Axial chest computed tomography of the patient.On examination, there was no lymphadenopathy or hepatosplenomegaly. The patient’s heart rate was 100/min, blood pressure was 106/68 mm Hg, and he occasionally experienced mild hypoxia to 94% on ambient air. Results of a basic metabolic panel were normal, with a blood urea nitrogen level of 10 mg/dL (3.57 mmol/L) and creatinine level of 0.7 mg/dL (61.88 μmol/L). White blood cell (WBC) count was 7300/μL, and absolute neutrophil count (ANC) was 5480/μL. Neutrophil recovery occurred beginning on posttransplant day 10, with WBC count of 700/μL and ANC of 532/μL on posttransplant day 10, correlating with the onset of the patient’s fevers. Platelet count was 48 × 103/μL, and hemoglobin was 8.2 g/dL. Results of liver function tests were normal. Blood, urine, sputum, and respiratory viral cultures were negative. Tests for cytomegalovirus, Epstein-Barr virus, human herpesvirus-6, adenovirus, parvovirus, cryptococcal antigen, aspergillus galactomannan antigen, β-glucan, and Clostridium difficile were negative. Chest computed tomography demonstrated multifocal ground-glass and consolidative pulmonary opacities (Figure, right). Computed tomography of the abdomen was unremarkable. A skin punch biopsy demonstrated subtle vacuolar change; rare epidermal dyskeratosis, including within a hair follicle; and superficial perivascular mononuclear cell infiltrate with occasional eosinophils.Perform bronchoscopy and biopsy of the pulmonary lesions

what would you do next?

What would you do next?

Obtain ferritin and soluble IL2Rα testing

Initiate empirical antiviral and antifungal therapy

Discontinue antibiotic therapy and consider systemic corticosteroids

Perform bronchoscopy and biopsy of the pulmonary lesions

c

male

61-70

White

original

https://jamanetwork.com/journals/jama/fullarticle/2661557

A 50-year-old woman with chronic pain and recurrent infections from common variable immunodeficiency presented to a new primary care physician for management of her pain medications. Her pain was related to multiple vertebral fractures due to chronic steroid use for an inflammatory polyarthritis that was not responsive to hydroxychloriquine and methotrexate. Her pain medication regimen (methadone, 20 mg [3×/d]; immediate-release morphine, 30 mg [5×/d]; gabapentin, 1200 mg [2×/d]; duloxetine, 60 mg/d; and celecoxib, 200 mg [2×/d]) helped her independently complete instrumental activities of daily living. She reported no adverse effects (eg, somnolence or constipation). A comprehensive urine drug screen using immunoassay and mass spectrometry was ordered (Table 1).The patient is taking methadone, hydromorphone, and codeine.The patient is taking methadone, morphine, hydromorphone, and codeine. How Would You Interpret These Results?

The patient is taking methadone and morphine.

The patient is taking methadone and codeine.

The patient is taking methadone, hydromorphone, and codeine.

The patient is taking methadone, morphine, hydromorphone, and codeine.

A

The patient is taking methadone and morphine.

With the increasing opioid dependence epidemic, clinicians must monitor the use of prescription opioids to identify misuse, addiction, and diversion (ie, selling or distributing prescribed medications). Urine drug screens can confirm whether patients on chronic opioids are using prescribed drugs and abstaining from illicit substances. Occasionally, it can be difficult to interpret a result as normal or abnormal based on the metabolites found in the urine.Mass spectrometry–based methods of detection can identify and quantify multiple drugs and metabolites simultaneously. Additionally, mass spectrometry can measure very low concentrations of excreted drugs and detect minor metabolites and impurities not quantifiable with immunoassays. Medicare midpoint reimbursements for mass spectrometry–based tests range from $158.98 to $343.07, depending on the number of drug classes being tested.1Accurate interpretation of drug screen results requires knowledge of the urine metabolites (Table 2).2-6 Some opioids produce metabolites chemically identical to other opioid medications, which may complicate the interpretation. Codeine, for example, is a pro-drug that metabolizes to morphine in most patients.2Urine drug screen results showed the expected morphine and methadone but also hydromorphone and codeine. Hydromorphone is a minor metabolite of morphine (found at ≤10% of the morphine urine concentration)7 that can be seen in patients prescribed higher daily doses of morphine and detected when morphine concentrations reach 10 000 ng/mL on assay.7 Codeine is not a metabolite of morphine, but it can be an impurity in the production of morphine (estimated at 0.04%-0.5% of the concentration of morphine).4 The patient’s hydromorphone and codeine urine concentrations are consistent with these findings. It is possible that the patient had an additional source of hydromorphone or codeine, which cannot be determined from the urine result. If concentrations were higher than the 10% or 0.5% of the morphine concentration, the patient could be taking hydromorphone or codeine.Screens using only immunoassay for common drugs of abuse are an alternative to mass spectrometry–based screens designed for pain management. Immunoassay methods are less expensive (Medicare reimbursement range, $20.22- $107.85)1 and allow physicians to quickly determine whether commonly abused drugs are absent and whether opiates are present; however, they are subject to false-positive and false-negative results, which vary based on the drug, drug class, and the assay used. Most semisynthetic opioids (ie, hydrocodone, oxycodone) and synthetic opioids (ie, fentanyl, methadone) are not reliably detected by an immunoassay designed to detect opiates. Immunoassays specifically designed to detect oxycodone show sensitivities and specificities at approximately 99%, while those specifically designed to detect synthetic opioids are approximately 95%.8 Mass spectrometry is used to confirm immunoassay results and has been recently advocated as a first-line test in chronic pain management.8After contacting her prior physician and reviewing the prescription drug-monitoring program (a statewide electronic database that collects information on dispensed controlled substances), there was no concern for misuse or abuse. An opioid consent and contract,9 which detailed the risks and benefits of opioid therapy and outlined expectations of the patient, was reviewed and signed by the patient. Although her daily opioid dosage was greater than 200 morphine milligram equivalents, the benefit of pain control that promotes independence was considered to outweigh the potential harms of therapy. The regimen was continued with a plan for a multidisciplinary approach to treating her pain and slowly tapering the opioids.Urine drug screens give reproducible objective data and are effective for monitoring opioid use in chronic pain management.Opioid contracts can provide structure and support for the patient and physician—discuss at the initiation of therapy.Hydromorphone can be found as a metabolite in patients on high-dose long-term morphine treatment.7Codeine can be an impurity in the production of morphine (range, 0.04%-0.5%) of the concentration of morphine.4

Diagnostic

A 50-year-old woman with chronic pain and recurrent infections from common variable immunodeficiency presented to a new primary care physician for management of her pain medications. Her pain was related to multiple vertebral fractures due to chronic steroid use for an inflammatory polyarthritis that was not responsive to hydroxychloriquine and methotrexate. Her pain medication regimen (methadone, 20 mg [3×/d]; immediate-release morphine, 30 mg [5×/d]; gabapentin, 1200 mg [2×/d]; duloxetine, 60 mg/d; and celecoxib, 200 mg [2×/d]) helped her independently complete instrumental activities of daily living. She reported no adverse effects (eg, somnolence or constipation). A comprehensive urine drug screen using immunoassay and mass spectrometry was ordered (Table 1).The patient is taking methadone, hydromorphone, and codeine.The patient is taking methadone, morphine, hydromorphone, and codeine.

how would you interpret these results?

How do you interpret these results?

The patient is taking methadone, hydromorphone, and codeine.

The patient is taking methadone and codeine.

The patient is taking methadone and morphine.

The patient is taking methadone, morphine, hydromorphone, and codeine.

c

female

41-50

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2643735

A previously healthy man in his 30s presented with spontaneous bruising, epistaxis, and haematuria. Acute promyelocytic leukemia (APML) was diagnosed by bone marrow aspirate morphology, immunophenotyping, and detection of the bcr1 variant of the PML-RARα fusion transcript in peripheral blood. He was commenced on treatment with the PETHEMA LPA 20051 protocol consisting of all-trans retinoic acid (ATRA) and idarubicin, an anthracycline based chemotherapy. Dexamethasone was prescribed to reduce the risk of ATRA syndrome, a potentially life threatening complication seen in these patients and characterized by fever, pulmonary infiltrates, hypotension, and leucocytosis.After 12 days of treatment, the patient developed pyrexia and was started on empiric antibiotics. Two days later he developed tender black spots on the scrotum that progressed to painful ulcers over 8 days (Figure, A). Systemic antifungal and antiviral therapy were added with no improvement. Peripheral blood cultures and skin swabs from the lesions did not identify bacterial or viral infection. Scrotal ultrasonography showed a subcutaneous hypervascular lesion with no abscess. The development and progression of scrotal ulceration coincided with recovery in neutrophil count from 0.3 × 109/L to 1.2 × 109/L and persistent pyrexia. As scrotal ulceration progressed, they enlarged and became necrotic with a black eschar. A specimen was obtained for histopathology.A, Clinical photograph of scrotum and penis shows ulceration and necrosis of penile and scrotal skin with surrounding inflammation. B, Scrotal biopsy histopathologic specimen (hematoxylin-eosin; original magnification ×20).Scrotal ulceration secondary to induction chemotherapy with ATRA What Is Your Diagnosis?

Fournier gangrene (necrotizing fasciitis of the perineum)

Scrotal ulceration secondary to induction chemotherapy with ATRA

Deep fungal infection

Mycobacterial infection

B. Scrotal ulceration secondary to induction chemotherapy with ATRA

B

Scrotal ulceration secondary to induction chemotherapy with ATRA

Histopathology on a skin biopsy showed intense inflammation, necrosis, and mature neutrophils with no evidence of leukemic infiltration (Figure, B). Tissue culture findings for bacteria and mycobacteria were negative.Acute promyelocytic leukemia (APML) is a subgroup of acute myeloid leukemia characterized by the presence of translocation (15;17) (q22;q21) giving rise to the PML/RARα fusion protein. Affected cells have a reduced ability to absorb retinoic acid which is needed for immature myeloid cells to differentiate. In APML immature promyelocytes accumulate in bone marrow unable to differentiate into neutrophils. Acute promyelocytic leukemia is the most curable type of leukemia because of its responsiveness to ATRA, a vitamin A derivative, which induces differentiation of leukemic cells into phenotypically mature myeloid cells. All-trans retinoic acid is used during the induction phase of chemotherapy with cure rates of approximately 80%.2 As ATRA is not effective at achieving lasting complete remissions, it is combined with conventional anthracycline-based chemotherapy for consolidation and then with 6-mercaptopurine and methotrexate for maintenance therapy.Differentiation syndrome, previously known as ATRA syndrome, is a potentially life-threatening syndrome seen in patients with APML during induction therapy with ATRA.3 The mechanism by which this occurs is poorly understood but appears to depend on the presence of malignant promyelocytes as it does not occur in patients treated with ATRA for other disorders and is never observed beyond induction therapy.To date there have been 30 reported cases of scrotal ulceration in patients receiving ATRA for APML. The mean (range) age is 30 (13-53) years and the mean (range) duration of ATRA therapy prior to scrotal ulceration is 17 (7-28) days. Fever is documented in 63% of cases, none of whom had other features of ATRA syndrome. In 1 of 8 cases biopsied, there was necrotizing vasculitis, and the remainder showed acute and chronic inflammation with predominant neutrophils. Leukemic cells were not reported in any of the specimens. Four of the 30 patients had surgery ranging from incision and hydrogen peroxide irrigation to hemicastration. One of 11 patients retreated with ATRA developed further scrotal ulceration. Ulceration of the labia and perineum has also been reported in 5 female patients treated with ATRA (age range, 8-52 years).The pathogenesis of scrotal ulceration in these patients is unclear and the histopathological findings are nonspecific. As scrotal ulceration coincides with recovery of white blood cell count in some cases it has been suggested that granulocyte colony-stimulating factor plays a role.4 All-trans retinoic acid also produces superoxide and cytokines which activate neutrophils and directly injure tissues.5,6 It is not known why ulceration in these patients is localized to scrotal skin.This rare complication can be easily misdiagnosed leading to unnecessary investigations, treatments, and surgery. Once recognized it responds to treatment with systemic corticosteroids. Further treatment with ATRA for consolidation and maintenance therapy is possible. Our patient was awaiting emergency surgery for extensive perineal debridement as treatment for Fournier gangrene when a dermatology opinion was sought. Following diagnosis methylprednisolone (125 mg daily) was commenced, ATRA discontinued and the patient remained on idarubicin. Within 2 days of stopping ATRA the fevers settled, inflammatory markers normalized and within three weeks the ulcers healed without scarring. Our patient was subsequently retreated with ATRA at the same dose during the consolidation phase two months later and did not develop further scrotal ulceration.It is important to recognize this condition because treatment with corticosteroids and/or discontinuation of ATRA is sufficient. At a time of high risk of morbidity due to background APML, these patients are at risk of major surgery and extensive debridement of genital and perineal tissue if the diagnosis is missed. Further treatment with ATRA is possible.

Dermatology

A previously healthy man in his 30s presented with spontaneous bruising, epistaxis, and haematuria. Acute promyelocytic leukemia (APML) was diagnosed by bone marrow aspirate morphology, immunophenotyping, and detection of the bcr1 variant of the PML-RARα fusion transcript in peripheral blood. He was commenced on treatment with the PETHEMA LPA 20051 protocol consisting of all-trans retinoic acid (ATRA) and idarubicin, an anthracycline based chemotherapy. Dexamethasone was prescribed to reduce the risk of ATRA syndrome, a potentially life threatening complication seen in these patients and characterized by fever, pulmonary infiltrates, hypotension, and leucocytosis.After 12 days of treatment, the patient developed pyrexia and was started on empiric antibiotics. Two days later he developed tender black spots on the scrotum that progressed to painful ulcers over 8 days (Figure, A). Systemic antifungal and antiviral therapy were added with no improvement. Peripheral blood cultures and skin swabs from the lesions did not identify bacterial or viral infection. Scrotal ultrasonography showed a subcutaneous hypervascular lesion with no abscess. The development and progression of scrotal ulceration coincided with recovery in neutrophil count from 0.3 × 109/L to 1.2 × 109/L and persistent pyrexia. As scrotal ulceration progressed, they enlarged and became necrotic with a black eschar. A specimen was obtained for histopathology.A, Clinical photograph of scrotum and penis shows ulceration and necrosis of penile and scrotal skin with surrounding inflammation. B, Scrotal biopsy histopathologic specimen (hematoxylin-eosin; original magnification ×20).Scrotal ulceration secondary to induction chemotherapy with ATRA

what is your diagnosis?

What is your diagnosis?

Deep fungal infection

Fournier gangrene (necrotizing fasciitis of the perineum)

Scrotal ulceration secondary to induction chemotherapy with ATRA

Mycobacterial infection

c

male

31-40

Black

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2632042

A woman in her 30s with a 1-year history of unintentional weight loss, mild diffuse abdominal pain, and occasional episodes of vomiting presented to the emergency department with a 24-hour history of intense abdominal pain, fever, and loose stools. An abdominal computed tomographic scan showed findings consistent with bowel perforation, and she was admitted to the intensive care unit after emergent exploratory laparotomy.Her medical history was significant for 1 other episode of idiopathic bowel perforation 3 years prior. She denied taking any medications. Dermatology was consulted to evaluate an asymptomatic skin eruption that had been present for at least 8 months before her hospitalization. Physical examination revealed numerous 5- to 10-mm nontender papules with a porcelain-white atrophic center and an erythematous halo, alongside scattered atrophic white scars (Figure, A and B). The lesions were distributed across her trunk, neck, and upper and lower extremities. Palms, soles, scalp, genitalia, and mucosal surfaces were spared. Her neurological and mental state examination had unremarkable results. Biopsy specimens from her thigh and back were obtained (Figure, C and D).Clinical photographs and biopsy specimens. A, Papules on the back with white atrophic center and an erythematous rim. B, Lesions on the thigh similar to those of the back, alongside atrophic white scars. C, Thigh biopsy shows hyperkeratosis and wedge-shaped avascular necrosis in dermis and subcutaneous tissue (hematoxylin-eosin stain, original magnification ×10). D, Back biopsy shows occlusion of dermal blood vessels, perivascular lymphocytic infiltration, and mucin deposition (hematoxylin-eosin stain, original magnification ×40). What Is Your Diagnosis?

Pancreatitis panniculitis

Malignant atrophic papulosis

Systemic lupus erythematosus

Lymphomatoid papulosis

B. Malignant atrophic papulosis

B

Malignant atrophic papulosis

Histopathologic examination revealed epidermal hyperkeratosis with wedge-shaped necrosis extending into the dermis and subcutaneous tissue (Figure, C), nonthrombotic arteriolar obliteration, and surrounding mucin deposition (Figure, D). Scant perivascular lymphocytic infiltration with focal fibrinoid necrosis of the dermal blood vessels was also present.Additional studies showed a positive antinuclear antibody titer result at 1:640. Levels of anti–double-stranded DNA antibodies, anti–extractable nuclear antigens, antineutrophil cytoplasmic antibodies, and anticardiolipin antibodies were within normal limits. Based on the previous findings, the diagnosis of malignant atrophic papulosis (AP) was made. The patient’s current condition, lack of effective treatments, and prognosis prompted the decision to withhold additional treatment and offer supportive and palliative care. Despite surgery and antibiotics, she died a few weeks later as a result of peritonitis and sepsis secondary to bowel perforation.Atrophic papulosis, also known as Köhlmeier-Degos disease, is a rare thrombo-obliterative vasculopathy first described by Köhlmeier in 1941 and documented as a separate entity by Degos in 1942.1 It usually affects middle-aged persons,2,3 although cases in children have been described. The disease has a male predominance (3:1),1,4 with an earlier onset being reported in women.2,5The etiology of AP remains unknown. Vasculitis, coagulopathy, and primary endothelial dysfunction are the most commonly suggested hypotheses.1,3 Predisposing conditions associated with AP include parvovirus B19 infection, lupus erythematosus, dermatomyositis, scleroderma, and antiphospholipid syndrome.4-6The disease can affect the skin, gastrointestinal tract, and central nervous system,2,3,6 with less common involvement of other organs.3,5 Cutaneous lesions start as erythematous papules7,8 that develop into porcelain-white scars surrounded by an erythematous rim with fine telangiectasias.8 The latter description is considered pathognomonic for AP.1-5 The lesions are usually asymptomatic2,7 and are distributed predominantly across the trunk and extremities, sparing the scalp and palmoplantar region.8 Systemic involvement can include bowel perforation, peritonitis, cerebral artery thrombosis, cerebral hemorrhage, among others.3,4Histopathologic findings1,7 include dermal perivascular lymphocytic infiltrate, interstitial mucin deposition, vacuolar interface dermatitis, intramural fibrin deposition, central epidermal atrophy, and the classic inverted wedge-shaped dermal sclerosis and necrosis.7Diagnosis of AP is usually based on the presence of pathognomonic lesions1,3,5 because no specific laboratory markers have been reported.1,2,7 Histopathologically, obliterative fibrous and mucinous arteriopathy in small and medium-sized vessels differentiates AP from other vasculitides or endotheliopathy syndromes.6There is no standardized treatment for AP.1-8 Reported strategies include use of anticoagulants, antiplatelet therapy, immunosuppresants, and systemic corticosteroids, most of which are ineffective.2-7 Eculizumab, a humanized monoclonal antibody directed against the complement C5 protein,6 is considered by some authors to be the treatment of choice for systemic AP.1-3,9 Subcutaneous treprostinil, a prostaglandin analogue, has shown promising results in eculizumab-resistant disease.10The clinical behavior of AP varies from a “benign” monosymptomatic cutaneous form1-3 to a “malignant” aggressive multisystemic variant that is typically fatal within 2 to 3 years after onset.5,9 Because systemic involvement may develop years after the onset of cutaneous lesions, regular follow-up of all patients with a diagnosis of benign AP must be performed.7 Death most commonly results from repeated gastrointestinal perforations and sepsis.10Atrophic papulosis is a challenging disease for dermatologists owing to its rarity, unknown etiology, ineffective treatment options, and ominous prognosis once it becomes systemic. Further studies are needed to elucidate the exact pathogenesis of this disease and improve its treatment and outcomes.

Dermatology

A woman in her 30s with a 1-year history of unintentional weight loss, mild diffuse abdominal pain, and occasional episodes of vomiting presented to the emergency department with a 24-hour history of intense abdominal pain, fever, and loose stools. An abdominal computed tomographic scan showed findings consistent with bowel perforation, and she was admitted to the intensive care unit after emergent exploratory laparotomy.Her medical history was significant for 1 other episode of idiopathic bowel perforation 3 years prior. She denied taking any medications. Dermatology was consulted to evaluate an asymptomatic skin eruption that had been present for at least 8 months before her hospitalization. Physical examination revealed numerous 5- to 10-mm nontender papules with a porcelain-white atrophic center and an erythematous halo, alongside scattered atrophic white scars (Figure, A and B). The lesions were distributed across her trunk, neck, and upper and lower extremities. Palms, soles, scalp, genitalia, and mucosal surfaces were spared. Her neurological and mental state examination had unremarkable results. Biopsy specimens from her thigh and back were obtained (Figure, C and D).Clinical photographs and biopsy specimens. A, Papules on the back with white atrophic center and an erythematous rim. B, Lesions on the thigh similar to those of the back, alongside atrophic white scars. C, Thigh biopsy shows hyperkeratosis and wedge-shaped avascular necrosis in dermis and subcutaneous tissue (hematoxylin-eosin stain, original magnification ×10). D, Back biopsy shows occlusion of dermal blood vessels, perivascular lymphocytic infiltration, and mucin deposition (hematoxylin-eosin stain, original magnification ×40).

what is your diagnosis?

What is your diagnosis?

Malignant atrophic papulosis

Pancreatitis panniculitis

Lymphomatoid papulosis

Systemic lupus erythematosus

a

female

0-10

White

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2631309

A woman in her 80s presented with a 1-year history of pruritic erythema on the trunk and extremities. The erythema did not respond to topical corticosteroid, oral roxithromycin (300 mg/d), or narrow-band UV-B phototherapy. The patient had a history of type 2 diabetes and hypertension and was treated with glimepiride, sitagliptin phosphate hydrate, and amlodipine besylate. The patient also had polymyalgia, which was treated with a low dose of prednisolone. The prednisolone therapy had been discontinued 2 months before her visit to the dermatology clinic when she had been hospitalized with pneumonia. Multiple tense blisters had subsequently appeared on the palms. Physical examination at the first visit revealed scaly erythematous plaques on the whole body and tense blisters on the arms, hands, soles, and buttocks. Neither scar formation or mucosal involvement was observed. A skin biopsy specimen was obtained from a bulla on the forearm. Histopathologic analysis revealed a subepidermal bulla with inflammatory infiltrates of neutrophils. The results of an IgG chemiluminescence enzyme immunoassay for bullous pemphigoid (BP) 180 noncollagenous (NC) 16A were negative. After treatment with oral prednisolone, 20 mg/d, the lesions healed without scar or milia formation (Figure 1).Clinical features before (A) and after (B) treatment with oral prednisolone, showing no scar formation. What Is Your Diagnosis?

Bullous pemphigoid

Epidermolysis bullosa acquisita

Anti–laminin γ1 pemphigoid

Linear IgA dermatosis

C. Anti–laminin γ1 pemphigoid

C

Anti–laminin γ1 pemphigoid

Direct immunofluorescence (IF) showed linear deposition of IgG and C3, but no IgA, at the basement membrane zone (BMZ). Indirect IF using 1 mol/L sodium chloride–split skin showed that the patient’s IgG antibodies labeled the dermal side of the split (Figure 2A). Serum anti–type VII collagen IgG antibodies detected by human type VII collagen enzyme-linked immunosorbent assay were within normal range. Immunoblotting of purified human laminin 211/221 (CC085, Chemicon/Merck Millipore) identified anti–laminin γ1 IgG antibodies (Figure 2B). Prednisolone was tapered without relapse of skin lesions. One year after her initial treatment, the patient’s condition was controlled with oral prednisolone, 7.5 mg/d.A, Indirect immunofluorescence using 1M sodium chloride–split skin showed reactivity of the patient’s IgG antibodies to the dermal side of the basement membrane zone. B, Immunoblot analysis of purified human laminin 211/221. IgG antibodies against laminin γ1 were detected in the patient’s serum but not in healthy control serum. mAb indicates mouse anti–human laminin γ1 monoclonal antibody (sc-13144, Santa Cruz Biotechnology).Anti–laminin γ1 pemphigoid is a rare subepidermal autoimmune blistering disease, characterized by circulating autoantibodies against a 200-kDa laminin γ1 protein at the dermal-epidermal junction. It was first described as anti-p200 pemphigoid in 19961,2; in 2009, Dainichi et al3 identified laminin γ1 as the autoantigen in 90% of cases and proposed a new name, anti–laminin γ1 pemphigoid.The clinical presentation of anti–laminin γ1 pemphigoid can be like that of bullous pemphigoid and the inflammatory variant of epidermolysis bullosa acquisita. Most patients present with itchy urticarial plaques and tense blisters, often on the acral sites and extremities. Lesions usually heal without scar or milia formation4 unless the disease is accompanied by other autoimmune bullous diseases that involve scar formation, such as epidermolysis bullosa acquisita or anti–laminin 332 mucous membrane pemphigoid.5The diagnosis of anti–laminin γ1 pemphigoid is confirmed by histopathologic analysis, IF microscopy analyses, and detection of the specific autoantibodies. Histopathological examination shows subepidermal split formation and typically accumulation of neutrophils and/or eosinophils in the papillary dermis. Direct IF shows linear deposits of IgG and C3 along the BMZ. If serum autoantibodies bind to the dermal side of the artificial split by indirect IF microscopy on 1M sodium chloride–split skin, the differential diagnoses would include epidermolysis bullosa acquisita, anti–laminin 332 pemphigoid, and anti–laminin γ1 pemphigoid. In the present case, no circulating anti–type VII collagen IgG antibodies were detected. Anti–laminin 332 pemphigoid can usually be clinically differentiated from anti–laminin γ1 pemphigoid by the lack of mucosal lesions, although 20% of patients with anti–laminin γ1 pemphigoid develop them. The diagnosis of anti–laminin γ1 pemphigoid is definitive with detection of anti–laminin γ1 IgG antibodies by immunoblotting studies, or human laminin γ1 enzyme-linked immunosorbent assay.The standard therapy for anti–laminin γ1 pemphigoid has not been defined. Most cases are successfully treated with mild or moderate immunosuppressive therapies such as oral corticosteroids, minocycline, dapsone, and cyclosporine.4In summary, subepidermal bullous disease with circulating autoantibodies against the dermal side of the basement membrane zone and healing without scar formation are the key criteria supporting the diagnosis of anti–laminin γ1 pemphigoid. Anti–laminin γ1 pemphigoid should be considered in patients with subepidermal blister formation without anti-BP180 or type VII collagen antibodies and can be diagnosed by the detection of anti–laminin γ1 autoantibodies.

Dermatology

A woman in her 80s presented with a 1-year history of pruritic erythema on the trunk and extremities. The erythema did not respond to topical corticosteroid, oral roxithromycin (300 mg/d), or narrow-band UV-B phototherapy. The patient had a history of type 2 diabetes and hypertension and was treated with glimepiride, sitagliptin phosphate hydrate, and amlodipine besylate. The patient also had polymyalgia, which was treated with a low dose of prednisolone. The prednisolone therapy had been discontinued 2 months before her visit to the dermatology clinic when she had been hospitalized with pneumonia. Multiple tense blisters had subsequently appeared on the palms. Physical examination at the first visit revealed scaly erythematous plaques on the whole body and tense blisters on the arms, hands, soles, and buttocks. Neither scar formation or mucosal involvement was observed. A skin biopsy specimen was obtained from a bulla on the forearm. Histopathologic analysis revealed a subepidermal bulla with inflammatory infiltrates of neutrophils. The results of an IgG chemiluminescence enzyme immunoassay for bullous pemphigoid (BP) 180 noncollagenous (NC) 16A were negative. After treatment with oral prednisolone, 20 mg/d, the lesions healed without scar or milia formation (Figure 1).Clinical features before (A) and after (B) treatment with oral prednisolone, showing no scar formation.

what is your diagnosis?

What is your diagnosis?

Bullous pemphigoid

Linear IgA dermatosis

Epidermolysis bullosa acquisita

Anti–laminin γ1 pemphigoid

d

female

0-10

original

https://jamanetwork.com/journals/jamapediatrics/fullarticle/2653914

A 5-year-old white girl presented with a history of recurrent fevers and urticaria since 2 months of age. The child had fevers (maximum temperature, 40°C) that lasted 3 to 5 days. Her mother reported that the fevers resolved spontaneously but continued to recur almost every month. The fever symptoms were associated with bilateral conjunctivitis, arthralgias, and irritability. The hivelike, nonpruritic urticaria did not improve with antihistamine medication and there were no known precipitating or aggravating factors. The child did not attend day care. Family history was noncontributory and her parents denied consanguinity.The child was hospitalized on multiple occasions during infancy for the fevers, and she had comprehensive sepsis evaluations, including lumbar punctures, with negative results. Findings from chest and abdominal imaging and bone marrow aspiration with biopsy were negative for a malignant process. Despite extensive evaluation, a definitive source for the fevers was not identified, and the patient was referred to our institution.On physical examination, the patient was febrile (temperature, 39°C) and appeared fussy. Growth measure findings were normal. Skin examination confirmed nonpruritic, macular and urticarial lesions on the face, back, and lower extremities (Figure). Bilateral conjunctival hyperemia without drainage was noted. There was neither swelling nor redness of the joints. Her right ankle and knee examination showed limited active and passive range of motion secondary to pain symptoms. Findings from the remainder of physical examination were normal.Erythematous macular and urticarial lesions with areas of confluence on back and lower extremities. What Is Your Diagnosis?

Chronic urticaria

Familial cold autoinflammatory syndrome

Muckle-Wells syndrome

Neonatal-onset multisystem inflammatory disorder

C. Muckle-Wells syndrome (MWS)

C

Muckle-Wells syndrome

Laboratory tests showed normal complete blood cell count, erythrocyte sedimentation rate of 40 mm/h, and C-reactive protein of 153 mg/L (to convert to nanomoles per liter, multiply by 9.524). Urinalysis, serum amyloid, and audiometric test results were normal. Ophthalmologic examination revealed an absence of papilledema and uveitis. The patient underwent an evaluation for cryopyrin-associated periodic syndromes because of the presence of fever, arthritis, and urticaria as an infant. Genetic analysis revealed a T348M mutation of the NLRP3 (formerly CIAS1) gene. The child was diagnosed with MWS (OMIM #191900).The cryopyrin-associated periodic syndromes or cryopyrinopathies are a group of rare, inherited, autoinflammatory disorders of interleukin 1–associated regulation.1 These syndromes occur because of genetic mutations in the NLRP3 gene (OMIM *606416), which encodes cryopyrin, a protein that regulates inflammation. Mutations in this gene result in unregulated production of interleukin 1, leading to symptoms of inflammation such as fever and arthralgias.1,2Cryopyrinopathies include the following 3 subtypes: MWS, familial cold autoinflammatory syndrome, and neonatal-onset multisystem inflammatory disorder.1,2 Familial cold autoinflammatory syndrome is characterized by intermittent urticaria, fever, and arthritis triggered by exposure to cold temperatures. Neonatal-onset multisystem inflammatory disorder has the most severe phenotype and presents in infancy as a systemic inflammatory condition with fever, arthritis, urticaria, and central nervous system disease.1,2First described in 1962, MWS is inherited as an autosomal dominant trait with variable penetrance. Symptoms start in infancy and early childhood, and the disease is characterized by recurrent nonpruritic urticaria with periodic fevers. Fevers occur at irregular intervals every few weeks, last 24 to 48 hours, and resolve spontaneously. Symptoms can be precipitated by stress, exercise, and cold or heat exposure. Arthralgia can affect any joint, but bony destruction is not usually seen. Conjunctivitis occurs with flares of the disease.1,2The main complications of MWS include sensorineural hearing loss (SNHL) and progressive amyloidosis. Inflammation within the cochlea or leptomeninges may be related to SNHL. Bilateral SNHL has been described in up to 85% of patients with MWS. The SNHL begins during early adolescence and often starts at high frequencies but can rapidly progress to profound hearing loss.3,4 Deposition of amyloid in the kidneys and liver also contributes to the MWS morbidity.1,2Confirmation of the diagnosis is achieved through genetic testing and identification of an NLRP3 mutation. Studies have detected cases of somatic mosaicism of the NLRP3 gene in individuals with clinical findings of cryopyrin-associated periodic syndromes, without evidence of the genetic mutation on the standard genetic tests.5 Histopathologic analysis of skin lesions shows perivascular and interstitial, mixed-inflammatory infiltrate of plasma cells, histiocytes, eosinophils, and mast cells.6Currently, there is no cure for the cryopyrinopathies. Treatment involves use of agents that target interleukin 1, such as rilonacept, canakinumab, and anakinra7,8 Most patients have a normal life span, and the development of complications such as amyloidosis and SNHL is rare with treatment. However, routine audiological monitoring is recommended for all patients with MWS; early detection and management of hearing loss is important for speech, language, and social development. Traditional screening pediatric audiograms test for standard frequencies only. Hence, comprehensive otolaryngologic assessments should include testing of high-frequency hearing thresholds.4,5 Our patient was successfully treated with anakinra injection medication and has been doing well. She currently has no disease complications.This case highlights the importance of investigating MWS as a possible diagnosis for infants with recurrent fevers and urticaria. Delay in diagnosis can result in irreversible and profound medical and developmental complications.

Pediatrics

A 5-year-old white girl presented with a history of recurrent fevers and urticaria since 2 months of age. The child had fevers (maximum temperature, 40°C) that lasted 3 to 5 days. Her mother reported that the fevers resolved spontaneously but continued to recur almost every month. The fever symptoms were associated with bilateral conjunctivitis, arthralgias, and irritability. The hivelike, nonpruritic urticaria did not improve with antihistamine medication and there were no known precipitating or aggravating factors. The child did not attend day care. Family history was noncontributory and her parents denied consanguinity.The child was hospitalized on multiple occasions during infancy for the fevers, and she had comprehensive sepsis evaluations, including lumbar punctures, with negative results. Findings from chest and abdominal imaging and bone marrow aspiration with biopsy were negative for a malignant process. Despite extensive evaluation, a definitive source for the fevers was not identified, and the patient was referred to our institution.On physical examination, the patient was febrile (temperature, 39°C) and appeared fussy. Growth measure findings were normal. Skin examination confirmed nonpruritic, macular and urticarial lesions on the face, back, and lower extremities (Figure). Bilateral conjunctival hyperemia without drainage was noted. There was neither swelling nor redness of the joints. Her right ankle and knee examination showed limited active and passive range of motion secondary to pain symptoms. Findings from the remainder of physical examination were normal.Erythematous macular and urticarial lesions with areas of confluence on back and lower extremities.

what is your diagnosis?

What is your diagnosis?

Chronic urticaria

Muckle-Wells syndrome

Neonatal-onset multisystem inflammatory disorder

Familial cold autoinflammatory syndrome

b

female

0-10

White

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2653282

An elderly woman was transferred from an extended care facility with lower abdominal pain. She was afebrile with a heart rate of 120 beats/min on admission and leukocytosis (white blood cell count, 23 000/μL [to convert to ×109/L, multiply by 0.001]). Computed tomography of the abdomen and pelvis and transvaginal ultrasonography revealed a large intrauterine abscess. An attempt to insert a peripherally inserted central catheter (PICC) into the right basilic vein was unsuccessful. An intravenous catheter in the left hand was established for the administration of antibiotics. The following day, the patient developed right upper extremity pain and swelling. Physical examination revealed tense and tender swelling of the right upper extremity that was more marked in the upper arm and caused significant impairment in motor function, but sensation to touch and pin prick was intact (Figure 1A). The right radial pulse was absent, but biphasic Doppler arterial signals were present in the right radial and ulnar artery. Duplex ultrasonographic imaging of the right upper extremity demonstrated a 12.8 × 2.6-cm heterogeneous fluid collection with active color flow (Figure 1B).Patient presentation (A) and ultrasonographic imaging (B) of the upper arm.Extensive deep vein thrombosis of the upper extremityCompartment syndrome resulting from infiltration of intravenous infusion therapy into the soft tissues of the upper extremity What Is Your Diagnosis?

Extensive deep vein thrombosis of the upper extremity

Compartment syndrome resulting from infiltration of intravenous infusion therapy into the soft tissues of the upper extremity

Secondary lymphedema of the upper extremity

Brachial artery pseudoaneurysm

D. Brachial artery pseudoaneurysm

D

Brachial artery pseudoaneurysm

Computed tomography angiography of the right upper extremity confirmed pseudoaneurysm measuring 3.8 cm, originating from the profunda brachii artery (Figure 2). The patient underwent open surgical repair. To gain proximal control, an incision was made in the right axilla and the proximal brachial artery was controlled with a silastic loop. A separate incision was then made over the pseudoaneurysm. The hematoma was evacuated and the pseudoaneurysm sac was excised. A small opening in the profunda brachii artery was sutured with horizontal mattress of 7-0 cardiovascular polypropylene (Ethicon). Postoperatively, the swelling and motor function in the right upper extremity improved with a palpable radial pulse.Extensive deep vein thrombosis of the upper extremity results in disproportional swelling of the hand and forearm compared with the upper arm. Duplex imaging ruled out deep venous thrombosis. The patient did not receive an intravenous infusion in the right arm since the PICC was not present. Secondary lymphedema is usually chronic and is often related to mastectomy with axillary node dissection and/or radiotherapy. Iatrogenic pseudoaneurysm of the upper extremity is an uncommon clinical entity caused by focal weakness within the arterial wall from arterial injury. Iatrogenic instrumentation, infection, or repetitive trauma are the most commonly described causes. Brachial and radial access are being increasingly used for cardiac and vascular interventions and carries a small risk of pseudoaneurysm formation.1 Intravenous substance abuse is a more frequent cause of infected pseudoaneurysms in the antecubital fossa. Patients with upper extremity pseudoaneurysms often present with a painful mass, swelling, or paresthesias due to local nerve compression.2 Alternatively, a patient may present with distal ischemia due to a thromboembolic event. Diagnosis often can be suspected on physical examination; however, duplex ultrasonography is the diagnostic study of choice. Computed tomographic arteriography may aid in operative planning.Pseudoaneurysms can be treated using surgical and percutaneous interventions. Percutaneous ultrasonography–guided thrombin injection used frequently for iatrogenic femoral artery pseudoaneurysms is less frequently utilized in the treatment of upper extremity pseudoaneurysms.3 In cases of pseudoaneurysm arising from a small branch, coil embolization can be performed.4 More proximal pseudoaneurysms in the axillary and subclavian arteries can be successfully managed with stent graft placement.5 This patient had an associated large hematoma causing limitation of motor function. This, in combination with the ill-defined neck of the pseudoaneurysm, prompted us to proceed with open surgical repair.

Surgery

An elderly woman was transferred from an extended care facility with lower abdominal pain. She was afebrile with a heart rate of 120 beats/min on admission and leukocytosis (white blood cell count, 23 000/μL [to convert to ×109/L, multiply by 0.001]). Computed tomography of the abdomen and pelvis and transvaginal ultrasonography revealed a large intrauterine abscess. An attempt to insert a peripherally inserted central catheter (PICC) into the right basilic vein was unsuccessful. An intravenous catheter in the left hand was established for the administration of antibiotics. The following day, the patient developed right upper extremity pain and swelling. Physical examination revealed tense and tender swelling of the right upper extremity that was more marked in the upper arm and caused significant impairment in motor function, but sensation to touch and pin prick was intact (Figure 1A). The right radial pulse was absent, but biphasic Doppler arterial signals were present in the right radial and ulnar artery. Duplex ultrasonographic imaging of the right upper extremity demonstrated a 12.8 × 2.6-cm heterogeneous fluid collection with active color flow (Figure 1B).Patient presentation (A) and ultrasonographic imaging (B) of the upper arm.Extensive deep vein thrombosis of the upper extremityCompartment syndrome resulting from infiltration of intravenous infusion therapy into the soft tissues of the upper extremity

what is your diagnosis?

What is your diagnosis?

Brachial artery pseudoaneurysm

Compartment syndrome resulting from infiltration of intravenous infusion therapy into the soft tissues of the upper extremity

Extensive deep vein thrombosis of the upper extremity

Secondary lymphedema of the upper extremity

a

female

71-80

White

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2654233

A man in his 50s with a history of smoking and chronic hypertension was admitted to our hospital with a 36-hour history of upper abdominal pain, nausea, and vomiting. He had no history of previous surgery or trauma. His systolic blood pressure was 109 mm Hg, his diastolic blood pressure was 70 mm Hg, and his pulse rate was 100 beats/min. A physical examination revealed moderate epigastric tenderness with rebound and guarding. Laboratory test results were remarkable for a white blood cell count of 13 970/μL, hemoglobin level of 8.4 g/dL, serum creatinine level of 1.67 mg/dL, serum amylase level of 57 U/L (reference range, 30-110 U/L), and serum triglyceride level of 282.42 mg/dL, with no evidence of coagulopathy. (To convert the white blood cell count to ×109 per liter, multiply by 0.001; hemoglobin level to grams per liter, by 10; serum creatinine level to micromoles per liter, by 88.4; serum amylase level to microkatals per liter, by 0.0167; and serum triglyceride level to millimoles per liter, by 0.0113.) Contrast-enhanced computed tomography (CECT) and mesenteric angiography were performed (Figure 1).A, Contrast-enhanced computed tomographic (CECT) image showing an intra-abdominal hyperdense mass (arrowhead) and free fluid in the upper abdomen. B, Visceral artery angiogram revealing an aneurysm (arrowhead). What Is Your Diagnosis?

Hemorrhagic pancreatitis

Acute perforation of a bleeding peptic ulcer

Rupture of a jejunal artery aneurysm

Rupture of a peripancreatic pseudoaneurysm

C. Rupture of a jejunal artery aneurysm

C

Rupture of a jejunal artery aneurysm

Patients with hemodynamic instability and generalized peritonitis or clinical deterioration with acute abdominal pain are usually experiencing one of a few intra-abdominal catastrophes: severe pancreatitis, ruptured abdominal aneurysm, bowel infarction, or digestive juices or sepsis release from perforation of a peptic ulcer or other gastrointestinal abnormality. Diagnosis always relies on imaging evaluation; when dealing with clinically deteriorating patients, computed tomography has the advantage of providing rapid, sensitive, and specific results.1 This patient’s CECT image showing high-attenuation fluid (34 HU) in the perihepatic and perisplenic regions (Figure 1) and his sudden onset of abdominal pain and anemia establish a diagnosis of intraperitoneal hemorrhage. With a normal serum amylase level, the clinical features and imaging results eliminated the diagnoses of pancreatitis and perforated peptic ulcer. Numerous specific computed tomographic signs of hemoperitoneum associated with a high-attenuation hematoma or sentinel clot, mesenteric fluid, and active arterial extravasation may indicate the source of bleeding and help direct management.2 The CECT images in this patient demonstrated the presence of a small area of hyperdense vessels, suggesting active bleeding with a large peripancreatic hematoma (Figure 1A). The CT finding of active bleeding indicated that endovascular management or surgical treatment should be considered. A selective superior mesenteric artery injection revealed vascular sclerosis and a 7-mm aneurysm of the distal branch of the first jejunal artery (Figure 1B).Jejunal artery aneurysms are rare, accounting for less than 3% of all splanchnic artery aneurysms,3 which have recognized morbid potential because of their tendency to rupture. Jejunal artery aneurysms have a 30% risk of rupture with a 20% death rate. Most jejunal artery aneurysms are solitary, more frequent in elderly patients, usually diagnosed after the occurrence of complications, and potentially lethal.4 Rupture is the most catastrophic complication although the precise mechanism is unclear. According to histologic analyses, heavy smoking, hypertension, and hyperlipidemia may have directly or indirectly contributed to aneurysmal rupture in our patient.4 Hemorrhage can be intraluminal or intra-abdominal with the rupture of a jejunal artery aneurysm.5 Management of this ruptured aneurysm poses a challenge for physicians owing to the lack of guidelines for surveillance and intervention.6 Treatment options are open surgical and endovascular procedures and should be determined on the basis of surgeon preference, patient characteristics, and aneurysm diameter, location, and morphologic features. Currently, transcatheter embolization almost always constitutes first-line therapy.7In this patient, emergent exploratory laparotomy showed more than 1500 mL of hemoperitoneum in the abdominal cavity and a large hematoma at the root of the mesentery located in the retroperitoneum that extended through the base of the transverse mesocolon and up to the body of the pancreas (Figure 2). The patient underwent successful endovascular embolization of the aneurysm with polyvinyl alcohol particles and thrombin topical, and his recovery was uneventful.A large hematoma in the root of the mesentery located in the retroperitoneum (arrowhead).Diagnosis of spontaneous hemoperitoneum is based primarily on radiologic findings. Jejunal artery aneurysms should be suspected in elderly patients with acute abdominal pain and hemodynamic instability.

Surgery

A man in his 50s with a history of smoking and chronic hypertension was admitted to our hospital with a 36-hour history of upper abdominal pain, nausea, and vomiting. He had no history of previous surgery or trauma. His systolic blood pressure was 109 mm Hg, his diastolic blood pressure was 70 mm Hg, and his pulse rate was 100 beats/min. A physical examination revealed moderate epigastric tenderness with rebound and guarding. Laboratory test results were remarkable for a white blood cell count of 13 970/μL, hemoglobin level of 8.4 g/dL, serum creatinine level of 1.67 mg/dL, serum amylase level of 57 U/L (reference range, 30-110 U/L), and serum triglyceride level of 282.42 mg/dL, with no evidence of coagulopathy. (To convert the white blood cell count to ×109 per liter, multiply by 0.001; hemoglobin level to grams per liter, by 10; serum creatinine level to micromoles per liter, by 88.4; serum amylase level to microkatals per liter, by 0.0167; and serum triglyceride level to millimoles per liter, by 0.0113.) Contrast-enhanced computed tomography (CECT) and mesenteric angiography were performed (Figure 1).A, Contrast-enhanced computed tomographic (CECT) image showing an intra-abdominal hyperdense mass (arrowhead) and free fluid in the upper abdomen. B, Visceral artery angiogram revealing an aneurysm (arrowhead).

what is your diagnosis?

What is your diagnosis?

Rupture of a jejunal artery aneurysm

Hemorrhagic pancreatitis

Acute perforation of a bleeding peptic ulcer

Rupture of a peripancreatic pseudoaneurysm

a

male

51-60

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2645911

A healthy 67-year-old man presented to the ocular oncology service with a 3-day history of acute-onset blurred vision and mild tenderness of his left eye. He denied notable ocular history aside from a recently documented elevated intraocular pressure (IOP) of 36 mm Hg OS and shallow anterior chamber (AC). Laser peripheral iridotomy had been performed but failed to deepen the AC. Subsequently, a choroidal mass was discovered, and he was referred for our opinion.On examination, refractive error was +3.00 D OU, and best-corrected visual acuity was 20/25 OD and 20/40 OS. Results of examination in the right eye were unremarkable, and IOP was 17 mm Hg. Examination of the left eye revealed elevated IOP of 26 mm Hg while the patient was taking dorzolamide/timolol. The AC was shallow, and episcleral vessels were congested. Ophthalmoscopic examination and wide-angle scanning laser ophthalmoscopy (Figure 1A) documented a ring-shaped peripheral ciliochoroidal mass accompanied by shallow serous retinal detachment inferiorly. Globe transillumination revealed an undefined mottled choroidal shadow inferiorly. B-scan ultrasonography (Figure 1B) and ultrasound biomicroscopy suggested an echolucent ciliochoroidal elevation without intrinsic vascular pulsations. Magnetic resonance imaging of the orbits confirmed the ring-shaped ciliochoroidal elevation with nonenhancement of the mass. Doppler ultrasonography showed normal flow parameters without evidence of a dural-cavernous fistula.A, Wide-angle fundus photograph demonstrating peripheral choroidal elevation, most prominent superotemporally, and numerous choroidal folds. B, B-scan ultrasonography showing extensive choroidal detachment.Proceed with sclerotomies, ie, creation of scleral windows What Would You Do Next?

Perform fine-needle aspiration biopsy

Perform plaque radiotherapy

Treat with oral corticosteroids

Proceed with sclerotomies, ie, creation of scleral windows

Uveal effusion syndrome

C

Treat with oral corticosteroids

Ciliochoroidal (uveal) effusion occurs when fluid is retained in the suprachoroidal and/or supraciliary space leading to engorgement and detachment of the choroid and ciliary body from the sclera.1,2 This peripheral elevation can simulate an intraocular mass.3,4 Underlying causes are divided into inflammatory (trauma, scleritis, or postphotocoagulation),1 hydrostatic (hypotony or dural-cavernous fistula),1 and drug-induced (selective serotonin reuptake inhibitors5 or sulfonamides) conditions. Uveal effusion syndrome (UES), first described in 1963 by Schepens and Brockhurst,6 is reserved for idiopathic cases.1,2 This disorder typically manifests in healthy, middle-aged men and can be bilateral.1,2Findings in UES include dilation of episcleral vessels, shallow AC, and, most notably, peripheral ciliochoroidal elevation associated with serous retinal detachment.1,2 Chronic subretinal fluid can lead to retinal pigment epithelial hyperplasia, resulting in a leopard-spot appearance after resolution of the effusion.1,2 Hypotheses regarding pathophysiology include vortex vein obstruction, congenital/intrinsic scleral abnormality, and/or reduced scleral permeability.1,2 Uveal effusion syndrome can further be subdivided into 3 types. Type 1 includes nanophthalmic eyes (axial length, ≤20 mm). Types 2 and 3 consist of nonnanophthalmic eyes with abnormal and normal sclera, respectively (mean axial length, 21.0 mm and 23.9 mm).1A broad differential, including choroidal melanoma, metastasis, lymphoma, hemangioma, granuloma, and exudative retinal detachment, should be considered.3 Shields et al4 found that among 1739 patients with pseudomelanoma, UES represented 1%. Had choroidal melanoma been this patient’s diagnosis, plaque brachytherapy would have been our treatment option of choice. However, several findings, including no shadow on globe transillumination, lack of vascular pulsations on ultrasonography, and nonenhancement of the mass on magnetic resonance imaging, excluded this diagnosis. In equivocal cases, fine-needle aspiration biopsy can help establish the diagnosis. Given the absence of an underlying condition, normal axial length (25.0 mm), and unremarkable sclera, this patient was classified as having type 3 UES.When mild and asymptomatic, UES can be managed with observation. Intervention is warranted when subretinal fluid threatens the macula or causes AC shallowing. Andrijević Derk et al7 used oral carbonic anhydrase inhibitors and topical prostaglandin analogues to increase scleral permeability in patients with UES (unspecified types). In 2 patients, the choroidal detachment resolved within 3 months; however, 1 patient later required surgery.7 Moderate-to-higher dose systemic steroids for UES have also been tried.2,5,8 From our experience, oral, subtenon, or intravitreal corticosteroids are efficacious in patients with UES; however, there is a paucity of literature surrounding this recommendation.Surgical techniques for UES include vortex vein decompression, sclerotomy, and partial/full-thickness sclerectomy with or without mitomycin C.1,9,10 Among 23 postsclerectomy eyes, Johnson and Gass9 found that subretinal fluid resolved within 6 months in 83% of patients. However, surgery has been reportedly ineffective for type 3 UES.1The patient received 80 mg of oral prednisone daily for 1 week, with slow taper over 6 weeks. Seven weeks after the initial visit, visual acuity improved to 20/20 OU, and IOP normalized (15 mm Hg OS). His effusion and retinal detachment resolved completely without complications (Figure 2).Wide-angle fundus photograph illustrating resolution of the choroidal effusion and retinal detachment after corticosteroids.

Ophthalmology

A healthy 67-year-old man presented to the ocular oncology service with a 3-day history of acute-onset blurred vision and mild tenderness of his left eye. He denied notable ocular history aside from a recently documented elevated intraocular pressure (IOP) of 36 mm Hg OS and shallow anterior chamber (AC). Laser peripheral iridotomy had been performed but failed to deepen the AC. Subsequently, a choroidal mass was discovered, and he was referred for our opinion.On examination, refractive error was +3.00 D OU, and best-corrected visual acuity was 20/25 OD and 20/40 OS. Results of examination in the right eye were unremarkable, and IOP was 17 mm Hg. Examination of the left eye revealed elevated IOP of 26 mm Hg while the patient was taking dorzolamide/timolol. The AC was shallow, and episcleral vessels were congested. Ophthalmoscopic examination and wide-angle scanning laser ophthalmoscopy (Figure 1A) documented a ring-shaped peripheral ciliochoroidal mass accompanied by shallow serous retinal detachment inferiorly. Globe transillumination revealed an undefined mottled choroidal shadow inferiorly. B-scan ultrasonography (Figure 1B) and ultrasound biomicroscopy suggested an echolucent ciliochoroidal elevation without intrinsic vascular pulsations. Magnetic resonance imaging of the orbits confirmed the ring-shaped ciliochoroidal elevation with nonenhancement of the mass. Doppler ultrasonography showed normal flow parameters without evidence of a dural-cavernous fistula.A, Wide-angle fundus photograph demonstrating peripheral choroidal elevation, most prominent superotemporally, and numerous choroidal folds. B, B-scan ultrasonography showing extensive choroidal detachment.Proceed with sclerotomies, ie, creation of scleral windows

what would you do next?

What would you do next?

Perform fine-needle aspiration biopsy

Perform plaque radiotherapy

Treat with oral corticosteroids

Proceed with sclerotomies, ie, creation of scleral windows

c

male

61-70

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2647969

An 11-year-old previously healthy boy was referred to the pediatric department with impaired vision after an episode of fever and vomiting. Ophthalmologic examination revealed bilateral mydriasis, with a reduced pupillary response to light and accommodation (Figure). Diluted norepinephrine (0.1%) was instilled in both eyes, which elicited supersensitive dilatation of the pupils bilaterally owing to reinnervation and upregulation of the postsynaptic receptors, consistent with tonic pupils. Uncorrected Snellen visual acuity was 20/32 OU for distance and 20/200 OU for near. Ocular motility was normal. Results of slitlamp examination and ophthalmoscopy showed no abnormalities.Bilateral mydriasis with a reduced pupillary response to light and accommodation in an 11-year-old boy.Results of complete blood cell counts, serum chemistry examination, cerebrospinal fluid examination, and virologic studies of blood and stool performed for exclusion of infection were all negative. Tumor, aneurysm, or traumatic lesion were excluded by cranial magnetic resonance imaging. Serum GQ1b ganglioside IgG antibodies associated with internal ophthalmoplegia in Fisher syndrome were not detected.Within the following 2 weeks, progressive generalized autonomic dysfunction developed including reduced food intake and weight loss, constipation, urinary retention, anhidrosis, xerostomia, and xerophthalmia. Ophthalmologic reexamination showed unaltered pupillary abnormality. Results of Schirmer test without topical anesthesia showed 0 mm of tear production. Lissamine green staining of the exposed interpalpebral areas showed moderate changes of the conjunctiva. Mild corneal staining was evaluated with cobalt blue illumination after fluorescein instillation. Artificial tears and ointment were initiated to treat the aqueous tear deficiency.Obtain blood sample to investigate for autoimmune autonomic ganglionopathy What Would You Do Next?

Prescribe phototropic variofocal glasses

Start pilocarpine eyedrops

Obtain blood sample to investigate for autoimmune autonomic ganglionopathy

Recommend genetic testing

Autoimmune autonomic ganglionopathy

C

Obtain blood sample to investigate for autoimmune autonomic ganglionopathy

Autoimmune autonomic ganglionopathy (AAG) is a rare acquired immune-mediated disorder directed against sympathetic, parasympathetic, and enteric ganglia, autonomic nerves, or central autonomic pathways.1 Patients with AAG frequently have orthostatic hypotension, upper and lower gastrointestinal tract symptoms, and bladder dysfunction, as well as tonic pupils and dry eye syndrome.In addition to traditional autonomic testing, a special blood sample to investigate for AAG-associated autoantibodies (Autoimmune Dysautonomia Evaluation, Mayo Clinic Laboratories) can be ordered. Antibodies against the α3 subunit of the ganglionic-type nicotinic acetylcholine receptor can be detected in approximately 50% of cases.2 The remaining 50% of patients with AAG lack detectable levels of ganglionic-type nicotinic acetylcholine receptor antibodies.2 The pattern of organ involvement and severity of autonomic failure as observed in this patient has particularly been described in cases of seropositive AAG with high antibody values.3 However, the results of autoimmune dysautonomia evaluation testing revealed no conspicuous autoantibodies. No genetic background has been reported for AAG, to our knowledge.The onset of generalized or selective autonomic failure can be acute or subacute with spontaneous improvement occurring in about one-third of patients, but recovery is often incomplete. Therefore, various strategies of immune-modulating treatment have been applied in patients with AAG.4 Before treatment, malignancy has to be excluded because prevalence of α3 subunit of the ganglionic-type nicotinic acetylcholine receptor antibodies in patients with cancer is 15-fold higher than in healthy control patients (7.5% vs 0.5%).5The pathophysiology of seronegative cases is not known, but an autoimmune mechanism is suspected because of the clinical similarity with seropositive AAG and the response of some patients with seronegative results to the same immune-modulating treatment.2 Although AAG occurs mainly in adults, pediatric cases have been described occasionally.6-10Response of pupillary dysfunction to treatment is reported to be variable. Only 3 pediatric cases were found in literature, to our knowledge.7,8,10 In 1 patient, impaired pupillary response was reversible. in the second patient, tonic pupils were recurrent over a period of 18 months. However, in the third patient, an improvement of autonomic symptoms was reported without comment on pupillary outcome. In this patient, the tonic pupils were refractory to treatment and have persisted.Three weeks after the onset of ocular symptoms, the patient received intravenous immunoglobulins (2 g/kg body weight). Treatment with artificial saliva, salinic laxatives, prokinetic agents, and parenteral nutrition was started because of gastrointestinal dysfunction. Urinary retention required suprapubic drainage.Because intravenous immunoglobulins showed no benefit during a period of 4 weeks, a combined immune-modulating treatment was administered. The regimen included immune adsorptions (9 sessions), rituximab (4 × 375 mg/m2 body surface area), and prednisolone (4 intravenous pulses of 300 mg, followed by 60 mg/m2 body surface area/d orally for 3 weeks, thereafter tapered to an alternate day dose of 8 mg/m2 body surface area).After addition of tamsulosin (0.4 mg/d) and low-dose pyridostigmine (60 mg/d), the suprapubic catheter could be removed after 17 weeks. Increasing doses of pyridostigmine (up to 150 mg/d) did not show any beneficial effect.Increased glare sensitivity and lack of accommodation remained unchanged and were treated conservatively with phototropic varifocal glasses. Best-corrected visual acuity was 20/16 for far and 20/20 for near in both eyes. Symptoms of dry eye improved using moistening agents.

Ophthalmology

An 11-year-old previously healthy boy was referred to the pediatric department with impaired vision after an episode of fever and vomiting. Ophthalmologic examination revealed bilateral mydriasis, with a reduced pupillary response to light and accommodation (Figure). Diluted norepinephrine (0.1%) was instilled in both eyes, which elicited supersensitive dilatation of the pupils bilaterally owing to reinnervation and upregulation of the postsynaptic receptors, consistent with tonic pupils. Uncorrected Snellen visual acuity was 20/32 OU for distance and 20/200 OU for near. Ocular motility was normal. Results of slitlamp examination and ophthalmoscopy showed no abnormalities.Bilateral mydriasis with a reduced pupillary response to light and accommodation in an 11-year-old boy.Results of complete blood cell counts, serum chemistry examination, cerebrospinal fluid examination, and virologic studies of blood and stool performed for exclusion of infection were all negative. Tumor, aneurysm, or traumatic lesion were excluded by cranial magnetic resonance imaging. Serum GQ1b ganglioside IgG antibodies associated with internal ophthalmoplegia in Fisher syndrome were not detected.Within the following 2 weeks, progressive generalized autonomic dysfunction developed including reduced food intake and weight loss, constipation, urinary retention, anhidrosis, xerostomia, and xerophthalmia. Ophthalmologic reexamination showed unaltered pupillary abnormality. Results of Schirmer test without topical anesthesia showed 0 mm of tear production. Lissamine green staining of the exposed interpalpebral areas showed moderate changes of the conjunctiva. Mild corneal staining was evaluated with cobalt blue illumination after fluorescein instillation. Artificial tears and ointment were initiated to treat the aqueous tear deficiency.Obtain blood sample to investigate for autoimmune autonomic ganglionopathy

what would you do next?

What would you do next?

Prescribe phototropic variofocal glasses

Recommend genetic testing

Start pilocarpine eyedrops

Obtain blood sample to investigate for autoimmune autonomic ganglionopathy

d

male

11-20

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2648267

A 51-year-old woman presented to our institution’s emergency department with an ocular surface lesion in the left eye. She had an 11-mm pigmented conjunctival lesion that was suspicious for melanoma with significant involvement of the caruncle, bulbar conjunctiva, and palpebral conjunctiva. The patient subsequently underwent a complete excision of the tumor and supplemental cryotherapy to the resection bed. Pathological results confirmed the diagnosis of conjunctival melanoma. The tumor had invaded the medial canthus and medial rectus insertion; however, no scleral invasion was observed during the intraoperative examination. Three months later, she had a new pigment deposition adjacent to the limbus in the area of the prior resection, for which she underwent additional excision and cryotherapy. Pathology specimens from this excision were negative for atypia. The patient was given mitomycin C as adjuvant therapy.Two months later, the patient presented for follow-up. Her visual acuity and intraocular pressure were at baseline and within normal limits, respectively. On slitlamp examination, a peaked pupil was noted (Figure 1). No new pigment was noted on the ocular surface. She also stated that she had pain to the eye.A, Slitlamp photography of the left eye demonstrating the pupil peaked toward the 9:30 area. B, Gonioscopy of the left eye demonstrating pigmented trabecular meshwork that is obscured by a focal area of peripheral anterior synechiae corresponding to the area of the peaked pupil (arrowhead).Continue administering mitomycin C and schedule a follow-up visit in 6 to 8 weeksDelay mitomycin C therapy for a few weeks What Would You Do Next?

Continue administering mitomycin C and schedule a follow-up visit in 6 to 8 weeks

Obtain an ultrasonographic biomicroscopy

Biopsy the limbal area around 9:30

Delay mitomycin C therapy for a few weeks

Peripheral anterior synechiae secondary to cryotherapy.

B

Obtain an ultrasonographic biomicroscopy

Conjunctival melanoma has a 10-year mortality rate of approximately 15% to 25%.1 Treatment usually consists of a complete excisional biopsy with adjuvant cryotherapy. Patients often undergo topical chemotherapy after surgical intervention with mitomycin C.Given this patient’s history of an extensive conjunctival melanoma requiring a large dissection and excision, it was necessary to evaluate the new peaked pupil with ultrasonographic biomicroscopy (UBM). Continuing or delaying mitomycin C therapy would not assess the etiology of the peaked pupil. A biopsy of the area would represent an overly aggressive intervention, having not completed the diagnostic UBM testing first.Ultrasonographic biomicroscopy would evaluate the ciliary body to exclude the possibility of intraocular extension, with the tumor potentially pushing forward and inducing focal peripheral anterior synechiae (PAS). The incidence of conjunctival melanoma with intraocular extension is extremely rare, but has been reported by multiple groups. One report2 describes an association between intraocular extension of conjunctival melanoma and a limbal location, with intraocular invasion likely because of breach of the Bowman membrane. Another report1 describes a patient who had a large recurrent conjunctival melanoma after undergoing multiple excisions who also had a history of penetrating keratoplasty; the melanoma had invaded the ciliary body, trabecular meshwork, and iris. Another case3 described intraocular extension several years after trabeculectomy surgery. One similarity shared among these cases was the need for multiple surgical procedures for a complete tumor excision, as well as a history of penetrating intraocular surgery, suggesting an iatrogenic role for intraocular spread. Notably, the inverse clinical presentation has been previously reported as well in a rare case of primary uveal melanoma metastasizing to the conjunctiva.4 In this case, no intraocular surgery had been completed before or after the melanoma resection.Ultrasonographic biomicroscopy results of the suspicious area showed no ciliary body tumor extension, but rather a focal PAS formation (Figure 2). The PAS noted on gonioscopy that caused the peaked pupil was attributed to inflammatory cicatricial changes from multiple applications of cryotherapy to the limbus. This finding has been observed among several patients with ocular surface squamous neoplasia and melanoma who were treated with cryotherapy. We have also observed microhyphemas on the first postoperative day in rare occasions. The patient continued to undergo topical mitomycin C therapy and was monitored without evidence of local recurrence. Unfortunately, a systemic workup has suggested a potential axillary lymph node metastasis, for which she is being followed up by an oncology service.Ultrasound biomicroscopy (longitudinal probe orientation at 9:30) demonstrating a focal area of peripheral anterior synechiae. No mass suspicious for tumor was observed in the ciliary body or iris.

Ophthalmology

A 51-year-old woman presented to our institution’s emergency department with an ocular surface lesion in the left eye. She had an 11-mm pigmented conjunctival lesion that was suspicious for melanoma with significant involvement of the caruncle, bulbar conjunctiva, and palpebral conjunctiva. The patient subsequently underwent a complete excision of the tumor and supplemental cryotherapy to the resection bed. Pathological results confirmed the diagnosis of conjunctival melanoma. The tumor had invaded the medial canthus and medial rectus insertion; however, no scleral invasion was observed during the intraoperative examination. Three months later, she had a new pigment deposition adjacent to the limbus in the area of the prior resection, for which she underwent additional excision and cryotherapy. Pathology specimens from this excision were negative for atypia. The patient was given mitomycin C as adjuvant therapy.Two months later, the patient presented for follow-up. Her visual acuity and intraocular pressure were at baseline and within normal limits, respectively. On slitlamp examination, a peaked pupil was noted (Figure 1). No new pigment was noted on the ocular surface. She also stated that she had pain to the eye.A, Slitlamp photography of the left eye demonstrating the pupil peaked toward the 9:30 area. B, Gonioscopy of the left eye demonstrating pigmented trabecular meshwork that is obscured by a focal area of peripheral anterior synechiae corresponding to the area of the peaked pupil (arrowhead).Continue administering mitomycin C and schedule a follow-up visit in 6 to 8 weeksDelay mitomycin C therapy for a few weeks

what would you do next?

What would you do next?

Biopsy the limbal area around 9:30

Obtain an ultrasonographic biomicroscopy

Delay mitomycin C therapy for a few weeks

Continue administering mitomycin C and schedule a follow-up visit in 6 to 8 weeks

b

female

51-60

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2649284

A 64-year-old man presented to the Department of Ophthalmology for evaluation of bilateral visual field (VF) loss. His VF loss was recognized on automated Humphrey VF screening and had remained unchanged during the subsequent 5 years (Figure, A). His ocular history was significant for mild nuclear sclerosis. His current medications included multivitamins and fish oil.Automated Humphrey visual field (VF) shows a right, dense inferior arcuate scotoma (A). The VF loss is stable when compared with previous VF testing. Color fundus photograph demonstrates small tilted right optic nerve with peripapillary atrophy (B). GHT indicates Glaucoma Hemifield Test; MD, mean deviation; PSD, pattern standard deviation; and VFI, visual field index.Neuro-ophthalmic examination revealed visual acuities of 20/30 OD and 20/25 OS that matched with the density of his cataracts. Color vision was within normal limits bilaterally. Pupils were symmetric without afferent defects. Applanation tonometry pressures were 18 mm Hg OD and 17 mm Hg OS. Slitlamp examination revealed mild nuclear sclerosis in each eye. Repeated automated Humphrey VF testing revealed bilateral inferior arcuate defects (mean deviation, −4.80 dB OD and −2.6 dB OS). Examination of his fundus revealed bilateral tilted optic nerves with peripapillary atrophy (Figure, B).Reassure the patient that VF loss is due to remote ischemic optic neuropathy and consider daily aspirinReassure the patient that VF loss is due to congenitally anomalous optic nerves and recommend annual evaluation to monitor VFPerform selective laser trabeculoplasty because the patient’s intraocular pressure is above target for his moderate glaucoma What Would You Do Next?

Reassure the patient that VF loss is due to remote ischemic optic neuropathy and consider daily aspirin

Order immediate magnetic resonance imaging study

Reassure the patient that VF loss is due to congenitally anomalous optic nerves and recommend annual evaluation to monitor VF

Perform selective laser trabeculoplasty because the patient’s intraocular pressure is above target for his moderate glaucoma

Bilateral superior segmental optic nerve hypoplasia

C

Reassure the patient that VF loss is due to congenitally anomalous optic nerves and recommend annual evaluation to monitor VF

The diagnosis of superior segmental optic nerve hypoplasia (SSONH) is a clinical one. It depends on the morphologic features of the optic nerve and its correlation with the VF loss that is typically asymptomatic with sparing of central visual acuity. This patient’s optic nerve head exhibits the classic signs of SSONH, including superior peripapillary scleral halo, thin superior neuroretinal rim, and thinning of the superior peripapillary retinal nerve fiber layer (RNFL) that is evident as a superior RNFL bundle defect. It also shows the superiorly located central retinal artery and vein bifurcation.Optical coherence tomography demonstrated bilateral superior RNFL thinning with a single inferior RNFL hump pattern compared with the normal superior and inferior hump pattern of RNFL thickness. Based on the findings of classic SSONH appearance as well as asymptomatic, stable inferior field loss corresponding to the superior optic nerve anomaly, the diagnosis of SSONH was established.Superior segmental optic nerve hypoplasia is an uncommon developmental disorder of the optic nerve that results in inferior arcuate or altitudinal VF loss. It is frequently mistaken for normal tension glaucomatous optic neuropathy, especially when associated with large cup-disc ratio in older patients. Additionally, cases of SSONH associated with glaucoma have been reported.1 It can also be mistaken for nonarteritic anterior ischemic optic neuropathy because the small cupless appearance of the optic nerve may mimic the disc-at-risk appearance, and the inferior field loss may simulate the classic inferior altitudinal field loss of nonarteritic anterior ischemic optic neuropathy.Partial SSONH in the offspring of insulin-dependent mothers with diabetes was first reported by Petersen and Walton2 in 1977. Unlike the generalized form of optic nerve hypoplasia, SSONH is not associated with midline intracranial malformations or pituitary hypofunction. The incidence of SSONH in offspring of mothers with diabetes has been reported to be 8.8%, suggesting that the condition is underdiagnosed, given the frequency of maternal diabetes.3 The term superior segmental optic nerve hypoplasia was coined by Kim et al4 in 1989.Management of SSONH is conservative and comprises patient reassurance, establishment of baseline examination (including fundus photographs [Figure, B], optical coherence tomography, and VF testing), as well as yearly ophthalmic examination to rule out development of glaucoma. Awareness of this clinical entity of partial optic nerve hypoplasia can spare the patient the time and cost of unnecessary ancillary testing, adverse effects of treatment, as well as fear of blindness.The findings above supportive of the diagnosis of SSONH were explained to the patient. He has follow-up appointments on an annual basis now instead of every 6 months and has stable VF performance and optic nerve parameters on optical coherence tomography.

Ophthalmology

A 64-year-old man presented to the Department of Ophthalmology for evaluation of bilateral visual field (VF) loss. His VF loss was recognized on automated Humphrey VF screening and had remained unchanged during the subsequent 5 years (Figure, A). His ocular history was significant for mild nuclear sclerosis. His current medications included multivitamins and fish oil.Automated Humphrey visual field (VF) shows a right, dense inferior arcuate scotoma (A). The VF loss is stable when compared with previous VF testing. Color fundus photograph demonstrates small tilted right optic nerve with peripapillary atrophy (B). GHT indicates Glaucoma Hemifield Test; MD, mean deviation; PSD, pattern standard deviation; and VFI, visual field index.Neuro-ophthalmic examination revealed visual acuities of 20/30 OD and 20/25 OS that matched with the density of his cataracts. Color vision was within normal limits bilaterally. Pupils were symmetric without afferent defects. Applanation tonometry pressures were 18 mm Hg OD and 17 mm Hg OS. Slitlamp examination revealed mild nuclear sclerosis in each eye. Repeated automated Humphrey VF testing revealed bilateral inferior arcuate defects (mean deviation, −4.80 dB OD and −2.6 dB OS). Examination of his fundus revealed bilateral tilted optic nerves with peripapillary atrophy (Figure, B).Reassure the patient that VF loss is due to remote ischemic optic neuropathy and consider daily aspirinReassure the patient that VF loss is due to congenitally anomalous optic nerves and recommend annual evaluation to monitor VFPerform selective laser trabeculoplasty because the patient’s intraocular pressure is above target for his moderate glaucoma

what would you do next?

What would you do next?

Perform selective laser trabeculoplasty because the patient’s intraocular pressure is above target for his moderate glaucoma

Reassure the patient that VF loss is due to congenitally anomalous optic nerves and recommend annual evaluation to monitor VF

Reassure the patient that VF loss is due to remote ischemic optic neuropathy and consider daily aspirin

Order immediate magnetic resonance imaging study

b

male

61-70

original

https://jamanetwork.com/journals/jamacardiology/fullarticle/2654126

A 34-year-old man with a history of ischemic cardiomyopathy requiring a heart transplant 11 months earlier presented to the hospital with subacute onset of shortness of breath. His posttransplant course was notable for moderate cellular rejection (International Society for Heart and Lung Transplantation grade 2R) within the first 6 weeks, which was treated with a pulse of corticosteroids. Subsequently, he had normal allograft function with no further rejection noted on routine surveillance biopsies. Three days prior to this presentation, he experienced an episode of mild chest pain associated with radiation down his left arm and vomiting. He did not seek medical attention at that time as he felt the pain was unlikely to be coming from his heart. Over the preceding days, he developed progressive dyspnea on exertion, which prompted him to present to the emergency department. His electrocardiogram (ECG) on presentation is shown in Figure, A. His bedside echocardiogram showed anteroseptal akinesis with apical thrombus and reduced left ventricular function (Figure, B and Video).A, Patient’s admission electrocardiogram demonstrated new ST elevations of 1 to 2 mm in the anterolateral leads with Q waves in I, aVL, and across the precordial leads. B, His bedside echocardiogram demonstrated anteroseptal akinesis with apical thrombus (arrowhead) and reduced left ventricular function.Order an emergent coronary angiogram and endomyocardial biopsy. What Would You Do Next?

Order an emergent coronary angiogram and endomyocardial biopsy.

Check cytomegalovirus viral load.

Administer empirical pulse-dose corticosteroids.

Perform an endomyocardial biopsy alone.

ST-elevation myocardial infarction in a transplanted heart

A

Order an emergent coronary angiogram and endomyocardial biopsy.

This patient had acute onset of cardiac allograft failure approximately 11 months posttransplant. Acute graft failure in a transplanted heart warrants emergent evaluation because several of the potential causes respond to timely management.Acute rejection occurs in 20% to 40% of heart transplant recipients and is the leading cause of mortality within the first year of transplant after the immediate perioperative period.1 Acute rejection can be histologically characterized as cellular or antibody mediated, and treatment protocols differ according to histopathological findings. Patients with frequent rejection are more likely to have early cardiac allograft vasculopathy (CAV). Other than retransplantation, patients with ischemic cardiomyopathy have the worst long-term survival after a heart transplant.Acute allograft dysfunction can also occur from any number of conditions that affect native hearts, including acute myocardial infarction, myocarditis (or other autoimmune cardiomyopathies), or hypertensive crisis. Rarer causes in transplant recipients include infections such as cytomegalovirus or toxoplasmosis, valvular disease (particularly right-sided heart failure from biopsy-associated tricuspid valve lesions), reactivation of the preexisting origin of their heart failure such as amyloidosis or sarcoidosis, and malignant neoplasms involving the myocardium in the context of immunosuppression.2This patient’s ECG revealed new ST elevations of 1 to 2 mm in the anterolateral leads with Q waves in I, aVL, and across the precordial leads concerning for the late presentation of an acute ST-elevation myocardial infarction. However, various ECG abnormalities, including changes in voltage, pseudoinfarct patterns,3 bundle-branch blocks, conduction diseases, and atrial and ventricular arrhythmias, can occur with acute rejection.4 Therefore, emergent coronary angiography and simultaneous endomyocardial biopsy were planned.Coronary angiography revealed a thrombotic occlusion of the mid-left anterior descending artery. Thus, endomyocardial biopsy was deferred given the unlikely scenario of acute cellular rejection based on tacrolimus level and recent biopsy results. Coronary artery disease can take several forms in patients after heart transplant. In particular, both CAV and coronary atherosclerosis can occur in transplanted hearts. Cardiac AV is a form of chronic rejection and describes coronary disease unique to cardiac allografts and characterized by diffuse concentric intimal hyperplasia and luminal narrowing of the allograft coronary arteries.5 Acute coronary syndrome from CAV leading to myocardial infarction has been described in other studies,6,7 but it more commonly leads to stable angina symptoms and progressive allograft dysfunction or is asymptomatic. Acute worsening of dyspnea is common with diaphoresis, acute fatigue, bradycardia, syncope, and/or vague chest discomfort. Thus, careful review of medical history and hypervigilance are important to detect aggressive CAV. In addition, CAV tends to occur distally and move proximally, which is opposite of traditional atherosclerosis. Coronary atherosclerosis can also occur in transplanted hearts. It tends to be more localized than CAV and is therefore more amenable to intervention.Because of cardiac denervation, heart transplant recipients often report atypical or completely absent angina symptoms.8 Therefore, an acute myocardial infarction may present with weakness, dyspnea, or ECG changes in the absence of symptoms.9 Vigilance and high clinical suspicion for coronary disease must therefore be maintained in posttransplant patients, especially in the setting of new ventricular dysfunction.The patient underwent coronary angiography, which showed occlusion of the left anterior descending artery. One drug-eluting stent was placed. He continued to have impaired left ventricular systolic function after revascularization, which is likely attributable to his late presentation. He receives warfarin sodium maintenance therapy for left ventricular thrombus.

Cardiology

A 34-year-old man with a history of ischemic cardiomyopathy requiring a heart transplant 11 months earlier presented to the hospital with subacute onset of shortness of breath. His posttransplant course was notable for moderate cellular rejection (International Society for Heart and Lung Transplantation grade 2R) within the first 6 weeks, which was treated with a pulse of corticosteroids. Subsequently, he had normal allograft function with no further rejection noted on routine surveillance biopsies. Three days prior to this presentation, he experienced an episode of mild chest pain associated with radiation down his left arm and vomiting. He did not seek medical attention at that time as he felt the pain was unlikely to be coming from his heart. Over the preceding days, he developed progressive dyspnea on exertion, which prompted him to present to the emergency department. His electrocardiogram (ECG) on presentation is shown in Figure, A. His bedside echocardiogram showed anteroseptal akinesis with apical thrombus and reduced left ventricular function (Figure, B and Video).A, Patient’s admission electrocardiogram demonstrated new ST elevations of 1 to 2 mm in the anterolateral leads with Q waves in I, aVL, and across the precordial leads. B, His bedside echocardiogram demonstrated anteroseptal akinesis with apical thrombus (arrowhead) and reduced left ventricular function.Order an emergent coronary angiogram and endomyocardial biopsy.

what would you do next?

What would you do next?

Order an emergent coronary angiogram and endomyocardial biopsy.

Perform an endomyocardial biopsy alone.

Administer empirical pulse-dose corticosteroids.

Check cytomegalovirus viral load.

a

male

31-40

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2648861

A woman in her 60s presented with a 3-month history of a progressive, asymptomatic cutaneous eruption on her chest and back. She had a complex history of breast cancer on the left side that was first diagnosed in 1991 and was treated with lumpectomy, radiotherapy, cyclophosphamide, methotrexate, and fluorouracil. In 2001, she experienced local disease recurrence and underwent complete mastectomy with axillary lymph node dissection on the left side and received adjuvant treatment with tamoxifen citrate and anastrozole. In 2014, she developed axillary lymphadenopathy on the right side and was found to have metastatic disease. She subsequently underwent axillary lymph node dissection on the right side, followed by treatment with doxorubicin hydrochloride and cyclophosphamide. Her most recent mammogram and positron-emission tomography–computed tomography (PET/CT) showed no evidence of active disease. At the time of her evaluation, the patient’s physical examination was remarkable for discrete erysipeloid plaques on her chest, back, and right shoulder (Figure 1A). The lesions were warm and indurated but nontender to palpation. Serum chemistry profile, complete blood cell counts, and hepatic and renal function testing had normal results. Lesional skin biopsies were performed (Figure 1B).A, Clinical examination shows discrete erysipeloid plaques on the anterior chest. B, Histopathologic analysis (hematoxylin-eosin stain, original magnification ×100). What Is Your Diagnosis?

Carcinoma erysipeloides (cutaneous metastases of breast cancer)

Erysipelas

Radiation dermatitis

Radiation-induced morphea

A. Carcinoma erysipeloides (cutaneous metastases of breast cancer)

A

Carcinoma erysipeloides (cutaneous metastases of breast cancer)

Histopathologic examination revealed large anaplastic cells with high nuclear to cytoplasmic ratios and conspicuous nucleoli forming glandlike structures within the dermis and dermal lymphatics (Figure 1B). In the context of her history and clinical presentation, these findings were consistent with a diagnosis of carcinoma erysipeloides. A repeated PET/CT demonstrated new fludeoxyglucose F 18–avid lesions in her brain, liver, and mediastinum. The patient was treated with doxorubicin and whole-brain radiotherapy, but eventually transitioned to eribulin mesylate due to disease progression. Shortly thereafter, because of therapy-related adverse effects, the patient elected for palliative care and died 3 months later.Cutaneous metastases occur in up to 10% of individuals with solid-organ and hematologic malignant neoplasms.1 In women, breast cancer is responsible for the majority of cases, which typically manifest as asymptomatic, flesh-colored to pink or red-brown papules and nodules.2 The most common sites involved are the chest wall and abdomen, likely reflecting their proximity to the primary tumor.1,2 Originally named for its resemblance to erysipelas, carcinoma erysipeloides accounts for only 1% to 4% of cases of cutaneous metastases of breast cancer, and most commonly occurs in the setting of invasive ductal carcinoma.3 Biopsies of carcinoma erysipeloides characteristically show tumor infiltration into dermal lymphatics. Pathomechanistically, this invasion causes lymphatic and capillary congestion, which is thought to impart its distinctive clinical features—erythema, induration, and warmth.Among all cancers, cutaneous metastases are associated with a poor prognosis. According to large retrospective analyses, after cutaneous metastases have developed, mean survival is between 7 and 31 months.4 This poor survival likely reflects the fact that most cutaneous metastases occur in patients with advanced cancer. In a small minority of patients, cutaneous metastases may be the initial sign of an occult cancer. In general, the management of cutaneous metastases centers on treating the underlying cancer. Following the diagnosis of cutaneous metastases, patients should be evaluated for visceral organ involvement and restaged if appropriate. In the absence of visceral metastases, skin-directed therapies alone may be sufficient to manage cutaneous metastases and include radiation, chemoradiation, photodynamic therapy, topical imiquimod and miltefosine, intralesional chemotherapy, and electrochemotherapy. Although patient responses may vary, a recent meta-analysis evaluating the outcomes of various skin-directed therapies for cutaneous metastases of all cancer types reported high objective clinical response rates to superficial radiation therapy (84%), photodynamic therapy (84%), and electrochemotherapy (75%), and lower response rates to intralesional chemotherapy (44%) and topical therapies (42%).5 Based on these data, a therapeutic algorithm for the management of cutaneous metastases of breast cancer is presented (Figure 2). For individuals with visceral metastases, systemic treatment is needed and should be selected on the basis of hormone receptor status, among other considerations. Systemic therapy alone, however, without the use of a skin-directed agent is often inadequate for managing cutaneous metastases, with overall response rates as low as 10% to 25%.5 Future studies are needed to better delineate the impact of a combination approach and to define the role of newer treatments such as oncolytic viruses, which have been shown to have an abscopal effect when injected intratumorally.Therapeutic algorithm for the management of cutaneous metastases of breast cancer.

Oncology

A woman in her 60s presented with a 3-month history of a progressive, asymptomatic cutaneous eruption on her chest and back. She had a complex history of breast cancer on the left side that was first diagnosed in 1991 and was treated with lumpectomy, radiotherapy, cyclophosphamide, methotrexate, and fluorouracil. In 2001, she experienced local disease recurrence and underwent complete mastectomy with axillary lymph node dissection on the left side and received adjuvant treatment with tamoxifen citrate and anastrozole. In 2014, she developed axillary lymphadenopathy on the right side and was found to have metastatic disease. She subsequently underwent axillary lymph node dissection on the right side, followed by treatment with doxorubicin hydrochloride and cyclophosphamide. Her most recent mammogram and positron-emission tomography–computed tomography (PET/CT) showed no evidence of active disease. At the time of her evaluation, the patient’s physical examination was remarkable for discrete erysipeloid plaques on her chest, back, and right shoulder (Figure 1A). The lesions were warm and indurated but nontender to palpation. Serum chemistry profile, complete blood cell counts, and hepatic and renal function testing had normal results. Lesional skin biopsies were performed (Figure 1B).A, Clinical examination shows discrete erysipeloid plaques on the anterior chest. B, Histopathologic analysis (hematoxylin-eosin stain, original magnification ×100).

what is your diagnosis?

What is your diagnosis?

Erysipelas

Carcinoma erysipeloides (cutaneous metastases of breast cancer)

Radiation-induced morphea

Radiation dermatitis

b

female

61-70

original

https://jamanetwork.com/journals/jama/fullarticle/2657353

A 7-month-old female infant presented with a 2-month history of brown macules on the back and thighs, without prodromal erythema or trauma. Her birth history was unremarkable, and her growth and development were normal. Her family history was unremarkable.Physical examination revealed 7 sharply marginated, irregularly shaped, polymorphic hyperpigmented macules of 10 to 15 mm in diameter, without scales, on the back and thighs. The hyperpigmented macules were of orange hue, with unevenness of the pigmentation (Figure 1). Vital signs were normal. There was no lymphadenopathy or hepatosplenomegaly. Laboratory test results, including complete blood cell count, liver function tests, and renal function, were normal.Brown macules on the patient’s upper back and right lumbar area.Perform a skeletal survey and refer for ophthalmologic consultation What Would You Do Next?

Administer topical antifungals

Take a more detailed drug history

Perform a skeletal survey and refer for ophthalmologic consultation

Stroke the skin lesion

Maculopapular cutaneous mastocytosis (polymorphic variant)

D

Stroke the skin lesion

The key clinical feature to the correct diagnosis in this case is the sharply marginated, nonscaly hyperpigmentation consistent with mastocytosis. In mastocytosis, within a few minutes after stroking a hyperpigmented lesion, the proliferated mast cells release histamine, leading to the transitory reactions of itching, erythema, wheal formation, or blistering on the lesion, a phenomenon known as Darier sign.1 Epidermomycosis (choice A) is unlikely without scales. Fixed drug eruption (choice B) can leave persistent, well-demarcated hyperpigmentation; however, the prodromal inflammatory stage was not present in this case. In café-au-lait macules as seen with neurofibromatosis 1 (choice C), the pigmentation has typically more of a brown tint than orange and it is uniform throughout the macule.The prevalence of mastocytosis is approximately 1 case per 10 000 persons.2 Mastocytosis is defined by abnormal clonal mast cell accumulation in various organs.1 Mastocytosis is traditionally classified as either cutaneous mastocytosis, in which the skin is the only organ involved, or systemic mastocytosis (either with or without skin involvement).3 More than 80% of all patients with mastocytosis have skin lesions, but other organs that can be affected include the gastrointestinal tract, lymph nodes, liver, and bone marrow.1 Cutaneous mastocytosis is classified into the following subtypes by the clinical patterns: maculopapular cutaneous mastocytosis (polymorphic or monomorphic variant), diffuse cutaneous mastocytosis, and mastocytoma.1 The pathophysiology has not been clearly elucidated; however, specific mutations in the proto-oncogene KIT, which encodes the receptor for stem cell factor (CD117), have been implicated. Mast cells develop from hematopoietic progenitors in response to stem cell factor.2 CD117 is also expressed on melanocytes, which may be responsible for the hyperpigmentation seen in the skin lesions.4Although nearly two-thirds of patients with mastocytosis are children5 and the initial lesions usually appear in the first 6 months of life,1 mastocytosis can develop during both childhood and adulthood. There are several important distinctions between these age groups. Approximately 80% of childhood-onset mastocytosis is polymorphic maculopapular cutaneous mastocytosis,1,6 which usually spontaneously resolves before puberty.7 On the other hand, monomorphic maculopapular cutaneous mastocytosis in children can persist into adulthood and progress to systemic mastocytosis with high serum tryptase levels.1 In contrast, in adult-onset mastocytosis, monomorphic maculopapular lesions are more common,1 of which up to 97% are associated with indolent systemic mastocytosis.8 About 50% of adult patients experience anaphylaxis, vs less than 10% of children.1 The anaphylaxis risk is correlated with the serum tryptase level and the severity of the skin lesions.1The diagnosis of cutaneous mastocytosis is highly likely with a positive Darier sign.1 Skin biopsy is desirable for confirmation of the clinical diagnosis.9 Laboratory testing of complete blood cell count, liver function tests and serum tryptase levels can be useful. Children with cutaneous mastocytosis usually do not require a bone marrow biopsy in the absence of hepatosplenomegaly, lymphadenopathy, peripheral blood abnormalities, or highly elevated levels of serum tryptase (>20 ng/mL). In contrast, a bone marrow biopsy is recommended for all adult patients with cutaneous mastocytosis.1,2The management of cutaneous mastocytosis in children has 3 points of focus: avoiding factors causing mast cell degranulation, including external stimuli, extremes of temperature, allergens, infections, and nonsteroidal anti-inflammatory drugs; relieving the symptoms; and annual follow-up with the above-noted laboratory investigations.9,10 A bone marrow biopsy should be considered if the patient has a high serum tryptase level (>20 ng/mL), blood count abnormalities, splenomegaly, or lymphadenopathy.2 For urticarial symptoms, H1 antihistamines are the mainstay of therapy. Leukotriene receptor antagonists are added in some refractory cases. Intramuscular epinephrine should be prescribed if anaphylaxis occurs.2The Darier sign was positive (Figure 2), and a skin biopsy confirmed the diagnosis of mastocytosis. The serum tryptase concentration was within normal limits. No signs or symptoms of systemic involvement were present, and bone marrow biopsy was not performed. The patient’s mother was counseled on measures to prevent mast call degranulation as described above.Darier sign on the right lumbar brown macule.

General

A 7-month-old female infant presented with a 2-month history of brown macules on the back and thighs, without prodromal erythema or trauma. Her birth history was unremarkable, and her growth and development were normal. Her family history was unremarkable.Physical examination revealed 7 sharply marginated, irregularly shaped, polymorphic hyperpigmented macules of 10 to 15 mm in diameter, without scales, on the back and thighs. The hyperpigmented macules were of orange hue, with unevenness of the pigmentation (Figure 1). Vital signs were normal. There was no lymphadenopathy or hepatosplenomegaly. Laboratory test results, including complete blood cell count, liver function tests, and renal function, were normal.Brown macules on the patient’s upper back and right lumbar area.Perform a skeletal survey and refer for ophthalmologic consultation

what would you do next?

What would you do next?

Administer topical antifungals

Stroke the skin lesion

Take a more detailed drug history

Perform a skeletal survey and refer for ophthalmologic consultation

b

female

0-10

original

https://jamanetwork.com/journals/jama/fullarticle/2656146

A 62-year-old woman with a 10-year history of hypertension presented with elevated serum creatinine (2.26 mg/dL; reference range, 0.6-1.2 mg/dL). She had not visited a physician for several years but reported feeling well with no active symptoms. She had no risk factors for hepatitis B, hepatitis C, or HIV and reported no use of nonsteroidal anti-inflammatory drugs or herbal medications. One year ago, her urine was tea-colored during an upper respiratory tract infection. Examination results were normal except for elevated blood pressure (154/90 mm Hg). Although her hemoglobin concentration was low (10.5 g/dL; reference range, 11.6-15.2 g/dL), white blood cell count, platelet count, and electrolytes were normal. Her kidneys appeared structurally normal on ultrasound. Urine studies were performed (Table).Urinary tract infection is the most likely diagnosis. How Do You Interpret These Test Results?

Urinary tract infection is the most likely diagnosis.

Proliferative glomerulonephritis is the most likely diagnosis.

Nonproliferative glomerulonephritis is the most likely diagnosis.

Hypertensive nephrosclerosis is the most likely diagnosis.

B

Proliferative glomerulonephritis is the most likely diagnosis.

Hematuria (>2 red blood cells [RBCs] per high-powered field) is the classical feature of proliferative glomerulonephritis.1 The differential diagnosis of hematuria includes urinary tract infections, nonproliferative glomerular diseases, tubulointerstitial kidney disease, structural abnormalities of the urinary tract (eg, stones, or tumors), or an instrumented urinary tract (eg, bladder catheterization) (Box).2IgA nephropathy; thin basement membrane disease; hereditary nephritis (Alport syndrome); proliferative glomerulonephritis excluding IgA nephropathy (eg, immune complex glomerulonephritis, pauci immune glomerulonephritis, and anti–glomerular basement membrane glomerulonephritis); nonproliferative glomerulonephritisRenal vein thrombosis; arterial emboli or thrombosis; renal infarct; arteriovenous fistulaAcute pyelonephritis; renal cystic diseases (eg, polycystic kidney disease, medullary sponge kidney); tuberculosis; analgesic nephropathy; acute interstitial nephritis; renal allograft rejectionNephrolithiasis (at any level of the urinary tract); urinary tract infection (at any level of the urinary tract [eg, cystitis, prostatitis, urethritis]); malignancy; renal trauma and urinary tract instrumentation; parasitic disease (eg, schistosomiasis); papillary necrosisa Conditions causing hematuria are presented in order of descending frequency of presentation, by origin.a Conditions causing hematuria are presented in order of descending frequency of presentation, by origin.A urine dipstick (Medicare fee, $2.97)3 detects heme peroxidase activity (specificity, 65%-99%),4 which may reflect intact RBCs, filtered free hemoglobin, or filtered myoglobin. Accordingly, a positive dipstick result requires microscopic evaluation of the sediment (Medicare fee, $4.18).3 A dipstick result that is negative for heme peroxidase (sensitivity, 91%-100%)4 rules out the presence of active proliferative glomerular conditions. Menstrual blood contaminating the urine may lead to false-positive results.When RBCs traverse an injured glomerular capillary into the urinary space, they may undergo a change in morphology from their usual biconcave shape and become dysmorphic. Phase contrast microscopy is thought to be the optimal method for detecting dysmorphic RBCs, but standard light microscopy (lowering of the condenser lens from the stage until optimal resolution of the RBC shape is seen) is of comparable quality.5 Proliferative glomerulonephritis is suggested when more than 15% of urine RBCs are dysmorphic (specificity, 85%; sensitivity, 47%)6 or if acanthocytes (a dysmorphic RBC with vesicle-shaped protrusions) constitute at least 10% of visualized RBCs (specificity, 85%; sensitivity, 42%).7Injured glomeruli allow the entry of RBCs into renal tubules where they interact with Tamm-Horsfall proteins to form casts. RBC casts suggest proliferative glomerulonephritis (specificity 78%)8 but may also be present anytime RBCs enter the renal tubule (eg, interstitial nephritis, glomerular hemorrhage due to excessive anticoagulats, and diseases associated with nephrotic syndrome).8High-grade proteinuria in the setting of hematuria suggests a proliferative glomerular lesion (specificity 91% for proteinuria >2 g/d vs <200 mg/d).9 However, the limited sensitivity of high-grade proteinuria (18% for proteinuria >2 g/d vs <200 mg/d) means that patients with hematuria and normal or minimally elevated protein excretion may still have a proliferative glomerular lesion.9The patient may have proliferative glomerulonephritis given the positive hematuria, RBC casts, and proteinuria. The absence of dysmorphic RBCs does not rule out a proliferative glomerulonephritis since sensitivity is only 47%.6 Measurement of serum complement, tests for antinuclear and antineutrophil cytoplasmic antibodies, and serology for hepatitis B, hepatitis C, and HIV were performed to screen for systemic conditions associated with proliferative glomerulonephritis.The combination of the patient’s urinalysis results, normal serological workup, and the history of previous episodes of possible hematuria during episodes of upper respiratory tract infection makes a diagnosis of IgA nephropathy (the most common form of proliferative glomerulonephritis) most likely.The diagnosis of proliferative glomerulonephritis and the underlying etiology can be confirmed with a renal biopsy, an invasive procedure associated with the risk of major bleeding requiring transfusion or angiographic intervention in up to 0.9% of cases.10 However, the need for a renal biopsy depends on whether the result will help establish the patient’s prognosis, inform management, or both.A kidney biopsy confirmed IgA nephropathy. The patient began taking an angiotensin converting enzyme inhibitor to reduce proteinuria and manage hypertension. Five months later, her kidney function remained stable, blood pressure was well controlled, and proteinuria was 0.5 g per day. She continues biannual follow-up with a nephrologist and her glomerular filtration rate remains stable.The following urine findings suggest proliferative glomerulonephritis: dipstick-positive hematuria combined with proteinuria, dysmorphic RBCs—particularly acanthocytes, and RBC casts.Proliferative glomerulonephritis should be suspected in individuals with the aforementioned urinary findings in addition to hypertension, edema, and variable degrees of renal insufficiency.A kidney biopsy may be required to guide the management of the underlying condition.

Diagnostic

A 62-year-old woman with a 10-year history of hypertension presented with elevated serum creatinine (2.26 mg/dL; reference range, 0.6-1.2 mg/dL). She had not visited a physician for several years but reported feeling well with no active symptoms. She had no risk factors for hepatitis B, hepatitis C, or HIV and reported no use of nonsteroidal anti-inflammatory drugs or herbal medications. One year ago, her urine was tea-colored during an upper respiratory tract infection. Examination results were normal except for elevated blood pressure (154/90 mm Hg). Although her hemoglobin concentration was low (10.5 g/dL; reference range, 11.6-15.2 g/dL), white blood cell count, platelet count, and electrolytes were normal. Her kidneys appeared structurally normal on ultrasound. Urine studies were performed (Table).Urinary tract infection is the most likely diagnosis.

how do you interpret these test results?

How do you interpret these results?

Hypertensive nephrosclerosis is the most likely diagnosis.

Proliferative glomerulonephritis is the most likely diagnosis.

Urinary tract infection is the most likely diagnosis.

Nonproliferative glomerulonephritis is the most likely diagnosis.

b

female

61-70

White

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2627296

A healthy woman in her 60s presented with multiple erythematous crusted plaques on her trunk that had appeared 4 weeks previously, sparing her limbs and facial region (Figure, A). She had a long-standing history of several outbreaks of skin lesions limited to both axillae and groin. Previous episodes had been successfully treated with various topical drugs that were administered by her primary care physician. No family history of similar lesions was recorded. Physical examination revealed multiple annular erythematous plaques surrounded by a peripheral crusted and pustular collarette on her trunk (Figure, B). No active lesions were present in her axillae, inframammary folds, or groin. After obtaining informed consent, 2 biopsy specimens were taken from the periphery of the lesion for hematoxylin-eosin stain and direct immunofluorescence (Figure, C and D). A skin swab specimen from a pustular lesion was taken for microbiological culture.A, Multiple erythematous and crusted plaques diffusely distributed on the dorsal trunk at presentation. B, An erythematous annular plaque, surrounded by a crusted and focally pustular peripheral collarette. C and D, Histopathologic images, hematoxylin-eosin. C, Biopsy specimen revealing suprabasilar acantholysis (original magnification ×4). D, Specimen from generalized lesions at clinical presentation (original magnification ×40). What Is Your Diagnosis?

Pemphigus foliaceus

Generalized Hailey-Hailey disease

IgA pemphigus

Pemphigus vulgaris

B. Generalized Hailey-Hailey disease

B

Generalized Hailey-Hailey disease

Histopathologic examination revealed wide areas of suprabasilar acantholysis showing a “dilapidated brick wall” morphologic characteristic. The epidermis was focally covered by a neutrophil-rich serous crust located in the overlying stratum corneum (Figure, C and D). A mild inflammatory infiltrate was identified on superficial papillary dermis. Direct immunofluorescence studies were negative for IgG, IgA, IgM, fibrin, and complement deposition. Subsequent microbiological cultures isolated Staphylococcus aureus in pustular exudate.At the initial visit, the patient was prescribed 3 weeks of treatment with topical betamethasone, combined with topical gentamicin, 0.1% cream, twice daily, and a short course of oral prednisone, 0.5 mg/kg/d. After this treatment, together with daily chlorhexidine washes, an evident clinical response was observed at her 1-month follow-up.Hailey-Hailey disease (HHD), or benign familiar pemphigus, is an inherited acantholytic disorder that was first described by brothers Howard and Hugh Hailey in 1939.1 Currently, loss-of-function mutations in the ATP2C1 gene, which encodes a calcium ATPase present on the Golgi apparatus, are known to be the cause of deficient intercellular adhesions in this disease.2 Transmitted through families as an irregular autosomal dominant trait, it presents most commonly as bilateral erythematous erosive and exudative plaques in large skin folds (eg, axillae, groin, anogenital area, neck). The typical course of the disease is chronic, relapsing-remitting, and frequently worsened by sweat, friction, tight clothes, and bacterial, fungal, or viral superinfections.To date, very few cases of generalized or disseminated HHD like that of our patient have been reported.3-5 Previous cases have related the acute worsening with several triggers, ranging from drug intake to warm weather or skin superinfections. In this case, superinfection by bacteria, as proven by microbiological cultures, might have caused a rapid dissemination of the disease.Differential diagnosis in HHD can be difficult and thus requires histopathologic examination of skin biopsy specimens with both hematoxylin-eosin stain and direct immunofluorescence. The presence of large areas of dyscohesive acantholytic suprabasilar cells, mimicking a “dilapidated brick wall,” is typical in HHD but might be observed focally in other diseases. The absence of deposition of fluorescein is most significant in these cases to rule out autoimmune bullous disorders, such as IgA pemphigus, pemphigus vulgaris, or pemphigus foliaceus. These entities may present a similar clinical or histopathological presentation in some cases.Treatment of recalcitrant forms of HHD can be really challenging, as very few treatments have actually proved efficacy in this clinical scenario.6 Systemic treatments are often used when disease is refractory to lifestyle modifications and first-line topical treatments, or when the disease is too diffuse to be treated focally. Oral microbial agents might be required to control certain infections that can act as triggers. Doxycycline might be a promising alternative in selected patients based on both its antibiotic and anti-inflammatory profile.7 Oral steroids and retinoid are frequently used, with varying results.8 Other immunosupressant agents, such as methotrexate, thalidomide, cyclosporine, dapsone, and glycopyrrolate, have been tried with different success rates.7 Pulsed dye laser therapy might offer a safe, effective treatment alternative in some patients with few associated adverse effects.9 Photodynamic therapy could be helpful in obtaining transitory improvements in patients with localized disease; however, pain during procedure and postoperative discomfort can be limiting in some patients.10

Dermatology

A healthy woman in her 60s presented with multiple erythematous crusted plaques on her trunk that had appeared 4 weeks previously, sparing her limbs and facial region (Figure, A). She had a long-standing history of several outbreaks of skin lesions limited to both axillae and groin. Previous episodes had been successfully treated with various topical drugs that were administered by her primary care physician. No family history of similar lesions was recorded. Physical examination revealed multiple annular erythematous plaques surrounded by a peripheral crusted and pustular collarette on her trunk (Figure, B). No active lesions were present in her axillae, inframammary folds, or groin. After obtaining informed consent, 2 biopsy specimens were taken from the periphery of the lesion for hematoxylin-eosin stain and direct immunofluorescence (Figure, C and D). A skin swab specimen from a pustular lesion was taken for microbiological culture.A, Multiple erythematous and crusted plaques diffusely distributed on the dorsal trunk at presentation. B, An erythematous annular plaque, surrounded by a crusted and focally pustular peripheral collarette. C and D, Histopathologic images, hematoxylin-eosin. C, Biopsy specimen revealing suprabasilar acantholysis (original magnification ×4). D, Specimen from generalized lesions at clinical presentation (original magnification ×40).

what is your diagnosis?

What is your diagnosis?

IgA pemphigus

Generalized Hailey-Hailey disease

Pemphigus foliaceus

Pemphigus vulgaris

b

female

61-70

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2629701

A white woman in her 50s presented to an oral medicine clinic for evaluation of asymptomatic pigmented lesions affecting the maxillary and mandibular gingiva of 6 years’ duration. The patient reported previous orolabial melanotic macules. Her medical history was significant for hypertension, hypercholesterolemia, asthma, and breast cancer. Medications included levalbuterol, nadolol, and cetirizine. Family medical history was significant for breast cancer and social history was unremarkable. Review of systems was positive for cutaneous ephelides. Physical examination revealed a 7 mm × 6 mm asymmetric, heterogeneously pigmented lesion without indurated borders on the gingiva associated with the left maxillary central incisor tooth (number 9) (Figure, A). A lesion similar in clinical appearance, although smaller, was observed on the gingiva associated with the right mandibular first premolar tooth (number 28) (Figure, B). Biopsy specimens were obtained with a 3 mm punch instrument from both lesions for routine histology which demonstrated similar microscopic findings (Figure, C and D).A, Heterogeneously pigmented lesion of the gingiva associated with the left maxillary central incisor. B, Heterogeneously pigmented lesion of the gingiva associated with the right mandibular first premolar. C, Mucosal epithelium exhibiting spongiosis and a diffuse proliferation of heavily pigmented dendritic melanocytes that extend the full thickness of the epithelium (arrowheads). Melanin incontinence is also noted (hematoxylin-eosin stain, original magnification ×100). D, Squamous mucosa exhibiting spongiosis with diffuse pigmentation in the basal cell layer and dendritic melanocytes (arrowheads) in the stratum spinosum (hematoxylin-eosin stain, original magnification ×200). What Is Your Diagnosis?

Oral melanotic macule

Oral malignant melanoma

Oral melanocytic nevus

Oral melanoacanthoma

D. Oral melanoacanthoma

D

Oral melanoacanthoma

Microscopic analysis of both lesions demonstrated acanthotic, spongiotic stratified squamous epithelium exhibiting numerous dendritic, pigmented melanocytes extending throughout the full thickness of the epithelium. This was accompanied by a dense lymphocytic infiltrate with focal exocytosis. These findings were consistent with oral melanoacanthoma (OMA). No further treatment was recommended for the patient and she reported pigment resolution of both lesions in the area of tissue biopsies.Oral melanoacanthoma is a benign melanocytic process most commonly observed in black women aged 30 to 50 years.1 This condition has been reported less frequently in Hispanic, Asian, and white patients with an overall female predilection.1 The pathophysiologic mechanism for OMA is most consistently associated with chronic irritation or acute regional trauma.1-4 A diffuse, rapidly enlarging area of macular pigmentation ranging from millimeters to centimeters characterizes the clinical presentation of OMA.1,4 Coloration of the lesion is brown to black with possible color heterogeneity throughout the lesion. Oral melanoacanthoma frequently manifests as a solitary lesion, and although rare, multifocal lesions have been reported.1 This condition is most frequently observed on the buccal mucosa and less commonly on the palate, lips, and tongue and may present unilaterally or bilaterally.1,4 Oral melanoacanthoma affecting the gingival tissues is rare, especially in patients who are white. This condition is typically asymptomatic, however, pruritus and/or burning sensations have been reported with these lesions, which may be treated with topical corticosteroids.5 Histologically, OMA is characterized by spongiotic epithelium containing dendritic pigmented melanocytes throughout the lesional epithelium.4 A mild to moderate inflammatory infiltrate composed of lymphocytes and occasional eosinophils is observed in the underlying connective tissue.4 Owing to its ominous clinical presentation, an incisional biopsy is necessary to establish a diagnosis of OMA and to rule out other pathologic abnormalities, namely oral malignant melanoma. Treatment is typically not indicated after diagnosis has been established and spontaneous regression of OMA has been observed after biopsy with low recurrence.1,4 Malignant transformation of oral melanoacanthoma has not been reported.6Oral melanotic macule, oral melanocytic nevus, and oral malignant melanoma were included in the differential diagnosis owing to clinical similarities. Oral melanotic macules are considered the most common oral mucosal lesions of melanocytic origin, which likely represent a reactive or physiologic process.3,4 These lesions are typically observed in women in the fourth and fifth decades without racial predilection.3,4 Oral melanotic macules may be associated with inherited conditions, such as Peutz-Jeghers syndrome, neurofibromatosis type I, and McCune-Albright syndrome.3 Oral melanotic macules commonly affect the hard palate, mucobuccal fold and gingivae, while labial melanotic macules are predominantly observed on the vermillion border of the lip.3,7,8 Although oral and labial melanotic macules tend to be solitary, multiple lesions have been reported.1 These lesions are considered benign without malignant potential.6 Oral melanocytic nevi are acquired benign lesions commonly affecting women in the third and fourth decades without reported racial predilection.4 These lesions occur most frequently on the hard palate, mucobuccal fold, and gingivae and, although multiple oral melanocytic nevi are rare, their multifocal presence has been previously reported.1 Current evidence does not suggest that oral melanocytic nevi are markers for development of malignant disease.8 Oral malignant melanoma represents a melanocytic neoplasm which is encountered less frequently than its cutaneous counterpart.9 Overall, dark-skinned races have a greater relative incidence of oral malignant melanoma with slightly higher frequency in men.4,10 Oral malignant melanoma generally presents as a slow-growing, asymptomatic lesion with irregular borders after the age of 50 years and can affect any intraoral mucosal surface, with the palate and gingivae the most commonly reported locations.9,10 Early detection of oral malignant melanoma is critical because 5-year survival rates range between 5% and 50%, with less than 10% of individuals with distant metastases surviving more than 5 years.9,10 Biopsy of any oral pigmented lesion is necessary to establish a definitive diagnosis and to rule out neoplastic conditions.

Dermatology

A white woman in her 50s presented to an oral medicine clinic for evaluation of asymptomatic pigmented lesions affecting the maxillary and mandibular gingiva of 6 years’ duration. The patient reported previous orolabial melanotic macules. Her medical history was significant for hypertension, hypercholesterolemia, asthma, and breast cancer. Medications included levalbuterol, nadolol, and cetirizine. Family medical history was significant for breast cancer and social history was unremarkable. Review of systems was positive for cutaneous ephelides. Physical examination revealed a 7 mm × 6 mm asymmetric, heterogeneously pigmented lesion without indurated borders on the gingiva associated with the left maxillary central incisor tooth (number 9) (Figure, A). A lesion similar in clinical appearance, although smaller, was observed on the gingiva associated with the right mandibular first premolar tooth (number 28) (Figure, B). Biopsy specimens were obtained with a 3 mm punch instrument from both lesions for routine histology which demonstrated similar microscopic findings (Figure, C and D).A, Heterogeneously pigmented lesion of the gingiva associated with the left maxillary central incisor. B, Heterogeneously pigmented lesion of the gingiva associated with the right mandibular first premolar. C, Mucosal epithelium exhibiting spongiosis and a diffuse proliferation of heavily pigmented dendritic melanocytes that extend the full thickness of the epithelium (arrowheads). Melanin incontinence is also noted (hematoxylin-eosin stain, original magnification ×100). D, Squamous mucosa exhibiting spongiosis with diffuse pigmentation in the basal cell layer and dendritic melanocytes (arrowheads) in the stratum spinosum (hematoxylin-eosin stain, original magnification ×200).

what is your diagnosis?

What is your diagnosis?

Oral melanoacanthoma

Oral malignant melanoma

Oral melanocytic nevus

Oral melanotic macule

a

female

51-60

White

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2629947

A female infant with relapsed refractory infantile acute lymphoblastic leukemia, blast crisis (>60% blasts), and central nervous system involvement was admitted for reinduction chemotherapy with cytarabine, vincristine, daunorubicin, methotrexate, and dexamethasone. Seventeen days after her last day of chemotherapy, while neutropenic, she became febrile and developed several vesicles with an erythematous base on the lower back (Figure, A) and left thigh. Tissue and blood cultures and a punch biopsy specimen of a vesicle on the lower back were obtained. Hematoxylin-eosin (Figures, B and C), gram (Figure, D), and periodic acid-Schiff stains were performed on the punch biopsy. Testing for herpes simplex virus and varicella zoster virus were also ordered.A, Scattered vesicles with an erythematous base on the lower back. B, Hematoxylin and eosin stain (original magnification ×200). C, Hematoxylin and eosin stain (original magnification ×600). D, Gram stain (original magnification ×600). What Is Your Diagnosis?

Herpes simplex virus

Disseminated varicella zoster virus

Listeriosis

Cutaneous Bacillus cereus infection

D. Cutaneous Bacillus cereus infection

D

Cutaneous Bacillus cereus infection

Microscopic evaluation of the punch biopsy specimen revealed focal epidermal and subepidermal necrosis (Figure, B) associated with numerous filamentous bacilli with septa (Figure, C). Gram stain revealed numerous gram-variable rods in the necrotic epidermis and dermis (Figure, D). The periodic acid-Schiff staining findings were negative for fungal elements. The polymerase chain reaction testing results for herpes simplex virus (HSV) and varicella zoster virus (VZV) were negative. Tissue and blood culture findings were positive for B cereus. Gentamicin and vancomycin were initiated for B cereus bacteremia. A computed tomographic scan with contrast of both thorax and brain was obtained revealing lesions consistent with disseminated B cereus in the liver and brain. Unfortunately, the patient died shortly after the diagnosis.Bacillus cereus is a gram-positive or gram-variable, spore-forming, aerobic rod found in soil, vegetables, marine environments, intestinal tracts of invertebrates, and human skin.1 Owing to its ubiquitous nature, it is often considered a contaminant when found in cultured specimens. The ability of B cereus to cause food poisoning and invasive infections is well documented.1,2 Invasive B cereus infections are primarily observed in immunocompromised patients, such as neonates and individuals with hematologic malignant diseases.1,2 The rising incidence of B cereus infections is likely secondary to indwelling intravascular catheters and fluoroquinolone prophylaxis for prolonged neutropenia.2 Other risk factors include direct inoculation, trauma, and contaminated hospital materials.The clinical manifestations of B cereus infections in patients with indwelling catheters or medical devices are variable and include fever, bacteremia, pneumonia, endophthalmitis, necrotizing fasciitis, osteomyelitis, endocarditis, cerebral abscess, and death.1 Primary cutaneous B cereus infections typically present as isolated vesicles, bulla, or pustules at the primary inoculation site or via contamination of a preexisting wound in the setting of trauma or surgery. In reported cases of primary cutaneous B. cereus infections in immunocompromised and immunocompetent patients, blood culture findings were negative and/or direct inoculation was documented in all cases.3-8 Primary cutaneous infections have not been associated with systemic symptoms or bacteremia.5Secondary cutaneous manifestations of B cereus bacteremia have not previously been described. Our patient presented with multiple, discrete vesicles on an erythematous base over the lower back and thighs in the setting of systemic symptoms and positive blood culture findings prior to the development of any rash or skin lesions. To our knowledge, this case is the first report of B cereus septicemia presenting as scattered vesicles. While the exact etiology in this patient is unknown, an indwelling catheter was determined to be the most likely portal of entry.The differential diagnosis for a vesicular or pustular eruption in a neutropenic patient includes HSV, VZV, drug eruption, Sweet syndrome, leukemia cutis, allergic or irritant contact dermatitis, invasive fungal infection, and listeriosis. The gold standard for diagnosing B cereus infections is tissue and/or blood cultures. When the skin is involved, a biopsy specimen should be obtained and sent for routine histologic analysis, gram stain, and bacterial/fungal cultures to exclude other etiologies. Flow cytometry should also be considered in patients with a preexisting diagnosis of leukemia to rule out leukemia cutis.Bacillus cereus is a highly resistant pathogen. The organism expresses a zinc dependent BcII metallo-β-lactamase that binds penicillins, cephalosporins, and carbapenems. Therefore, B cereus is resistant to all β-lactam medications (including cephalosporins), except for carbapenems. The first-line treatment is vancomycin or clindamycin; fluoroquinolones and imipenem are considered second-line therapies.9 However, resistance to carbapenems, fluoroquinolones, and clindamycin is being reported, especially in patient populations where the incidence of B cereus infections are increasing (eg, individuals with malignant disease or neutropenia).10Bacillus cereus should be considered in the differential diagnosis for any vesicular and pustular skin eruption in an immunocompromised patient. Cutaneous manifestations may be an early sign of B cereus bacteremia or sepsis, which should prompt early and aggressive antibiotic therapy, as illustrated by this case.

Dermatology

A female infant with relapsed refractory infantile acute lymphoblastic leukemia, blast crisis (>60% blasts), and central nervous system involvement was admitted for reinduction chemotherapy with cytarabine, vincristine, daunorubicin, methotrexate, and dexamethasone. Seventeen days after her last day of chemotherapy, while neutropenic, she became febrile and developed several vesicles with an erythematous base on the lower back (Figure, A) and left thigh. Tissue and blood cultures and a punch biopsy specimen of a vesicle on the lower back were obtained. Hematoxylin-eosin (Figures, B and C), gram (Figure, D), and periodic acid-Schiff stains were performed on the punch biopsy. Testing for herpes simplex virus and varicella zoster virus were also ordered.A, Scattered vesicles with an erythematous base on the lower back. B, Hematoxylin and eosin stain (original magnification ×200). C, Hematoxylin and eosin stain (original magnification ×600). D, Gram stain (original magnification ×600).

what is your diagnosis?

What is your diagnosis?

Cutaneous Bacillus cereus infection

Herpes simplex virus

Disseminated varicella zoster virus

Listeriosis

a

female

21-30

original

https://jamanetwork.com/journals/jamaneurology/fullarticle/2649255

A teenage Chinese girl with intermittent limp and increasing headache was admitted to the hospital. She began to limp intermittently ten years earlier. A brain magnetic resonance imaging (MRI) showed multiple parenchymal lesions involving the pons, bilateral amygdala, and the left temporal pole (Figure 1A). She refused further investigations until a year earlier, when she developed mild headache. Magnetic resonance imaging showed minor focal enlargement of the lesions in the left temporal pole. One month before hospital admission, her headache aggravated and became intolerable. Enhanced MRI showed remarkable progression of the lesions in the left temporal lobe, involving the temporal pole and the parasylvian region, along with a newly developed mass in the third ventricle and obstructive hydrocephalus. The lesions in the pons and the right amygdala remained stable (Figure 1B). Spinal cord MRI was normal. There was no history of tumors elsewhere. Family history was unremarkable. Her consciousness was intact, but her memory and concentration were poor. Pupil reflection was normal. There were multiple congenital nevi distributed over the body, 2 of which on the legs were more than 5 cm in diameter, and another 3 on her back and face were more than 3 cm. There were no focal motor or sensory deficits. Muscle stretch reflexes were normal. The rest of the neurologic and systemic examination was unremarkable. Gene examinations showed a mutation in the N-ras-2 gene.A and B, T1-weighted axial brain magnetic resonance imaging at the levels of pons, midbrain, and thalamus, performed ten years earlier, shows multiple parenchymal lesions including the pons, bilateral amygdala, and the left temporal pole (arrowheads). Sequence, spin echo; repetition time, 650.0 milliseconds; echo time, 14.0 milliseconds; field of view, 144 × 230; slice, 5.0 mm; window, 1054; contrast, 640. C and D, Enhanced, T1-weighted axial brain magnetic resonance imaging at the levels of pons, midbrain, and thalamus, performed at the most recent hospital admission, shows remarkable progression of the lesions in the left temporal lobe, involving the temporal pole and the parasylvian region, along with a newly developed mass in the third ventricle (arrowhead) and obstructive hydrocephalus. The lesions in the pons and the right amygdala remained stable. Sequence, fast spin echo; repetition time, 600.0 milliseconds; echo time, 9.0 milliseconds; field of view, 230 × 230; slice, 5.0 mm; window, 1087; contrast, 524. What Is Your Diagnosis?

Metastatic melanoma

Primary intracranial melanoma

Neurocutaneous melanosis

Lymphoma

C. Neurocutaneous melanosis

C

Neurocutaneous melanosis

The key to the correct diagnosis is the location of the multiple intracranial parenchymal lesions, the 10-year history, and the presence of multiple large congenital nevi, suggesting the diagnosis of neurocutaneous melanosis. Neurocutaneous melanosis (NM) is a rare congenital disorder characterized by the presence of large or multiple congenital cutaneous nevi along with intracranial leptomeningeal melanocytosis.1 The diagnosis of this disease is quite difficult. Criteria proposed by Fox and revised by Kadonaga and Frieden2 are as follows: large or multiple (≥3) congenital nevi associated with meningeal melanosis; no evidence of cutaneous melanoma; and no evidence of meningeal melanoma except in patients whose skin examination reveals no malignant lesions.2,3 Although an experienced physician may associate the intracranial tumors with melanocytic ones in view of the multiple congenital nevi over the body, there is no way to determine the nature of the tumors and make the diagnosis without biopsy and pathological examinations. In this case, robotic frameless stereotactic biopsy of the lesions in the left temporal lobe and in the third ventricle was performed. As revealed by hematoxylin-eosin and immunohistological stainings, the lesions were melanocytic in origin. Also, the lesions showed strong immunoreactivity to markers related to melanocytic tumors including Vimentin, S100, HMB45, and Melan A. Considering that there is no evidence of melanoma elsewhere and the 10-year history, metastatic melanocytic tumors are excluded. Moreover, the multiorigination, the correspondence of the original sites (bilateral mesial temporal lobe and the brainstem) to the most frequent sites of the leptomeningeal involvement of NM,4-6 and the involvement of N-ras-2 gene3,7 are all typical characteristics of NM. Therefore, the diagnosis of NM can be established based on the previously mentioned criteria.2Our case is interesting because the 10-year disease history is, to our knowledge, the longest in patients with NM. In addition, our case revealed the evolvement of the intracranial part of NM, which is different from the previous description of transition from meningeal melanocytoma to primary cerebral melanoma.8,9 The rapid progression of the lesions in the left temporal lobe and the third ventricle within a year showed the heterogeneity of the tumors and the malignant transformation potential. The newly developed lesion in the third ventricle that led to hydrocephalus showed high malignancy with a Ki-67 rate of more than 60%.The patient in this case underwent ventriculoperitoneal shunt placement to address hydrocephalus as soon as the diagnosis was confirmed. Although there is no special treatment with definite efficacy to NM,10 a concurrent chemoradiotherapy (temozolomide, 4-week, 200 mg/m2 daily) was conducted to contain the tumor. Four months later, multiple subdural extramedullary masses were found by MRI on the cervical, thoracic, lumbar, and sacral levels. Also, the patient developed unremitting ostalgia that had to be alleviated by morphine. She refused any further chemotherapy or aggressive treatment. Follow-up examinations were planned.

Neurology

A teenage Chinese girl with intermittent limp and increasing headache was admitted to the hospital. She began to limp intermittently ten years earlier. A brain magnetic resonance imaging (MRI) showed multiple parenchymal lesions involving the pons, bilateral amygdala, and the left temporal pole (Figure 1A). She refused further investigations until a year earlier, when she developed mild headache. Magnetic resonance imaging showed minor focal enlargement of the lesions in the left temporal pole. One month before hospital admission, her headache aggravated and became intolerable. Enhanced MRI showed remarkable progression of the lesions in the left temporal lobe, involving the temporal pole and the parasylvian region, along with a newly developed mass in the third ventricle and obstructive hydrocephalus. The lesions in the pons and the right amygdala remained stable (Figure 1B). Spinal cord MRI was normal. There was no history of tumors elsewhere. Family history was unremarkable. Her consciousness was intact, but her memory and concentration were poor. Pupil reflection was normal. There were multiple congenital nevi distributed over the body, 2 of which on the legs were more than 5 cm in diameter, and another 3 on her back and face were more than 3 cm. There were no focal motor or sensory deficits. Muscle stretch reflexes were normal. The rest of the neurologic and systemic examination was unremarkable. Gene examinations showed a mutation in the N-ras-2 gene.A and B, T1-weighted axial brain magnetic resonance imaging at the levels of pons, midbrain, and thalamus, performed ten years earlier, shows multiple parenchymal lesions including the pons, bilateral amygdala, and the left temporal pole (arrowheads). Sequence, spin echo; repetition time, 650.0 milliseconds; echo time, 14.0 milliseconds; field of view, 144 × 230; slice, 5.0 mm; window, 1054; contrast, 640. C and D, Enhanced, T1-weighted axial brain magnetic resonance imaging at the levels of pons, midbrain, and thalamus, performed at the most recent hospital admission, shows remarkable progression of the lesions in the left temporal lobe, involving the temporal pole and the parasylvian region, along with a newly developed mass in the third ventricle (arrowhead) and obstructive hydrocephalus. The lesions in the pons and the right amygdala remained stable. Sequence, fast spin echo; repetition time, 600.0 milliseconds; echo time, 9.0 milliseconds; field of view, 230 × 230; slice, 5.0 mm; window, 1087; contrast, 524.

what is your diagnosis?

What is your diagnosis?

Neurocutaneous melanosis

Lymphoma

Primary intracranial melanoma

Metastatic melanoma

a

female

11-20

Chinese

original

https://jamanetwork.com/journals/jamapediatrics/fullarticle/2646852

A previously healthy 15-year-old boy presented to our hospital with pain and purpura of his left thigh after an intramuscular injection in that leg. Ten days prior, he had presented to a referring hospital’s emergency department for nausea and vomiting and was given 20 mg of intramuscular dicyclomine. He reported severe pain at the time and site of injection. Within a few hours, he noticed swelling and purpura overlying the site of injection.Over the next 2 weeks, the swelling persisted and the purpura intensified, becoming black centrally (Figure A and B). Pain worsened over this period, initially restricting use of the leg, then preventing any weight bearing, prompting his admission to our hospital 10 days after the injection. He also reported numbness and occasional tingling of the skin involved. The patient denied fever or chills, and his nausea and vomiting had resolved.A, Teenage boy with development of retiform purpura of the left thigh following intramuscular dicyclomine injection. At 2 days after injection, red to purple retiform changes developed on the left thigh. B, Worsening retiform purpura with central necrosis was noted 13 days after the injection.Findings of a physical examination were significant for retiform purpura of the left thigh, approximately 8 × 12 cm in size. Palpation of the area elicited severe pain. Popliteal, posterior tibial, dorsalis pedis, and femoral pulses were strong. There was no swelling of the remainder of the leg, and findings of joint examinations were normal. Sensation was intact throughout the leg with the exception of the skin involved, which had diminished light touch.Blood test results revealed a normal complete blood cell count, normal coagulation profile, and an elevated creatine phosphokinase level of 477 U/L (normal range, 22-198 U/L; to convert to microkatals per liter, multiply by 0.0167). Magnetic resonance imaging of the thigh was completed, and a skin biopsy was performed for culture and histology. What Is Your Diagnosis?

Pyomyositis

Nicolau syndrome (livedoid dermatitis)

Retained foreign body

Necrotizing fasciitis

B. Nicolau syndrome (livedoid dermatitis)

B

Nicolau syndrome (livedoid dermatitis)

Magnetic resonance imaging demonstrated enhancing fluid collections within the left vastus lateralis muscle, consistent with myonecrosis. Results of the tissue cultures from the skin biopsy were negative for bacteria, fungus, and acid-fast bacilli. Histopathology showed nonspecific epidermal and eccrine gland necrosis. The patient’s symptoms improved with no specific treatment beside analgesics.Intramuscular injections are one of the most routine medical interventions and are considered safe. Still, adverse reactions are common, with 1 study finding that 38.3% of children receiving a hepatitis B vaccine had local redness and swelling and 6.7% showed bruising.1 Serious reactions such as tissue necrosis are rarer.Nicolau syndrome is a clinical diagnosis described as livedoid dermatitis (embolia cutis medicamentosa) at the site of injection accompanied by inflammation and ischemic necrosis of the skin and underlying tissue. Both adipose and muscle tissue can be involved. Biopsy of affected tissue is nonspecific and shows ischemic necrosis.2 A hallmark of the syndrome is intense pain at the injection site shortly after the injection, followed by hemorrhagic patches with formation of a livedoid purpura and then the development of tissue necrosis.3,4 Nicolau syndrome is known to be more common in children, especially younger than age 3 years, but it can happen at any age.4,5In its most severe course, Nicolau syndrome can lead to superinfection with pseudomonas, compartment syndrome, or irreversible necrosis. Other possible sequelae, such as paralysis, renal failure, and death, have also been reported.4 About 30% of patients can have hypoesthesia in the affected area.4Several different medications given by means of intramuscular injection have been known to cause Nicolau syndrome including penicillin, glucocorticoids, nonsteroidal anti-inflammatory drugs, and others. It was first described in the 1920s following Bismuth injections for the management of syphilis.3,6Although the pathogenesis of Nicolau syndrome and other similar reactions are not understood, several possible explanations exist. Some researchers have hypothesized that the instramuscular injection itself is more the culprit than the medication injected,3 while others believe the opposite. Thrombosis formation secondary to accidental intra-arterial or intravenous injection and perivascular injection leading to vasospasm are 2 leading theories. Other thoughts include perivascular inflammation from direct cytotoxicity of the medication or crystallization of the drug out of solution causing vascular occlusion.4,7The treatment of patients with Nicolau syndrome focuses on managing the impactful sequelae. Compartment syndrome requires fasciotomy, and extensive necrosis may require surgical debridement or even amputation. Superinfection requires intravenous antibiotics. Some experts have advocated using anticoagulants, steroids, and/or hyperbaric oxygen; however, to our knowledge, these treatments have not been well studied.4,8The only known way to reduce the risk of Nicolau syndrome is to aspirate the needle before injecting to ensure the injection is indeed intramuscular and not intravenous or intra-arterial.2 When alternatives are available, avoidance of the intramuscular route of administration should be considered.

Pediatrics

A previously healthy 15-year-old boy presented to our hospital with pain and purpura of his left thigh after an intramuscular injection in that leg. Ten days prior, he had presented to a referring hospital’s emergency department for nausea and vomiting and was given 20 mg of intramuscular dicyclomine. He reported severe pain at the time and site of injection. Within a few hours, he noticed swelling and purpura overlying the site of injection.Over the next 2 weeks, the swelling persisted and the purpura intensified, becoming black centrally (Figure A and B). Pain worsened over this period, initially restricting use of the leg, then preventing any weight bearing, prompting his admission to our hospital 10 days after the injection. He also reported numbness and occasional tingling of the skin involved. The patient denied fever or chills, and his nausea and vomiting had resolved.A, Teenage boy with development of retiform purpura of the left thigh following intramuscular dicyclomine injection. At 2 days after injection, red to purple retiform changes developed on the left thigh. B, Worsening retiform purpura with central necrosis was noted 13 days after the injection.Findings of a physical examination were significant for retiform purpura of the left thigh, approximately 8 × 12 cm in size. Palpation of the area elicited severe pain. Popliteal, posterior tibial, dorsalis pedis, and femoral pulses were strong. There was no swelling of the remainder of the leg, and findings of joint examinations were normal. Sensation was intact throughout the leg with the exception of the skin involved, which had diminished light touch.Blood test results revealed a normal complete blood cell count, normal coagulation profile, and an elevated creatine phosphokinase level of 477 U/L (normal range, 22-198 U/L; to convert to microkatals per liter, multiply by 0.0167). Magnetic resonance imaging of the thigh was completed, and a skin biopsy was performed for culture and histology.

what is your diagnosis?

What is your diagnosis?

Retained foreign body

Pyomyositis

Necrotizing fasciitis

Nicolau syndrome (livedoid dermatitis)

d

male

11-20

Black

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2647247

A previously healthy 4-year-old girl with a history of prematurity (31 weeks’ gestational age) presented as a transfer from an outside facility with abdominal pain. She had presented to an outside emergency department 2 days prior with lower abdominal pain that subsequently localized to the right lower quadrant. Her pain was accompanied by anorexia and nonbloody, nonbilious emesis. She denied fevers or chills. She was noted to have voluntary guarding and focal right lower quadrant tenderness to palpation. Laboratory analyses demonstrated a mild leukocytosis (white blood cell count = 14 × 103/μL [to convert to ×109/L, multiply by 0.001]) and normal urinalysis results. Abdominal ultrasonography images were obtained that failed to show her appendix and demonstrated no secondary signs of inflammation. Because of her notable tenderness, she was admitted for observation at the referring facility. No antibiotics were initiated, and her activity improved with intravenous hydration. However, her right lower abdominal pain persisted, prompting further evaluation. Computed tomography images of the abdomen and pelvis were obtained, and the representative images are shown in Figure 1. She was transferred to our facility for surgical evaluation. In our emergency department, pelvic ultrasonography images were obtained that failed to show both the appendix and right adnexal structures.Computed tomographic images. Axial (A) and (B) coronal sections demonstrate an inflamed retrocecal mass. What Is Your Diagnosis?

Perforated appendicitis

Meckel diverticulitis

Crohn disease

Ectopic ovarian torsion

D. Ectopic ovarian torsion

D

Ectopic ovarian torsion

Computed tomography images demonstrated a retrocecal mass with surrounding inflammation. Gonadal vessels arose from this cyst-containing mass and are demonstrated in Figure 1B. These findings, along with the inability to identify the right adnexal structures on pelvic ultrasonography, are imaging characteristics that are suggestive of a torsed ectopic ovary. We proceeded with a diagnostic laparoscopy. On initial exploration, we identified a unicornuate uterus with normal-appearing left adnexa and absent right adnexal structures. A normal-appearing appendix was noted and retrocecal mobilization identified a necrotic right ovary and fallopian tube adherent to the retroperitoneum within the right paracolic gutter (Figure 2).Intraoperative image demonstrating exposure of a torsed ectopic right ovary (RO) and fallopian tube (RF) during mobilization of the cecum (Cec). Relationship to the iliac vessels (IV) is highlighted.Ectopic or undescended ovaries are defined by their location outside of the true pelvis.1 During normal development, ovaries form from the urogenital ridge on the posterior aspect of the peritoneal cavity during the fifth week of gestation. Ovarian descent to the true pelvis is mediated by chemotactic factors and the gubernaculum. The etiology of ovarian maldescent is unknown but is posited to arise from a lack of migration or growth restriction of the urogenital ridge. Given their shared embryonic origin, ovarian maldescent is associated with renal anomalies in approximately 20% of cases.2The prevalence of ectopic ovaries is estimated as less than 1%.1 The incidence of ovarian maldescent is increased among women with an unicornuate uterus (approximately 40%) and mullerian agenesis (approximately 20%).2 Ovarian maldescent is associated with infertility, as a recent review demonstrated that 77% of cases were identified during infertility evaluations.2 Notably, there is an increased risk of experiencing an ectopic pregnancy (4%).3 The formation of cysts and tumors have been documented in case reports.4 Ectopic ovaries have also been associated with recurrent, cyclic abdominal pain that accompanies menstruation.5Ectopic ovarian torsion has not been previously described. Ovarian torsion is a relatively common cause of abdominal pain, accounting for 2.7% of all cases among women younger than 20 years.6 Torsion may occur at any age but is most common among women of reproductive age. Ovarian torsion presents a surgical emergency that requires emergent detorsion. Historically, an oophorectomy has been performed when a torsed ovary does not appear viable, but recent evidence supports ovarian preservation to optimize fertility potential.6 Specifically, follicular development has been demonstrated by follow-up ultrasonography among more than 90% of women with necrotic-appearing ovaries at the time of initial exploration.7,8 Despite this information, many clinicians continue to perform oophorectomies in patients who present with torsion and have a necrotic-appearing ovary.9Ectopic ovaries are associated with infertility and recurrent abdominal pain. This patient was premenarchal with a necrotic but otherwise normal-appearing ovary lacking any appreciable cause for her acute adnexal torsion. We elected to proceed with a salpingo-oophorectomy in this setting given the lack of any communication with the uterus, the normal appearance of the left adnexa, and the association between ectopic ovaries with infertility, ectopic pregnancy, pain with menstruation, and a potential risk of recurrent torsion. This patient had an uneventful recovery and was discharged on her first postoperative day. A pathologic review demonstrated ovarian and fallopian tube tissue with evidence of extensive hemorrhagic necrosis and no evidence of cysts or tumors.

Surgery

A previously healthy 4-year-old girl with a history of prematurity (31 weeks’ gestational age) presented as a transfer from an outside facility with abdominal pain. She had presented to an outside emergency department 2 days prior with lower abdominal pain that subsequently localized to the right lower quadrant. Her pain was accompanied by anorexia and nonbloody, nonbilious emesis. She denied fevers or chills. She was noted to have voluntary guarding and focal right lower quadrant tenderness to palpation. Laboratory analyses demonstrated a mild leukocytosis (white blood cell count = 14 × 103/μL [to convert to ×109/L, multiply by 0.001]) and normal urinalysis results. Abdominal ultrasonography images were obtained that failed to show her appendix and demonstrated no secondary signs of inflammation. Because of her notable tenderness, she was admitted for observation at the referring facility. No antibiotics were initiated, and her activity improved with intravenous hydration. However, her right lower abdominal pain persisted, prompting further evaluation. Computed tomography images of the abdomen and pelvis were obtained, and the representative images are shown in Figure 1. She was transferred to our facility for surgical evaluation. In our emergency department, pelvic ultrasonography images were obtained that failed to show both the appendix and right adnexal structures.Computed tomographic images. Axial (A) and (B) coronal sections demonstrate an inflamed retrocecal mass.

what is your diagnosis?

What is your diagnosis?

Perforated appendicitis

Meckel diverticulitis

Crohn disease

Ectopic ovarian torsion

d

female

0-10

White

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2648732

A 62-year-old woman presented to the emergency department with severe substernal pain radiating to the left shoulder and back and subsequent swelling of the left side of her neck. She had been recently treated at an outpatient facility for a viral illness with multiple episodes of forceful coughing. There was no recent history of trauma to the neck or chest.Physical examination revealed normal vital signs and soft tissue swelling over the left supraclavicular area. No overlying skin changes or crepitus were appreciated. Laboratory data revealed leukocytosis (white blood cell count, 18 000/µL; to convert to ×109 per liter, multiply by 0.001). A computed tomographic scan demonstrated extensive edema of the left neck, with fat stranding seen in the subcutaneous tissues extending into the left jugular, carotid, and esophageal spaces (Figure, A). Mediastinal edema and bilateral pleural effusions were also seen on computed tomographic scan (Figure, B). Owing to the concern for esophageal perforation, a barium swallow was performed, showing no extravasation of contrast.A, Computed tomographic scan shows extensive soft tissue inflammation in the left neck (arrowhead). B, Computed tomographic scan shows bilateral pleural effusions (red arrowheads) and mediastinal edema (white arrowhead). What Is Your Diagnosis?

Acute jugular thrombosis

Spontaneous chylothorax

Contained esophageal perforation

Descending necrotizing mediastinitis

B. Spontaneous chylothorax

B

Spontaneous chylothorax

Ultrasonography-guided left thoracentesis yielded milky fluid. Laboratory analysis confirmed chylothorax, with triglyceride level of 1760 mg/dL (to convert to millimoles per liter, multiply by 0.0113), without microbiology growth. Workup for malignancy, including computed tomographic scan of the neck, chest, abdomen, and pelvis, and screening laboratory test results were negative. With this, a diagnosis of spontaneous chylothorax was made, presumably due to thoracic duct rupture from episodes of coughing. The patient began a low-fat diet and was observed to have improvement with regard to her neck swelling and pleural effusions. She was discharged after 4 days of hospitalization. At follow-up, there was complete resolution of her symptoms. A computed tomographic scan 6 weeks later demonstrated complete resolution of the pleural effusions, normal appearing mediastinum, and no signs of soft tissue inflammation. Given the presentation and clinical course, we suspect the etiology of her bilateral chylothoraces was rupture of the thoracic duct in the left neck, as it enters the jugular or subclavian vein, secondary to coughing.Spontaneous chylothoraces are a rare cause of pleural effusions and pose a diagnostic challenge, as patients present with acute onset of atypical symptoms.1-3 In most cases, the clinical history can lead to the etiology, linking chylothoraces to an undiagnosed malignancy, systemic disease, or trauma. Garcia Restoy et al2 observed that patients usually describe a combination of chest and supraclavicular pain or dyspnea on presentation. In this review of previous reports, all had presented with some degree of supraclavicular or neck swelling.2 This current patient presented with previously described symptoms of this rare pathology. In the absence of an alternative diagnosis, coughing may explain the etiology of bilateral spontaneous chylothoraces.Disruption of the thoracic duct leads to chyle leaks, the severity of these varying based on the cause and location of the injury. A chyloma initially develops, a contained collection below the pleura, and subsequently ruptures into the pleural space. The laterality of these effusions can hint to the location of the injury, most commonly presenting as isolated right- or left-sided effusions, and less frequently bilaterally.4 The etiology of chylothoraces includes nontraumatic causes such as malignancy, congenital duct abnormalities, and systemic diseases (eg, sarcoidosis and amyloidosis). Traumatic causes may be iatrogenic and noniatrogenic, with thoracic surgery as the primary cause of iatrogenic trauma. Among these, esophageal surgery has an incidence as high as 4%.4 Noniatrogenic disruptions constitute 20% of traumatic cases, secondary to penetrating or blunt trauma. Forceful emesis or coughing, as a source of minor trauma, has been linked to the development of chylothoraces.4Diagnosis is made by fluid analysis; triglyceride levels greater than 110 mg/dL are diagnostic, and levels less than 50 mg/dL will be chyle in fewer than 5% of cases.5 An initial priority must be to rule out undiagnosed malignancy. Prompt diagnosis and treatment of systemic diseases, in the case of malignancy or sarcoidosis, will usually lead to resolution. Traumatic cases can be initially managed nonoperatively, with drainage and dietary restrictions, nutrition with medium chain fatty acids, or nothing per oral with total parenteral nutrition. Surgical intervention is reserved for severe or nonresolving cases and consists of mass ligation of the thoracic duct near its origin via thoracotomy or thoracoscopy, with an associated success rate approximating 90%.5This case report raises awareness of this rare condition. We also stress that a thorough workup is necessary prior to assuming that coughing has ruptured the thoracic duct leading to bilateral chylothoraces (ie, this is a diagnosis of exclusion).

Surgery

A 62-year-old woman presented to the emergency department with severe substernal pain radiating to the left shoulder and back and subsequent swelling of the left side of her neck. She had been recently treated at an outpatient facility for a viral illness with multiple episodes of forceful coughing. There was no recent history of trauma to the neck or chest.Physical examination revealed normal vital signs and soft tissue swelling over the left supraclavicular area. No overlying skin changes or crepitus were appreciated. Laboratory data revealed leukocytosis (white blood cell count, 18 000/µL; to convert to ×109 per liter, multiply by 0.001). A computed tomographic scan demonstrated extensive edema of the left neck, with fat stranding seen in the subcutaneous tissues extending into the left jugular, carotid, and esophageal spaces (Figure, A). Mediastinal edema and bilateral pleural effusions were also seen on computed tomographic scan (Figure, B). Owing to the concern for esophageal perforation, a barium swallow was performed, showing no extravasation of contrast.A, Computed tomographic scan shows extensive soft tissue inflammation in the left neck (arrowhead). B, Computed tomographic scan shows bilateral pleural effusions (red arrowheads) and mediastinal edema (white arrowhead).

what is your diagnosis?

What is your diagnosis?

Spontaneous chylothorax

Descending necrotizing mediastinitis

Acute jugular thrombosis

Contained esophageal perforation

a

female

61-70

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2633694

A 14-year-old girl presented to the emergency department after experiencing 2 weeks of fever, malaise, photophobia, phonophobia, headache, nausea, vomiting, and neck stiffness. Computed tomography scan results of her head did not reveal any acute intracranial pathology. Her systemic inflammatory markers were elevated, including a left-shifted leukocytosis with a white blood cell count of 15 200 μL (normal values, 4100-8900 μL) (to convert to × 109/L, multiply by 0.001), a platelet count of 458 × 103 μL (150-450 × 103 μL) (to convert to × 109/L, multiply by 1.0), and a C-reactive protein level of 17.3 mg/L (<8.0 mg/L) (to convert to nanomoles per liter, multiply by 9.524). Cerebrospinal fluid studies were suggestive of aseptic meningitis: elevated protein levels (0.139 g/dL, 0-0.035 g/dL) (to convert to grams per liter, multiply by 10.0), increased neutrophils (32%, 2% ± 4%), normal opening pressure, and normal glucose levels.On day 2 of her hospitalization, she complained of left-eye blurred vision. Her visual acuity was 20/20 OD and 20/70 OS. Both eyes had normal pupillary responses, color vision, and intraocular pressures. The results of an anterior chamber examination were unremarkable in each eye. The results of a dilated fundus examination of both eyes revealed significant inflammation, including 1+ vitreous cell levels, marked disc edema, intraretinal hemorrhages, and extensive sheathing of the retinal venules (Figure).Bilateral fundus photographs of the right eye (A) and left eye (B) on presentation. What Would You Do Next?

Initiate systemic corticosteroids

Treat with an intraocular corticosteroid injection

Evaluate for systemic infectious disease

Begin administering intravenous acyclovir

Frosted branch angiitis

C

Evaluate for systemic infectious disease

This patient had bilateral frosted branch angiitis (FBA) that was affecting the retinal blood vessels. Frosted branch angiitis is a rare phenomenon that may be idiopathic or associated with infectious, inflammatory, or neoplastic etiologies, although the exact cause is unknown.1 Common infectious entities that present with FBA include cytomegalovirus retinitis and Epstein-Barr virus, but other infectious diseases, such as tuberculosis, toxoplasmosis, and syphilis, may also resemble FBA.1 There are isolated reports of FBA in the presence of systemic inflammatory diseases such as granulomatosis with polyangiitis, antiphospholipid antibody syndrome, and systemic lupus erythematosus; however, it is crucial to rule out an infectious disease before initiating treatment with intraocular or systemic corticosteroids. If other clinical findings suggest acute retinal necrosis (eg, dense vitritis and peripheral patches of coalescing retinitis), then it would be appropriate to start empirical treatment with intravenous acyclovir, but the level of suspicion for viral retinitis was not high for this patient because her results for Lyme disease, cytomegalovirus, herpes simplex virus, and Epstein-Barr virus serologies were negative. In addition, cerebrospinal fluid studies including Gram stain, Lyme antibodies, and polymerase chain reactions for herpes simplex virus, varicella-zoster virus, West Nile virus, enterovirus, and arbovirus all had negative results.In 1976, Ito et al2 described FBA as an idiopathic retinal vasculitis that predominantly affects venules with a lesser degree of retinal arteriole involvement. The descriptive name is derived from the thick sheathing surrounding the vasculature that resembles frosted tree branches in winter. In 1997, Kleiner3 classified “true” FBA as idiopathic and defined 2 other subtypes based on the underlying pathology (eg, neoplastic vascular infiltration or lymphocytic reaction because of infection or inflammation). Frosted branch angiitis has been reported after prodromal viral illness as well as after an initiating event, such as an intravitreal injection, so FBA is hypothesized to be a hypersensitivity reaction possibly involving an immune-complex deposition.1The patient also had oral and genital ulcers, leading to the diagnosis of Behçet disease (BD) with neurologic and ocular involvement. Behçet disease is a chronic relapsing multisystem vasculitis diagnosed by clinical findings, including the classic triad of painful oral and genital ulcers with intraocular inflammation.4,5 While bilateral posterior uveitis with occlusive, hemorrhagic retinal vasculitis is the most typical manifestation of ocular BD, anterior uveitis or panuveitis may also occur.6 Frosted branch angiitis is not common in BD,1 so it is crucial to rule out infectious etiologies before initiating immunosuppressive therapy.The highest prevalence of BD occurs in China, Iran, and Turkey (80–370 cases per 100 000 population), whereas the incidence in North America is low (approximately 0.38 cases per 100 000 population).5 The pathophysiology is not very well understood, but the systemic vasculitis is likely related to a complex interplay between genetic and environmental risk factors. Although there is an association with the human leukocyte antigen B-51, the presence of this human leukocyte antigen haplotype is not necessary to make the diagnosis. Neurological BD occurs in 5% to 10% of cases. Of these cases, only 3.6% are juvenile (patients younger than 16 years) and most present with dural sinus venous thrombosis, not aseptic meningitis as with this patient.7Behçet disease is typically treated acutely with high-dose intravenous corticosteroids followed by a slow oral prednisone taper. Because of the severity of the inflammation, systemic steroid-sparing immunomodulatory therapy is usually required. Several studies have shown that azathioprine and cyclosporine are effective treatments for BD ocular inflammation.8,9 Because neurological BD, including ocular disease, may result in significant morbidity (eg, vision loss), a panel of uveitis experts has recommended using antitumor necrosis factor agents such as infliximab and adalimumab in addition to azathioprine or cyclosporine for patients with severe BD.10The patient received high-dose systemic corticosteroids and started azathioprine. Three weeks later, the FBA and retinal edema had resolved, although her retinal exudates persisted and formed a macular star. After 2 months, her visual acuity was 20/20 OU.

Ophthalmology

A 14-year-old girl presented to the emergency department after experiencing 2 weeks of fever, malaise, photophobia, phonophobia, headache, nausea, vomiting, and neck stiffness. Computed tomography scan results of her head did not reveal any acute intracranial pathology. Her systemic inflammatory markers were elevated, including a left-shifted leukocytosis with a white blood cell count of 15 200 μL (normal values, 4100-8900 μL) (to convert to × 109/L, multiply by 0.001), a platelet count of 458 × 103 μL (150-450 × 103 μL) (to convert to × 109/L, multiply by 1.0), and a C-reactive protein level of 17.3 mg/L (<8.0 mg/L) (to convert to nanomoles per liter, multiply by 9.524). Cerebrospinal fluid studies were suggestive of aseptic meningitis: elevated protein levels (0.139 g/dL, 0-0.035 g/dL) (to convert to grams per liter, multiply by 10.0), increased neutrophils (32%, 2% ± 4%), normal opening pressure, and normal glucose levels.On day 2 of her hospitalization, she complained of left-eye blurred vision. Her visual acuity was 20/20 OD and 20/70 OS. Both eyes had normal pupillary responses, color vision, and intraocular pressures. The results of an anterior chamber examination were unremarkable in each eye. The results of a dilated fundus examination of both eyes revealed significant inflammation, including 1+ vitreous cell levels, marked disc edema, intraretinal hemorrhages, and extensive sheathing of the retinal venules (Figure).Bilateral fundus photographs of the right eye (A) and left eye (B) on presentation.

what would you do next?

What would you do next?

Evaluate for systemic infectious disease

Initiate systemic corticosteroids

Treat with an intraocular corticosteroid injection

Begin administering intravenous acyclovir

a

female

11-20

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2643485

A 55-year-old man presented to the emergency department following an unwitnessed assault, sustaining multiple facial contusions and lacerations. He was initially agitated and admitted to the intensive care unit with hemodynamic instability. The oral-maxillofacial surgery service was consulted for assessment of the facial lacerations, and the oculoplastic service was consulted for possible damage to the nasolacrimal system. The patient’s medical history at this point was unknown.From an ophthalmic standpoint, a single, deep laceration extended inferomedially from the right upper zygoma across the nasal dorsum and involving the eyelid-cheek junction (Figure 1). A significant amount of clear fluid was noted to be continually draining from the wound site. What Would You Do Next?

Perform nasolacrimal duct irrigation

Explore, irrigate, and close the wound

Order computed tomography of the head/facial bones

Order magnetic resonance imaging of the head

Cerebrospinal fluid rhinorrhea

C

Order computed tomography of the head/facial bones

Although the physical examination in this case could indicate involvement of the nasolacrimal duct, this should not be the immediate concern. Encountering clear fluid from such a location should prompt suspicion of a cerebrospinal fluid (CSF) leak rather than tear fluid. While nasolacrimal duct irrigation could be conducted to rule out nasolacrimal duct trauma (and was conducted while awaiting imaging results), the salient point to be noted here is that immediate imaging is mandatory, in particular, looking for a basal skull fracture. Hence, option C is the most appropriate next step. Option D, magnetic resonance imaging of the head, would not provide adequate visualization of bony structures, and a computed tomographic scan would be the most expedient next step in a trauma setting.Computed tomography of the patient’s head and facial bones (2-mm slice thickness) revealed a diffuse permeative bony process involving the midskull base and the sinonasal cavity, with focal dehiscence of the right sphenoid sinus posteriorly, the medial portion of the greater wings of the sphenoid sinuses, and the superior posterior walls of the maxillary sinuses (Figure 2). Abnormal tissue was noted in the right nasopharyngeal mucosa roof, with an enlarged high left level 2a lymph node and equivocal right level 1a node. This constellation of findings could be in keeping with osteoradionecrosis related to previously treated nasopharyngeal carcinoma or aggressive skull base fractures/sinonasal osteomyelitis. In this particular case, it was discovered that the patient had a history of nasopharyngeal carcinoma diagnosed in 2009, treated with radiation and chemotherapy. The clear fluid noted from the laceration was CSF, most likely secondary to a fistula between the sinuses and the compromised skull base.Commuted tomography axial image of the head and facial bones showing erosive changes at the skull base in the region of the clivus.Cerebrospinal fluid rhinorrhea can commonly occur following head trauma. In the presence of a skull base fracture and clinical CSF leak, further confirmatory testing is not indicated.1 In this patient, a complete history and frank rhinorrhea and otorrhea were absent, making diagnosis more challenging. Simple exploration and closure of the wound would have missed the more significant findings. Computed tomography of the head and facial bones should be the priority and organized with urgency.Ophthalmologists may encounter CSF leaks in a variety of settings, including orbital tumors with intracranial extension into subarachnoid space, orbital surgery that compromises the integrity of the cribriform plate, or craniocerebral trauma. The overall incidence of CSF fistulas following craniocerebral injury is 0.5% to 3%, with rates upwards of 25% for midfacial injuries.2,3 Cerebrospinal fluid leaks may also rarely occur in dacryocystorhinostomies.4Treatment of CSF leaks is dictated by the nature of the fistula, its location, and flow volume. Sinonasal and intracranial lesions can cause spontaneous CSF leaks, often resulting from skull base dehiscence and bony erosions.5In this case, the patient’s history of radiation therapy with osteonecrosis likely predisposed him to acquire skull base dehiscence. The underlying etiology of CSF leak has important implications for prognosis and treatment, and in this case, further imaging to screen for carcinoma recurrence was also warranted. Magnetic resonance imaging confirmed there was no recurrence of carcinoma; therefore, conservative treatment was pursued. The patient’s CSF leak resolved spontaneously. He was admitted to hospital for treatment of his other injuries acquired as a result of the trauma and subsequently died of comorbidities related to the trauma.

Ophthalmology

A 55-year-old man presented to the emergency department following an unwitnessed assault, sustaining multiple facial contusions and lacerations. He was initially agitated and admitted to the intensive care unit with hemodynamic instability. The oral-maxillofacial surgery service was consulted for assessment of the facial lacerations, and the oculoplastic service was consulted for possible damage to the nasolacrimal system. The patient’s medical history at this point was unknown.From an ophthalmic standpoint, a single, deep laceration extended inferomedially from the right upper zygoma across the nasal dorsum and involving the eyelid-cheek junction (Figure 1). A significant amount of clear fluid was noted to be continually draining from the wound site.

what would you do next?

What would you do next?

Order magnetic resonance imaging of the head

Order computed tomography of the head/facial bones

Perform nasolacrimal duct irrigation

Explore, irrigate, and close the wound

b

male

51-60

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2643962

A woman in her 60s presented 1 week after undergoing cataract surgery in the right eye complaining of persistent blurry vision. Her ocular history was notable for a previous uncomplicated cataract surgery in the left eye that had a good visual outcome. On postoperative day 1, her visual acuity was 20/60 OD, attributed to mild corneal edema, with an intraocular pressure of 18 mm Hg. A dilated fundus examination was not performed. At postoperative week 1, the best-corrected visual acuity was 20/50 OD, her intraocular pressure was 17 mm Hg, and there was no afferent pupillary defect. The cornea was clear and there were trace anterior chamber cells. A dilated examination revealed multiple spots of retinal whitening with tiny intraretinal hemorrhages concentrated in the posterior pole (Figure, A). The patient was referred urgently for consultation by a retina specialist. Optical coherence tomography revealed intraretinal cystoid abnormalities in the macula and hyperreflective patches in the nerve fiber layer and inner nuclear layer (Figure, B).A, Fundus photograph of the right eye demonstrating multifocal patches of inner retinal whitening in the posterior pole. B, Optical coherence tomography through the macula demonstrating mild intraretinal cystoid abnormalities and hyperreflective thickened areas in the nerve fiber and inner nuclear layer, corresponding to the white retinal patches. What Would You Do Next?

Start systemic steroids

Obtain more information on the patient’s history

Vitreous tap and injection of foscarnet

Infectious and autoimmune workup

Unilateral Purtscher-like retinopathy

B

Obtain more information on the patient’s history

Purtscher retinopathy, described by Otmar Purtscher in 1910, classically occurs in the setting of trauma, such as automobile crashes, chest compression, or the fracture of long bones.1-3 It is acute in onset and often bilateral (60%).2,3 Retinal changes include cotton-wool spots (93%), retinal hemorrhages (63%), and characteristic Purtscher flecken (65%), which are areas of intraretinal whitening that, unlike cotton-wool spots, do not obscure retinal blood vessels but are instead separated from vessels by a clear intervening space.2,3 The retinal changes are found in the peripapillary and macular regions and spare the periphery.2,3 Optical coherence tomography can reveal thickening of the nerve fiber layer, as in classic cotton-wool spots, and also thickening of the inner nuclear layer, resembling paracentral middle acute maculopathy.4 Purtscher-like retinopathy presents with identical findings, but it is seen in nontraumatic situations such as pancreatitis, renal failure, hemolytic uremic syndrome, pregnancy, childbirth, connective tissue disorders, cryoglobulinemia, multiple myeloma, valsalva, retrobulbar, and peribulbar injections.2,3The mechanisms underlying Purtscher and Purtscher-like retinopathy are unclear, but it is thought that transient vasoconstrictive events, such as compression from increased orbital volume, epinephrine in retrobulbar blocks, or microemboli composed of fat, air, or even clumps of activated leukocytes associated with complement activation may block the small peripapillary retinal capillaries, leading to retinopathy.2,3,5-9Clinically, patients present with decreased vision or visual field changes. Among most, visual acuity improves spontaneously over weeks to months. Anecdotally, systemic corticosteroids and vasodilators, such as papaverine, have been used in treatment; however, there is no evidence that these interventions improve visual outcomes beyond observation. Vitreous tap and injection is not indicated in Purtscher or Purtscher-like retinopathy, and infectious and autoimmune workup is not indicated in a healthy patient before obtaining additional information on his or her history.Further information on this patient’s history revealed that she had no medical problems and that she had not experienced any trauma since undergoing her surgery. Notably, the first cataract surgery that she underwent had been performed under topical anesthesia, but she had been extremely anxious and had difficulty keeping her eye still. For surgery in the right eye, she requested an anesthetic block. Before the surgery, 5 mL of peribulbar block consisting of 1% lidocaine, 0.375% bupivacaine, and 5 units/mL of hyaluronidase, without epinephrine, was administered using a 25-gauge, 7/8-in needle. The surgeon noted that the orbit was tight after the block and massaged the eyelids before initiating surgery. The phacoemulsification and insertion of the intraocular lens were uneventful.Five prior cases of Purtscher-like retinopathy after peribulbar or retrobulbar anesthesia have been reported.5-9 Two have been in the setting of pterygium surgery and 3 have been in the setting of cataract surgery. Anesthetics used have included lignocaine with epinephrine,7 lidocaine with epinephrine,9 and lidocaine without epinephrine.5,6,8 The volume injected has ranged from 3 mL to 5 mL, and needles ranged from 2.5 cm to 5 cm and were from 23 to 25 gauge.5-9 The visual acuity among these patients ranged from 20/20 to 20/200 on presentation, and improved in all cases, although residua, such as scotomas or afferent pupillary defect, persisted among all patients.In this patient, a comprehensive metabolic panel, a complete blood cell count, amylase, and lipase levels, and a lipid profile all had normal results, excluding alternative etiologies other than the administration of a peribulbar block that could have resulted in Purtscher-like retinopathy. It was recommended that the patient continue a routine post-surgical eyedrop regimen consisting of a topical steroid taper and nonsteroidal antiinflammatory drugs. One month after undergoing surgery, although the retinal lesions had mostly resolved, her visual acuity remained unchanged at 20/60.

Ophthalmology

A woman in her 60s presented 1 week after undergoing cataract surgery in the right eye complaining of persistent blurry vision. Her ocular history was notable for a previous uncomplicated cataract surgery in the left eye that had a good visual outcome. On postoperative day 1, her visual acuity was 20/60 OD, attributed to mild corneal edema, with an intraocular pressure of 18 mm Hg. A dilated fundus examination was not performed. At postoperative week 1, the best-corrected visual acuity was 20/50 OD, her intraocular pressure was 17 mm Hg, and there was no afferent pupillary defect. The cornea was clear and there were trace anterior chamber cells. A dilated examination revealed multiple spots of retinal whitening with tiny intraretinal hemorrhages concentrated in the posterior pole (Figure, A). The patient was referred urgently for consultation by a retina specialist. Optical coherence tomography revealed intraretinal cystoid abnormalities in the macula and hyperreflective patches in the nerve fiber layer and inner nuclear layer (Figure, B).A, Fundus photograph of the right eye demonstrating multifocal patches of inner retinal whitening in the posterior pole. B, Optical coherence tomography through the macula demonstrating mild intraretinal cystoid abnormalities and hyperreflective thickened areas in the nerve fiber and inner nuclear layer, corresponding to the white retinal patches.

what would you do next?

What would you do next?

Start systemic steroids

Infectious and autoimmune workup

Obtain more information on the patient’s history

Vitreous tap and injection of foscarnet

c

female

61-70

White

original

https://jamanetwork.com/journals/jamacardiology/fullarticle/2649269

A man in his 80s presented to the emergency department after falling in his bathroom. There was no associated loss of consciousness, chest pain, dyspnea, or palpitations. For the past several weeks he had noted generalized weakness and fatigue. His medical history was pertinent for a dual-chamber pacemaker implant 3 years earlier for intermittent symptomatic second-degree atrioventricular (AV) block. Additional comorbidities included hypertension and well-controlled type 1 diabetes with no recent changes in his medications. Initial vital signs showed a systolic blood pressure of 110 mm Hg and results of physical examination demonstrated clear lungs. Results of cardiovascular examination demonstrated no gallops, murmurs, or rubs. Results of electrocardiography performed on admission are shown in Figure 1. His pacemaker was programmed to a DDDR (dual-chamber, rate-adaptive) pacing mode with an AV delay of 300 milliseconds and tracking rates from 60 to 110 pulses per minute. The postventricular atrial refractory period was programmed to 200 milliseconds.Increase the atrial pacing rate to 70 beats per minuteShorten the programmed AV delay to 150 millisecondsIncrease the postventricular atrial refractory period to 250 milliseconds What Would You Do Next?

Increase the atrial pacing rate to 70 beats per minute

Shorten the programmed AV delay to 150 milliseconds

Increase the postventricular atrial refractory period to 250 milliseconds

Refer the patient for pacemaker lead revision

Intact retrograde ventriculoatrial conduction in the setting of complete anterograde AV block

B

Shorten the programmed AV delay to 150 milliseconds

Careful analysis of the ECG results suggests the presence of a retrograde P wave located at the terminal portion of the QRS complex best seen in lead V1 and the inferior leads. On device interrogation, the patient was pacing in the atrium and the ventricle and retrograde ventriculoatrial (VA) conduction was confirmed. Progressive reduction in the programmed AV delay demonstrated intermittent retrograde P waves until an AV delay of 150 milliseconds (Figure 2). The patient’s symptoms resolved completely after device reprogramming.Lead II recording with the atrioventricular delay shortened to 150 milliseconds results in normalization of the PR interval with resolution of retrograde P waves (due to retrograde refractoriness of ventriculoatrial conduction). Lead II from the initial electrocardiogram in Figure 1 with retrograde P waves (arrowheads) is shown for comparison.At implantation, the pacemaker was programmed to a prolonged AV delay to reduce right ventricular pacing and encourage intrinsic electrical conduction. In a post hoc analysis of the Mode Selection Trial (MOST), pacing more than 40% of the time was associated with an increased risk of hospitalizations due to heart failure as well as atrial fibrillation.1,2 In pacing system evaluations prior to presentation, the patient’s programming strategy led to ventricular pacing 20% of the time. Over time, worsening of the patient’s AV conduction resulted in an increase in ventricular pacing to 90% or more of the time. In addition, a consequence of the programmed prolonged AV delay was to facilitate VA conduction by providing more time for the AV node to recover from refractoriness.The cardiac conduction system has the ability for both antegrade AV and retrograde VA conduction and impaired conductivity in 1 direction does not necessarily compromise reverse conduction.3 Retrograde VA conduction can be associated with “pacemaker syndrome” owing to mistiming of atrial and ventricular contraction with atrial contraction against a closed AV valve during simultaneous ventricular contraction.4 This mistiming results in atrial distension and elevated pressures that activate inhibitory atrial and cardiopulmonary reflexes. Elevation of catecholamines and atrial natriuretic peptide is followed by a vasodepressor effect that has been deemed responsible for the reduction of resting cardiac output by 20% to 30%,4,5 with more severe hemodynamic consequences when intact retrograde 1:1 VA conduction is present.5 The incidence of pacemaker syndrome varies widely (7%-30%) depending on the etiologic factors of bradycardia (ie, sinus node dysfunction) and pacing mode (ie, ventricular pacing). Signs and symptoms of pacemaker syndrome include lethargy, fatigue, palpitations, chest pain, dyspnea, peripheral edema, exercise intolerance, syncope, and appreciation of venous pulsation on jugular venous examination (cannon A waves).4 This condition is likely underreported owing to the nonspecific nature of the symptoms.Treatment of pacemaker syndrome includes restoration of appropriate AV synchrony. For patients with single-chamber devices, upgrade to a dual-chamber pacemaker is usually required.5 In this patient, initial programming of a long AV interval to encourage intrinsic AV conduction became inappropriate when progressive loss of antegrade conduction facilitated retrograde VA conduction and was completely reversed by programming a shorter AV interval. This case emphasizes the importance of carefully evaluating the pacing system programming as clinical conditions change.After the programming change, the patient’s symptoms resolved, and he has had no further falls after 3 years of follow-up.

Cardiology

A man in his 80s presented to the emergency department after falling in his bathroom. There was no associated loss of consciousness, chest pain, dyspnea, or palpitations. For the past several weeks he had noted generalized weakness and fatigue. His medical history was pertinent for a dual-chamber pacemaker implant 3 years earlier for intermittent symptomatic second-degree atrioventricular (AV) block. Additional comorbidities included hypertension and well-controlled type 1 diabetes with no recent changes in his medications. Initial vital signs showed a systolic blood pressure of 110 mm Hg and results of physical examination demonstrated clear lungs. Results of cardiovascular examination demonstrated no gallops, murmurs, or rubs. Results of electrocardiography performed on admission are shown in Figure 1. His pacemaker was programmed to a DDDR (dual-chamber, rate-adaptive) pacing mode with an AV delay of 300 milliseconds and tracking rates from 60 to 110 pulses per minute. The postventricular atrial refractory period was programmed to 200 milliseconds.Increase the atrial pacing rate to 70 beats per minuteShorten the programmed AV delay to 150 millisecondsIncrease the postventricular atrial refractory period to 250 milliseconds

what would you do next?

What would you do next?

Increase the atrial pacing rate to 70 beats per minute

Refer the patient for pacemaker lead revision

Shorten the programmed AV delay to 150 milliseconds

Increase the postventricular atrial refractory period to 250 milliseconds

c

male

81-90

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2648317

A woman in her 60s presented for evaluation of multiple painful cutaneous nodules that had developed over the previous 2 months. The patient had a history of IgGκ multiple myeloma, diagnosed approximately 6 months earlier. At that time, flow cytometry showed a κ-restricted plasma cell population positive for CD38 and CD138 but negative for CD3, CD20, and CD45 expression. Cytogenetic analysis with fluorescent in situ hybridization did not reveal high-risk genetic markers. The patient demonstrated no evidence of end organ disease, and her myeloma was classified as stage II. Since her initial diagnosis, she had completed 4 cycles of lenalidomide, bortezomib, and dexamethasone (RVD) therapy in addition to irradiation for lytic lesions of the thoracic and lumbar spine. Physical examination revealed scattered red-violaceous nodules, with the largest measuring approximately 6.0 × 5.5 × 2.5 cm (Figure, A). They were found in the mouth, the trunk, and on all 4 extremities. The lesions were nonulcerated, round with a smooth surface, fixed, and firm and tender to touch. Serum protein levels were normal. An ultrasound-guided needle biopsy and immunohistochemical analysis of the largest lesion on the patient’s right shoulder were performed (Figure, B and C). What Is Your Diagnosis?

Hemangioma

Neutrophilic dermatoses

Plasmacytoma

Leukemia cutis

C. Plasmacytoma

C

Plasmacytoma

Positron emission tomography–computed tomography demonstrated innumerable foci of hypermetabolic activity within the subcutaneous soft tissue but without evidence of direct medullary extension. Biopsy showed diffuse involvement of a monotypic κ-restricted plasma cell dyscrasia with necrosis (Figure, B). The tissue core sample showed extensive necrosis; however, nonnecrotic regions demonstrated a dense monomorphic infiltrate of primarily immature atypical cells with a plasmacytoid appearance. Immunohistochemical stains revealed diffuse CD138 positivity (Figure, C) but negativity for CD3, CD20, CD56, BCL6, and c-kit. These findings were consistent with the patient’s history of κ-restricted multiple myeloma.The development of her cutaneous and mucosal plasmacytomas, despite 4 cycles of RVD, was concerning for refractory disease, and the treatment regimen was switched to dexamethasone, cyclophosphamide, etoposide, and cisplatin (DCEP). The patient received the first cycle of DCEP (day 1-4) as an inpatient without complications. No skin breakdown or ulceration was noted during chemotherapy. At her 1-week follow-up visit, the cutaneous plasmacytomas were found to be smaller, less firm in consistency, and reportedly less tender.Multiple myeloma is characterized by a clonal proliferation of plasma cells in the bone marrow. Clinical manifestations are typically related to organ damage, such as hypercalcemia, renal insufficiency, anemia, and bone lesions, referred to as “CRAB” symptoms. Extramedullary involvement may occur at any time during the course of the disease and in up to 45% of patients at the time of relapse.1 However, skin involvement was found in fewer than 5% to 10% of patients with myeloma.2 Some suggest a correlation between the proliferation of plasma cells outside the bone marrow and total body tumor cell mass.3 As such, skin findings are often associated with higher tumor burden and more aggressive disease.4 Cutaneous plasmacytomas may occur secondary to multiple myeloma or as primary lesions, without evidence of an underlying plasma cell dyscrasia. All classes of immunoglobulins have been implicated in cases of secondary plasmacytomas, although subtype IgG is the most common.5 In cases of extramedullary disease without evidence of direct tumor extension, hematogenous spread involving loss of cell adhesion molecules such as VLA-4, CD44, and CD56 have been proposed, although this remains incompletely understood.1Morphologically, the usual appearance of cutaneous plasmacytomas are of red-violaceous papules or nodules with or without ulceration. These lesions can range from 1 to 5 cm in diameter with variable distribution, although the trunk and abdominal regions are predominantly involved. Multiple lesions are more common than solitary lesions.6 On palpation, these nodules are smooth with a firm consistency and may be associated with substantial tenderness.Resection of solitary cutaneous plasmacytomas and intralesional injections with either steroids or tumor necrosis factor have shown an overall beneficial response.7 However, extensive and widespread disease, as in the present patient, may require chemotherapy and/or irradiation. While multiple myeloma is considered an incurable disease, studies in the last decade report an increase in 5-year survival rates from 28% to 49%; which has been largely attributed to novel therapies including immunomodulatory agents and proteasome inhibitors.8 Unfortunately, the presence of extramedullary involvement at any time during the disease course has been associated with poor prognosis regardless of therapy.1,4 Currently, various options exist for the treatment of multiple myeloma including immunomodulatory agents, proteasome inhibitors, cytotoxic agents, and stem cell transplantation.9 In relapsed or refractory disease, salvage options have included DCEP, which has shown a beneficial response but is associated with significant treatment-related mortality.10Recognition of the various cutaneous manifestations of multiple myeloma is important because it may indicate extramedullary involvement or relapsed disease, either of which warrants consideration of a new treatment regimen. The advances in chemotherapy allow more options for those with extramedullary manifestations who may not respond to conventional therapy. Responses to newer approaches such as kinesin-spindle protein inhibitors, monoclonal antibodies (anti-CD38, SLAMF7), and histone deacetylase inhibitors are encouraging, and the addition of these agents may further improve response rates.9

Oncology

A woman in her 60s presented for evaluation of multiple painful cutaneous nodules that had developed over the previous 2 months. The patient had a history of IgGκ multiple myeloma, diagnosed approximately 6 months earlier. At that time, flow cytometry showed a κ-restricted plasma cell population positive for CD38 and CD138 but negative for CD3, CD20, and CD45 expression. Cytogenetic analysis with fluorescent in situ hybridization did not reveal high-risk genetic markers. The patient demonstrated no evidence of end organ disease, and her myeloma was classified as stage II. Since her initial diagnosis, she had completed 4 cycles of lenalidomide, bortezomib, and dexamethasone (RVD) therapy in addition to irradiation for lytic lesions of the thoracic and lumbar spine. Physical examination revealed scattered red-violaceous nodules, with the largest measuring approximately 6.0 × 5.5 × 2.5 cm (Figure, A). They were found in the mouth, the trunk, and on all 4 extremities. The lesions were nonulcerated, round with a smooth surface, fixed, and firm and tender to touch. Serum protein levels were normal. An ultrasound-guided needle biopsy and immunohistochemical analysis of the largest lesion on the patient’s right shoulder were performed (Figure, B and C).

what is your diagnosis?

What is your diagnosis?

Plasmacytoma

Neutrophilic dermatoses

Leukemia cutis

Hemangioma

a

female

61-70

original

https://jamanetwork.com/journals/jama/fullarticle/2654794

A 67-year-old man with granulomatous polyangiitis (Wegener granulomatosis) complicated by end-stage renal disease requiring hemodialysis and mild pulmonary fibrosis, was hospitalized with a 2-week history of worsening dyspnea and dry cough. He was taking 20 mg prednisone and 150 mg azathioprine daily.On examination, he was afebrile and had diffuse rhonchi and expiratory wheezes. A chest computed tomography (CT) scan revealed bilateral nodular infiltrates and a 1.3-cm cavitary nodule in the right upper lobe. Bronchoscopy was performed on day 2. Blood and bronchoalveolar lavage fluid test results are presented in the Table.The patient does not meet criteria for invasive pulmonary aspergillosis.The patient is not at risk for invasive pulmonary aspergillosis and the results reflect colonization. How Would You Interpret This Patient’s Test Results?

The patient has proven invasive pulmonary aspergillosis.

The patient has probable invasive pulmonary aspergillosis.

The patient does not meet criteria for invasive pulmonary aspergillosis.

The patient is not at risk for invasive pulmonary aspergillosis and the results reflect colonization.

B

The patient has probable invasive pulmonary aspergillosis.

Invasive aspergillosis primarily occurs in patients who have specific risk factors, such as prolonged neutropenia, history of allogeneic hematopoietic cell or solid organ transplantation, use of high-dose corticosteroids or inherited severe immunodeficiency. Dense, well-circumscribed nodular lesion(s) on CT scan, with or without surrounding hazy infiltrate (halo sign) and cavitary lesions, are characteristic but not specific for invasive pulmonary aspergillosis.The Aspergillus galactomannan enzyme immunoassay detects polysaccharides that are present in the cell wall of Aspergillus species and that can be found in serum and bronchoalveolar lavage fluid during invasive infection.1,2The role of the galactomannan assay in the diagnosis of invasive aspergillosis has been studied most often in neutropenic patients and allogeneic hematopoietic cell transplant recipients.2,3 In these patient groups, the reported sensitivity of the assay in serum is 70% to 82% and specificity is 81% to 92%, and in bronchoalveolar lavage fluid, sensitivity is 73% to 100% and specificity is 68% to 92%.2 In solid organ transplant recipients, sensitivity is 21% to 86% and specificity is 80% to 89% in serum, and in broncholveolar lavage fluid, sensitivity is 60% to 90% and spedificity is 90% to 96%.4,5 The sensitivity of the assay is higher in bronchoalveolar lavage fluid than in serum, especially in lung transplant recipients.6False-negative results occur in patients who are receiving antifungal agents other than fluconazole.7 False-positive results occur in patients who are colonized but not infected with Aspergillus species and in those who have infection with Fusarium species, Histoplasma capsulatum, and Blastomyces dermatitidis because these fungi have similar galactomannans in their cell walls.False-positive reactions with piperacillin-tazobactam have been reported in the past, but manufacturing changes have eliminated this problem. Other reported causes of false-positive results include severe mucositis, severe gastrointestinal graft vs host disease, blood products collected in certain commercially available infusion bags, multiple myeloma (IgG type), and flavored ice pops or frozen desserts containing sodium gluconate.The time required to receive galactomannan test results is 2 to 7 days if the test is sent to a reference laboratory. The cost to Medicare is $90.This patient was at high risk for invasive pulmonary aspergillosis because of prolonged therapy with prednisone. Based on radiological findings and a positive galactomannan assay in bronchoalveolar lavage fluid, he was diagnosed with probable invasive pulmonary aspergillosis and started on voriconazole (Box).8,9 Two days later, Aspergillus fumigatus was recovered in bronchoalveolar lavage fluid culture. Pseudomonas aeruginosa was also present in the culture but was considered to be only colonizing the airways.Presence of host risk factors and radiological criteria and histopathologic or cytopathologic evidence of septate hyphae suggestive of Aspergillus species and compatible tissue damage in a specimen taken from a sterile site; orRecovery of Aspergillus species by culture from a sterile sitePresence of host risk factors and radiological criteria and recovery of Aspergillus species in culture from a nonsterile site; orEvidence of septate hyphae suggestive of Aspergillus species in a specimen from a nonsterile site; orAspergillus galactomannan detected in serum or bronchoalveolar lavage fluid; orPresence of host risk factors and radiological criteria in the absence of microbiological evidence and no alternative diagnosis to explain these findingsAbbreviation: EORTC-MSG, European Organization for Research and Treatment of Cancer-Mycoses Study Group.Abbreviation: EORTC-MSG, European Organization for Research and Treatment of Cancer-Mycoses Study Group.Proven invasive pulmonary aspergillosis requires proof of tissue invasion by histopathological examination or positive culture from a normally sterile site.8 In this patient, the diagnosis of proven invasive pulmonary aspergillosis could not be made because the transbronchial lung biopsy did not show hyphae invading lung tissue. For patients who have hematological malignancies or have received a hematopoietic stem cell transplant, lung biopsy is rarely performed because of thrombocytopenia, and thus, most cases of invasive pulmonary aspergillosis in these patient groups are deemed probable or possible (Box).The Fungitell assay detects (1,3) β-D-glucan, another cell wall component of many different fungi. A positive Fungitell result supports the diagnosis of an invasive fungal infection but is not specific for aspergillosis.10The patient was discharged home to continue therapy with voriconazole. Eight weeks later, a chest CT showed marked improvement. He completed 16 weeks of antifungal therapy with voriconazole. Three months later, he remained asymptomatic.When invasive pulmonary aspergillosis is suspected, the following tests should be ordered immediately: a high-resolution CT scan of the thorax, serum galactomannan, and consultation for bronchoscopy with bronchoalveolar lavage for galactomannan assay, fungal stain, and culture.The sensitivity of the galactomannan assay for invasive pulmonary aspergillosis is higher in bronchoalveolar lavage fluid than in serum.In patients who have risk factors and radiologic findings suggesting invasive aspergillosis, a positive galactomannan in serum or bronchoalveolar lavage fluid confirms a diagnosis of probable invasive pulmonary aspergillosis.In patients with risk factors for invasive aspergillosis and radiologic findings consistent with invasive pulmonary aspergillosis, antifungal therapy should be started while awaiting cultures and galactomannan test results.

Diagnostic

A 67-year-old man with granulomatous polyangiitis (Wegener granulomatosis) complicated by end-stage renal disease requiring hemodialysis and mild pulmonary fibrosis, was hospitalized with a 2-week history of worsening dyspnea and dry cough. He was taking 20 mg prednisone and 150 mg azathioprine daily.On examination, he was afebrile and had diffuse rhonchi and expiratory wheezes. A chest computed tomography (CT) scan revealed bilateral nodular infiltrates and a 1.3-cm cavitary nodule in the right upper lobe. Bronchoscopy was performed on day 2. Blood and bronchoalveolar lavage fluid test results are presented in the Table.The patient does not meet criteria for invasive pulmonary aspergillosis.The patient is not at risk for invasive pulmonary aspergillosis and the results reflect colonization.

how would you interpret this patient’s test results?

How do you interpret these results?

The patient is not at risk for invasive pulmonary aspergillosis and the results reflect colonization.

The patient has probable invasive pulmonary aspergillosis.

The patient does not meet criteria for invasive pulmonary aspergillosis.

The patient has proven invasive pulmonary aspergillosis.

b

male

61-70

original

https://jamanetwork.com/journals/jama/fullarticle/2654360

A 4-year-old boy presented with a pink nodule on his left cheek. The lesion started as a hyperpigmented macule 3 years ago and since then had been gradually increasing in size and developing into a pink nodule. The lesion was pruritic at times and sometimes bled with minor trauma. The boy was otherwise healthy, with an unremarkable medical history and with no history of trauma or exposure to radiation. On physical examination, there was a 1-cm well-circumscribed, symmetrical, pinkish, dome-shaped nodule with central erosions on the left cheek (Figure 1). Hair, nails, and mucosae were of normal appearance, and the remainder of the examination was unremarkable. What Would You Do Next?

Obtain a biopsy for hematoxylin-eosin stain

Obtain a biopsy for fungal culture

Treat with cryotherapy

Treat with pulsed dye laser therapy

Epithelioid Spitz nevus

A

Obtain a biopsy for hematoxylin-eosin stain

The key to the correct diagnosis is the early onset of a pink, symmetrical, solitary, smooth, and dome-shaped nodule on the cheek of a young boy. The differential diagnosis includes Spitz nevus, pyogenic granuloma, sporotrichosis, and amelanotic malignant melanoma. A biopsy for fungal culture is needed to diagnose sporotrichosis, but sporotrichosis typically has a granulomatous appearance and erosions or ulcerations with purulent drainage can be seen on the surface. Cryotherapy and pulsed dye laser therapy can be used in pyogenic granulomas, but pyogenic granulomas predominantly occur in the second decade of life, mostly in young adult females.1 Amelanotic malignant melanomas rarely occur in young children and are usually ulcerated and asymmetrical. There are different types of Spitz nevi, which cannot be completely differentiated clinically; therefore, a skin biopsy for hematoxylin-eosin stain is needed to confirm the diagnosis.Spitz nevi are uncommon melanocytic neoplasms with an overall estimated incidence ranging from 1.4 to 7 per 100 000 persons per year.2 The lesions usually occur before age 20 years, with some presenting at birth.3 Most Spitz nevi present as asymptomatic, symmetrical, solitary, smooth, firm, and dome-shaped nodules, with pinkish, red, or black coloration depending on the melanin content. They are usually less than 2 cm in diameter, although there is often a period of more rapid growth following initial slow growth. They are most commonly found on the lower extremities and head.4 They are highly vascular and can bleed with slight trauma. In this case, the asymmetry of the lesion shown in Figure 1 is a result of the punch biopsy; the lesion was symmetrical prior to biopsy.Histologically, Spitz nevi are usually composed of spindle melanocytes or mixed spindle and epithelioid melanocytes extending from the epidermis into the reticular dermis in an inverted-wedge configuration. Unlike the common Spitz nevus, an epithelioid Spitz nevus is nearly exclusively composed of large epithelioid cells with abundant cytoplasm. Some nevus cells are multinucleated. Melanin is absent or symmetrically distributed and is usually absent in the deepest part.5 Since pleomorphism and mitotic activity can be present, Spitz nevi are sometimes misdiagnosed as other malignant tumors. Histologic features that indicate a Spitz nevus rather than melanoma include nevus cell maturation in deeper parts, minimal or absent pagetoid spread, absence or scarcity of melanin deep in the lesion, Kamino bodies, low nuclear to cytoplasmic ratio, and restriction of mitotic activity. Although pleomorphism and mitotic activity may present in Spitz nevi, expression of Ki-67 by the tumor cells is usually less than 1%. Dermoscopy (direct microscopic examination of the surface and architecture of pigmented skin lesions) reveals a starburst appearance and globular pattern.5,6 Clinically, unlike melanomas, Spitz nevi affect young children and are small, symmetric, and lack surface ulceration.Dermatologists usually consider age in their choice of management and may choose a “wait and see” approach in children younger than 12 years. A dermoscopic follow-up of every 6 months for the first 2 or 3 years and then yearly is suggested.7 If left untreated, Spitz nevi usually tend to remain as stable papules or nodules after the period of rapid growth and lack of aggressive behavior.6 Another option is surgical removal by either punch biopsy or excision if the lesion occurs in a cosmetically sensitive site.8 Spitz nevus usually does not recur after excision.Histopathological examination of the lesion revealed many large, nonpigmented and pleomorphic epithelioid cells in the dermis with large nuclei and abundant cytoplasm (Figure 2, top and bottom left), consistent with epithelioid Spitz nevus. The majority of epithelioid cells were S100 and melan-A positive (Figure 2, bottom right). Ki-67 expression was less than 1%. Because of the location on the face and history of bleeding with trauma, the nodule was completely excised. At 1 year of follow-up, no recurrence of the lesion has been detected.

General

A 4-year-old boy presented with a pink nodule on his left cheek. The lesion started as a hyperpigmented macule 3 years ago and since then had been gradually increasing in size and developing into a pink nodule. The lesion was pruritic at times and sometimes bled with minor trauma. The boy was otherwise healthy, with an unremarkable medical history and with no history of trauma or exposure to radiation. On physical examination, there was a 1-cm well-circumscribed, symmetrical, pinkish, dome-shaped nodule with central erosions on the left cheek (Figure 1). Hair, nails, and mucosae were of normal appearance, and the remainder of the examination was unremarkable.

what would you do next?

What would you do next?

Treat with cryotherapy

Treat with pulsed dye laser therapy

Obtain a biopsy for fungal culture

Obtain a biopsy for hematoxylin-eosin stain

d

male

0-10

original

https://jamanetwork.com/journals/jama/fullarticle/2654361

A 53-year-old woman presented for a prescription refill of hydrocodone/acetaminophen 10 mg/325 mg. She had chronic low back pain and partial paralysis from a thoracic spinal cord infarction, secondary to aortic dissection from prior cocaine use. Taking 2 to 3 tablets of hydrocodone/acetaminophen daily improved her back pain from 5 to 2 on a 10-point scale. She reported no recent illicit substance or drug use and stated her last dose of hydrocodone was that day. The patient had not achieved pain control with prior nonopioid pharmacologic pain management, including duloxetine and gabapentin. Although past cocaine use was a risk factor for opioid misuse, a trial of hydrocodone was initiated, after discussion of risks and benefits, with a plan for careful monitoring. The state prescription drug monitoring program showed no other prescribers of controlled substances. A urine immunoassay drug screen was ordered to evaluate for medication misuse and illicit use (Table).The patient is not using hydrocodone but is using cocaine.The patient is not using hydrocodone but may be using cocaine.The patient may be using hydrocodone but is using cocaine.The patient may be using both hydrocodone and cocaine. How Would You Interpret These Results?

The patient is not using hydrocodone but is using cocaine.

The patient is not using hydrocodone but may be using cocaine.

The patient may be using hydrocodone but is using cocaine.

The patient may be using both hydrocodone and cocaine.

C

The patient may be using hydrocodone but is using cocaine.

The use of opioids for treating chronic noncancer pain has increased substantially, correlating with an increase in opioid use disorder and overdose.1 The Centers for Disease Control and Prevention (CDC) guidelines for prescribing opioids for chronic pain suggest performing a urine drug screening before initiating treatment and considering screening at least annually.2A urine drug screen is commonly performed using immunoassay panels that detect illicit drugs and frequently prescribed substances with potential for misuse. The drugs detected by these tests can vary, but a urine drug screen typically tests for opiates, opioids, cocaine, amphetamines, benzodiazepines, and cannabinoids. Different laboratories use different assays, and clinicians should be familiar with the drugs and metabolites measured by their laboratory and the associated detection thresholds and assay limitations.Most opiate immunoassays are calibrated to detect morphine and codeine; they have varying performance to detect semisynthetic opioids (eg, hydrocodone and oxycodone) and do not detect synthetic opioids (eg, methadone and fentanyl) (Box).3 Immunoassays designed to detect semisynthetic and synthetic opioids have better diagnostic accuracy. Methadone immunoassays can have sensitivities greater than 95%.4 Hydrocodone is the most commonly prescribed opioid in the United States,5 yet some opiate screens are not sufficiently sensitive to detect it. For example, in one study, 72% (81/112) of urine specimens that had unexpected negative opiate immunoassay results were positive for hydrocodone or hydromorphone by gas chromatography mass spectrometry.6Diagnostic accuracy of drug screens varies by drug class and assay manufacturer. Cocaine immunoassays have positive predictive values near 100%.4,7 The Medicare midpoint reimbursement for urine drug screening ranges from $20.22 to $107.85 based on the complexity of instrumentation used to read assay results.8 Immunoassays can be an inexpensive method for screening, although the limitations must be well understood.9CDC guidelines note that a urine drug screening may be clinically useful to determine whether patients are taking prescribed opioids, other substances with risk of misuse, or both.3 This patient’s negative opiate screen may raise suspicion for nonadherence or diversion (giving or selling the medication to others). However, because the opiate screen used has limited cross-reactivity and a high cutoff (2000 ng/mL) for detecting hydrocodone,10 the negative result may be false. False-negative results may also occur when metabolite concentration is low. A test that improves overall diagnostic accuracy by increasing the sensitivity and specificity for hydrocodone and its metabolites would be necessary to confirm its absence. In contrast, the false-positive rate for a cocaine urine drug screening is near zero.Assays using mass spectrometry can provide definitive drug and metabolite identification with improved sensitivity and specificity over immunoassay methods; however, results may take longer, and cost is more than the widely available immunoassay screens. Medicare midpoint reimbursement for mass spectrometry–based drug tests ranges from $158.98 to $343.07, depending on the number of drug classes included.8The patient restated that she had not used cocaine and was taking hydrocodone daily. The physician informed the patient that given the likelihood of cocaine use, she would no longer prescribe hydrocodone but wanted to continue caring for the patient. Naproxen and topical lidocaine were recommended, and the patient was referred to a pain management program. The patient canceled her next appointment. The state prescription drug monitoring program revealed new hydrocodone prescriptions from another clinician.Centers for Disease Control and Prevention guidelines recommend obtaining a urine drug screening prior to the initiation of opioids for chronic pain and considering at least yearly screens thereafter.Clinicians must be familiar with the drugs and metabolites measured by a given urine drug screening and the associated detection thresholds and assay limitations.Opiate immunoassays may not detect semisynthetic opioids with adequate sensitivity and will not detect synthetic opioids.Patients should not be dismissed from care based on urine drug screening results. Unexpected results may require confirmation and should be used to modify the care plan, which may involve discontinuing opioids.

Diagnostic

A 53-year-old woman presented for a prescription refill of hydrocodone/acetaminophen 10 mg/325 mg. She had chronic low back pain and partial paralysis from a thoracic spinal cord infarction, secondary to aortic dissection from prior cocaine use. Taking 2 to 3 tablets of hydrocodone/acetaminophen daily improved her back pain from 5 to 2 on a 10-point scale. She reported no recent illicit substance or drug use and stated her last dose of hydrocodone was that day. The patient had not achieved pain control with prior nonopioid pharmacologic pain management, including duloxetine and gabapentin. Although past cocaine use was a risk factor for opioid misuse, a trial of hydrocodone was initiated, after discussion of risks and benefits, with a plan for careful monitoring. The state prescription drug monitoring program showed no other prescribers of controlled substances. A urine immunoassay drug screen was ordered to evaluate for medication misuse and illicit use (Table).The patient is not using hydrocodone but is using cocaine.The patient is not using hydrocodone but may be using cocaine.The patient may be using hydrocodone but is using cocaine.The patient may be using both hydrocodone and cocaine.

how would you interpret these results?

How do you interpret these results?

The patient may be using hydrocodone but is using cocaine.

The patient may be using both hydrocodone and cocaine.

The patient is not using hydrocodone but is using cocaine.

The patient is not using hydrocodone but may be using cocaine.

a

female

51-60

original

https://jamanetwork.com/journals/jama/fullarticle/2653717

A 39-year-old man with a history of ischemic stroke 10 years ago presented after 1 day of right calf swelling and shortness of breath. He reported no trauma, surgery, recent prolonged mobility limitation, or family history of thrombosis. His only medication was aspirin, 81 mg daily. On examination, his heart rate was 106/min, respiratory rate was 28/min, and swelling of the right calf was noted. A heparin drip was initiated for suspected pulmonary embolism, which was confirmed with computed tomography pulmonary angiography. Routine laboratory values were unremarkable. Warfarin was administered for long-term anticoagulation. Given the unprovoked thrombotic events at a young age, a hypercoagulable state was suspected, and testing for the antiphospholipid syndrome was performed. Two days later, results revealed elevated titers of anticardiolipin and anti–β2 glycoprotein I antibodies and negative lupus anticoagulant screening assays (Table 1).Results should be repeated in 12 weeks to confirm diagnosis of antiphospholipid syndrome. How Would You Interpret These Test Results?

Results are sufficient to diagnose antiphospholipid syndrome.

Results should be repeated in 12 weeks to confirm diagnosis of antiphospholipid syndrome.

Results are uninterpretable due to heparin therapy.

Results are uninterpretable due to warfarin therapy.

B

Results should be repeated in 12 weeks to confirm diagnosis of antiphospholipid syndrome.

Antiphospholipid syndrome is a disorder associated with recurrent thromboembolic events or complications of pregnancy (unexplained fetal death at >10 weeks’ gestation, ≥3 spontaneous abortions at <10 weeks’ gestation, early preeclampsia) in the presence of persistent elevation of antiphospholipid antibodies (evaluated with 2 tests performed ≥12 weeks apart).1 The etiology of antiphospholipid antibodies is related to an interaction between genetic and environmental factors. Antiphospholipid antibodies are directed toward phospholipid-binding proteins and promote a prothrombotic state by activating platelets, monocytes, and the endothelium, and by inhibiting natural anticoagulant and fibrinolytic systems.A diagnosis of antiphospholipid syndrome requires presence of at least 1 of 3 antiphospholipid antibodies: anticardiolipin antibodies (IgG or IgM elevated to >40 phospholipid units or to >99th percentile of controls), anti–β2 glycoprotein I antibodies (IgG or IgM elevated to >99th percentile of controls), or presence of lupus anticoagulant.2 These tests can be ordered separately or together as a panel. IgA antibodies can be detected for each test but are not part of diagnostic criteria for antiphospholipid syndrome. Testing for anticardiolipin and anti–β2 glycoprotein I antibodies is based on enzyme-linked immunosorbent assays (ELISA) and is unaffected by anticoagulation.3 Antiphospholipid antibodies may be transiently detectable in healthy individuals and in some patients with rheumatologic disorders, infections, or malignancy.4 Thus, a single elevated antiphospholipid antibody titer has limited value.1 Given the absence of a criterion standard and variable threshold values and assay designs, there are wide variations in sensitivity and specificity of antiphospholipid antibodies for antiphospholipid syndrome (Table 2).7Lupus anticoagulant is detected through coagulation-based assays such as activated partial thromboplastin time and dilute Russell viper venom time.8 The latter uses viper venom, which activates factor X in the presence of phospholipids. Antiphospholipid antibodies can prolong clotting times by inhibiting phospholipids in test reagents. In the setting of a prolonged clotting time, a mixing study can establish factor deficiencies. In the absence of clotting factor deficiencies, excess phospholipid is able to overcome the antiphospholipid antibodies, confirming their presence.3 Heparin, low–molecular-weight heparin, warfarin, and direct oral anticoagulants can interfere with lupus anticoagulant testing. Therefore, testing for lupus anticoagulant should be performed when the patient is not taking these anticoagulant medications.9 The 2017 Medicare midpoint reimbursement for anti-cardiolipin and anti–β2 glycoprotein I antibody testing is $47.17 each. Reimbursement for lupus anticoagulant testing via the dilute Russell viper venom screening is $17.75 and confirmation time is $33.32.10This patient presented with unprovoked venous thromboembolism at a young age (<45 years) and had prior history of stroke. Testing for antiphospholipid syndrome is indicated in young patients with unexplained, recurrent, or unusual site thrombosis or in women with complications of pregnancy. This patient had elevated levels of anticardiolipin and anti–β2 glycoprotein I antibodies. Anticoagulation does not affect these ELISA-based tests but a definitive diagnosis of antiphospholipid syndrome requires persistent elevation of any one antiphospholipid antibody via testing at least 12 weeks apart.1No other specific laboratory tests diagnose antiphospholipid syndrome. Presence of antiphospholipid antibodies may be suggested by a false-positive screening for syphilis because the antigen in the VDRL test contains cardiolipin.Titers of anticardiolipin and anti–β2 glycoprotein I antibodies were elevated 12 weeks later, consistent with antiphospholipid syndrome. The patient received warfarin (target international normalized ratio, 2-3) in addition to aspirin, with plans for indefinite anticoagulation. No further thrombotic events have occurred at 5-year follow-up.Antiphospholipid syndrome diagnosis is based on clinical criteria (thrombosis or complications of pregnancy) and laboratory tests.Laboratory criteria require persistent elevation of 1 of 3 laboratory tests (performed ≥12 weeks apart): anticardiolipin antibodies, anti–β2 glycoprotein I antibodies, or lupus anticoagulant.ELISA-based testing for anticardiolipin and anti–β2 glycoprotein I antibodies is unaffected by anticoagulation.Lupus anticoagulant testing should ideally be performed when the patient is not taking anticoagulation medication.

Diagnostic

A 39-year-old man with a history of ischemic stroke 10 years ago presented after 1 day of right calf swelling and shortness of breath. He reported no trauma, surgery, recent prolonged mobility limitation, or family history of thrombosis. His only medication was aspirin, 81 mg daily. On examination, his heart rate was 106/min, respiratory rate was 28/min, and swelling of the right calf was noted. A heparin drip was initiated for suspected pulmonary embolism, which was confirmed with computed tomography pulmonary angiography. Routine laboratory values were unremarkable. Warfarin was administered for long-term anticoagulation. Given the unprovoked thrombotic events at a young age, a hypercoagulable state was suspected, and testing for the antiphospholipid syndrome was performed. Two days later, results revealed elevated titers of anticardiolipin and anti–β2 glycoprotein I antibodies and negative lupus anticoagulant screening assays (Table 1).Results should be repeated in 12 weeks to confirm diagnosis of antiphospholipid syndrome.

how would you interpret these test results?

How do you interpret these results?

Results should be repeated in 12 weeks to confirm diagnosis of antiphospholipid syndrome.

Results are uninterpretable due to heparin therapy.

Results are uninterpretable due to warfarin therapy.

Results are sufficient to diagnose antiphospholipid syndrome.

a

male

31-40

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2618140

A man in his 50s with a history of both hypertension and a pulmonary tumor that was resected 10 years earlier (Figure, A) presented with generalized phymatous changes affecting his entire face, as well as a few pustular lesions and a diffuse erythema that gave him an appearance of leonine facies (Figure, B). He complained of substantial, progressive seborrheic hyperplasia and flushing episodes over the past year, accompanied by ocular manifestations that included swelling of his eyelids. Ophthalmological examination showed features of chronic blepharitis and lagophthalmos. Detailed anamnesis revealed a history of intense diarrhea in prior months. A biopsy specimen from the skin of the forehead was obtained and analyzed under hematoxylin-eosin staining (Figure, C). A computed tomography (CT) scan completed the etiological investigation (Figure, D).A, Immunohistochemical analysis of the earlier lung tumor using chromogranin A; panoramic view shows that most of the cells diffusely express chromogranin (original magnification ×20). B, Leonine facies presentation shows phymatous changes, diffuse erythema, pustular lesions, and seborrheic hyperplasia. C, Forehead skin shows scarce lymphocytic infiltrate close to follicular structure along with sebaceous hyperplasia (hematoxylin-eosin, original magnification ×40). D, Liver computed tomographic (CT) image showing multiple metastatic hepatic masses. What Is Your Diagnosis?

Leprosy

Mastocytosis

Carcinoid syndrome

Leishmaniasis

C. Carcinoid syndrome

C

Carcinoid syndrome

Ten years earlier, the patient had undergone surgery for a neuroendocrine pulmonary neoplasm. Its cells expressed pancytokeratins AE1-AE3, synaptophysin, and chromogranin and were negative for thyroid transcription factor-1 and bombesin, consistent with a typical carcinoid tumor. Surgical margins were clear, and no sign of recurrence had been detected since surgery.However, at the time of consultation, laboratory tests showed elevated liver function enzymes and 5-OH-indolacetic acid in a 24-hour urine sample of 31 mg (normal range, 0-5 mg), suggesting the presence of a serotoninergic neoplasia. A CT scan revealed multiple liver masses compatible with metastasis, and a hepatic biopsy confirmed their neuroendocrine origin, consistent with his primary lung tumor.The skin biopsy specimen showed abundant sebaceous glands localized around hair follicles, accompanied by slight perivascular inflammatory infiltrates and superficial edema. Thus, we established the diagnosis of severe paraneoplastic phymatous rosacea secondary to carcinoid syndrome.Subsequently, apart from symptomatic measures, the patient received several lines of oncologic treatment including somatostatin, everolimus, and temozolomide to control tumor progression and ameliorate his systemic symptoms. However, all efforts were insufficient, and he died shortly after these treatments.Carcinoid syndrome is an infrequent process secondary to circulating vasoactive products such as serotonin, bradykinin, prostaglandins, and others secreted by a neuroendocrine tumor. The incidence of carcinoid tumors is approximately 1.5 per 100 000 population.1,2 However, for carcinoid syndrome to develop, neuroendocrine substances must avoid liver metabolism and escape to systemic circulation,3,4 which only happens in about 10% of patients.1,2 In the present case, the cause of the carcinoid syndrome was the metastatic involvement of the liver, but it can also occur secondary to extra-abdominal tumors or due to an excessive production of mediators by large or multiple intra-abdominal tumors.1Clinical manifestations include diarrhea, bronchospasm, and heart failure, as well as recognized cutaneous manifestations.1,2,5,6 Most patients experience flushing symptoms, which normally affect the face, neck, and upper trunk. Physiological and carcinoid flushing can be similar, and both have common triggers such as stress, alcohol, and spicy food among others.2,4,5 Nonetheless, symptoms vary depending on the site, since tumors originating in the embryological foregut (ie, stomach, lung, pancreas, and biliary tract) produce a certain characteristic tone described as bright salmon pink, while patients with tumors in the appendix or ileum develop a cyanotic coloration.1,4 As happened in this patient’s case, flushing episodes have been reported to become chronic and lead to the appearance of a severe rosacea with secondary phymatous changes.2,6-8Other cutaneous manifestations that can arise in carcinoid syndrome are pellagroid lesions in relation to niacin deficit secondary to an excessive consumption of tryptophan directed to the overproduction of serotonin metabolites.1,2 A specific variant of scleroderma affecting predominantly the lower extremities has also been described in carcinoid syndrome.1,5 Other less frequent skin findings include cutaneous metastasis, angioedema, pachydermoperiostosis, gangrenous pyoderma, erythema annulare centrifugum, or lichen sclerosus et atrophicus.1,3,5Symptomatic medications are recommended (eg, antihistamines, corticosteroids, niacin), but treatment should be provided for the underlying disease. Surgical treatment is indicated when possible, but most cases are not susceptible owing to the presence of advanced metastatic disease. In those cases, somatostatin analogues are used to reduce carcinoid symptoms and tumor progression.1,2,4We present an extraordinarily severe case of paraneoplastic phymatous rosacea in the context of carcinoid syndrome and highlight its dermatological symptoms. Increased awareness of these clinical manifestations might aid in early diagnosis and treatment that could improve these patients’ prognoses.

Dermatology

A man in his 50s with a history of both hypertension and a pulmonary tumor that was resected 10 years earlier (Figure, A) presented with generalized phymatous changes affecting his entire face, as well as a few pustular lesions and a diffuse erythema that gave him an appearance of leonine facies (Figure, B). He complained of substantial, progressive seborrheic hyperplasia and flushing episodes over the past year, accompanied by ocular manifestations that included swelling of his eyelids. Ophthalmological examination showed features of chronic blepharitis and lagophthalmos. Detailed anamnesis revealed a history of intense diarrhea in prior months. A biopsy specimen from the skin of the forehead was obtained and analyzed under hematoxylin-eosin staining (Figure, C). A computed tomography (CT) scan completed the etiological investigation (Figure, D).A, Immunohistochemical analysis of the earlier lung tumor using chromogranin A; panoramic view shows that most of the cells diffusely express chromogranin (original magnification ×20). B, Leonine facies presentation shows phymatous changes, diffuse erythema, pustular lesions, and seborrheic hyperplasia. C, Forehead skin shows scarce lymphocytic infiltrate close to follicular structure along with sebaceous hyperplasia (hematoxylin-eosin, original magnification ×40). D, Liver computed tomographic (CT) image showing multiple metastatic hepatic masses.

what is your diagnosis?

What is your diagnosis?

Leishmaniasis

Carcinoid syndrome

Leprosy

Mastocytosis

b

male

51-60

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2622082

A woman in her 50s presented for evaluation of itching skin lesions. The lesions had been present for months and increased gradually. Mucosae were unaffected. Treatment with topical steroids showed no lasting effect. Skin examination revealed multiple flaccid pustules on scaly, erythematous plaques on her trunk, with an annular and circinate pattern (Figure, A and B).A and B, Clinical presentation showed flaccid pustules on scaly, erythematous plaques on the trunk. C, Subcorneal acantholysis of keratinocytes (yellow arrowheads) resulting in intraepidermal separation/blistering and an inflammatory infiltrate consisting of neutrophilic granulocytes (black arrowheads) (hematoxylin-eosin staining, original magnification × 100; inset original magnification × 400). D, Discrete subcorneal intercellular IgA depositions (white arrowheads) (direct immunofluorescence with FITC-labeled antihuman IgA antibodies, original magnification × 400). What Is The Diagnosis?

Tinea corporis

IgA pemphigus

Duhring disease

Psoriasis pustulosa

B. IgA pemphigus

B

IgA pemphigus

A biopsy revealed a subcorneal neutrophilic inflammatory infiltrate and acantholysis (Figure, C). Special stains and microbiologic examination findings were negative. Direct immunofluorescence microscopy revealed very subtle subcorneal intercellular IgA depositions (Figure, D). Immunoblots with recombinant desmosomal proteins (desmogleins 1 and 3 and desmocollins 1, 2, and 3) disclosed IgA-autoantibodies against desmocollin 3.IgA pemphigus is relatively rare and caused by IgA autoantibodies against desmosomal proteins.1 It is traditionally subdivided into the subcorneal pustular dermatosis and the intraepidermal neutrophilic types.2 Nevertheless, many cases of IgA pemphigus show atypical characteristics with IgA reactivity against various antigens in the epidermis and the alternative term IgA pemphigus spectrum has therefore recently been suggested.3 The key clinical feature of IgA pemphigus is the presence of flaccid, sterile pustules on scaly, erythematous plaques. Because skin pustules are often caused by infections, the major differential diagnoses include impetigo (bacterial infection) and tinea (dermatophyte infection). If the microbiology is sterile, direct immunofluorescence is indispensable to distinguish IgA pemphigus from other sterile pustular dermatoses, such as psoriasis pustulosa, acute generalized exanthematous pustulosis, pemphigus foliaceus, and linear IgA dermatosis. The sample for direct immunofluorescence should be taken from perilesional skin and not from a lesion directly. The combination of subcorneal acantholysis in histologic analysis and intercellular IgA depositions in the upper epidermis in direct immunofluorescence—which can be subtle—is diagnostic for IgA pemphigus. Serological tests (indirect immunofluorescence or immunoblot) can be helpful to support the diagnosis, but frequently fail to identify the target antigen. Sensitivity of indirect immunofluorescence is reported to be only 50%, immunoblot techniques available in specialized centers can have a sensitivity of up to 60%.2IgA pemphigus has been reported in association with malignant diseases4-6 and other disorders, such as inflammatory bowel disease7 and rheumatoid arthritis.8 The disease is responsive to oral glucocorticoids, but often adjuvant therapy is required to allow for steroid tapering. Dapsone and colchicine are frequently used immunomodulators that inhibit recruitment of neutrophilic granulocytes to the skin. Further steroid-sparing agents are acitretin, and long-term immunosuppressants, such as azathioprine.9 This patient did not improve on several immunosuppressive drugs and dapsone, but responded to treatment with colchicine.

Dermatology

A woman in her 50s presented for evaluation of itching skin lesions. The lesions had been present for months and increased gradually. Mucosae were unaffected. Treatment with topical steroids showed no lasting effect. Skin examination revealed multiple flaccid pustules on scaly, erythematous plaques on her trunk, with an annular and circinate pattern (Figure, A and B).A and B, Clinical presentation showed flaccid pustules on scaly, erythematous plaques on the trunk. C, Subcorneal acantholysis of keratinocytes (yellow arrowheads) resulting in intraepidermal separation/blistering and an inflammatory infiltrate consisting of neutrophilic granulocytes (black arrowheads) (hematoxylin-eosin staining, original magnification × 100; inset original magnification × 400). D, Discrete subcorneal intercellular IgA depositions (white arrowheads) (direct immunofluorescence with FITC-labeled antihuman IgA antibodies, original magnification × 400).

what is the diagnosis?

What is your diagnosis?

Duhring disease

Tinea corporis

Psoriasis pustulosa

IgA pemphigus

d

female

51-60

White

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2628748

A 4-year-old girl with newly diagnosed acute lymphocytic leukemia, receiving her initial course of chemotherapy with vincristine, daunorubicin, and methotrexate, developed a painful lesion on her left triceps. The tender area was beneath an adhesive bandage placed where she had received DTaP (diphtheria-tetanus-pertussis) and polio vaccinations 3 weeks earlier. Otherwise, she appeared remarkably well, and her vital signs were normal. Removing the bandage revealed a tender indurated gray-violet plaque (Figure, A). White blood cell and neutrophil counts were low at 0.4 K/μL (normal range, 4.86-13.18 K/μL) and 0.18 K/μL (normal range, 1.60-8.29 K/μL), respectively. Blood culture findings were negative. Punch biopsy specimens were obtained for histopathologic analysis (Figure, B) and fungal culture (Figure, C).A, Gray-violet plaque on posterior upper arm at site of adhesive portion of bandage. B, Broad nonseptate hyphae surrounding and infiltrating dermal blood vessels (hematoxylin-eosin; original magnification ×400). Of note, occasional septae are seen in this specimen, consistent with the characteristic finding that mucormycetes are pauciseptate, rather than aseptate, molds. C, Nonseptate hyphae with round terminal sporangia and free spores (lactophenol cotton blue mount; original magnification ×400). What Is Your Diagnosis?

Mucormycosis

Cutaneous diphtheria

Pseudomonal ecthyma gangrenosum

Aspergillosis

A. Mucormycosis

A

Mucormycosis

Histopathologic examination showed prominent broad nonseptated hyphae in the superficial and deep dermis surrounding and infiltrating several blood vessels, along with overlying areas of focal vacuolar interface changes at the dermal-epidermal junction (Figure, B). Microscopic examination of organisms grown from tissue culture revealed wide nonseptate hyphae with irregular branching, round terminal sporangia, and free spores (Figure, C). The histopathologic and tissue culture findings were consistent with a diagnosis of mucormycosis. The cutaneous lesion was completely excised. Treatment with intravenous liposomal amphotericin B was initiated. Her skin findings did not recur.Mucormycosis refers to an infection caused by fungi in the order Mucorales, which contains the genera Mucor, Absidia, and Rhizopus. These fungi are ubiquitous in the environment and are opportunistic pathogens that often cause fatal infections. A retrospective study1 in children showed that mucormycosis was most commonly associated with hematologic malignancy (46%), followed by hematopoietic stem cell transplant (16%), other malignancies (7%), and solid organ transplant, trauma or surgery, and diabetes mellitus (5% each). Neutropenia was present in 46% of patients. Approximately one-third of these cases ended fatally. Risk factors in adults are similar and include immunocompromised states and history of trauma. Members of Mucor and related genera have been previously noted to cause cutaneous infections in susceptible patients at the attachment site of adhesive bandages and dressings, catheters, and drains.2,3 Nosocomial outbreaks have also been linked to contaminated materials, such as hospital bed sheets, tongue depressors, and ostomy bags. A presumptive diagnosis of mucormycosis can be made when the histopathologic examination shows broad, largely nonseptate hyphae. The diagnosis is confirmed by microscopic examination of cultured material that shows wide (6-15 μm), largely nonseptate hyphae with irregular branching at 90° and long sporangiophores with round, spore-filled, terminal sporangia. Aspergillosis, notably with Aspergillus fumigatis and Aspergillus niger, has also been reported at the site of adhesive bandages and tape in immunosuppressed patients.4,5 On histopathological examination, aspergillosis appears as smaller, septate hyphae with regular 45° branching. Infection control guidelines have been proposed for tape storage and use but have not been widely implemented.6Aggressive cutaneous bacterial infections are on the differential diagnosis for cutaneous plaques in immunosuppressed patients. Pseudomonal ecthyma gangrenosum is a necrotizing infection resulting from sepsis and subsequent angioinvasion by the gram-negative rod Pseudomonas aeruginosa. Pseudomonas invades the skin via hematogenous dissemination, not by percutaneous inoculation. Patients almost invariably show signs of sepsis.Cutaneous diphtheria can cause ulceronecrotic plaques, surmounted by an adherent grayish membrane. It is transmitted by direct cutaneous inoculation of Corynebacterium diphtheriae via contaminated objects into the skin, usually in tropical climates.7 It is not caused by diphtheria vaccination, which uses diphtheria toxoid (the toxin produced by C diphtheriae), not the organisms themselves.Early diagnosis and treatment of cutaneous mucormycosis is vitally important. These fungi often invade endothelial cells and dissiminate hematogenously, leading to poor outcomes.8 Mucormycosis is resistant to many commonly used antifungal medications. Liposomal amphotericin B is the first-line treatment for mucormycoses,2,8,9 at a recommended minimum daily dose of 5 mg/kg and in combination with surgical excision.9 Prompt excision is particularly important in cases of percutaneous inoculation. Posaconazole is considered second line therapy. Isavuconazole shows little in vitro activity against Mucorales but shows promise in the clinical setting.8 Voriconazole, which can treat aspergillosis, is not effective against mucormycoses and may enhance the virulence of Rhizopus oryzae.10A high index of suspicion is necessary for rapid diagnosis and intervention in fungal infections in immunocompromised patients. Suspicious skin lesions should be biopsied immediately for histopathological examination and tissue culture. A fungal wet-prep or prompt frozen processing of the biopsy specimen may expedite diagnosis. Proper antimicrobial therapy and debridement or excisional surgery should be initiated as soon as possible to increase the chances of survival.

Dermatology

A 4-year-old girl with newly diagnosed acute lymphocytic leukemia, receiving her initial course of chemotherapy with vincristine, daunorubicin, and methotrexate, developed a painful lesion on her left triceps. The tender area was beneath an adhesive bandage placed where she had received DTaP (diphtheria-tetanus-pertussis) and polio vaccinations 3 weeks earlier. Otherwise, she appeared remarkably well, and her vital signs were normal. Removing the bandage revealed a tender indurated gray-violet plaque (Figure, A). White blood cell and neutrophil counts were low at 0.4 K/μL (normal range, 4.86-13.18 K/μL) and 0.18 K/μL (normal range, 1.60-8.29 K/μL), respectively. Blood culture findings were negative. Punch biopsy specimens were obtained for histopathologic analysis (Figure, B) and fungal culture (Figure, C).A, Gray-violet plaque on posterior upper arm at site of adhesive portion of bandage. B, Broad nonseptate hyphae surrounding and infiltrating dermal blood vessels (hematoxylin-eosin; original magnification ×400). Of note, occasional septae are seen in this specimen, consistent with the characteristic finding that mucormycetes are pauciseptate, rather than aseptate, molds. C, Nonseptate hyphae with round terminal sporangia and free spores (lactophenol cotton blue mount; original magnification ×400).

what is your diagnosis?

What is your diagnosis?

Mucormycosis

Cutaneous diphtheria

Pseudomonal ecthyma gangrenosum

Aspergillosis

a

female

0-10

White

original

https://jamanetwork.com/journals/jamapediatrics/fullarticle/2633489

A 3-day-old premature male infant, born at 26 weeks’ gestational age, presented to the dermatology department with a skin rash on the bilateral lower extremities. History was notable for preterm premature rupture of membranes for 10 days. The neonate was born via urgent cesarean delivery owing to breech positioning. The mother was otherwise in good health with normal prenatal care and had no history of sexually transmitted diseases. During the first few days of life, the neonate had recurrent hypoxic episodes. He was receiving intravenous antibiotics for suspected sepsis and bacitracin for the topical lesions. Per the primary team, the rash was first noted at 3 days of life.Physical examination demonstrated a small, ill-appearing neonate with multiple, grouped vesicles and punched-out ulcerations on his scalp, axilla, extremities, and scrotum (Figure, A-D). He also had witnessed respiratory desaturations requiring urgent intubation. Initial laboratory evaluation demonstrated a normal complete blood cell count and serum chemistry with the exception of a high lymphocyte count (34%, normal level <25% [to convert to proportion of 1.0, multiply by 0.01]) and high aspartate aminotransferase level (117 IU/L, normal level 8-39 IU/L [to convert to microkatals per liter, multiply by 0.0167]). A chest radiograph demonstrated increased pulmonary markings bilaterally.Neonate with grouped vesicles on an erythematous base on the scalp and bilateral lower extremities. What Is Your Diagnosis?

Candidiasis

Transient neonatal pustular melanosis

Congenital varicella

Herpes simplex virus

D. Herpes simplex virus

D

Herpes simplex virus

A bedside Tzanck smear demonstrated numerous multinucleated giant cells. Intravenous acyclovir, dosing at 20 mg/kg every 8 hours, was promptly initiated. A skin biopsy from the extremity demonstrated necrotic ulceration, with dyskeratotic keratinocytes containing intranuclear herpes viral inclusions. Herpes simplex virus (HSV) group was isolated from a viral skin culture, and a blood serum polymerase chain reaction result was positive for HSV2 DNA. The lumbar puncture had a positive polymerase chain reaction for HSV2 DNA, high total protein count, and xanthochromia. The respiratory sputum additionally affirmed the presence of HSV. Ophthalmology consultation deemed no ocular involvement. Intravenous acyclovir was continued for 3 weeks before transitioning to a 6-month oral course of acyclovir 300 mg/m2, divided into 3 times daily, on discharge.This case highlights the presentation of neonatal disseminated HSV, with the infant exhibiting respiratory distress and characteristic skin vesicles. There are approximately 1500 cases of neonatal HSV annually in the United States.1,2 Three primary mechanisms for transmission include intrauterine (5%), peripartum (85%), and postnatal (10%).3,4 Most intrauterine infection is caused by HSV2, supporting the role of an ascending maternal infection.4 Viral exposure before 20 weeks can lead to spontaneous abortion or congenital anomalies involving the skin and central nervous system. Peripartum infection is the most common, owing to exposure to secretions in the birth canal.4 Risk factors for peripartum transmission include maternal antibody status, premature prolonged rupture of membranes, use of fetal scalp monitors, and vaginal delivery.1,5 However, most neonates are born to mothers without known risk factors.6 Postnatal infection may be acquired from family members or health care workers.Disseminated HSV is defined as visceral organ involvement in addition to or other than ocular or central nervous system disease.3,4 Delay in diagnosis of HSV, particularly central nervous system or disseminated disease, can have devastating consequences including long-term neurologic impairment or death. Unfortunately, characteristic lesions of HSV infection can be subtle, absent, or atypical in many cases.7-9 The initial site of skin involvement is frequently the area that first comes into contact with maternal lesions, such as the face for a cephalic presentation or the buttocks and extremities for breech presentation, as in this case. The cutaneous manifestations may lag behind visceral involvement.4 Notably, neonates may present with respiratory distress as the primary manifestation of disease, with nonspecific opacities on chest radiograph, as demonstrated in this patient.6,10 Although there are a myriad of causes of neonatal respiratory distress including bronchopulmonary dysplasia, disseminated HSV should be included on the differential list.For diagnosis, a Tzanck prep and cutaneous biopsy should be performed. The nature of the primary lesion determines the sensitivity of the Tzanck with vesicular lesions more likely to be positive (67%) than pustules (55%) or ulcers (17%).4 Viral cultures of the skin, conjunctiva, pharynx, and cerebrospinal fluid should be performed but should not delay treatment. Polymerase chain reaction of the serum or cerebrospinal fluid is considered the gold standard of diagnosis for disseminated disease. A low threshold should ensue for evaluating the pulmonary status with a chest radiograph.6,10 The most common associated laboratory abnormalities include transaminitis, an elevated C-reactive protein, and thrombocytopenia.6 Other pustular eruptions common in the neonatal period include erythema toxicum neonatorum and transient neonatal pustular melanosis, presenting characteristically in healthy neonates; infectious etiologies include candidiasis, scabies, and bullous syphilis, with potassium hydroxide, mineral oil prep, and laboratory evaluation helping to differentiate among the latter causes.Disseminated disease requires an extended 21 days of intravenous therapy.3,4 After intravenous dosing, suppressive oral acyclovir should be given for a total duration of 6 months.3,4 For mothers with a known history of herpes infection, suppressive therapy at 36 weeks of gestation is recommended. Overall, the morbidity associated with primary HSV in the neonate is substantial, ranging from 30% to 50%.2 Delay in treatment results in significant morbidity and mortality. Disseminated HSV is an important differential for neonates in respiratory distress with or without skin lesions. Prompt initiation of empirical acyclovir therapy can be lifesaving and can prevent neurologic and fatal consequences.

Pediatrics

A 3-day-old premature male infant, born at 26 weeks’ gestational age, presented to the dermatology department with a skin rash on the bilateral lower extremities. History was notable for preterm premature rupture of membranes for 10 days. The neonate was born via urgent cesarean delivery owing to breech positioning. The mother was otherwise in good health with normal prenatal care and had no history of sexually transmitted diseases. During the first few days of life, the neonate had recurrent hypoxic episodes. He was receiving intravenous antibiotics for suspected sepsis and bacitracin for the topical lesions. Per the primary team, the rash was first noted at 3 days of life.Physical examination demonstrated a small, ill-appearing neonate with multiple, grouped vesicles and punched-out ulcerations on his scalp, axilla, extremities, and scrotum (Figure, A-D). He also had witnessed respiratory desaturations requiring urgent intubation. Initial laboratory evaluation demonstrated a normal complete blood cell count and serum chemistry with the exception of a high lymphocyte count (34%, normal level <25% [to convert to proportion of 1.0, multiply by 0.01]) and high aspartate aminotransferase level (117 IU/L, normal level 8-39 IU/L [to convert to microkatals per liter, multiply by 0.0167]). A chest radiograph demonstrated increased pulmonary markings bilaterally.Neonate with grouped vesicles on an erythematous base on the scalp and bilateral lower extremities.

what is your diagnosis?

What is your diagnosis?

Herpes simplex virus

Transient neonatal pustular melanosis

Candidiasis

Congenital varicella

a

male

0-10

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2643439

A 28-year-old woman visited the emergency department for a sudden, diffuse, and painful enlargement of the upper quadrants of the left breast with edema and palpable axillary lymph nodes without clinical signs of inflammation or infection (Figure 1A). She had neither fever nor skin redness but was experiencing fatigue.Initial presentation of the patient. A, Asymmetric mass in the upper quadrant of the left breast. B, Breast ultrasonogram revealing hypoechogenicity of the breast tissue with periductal small cysts.The patient had stopped breastfeeding 10 months before the emergency department admission, and she had a recent history of pneumonia self-medicated with antibiotics. She had no family history of breast or ovarian cancer and no history of drug addiction or hyaluronic acid or free silicone injections in the breast. She denied any trauma to the breast.On physical examination, the patient had a 6-cm hard mass without nipple discharge or retraction and left axillary palpable lymph nodes. Breast ultrasonography revealed diffuse nonspecific hypoechogenicity of the breast tissue with periductal small cysts (Figure 1B). Mammography revealed asymmetric density and distortion in the left upper quadrants.Multiple 14-gauge ultrasound-guided biopsies in the upper quadrants of the left breast and fine-needle aspiration cytologic testing of an enlarged lymph node revealed granulomatous inflammation with epithelioid histiocytes, lymphocytes, plasma cells, and eosinophils. Lymph nodes were normal.Blood test results were as follows: hepatitis B surface antigen, hepatitis C antibody, human immunodeficiency virus enzyme-linked immunosorbent assay, and whole-blood interferon γ release assay (QuantiFERON), negative; IgG cytomegalovirus, positive; fibrinogen level, 234 mg/dL (to convert to micromoles per liter, multiply by 0.0294); erythrocyte sedimentation rate, 4 mm/h; leukocyte count, 7660/µL (to convert to ×109/L, multiply by 0.001); no acquired immunosuppression; and no hematologic disorders. What Is Your Diagnosis?

Inflammatory breast cancer

Tuberculous mastitis

Idiopathic granulomatous mastitis

Mastitis caused by immunosuppression

C. Idiopathic granulomatous mastitis

C

Idiopathic granulomatous mastitis

Idiopathic granulomatous mastitis (IGM) is a rare chronic inflammatory disease of the breast that can clinically and radiologically mimic breast carcinoma. It is a rare disease with an unknown origin.1 Various factors, such as microbiological agents, autoimmunity, smoking, hormonal imbalance, gestation, birth and breastfeeding, α1-antitrypsin deficiency, and foreign-body reaction, have been considered as possible causes of the disease. It usually presents as a unilateral, hard, painful breast mass associated with inflammation of the skin, without signs of systemic disease. Enlarged lymph nodes may also occur, as observed in this patient.2,3At mammography, IGM has nonspecific findings, as also seen in this patient. It usually appears as unilateral focal asymmetry, architectural distortion, or an irregular mass. Furthermore, because of the young age of most affected patients, high fibroglandular density usually can mask lesion detection.Ultrasonography often reveals a hypoechoic mass with irregular, indistinct, and angular margins, mimicking cancer or diffuse hypoecogenicity.2 In this patient, the diffuse hypoecogenicity of the breast tissue associated with microcysts close to the ducts resembled the pathologic findings of periductal mastitis with small periductal granuloma.At histologic analysis, nonnecrotizing granulomas around the lobules are associated with inflammatory infiltrates composed of multinucleated giant cells, plasma cells, epithelioid histiocytes, and lymphocytes (Figure 2).Histologic analysis. The lobules of the breast were surrounded and destroyed by granulomatous inflammation; the granulomas were composed of epithelioid histiocytes accompanied by lymphocytes, plasma cells, and eosinophils.The clinical differential diagnosis should be performed initially with breast cancer mastitis in young individuals and with infective mastitis or mastitis caused by immunosuppression. The incidence of breast cancer in young individuals is sporadic, and this patient had no family history of breast or ovarian cancer, but she could have had a rare pregnancy-associated breast cancer.Histologic analysis is mandatory in this type of patient. In this patient, histologic analysis of several biopsy specimens of the upper quadrant of the breast and in the axilla excluded cancer. Multidisciplinary evaluation considered the results of ultrasound-guided biopsy to be adequate and determined that excisional biopsy was not necessary for diagnosis. Surgical biopsy would have had a significant effect on the aesthetic outcome of the breast because of the scar.Furthermore, the patient recently had severe pneumonia, which she self-medicated with a generic antibiotic treatment. Tuberculous mastitis also should be taken into account. Blood tests are necessary for a correct diagnosis and to exclude mastitis caused by immunosuppression before starting immunosuppressive therapy. A negative whole-blood interferon γ release assay test result in this patient excluded tuberculosis, and a negative human immunodeficiency virus test result excluded other possible causes of immunosuppression.In the treatment of IGM, general antibiotics are often used without success. Conservative treatment (follow-up, corticosteroid therapy, or treatment with immunomodulators) has gained popularity in the past 20 years. Surgery is currently suggested only for nonresponders. This case was a self-limiting condition, and clinical improvement occurred without any therapy after 2 months. Complete resolution was observed after 5 months.

Surgery

A 28-year-old woman visited the emergency department for a sudden, diffuse, and painful enlargement of the upper quadrants of the left breast with edema and palpable axillary lymph nodes without clinical signs of inflammation or infection (Figure 1A). She had neither fever nor skin redness but was experiencing fatigue.Initial presentation of the patient. A, Asymmetric mass in the upper quadrant of the left breast. B, Breast ultrasonogram revealing hypoechogenicity of the breast tissue with periductal small cysts.The patient had stopped breastfeeding 10 months before the emergency department admission, and she had a recent history of pneumonia self-medicated with antibiotics. She had no family history of breast or ovarian cancer and no history of drug addiction or hyaluronic acid or free silicone injections in the breast. She denied any trauma to the breast.On physical examination, the patient had a 6-cm hard mass without nipple discharge or retraction and left axillary palpable lymph nodes. Breast ultrasonography revealed diffuse nonspecific hypoechogenicity of the breast tissue with periductal small cysts (Figure 1B). Mammography revealed asymmetric density and distortion in the left upper quadrants.Multiple 14-gauge ultrasound-guided biopsies in the upper quadrants of the left breast and fine-needle aspiration cytologic testing of an enlarged lymph node revealed granulomatous inflammation with epithelioid histiocytes, lymphocytes, plasma cells, and eosinophils. Lymph nodes were normal.Blood test results were as follows: hepatitis B surface antigen, hepatitis C antibody, human immunodeficiency virus enzyme-linked immunosorbent assay, and whole-blood interferon γ release assay (QuantiFERON), negative; IgG cytomegalovirus, positive; fibrinogen level, 234 mg/dL (to convert to micromoles per liter, multiply by 0.0294); erythrocyte sedimentation rate, 4 mm/h; leukocyte count, 7660/µL (to convert to ×109/L, multiply by 0.001); no acquired immunosuppression; and no hematologic disorders.

what is your diagnosis?

What is your diagnosis?

Tuberculous mastitis

Inflammatory breast cancer

Mastitis caused by immunosuppression

Idiopathic granulomatous mastitis

d

female

21-30

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2645754

A 69-year-old white man presented to the emergency department after a tractor-on-tree collision. Contrast-enhanced computed tomography demonstrated an incidental right infrarenal, retroperitoneal mass measuring 9.7 × 7.7 × 9.1 cm (Figure 1A), with dilated tortuous supply from a lumbar artery branch and retroperitoneal lymphadenopathy. He denied any history of systemic symptoms, pain, urinary symptoms, or abnormal bowel function but described 6 years of decreased appetite. Laboratory evaluation of plasma-free metanephrine levels showed a slight elevation in normetanephrine levels (1.21 nmol/L). Given the dramatic arterial enhancement and hypertrophied perivascular plexus, biopsy was not performed, and preoperative arterial embolization was deemed appropriate to minimize intraoperative blood loss.A, Contrast-enhanced computed tomography scan demonstrating an incidental right infrarenal, retroperitoneal mass measuring 9.7 × 7.7 × 9.1 cm, with dilated tortuous supply from a lumbar artery branch. B, Flush aortogram outlining supply to the mass from a hypertrophied lumbar artery (blue arrowhead) and from a branch of the internal iliac artery (red arrowhead).At preoperative embolization, initial aortography identified the predominant lumbar artery branch and also demonstrated supply from a branch of the internal iliac artery (Figure 1B). These branches were embolized and the mass was devascularized. Twenty-four hours following embolization, surgical exploration was performed through a periumbilical midline incision. With no evidence of distant metastasis (peritoneal or liver), the mass was resected with partial resection of the iliopsoas muscle to achieve negative margins in conjunction with aortocaval lymphadenectomy of the enlarged lymph nodes. The mass was running parallel to the right ureter, which was meticulously dissected, and the right kidney was successfully saved. There were no complications, and the postoperative course was uneventful. What Is Your Diagnosis?

Angiosarcoma

Leiomyosarcoma

Pheochromocytoma

Unicentric Castleman disease

D. Unicentric Castleman disease

D

Unicentric Castleman disease

Castleman disease (CD) is a rare, nonneoplastic lymphoproliferative disease.1 While CD may develop within any lymph node, it is most commonly found in the mediastinum.1 Retroperitoneal CD typically presents as a single, large, poorly circumscribed mass, while CD in other sites presents as an enlarged, well-defined node or group of nodes.2 Ninety percent of CD presents as unicentric, localized disease, and the remaining 10% is classified as multicentric.1 Unicentric CD is usually asymptomatic with a good prognosis and rare recurrence following resection.1 In contrast, multicentric CD is associated with systemic issues, such as B symptoms (ie, fever, night sweats, and weight loss), hepatosplenomegaly, and human immunodeficiency virus/human herpesvirus 8 infection. Multicentric CD requires intervention with steroids, chemotherapy, and radiotherapy.3Castleman disease is often not included in the differential of retroperitoneal masses. In this patient, angiosarcoma was suspected, given the hypervascularity. Both pheochromocytoma and paraganglioma, an extra-adrenal pheochromocytoma arising from the organ of Zuckerkandl, were considered. However, the patient was normotensive and without paraneoplastic symptoms.4 Liposarcoma and leiomyosarcoma were considered because of the size and location of the mass.In contrast to unicentric CD, retroperitoneal CD presents with its own morphologic and radiographic appearance. Retroperitoneal CD is more likely to present as a large, infiltrating mass, in contrast to the focal, well-defined lesions in the more common supradiaphragmatic CD.2 Under the microscope, unicentric CD in nonretroperitoneal sites demonstrates classic atretic follicles with onion-skin pattern of the mantle zones and hyalinized vasculature (Figure 2). These features are also seen in retroperitoneal CD but in the background of markedly increased interfollicular expansion between the atretic follicles in a stroma-rich presentation.5 This combination of unusual morphologic and radiographic appearance makes retroperitoneal CD difficult to recognize, particularly in subtotal biopsy specimens that may only sample the interfollicular component without the pathognomonic atretic follicles. The findings in this patient conform to the typical appearance of retroperitoneal CD, with complete excision of the specimen avoiding any possibility of misdiagnosis owing to incomplete sampling.Photomicrograph of an atretic lymphoid follicle with concentric hyalinization of the mantle zone and hyalinized vasculature (hematoxylin-eosin, original magnification ×40).This patient underwent computed tomography 5 and 18 months postoperatively and has no evidence of recurrence. This case highlights the importance of considering unicentric CD in the differential of a large, hypervascular retroperitoneal mass.

Surgery

A 69-year-old white man presented to the emergency department after a tractor-on-tree collision. Contrast-enhanced computed tomography demonstrated an incidental right infrarenal, retroperitoneal mass measuring 9.7 × 7.7 × 9.1 cm (Figure 1A), with dilated tortuous supply from a lumbar artery branch and retroperitoneal lymphadenopathy. He denied any history of systemic symptoms, pain, urinary symptoms, or abnormal bowel function but described 6 years of decreased appetite. Laboratory evaluation of plasma-free metanephrine levels showed a slight elevation in normetanephrine levels (1.21 nmol/L). Given the dramatic arterial enhancement and hypertrophied perivascular plexus, biopsy was not performed, and preoperative arterial embolization was deemed appropriate to minimize intraoperative blood loss.A, Contrast-enhanced computed tomography scan demonstrating an incidental right infrarenal, retroperitoneal mass measuring 9.7 × 7.7 × 9.1 cm, with dilated tortuous supply from a lumbar artery branch. B, Flush aortogram outlining supply to the mass from a hypertrophied lumbar artery (blue arrowhead) and from a branch of the internal iliac artery (red arrowhead).At preoperative embolization, initial aortography identified the predominant lumbar artery branch and also demonstrated supply from a branch of the internal iliac artery (Figure 1B). These branches were embolized and the mass was devascularized. Twenty-four hours following embolization, surgical exploration was performed through a periumbilical midline incision. With no evidence of distant metastasis (peritoneal or liver), the mass was resected with partial resection of the iliopsoas muscle to achieve negative margins in conjunction with aortocaval lymphadenectomy of the enlarged lymph nodes. The mass was running parallel to the right ureter, which was meticulously dissected, and the right kidney was successfully saved. There were no complications, and the postoperative course was uneventful.

what is your diagnosis?

What is your diagnosis?

Leiomyosarcoma

Angiosarcoma

Pheochromocytoma

Unicentric Castleman disease

d

male

61-70

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2630813

A man in his late 20s with a history of Alport syndrome presented on referral for a bilateral retina problem after experiencing right-sided herpes zoster ophthalmicus. He denied risk factors for human immunodeficiency virus, and serologic testing results were negative. He had completed treatment for keratouveitis and reported some residual blurring of his vision in the right eye. His ocular history was unremarkable. His uncorrected visual acuity was 20/60 OD and 20/40 OS. Pupillary responses, confrontation visual fields, motility, external examination, and intraocular pressure were normal. Slitlamp examination revealed superficial keratitis and anterior stromal haze in the right eye but otherwise was normal. Fundus examination (Figure, A) revealed a poor foveal light reflex with an irregular-shaped area of red discoloration in the fovea and surrounding subtle flecking of the retina in both eyes. No other abnormalities were found on ophthalmoscopic examination. Spectral-domain optical coherence tomography (Figure, B) showed an irregular foveal contour with trace epiretinal membrane formation, with no evidence of foveoschisis or outer retinal changes. Fundus autofluorescence was normal.A, Color fundus photograph demonstrating pseudohole formation with pigment mottling, right eye. B, Spectral-domain optical coherence tomography revealing distortion of foveal contour without epiretinal membrane formation, right eye. Similar examination and optical coherence tomographic findings were present in the left eye.Perform pars plana vitrectomy with internal limiting membrane peelingPerform aqueous/vitreous tap for viral polymerase chain reaction and inject foscarnet intravitreallyObserve and repeat spectral-domain optical coherence tomography in 6 months to 1 year What Would You Do Next?

Perform pars plana vitrectomy with internal limiting membrane peeling

Perform aqueous/vitreous tap for viral polymerase chain reaction and inject foscarnet intravitreally

Observe and repeat spectral-domain optical coherence tomography in 6 months to 1 year

Perform intravitreal injection of ocriplasmin

Lamellar macular hole, both eyes

C

Observe and repeat spectral-domain optical coherence tomography in 6 months to 1 year

Alport syndrome can be associated with multiple ocular findings including macular pathologies such as lamellar or full-thickness macular holes.1 In this case, a macular pseudohole is seen clinically, and optical coherence tomographic examination reveals a lamellar macular hole with intact outer retina. Vitrectomy with membrane peeling should be offered for symptoms of distortion owing to epiretinal membrane formation or substantial retinal changes such as cystoid abnormalities, disruption of the ellipsoid zone, and full-thickness macular hole formation. Ocriplasmin has been shown to be most successful in selected cases of vitreomacular adhesion and may induce closure of small full-thickness macular holes, neither of which are seen in this case. The clinical examination does not suggest worsening herpetic retinitis after completion of treatment for keratouveitis, so intravitreal antivirals are not indicated. Therefore, observation with serial examination and optical coherence tomography are warranted for this case.Alport syndrome is a genetic disorder of type IV collagen, with consequent systemic abnormalities in basement membrane production manifesting as glomerulonephritis, hearing loss, and ocular changes. Most commonly, Alport syndrome is inherited in an X-linked fashion (85%), followed by autosomal recessive fashion (10%-15%), and rarely by autosomal dominant fashion.1 Described ocular abnormalities include posterior polymorphous corneal dystrophy, corneal clouding owing to accumulation of mucopolysaccharides, conjunctival telangiectasia, anterior lenticonus, cataract, and retinal flecks as well as macular holes.1 These findings are often absent in childhood and become more apparent with aging.2 While dot and fleck retinopathy is the most common ocular sign of Alport syndrome (85%),3 a range of macular pathology from lamellar macular holes to giant macular holes have been reported as well as vitelliform lesions and foveal and midperipheral retinoschisis.4-6It is suspected that these macular pathologies may be secondary to abnormalities in type IV collagen, causing weakness of the internal limiting membrane. Others postulate that abnormal type IV collagen in the Bruch membrane may allow collection of intraretinal fluid within the retina prior to hole formation7 or that an anomalous vitreoretinal interface may also contribute to vitreomacular interface abnormalities.1Although the development of these macular abnormalities is not well understood, a few observational case reports have shown that lamellar macular holes can transform into full-thickness macular holes.4,6 Interestingly, Shah et al4 documented the coalescence of multiple small macular holes into a single large macular hole. Progressive vision loss is a distinct possibility in patients with Alport syndrome with early macular changes such that monitoring with fundus examination as well as optical coherence tomography might be appropriate in some cases where disruption of the outer retina or full-thickness macular hole formation may improve with internal limiting membrane peeling.The patient was informed of the association of Alport syndrome and lamellar macular hole and asked to return with any new symptoms of metamorphopsia or reduced vision. He was followed up, and repeated refraction was performed after the corneal haze improved with best-corrected visual acuity of 20/30 OU.

Ophthalmology

A man in his late 20s with a history of Alport syndrome presented on referral for a bilateral retina problem after experiencing right-sided herpes zoster ophthalmicus. He denied risk factors for human immunodeficiency virus, and serologic testing results were negative. He had completed treatment for keratouveitis and reported some residual blurring of his vision in the right eye. His ocular history was unremarkable. His uncorrected visual acuity was 20/60 OD and 20/40 OS. Pupillary responses, confrontation visual fields, motility, external examination, and intraocular pressure were normal. Slitlamp examination revealed superficial keratitis and anterior stromal haze in the right eye but otherwise was normal. Fundus examination (Figure, A) revealed a poor foveal light reflex with an irregular-shaped area of red discoloration in the fovea and surrounding subtle flecking of the retina in both eyes. No other abnormalities were found on ophthalmoscopic examination. Spectral-domain optical coherence tomography (Figure, B) showed an irregular foveal contour with trace epiretinal membrane formation, with no evidence of foveoschisis or outer retinal changes. Fundus autofluorescence was normal.A, Color fundus photograph demonstrating pseudohole formation with pigment mottling, right eye. B, Spectral-domain optical coherence tomography revealing distortion of foveal contour without epiretinal membrane formation, right eye. Similar examination and optical coherence tomographic findings were present in the left eye.Perform pars plana vitrectomy with internal limiting membrane peelingPerform aqueous/vitreous tap for viral polymerase chain reaction and inject foscarnet intravitreallyObserve and repeat spectral-domain optical coherence tomography in 6 months to 1 year

what would you do next?

What would you do next?

Perform aqueous/vitreous tap for viral polymerase chain reaction and inject foscarnet intravitreally

Perform pars plana vitrectomy with internal limiting membrane peeling

Observe and repeat spectral-domain optical coherence tomography in 6 months to 1 year

Perform intravitreal injection of ocriplasmin

c

male

21-30

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2632247

A 66-year-old white woman presented with a 2-month history of a “cloudy spot” in her left eye. She denied eye pain, transient vision loss, photophobia, or photopsias but reported right-sided jaw pain migrating to include both temples, ears, neck, and left shoulder. The jaw became more painful and fatigued with chewing, associated with an 3.6-kg weight loss over 3 months. A mouth guard prescribed by her dentist for temporomandibular joint disease had provided substantial relief over the past 2 months. She denied any history of hypertension, hyperlipidemia, type 2 diabetes, or human immunodeficiency virus exposure but had a 20 pack/year cigarette smoking history.Uncorrected visual acuity was 20/25 OU. Automated perimetry revealed a small paracentral relative scotoma in the left eye. Superficial temporal artery pulses were palpable without tenderness, and anterior segment examination was unremarkable in both eyes. Fundus examination revealed healthy-appearing optic discs in both eyes and an arc-shaped area of retinal whitening in the nasal macula concentric to the optic disc in the left eye (Figure 1, A). No intra-arterial plaques were noted. Optical coherence tomography through the lesion showed localized hyperreflectivity and thickening of the retinal nerve fiber and ganglion cell layers (Figure 1, B). Fluorescein angiography revealed normal choroidal and retinal arterial perfusion. Erythrocyte sedimentation rate was 2 mm/h, C-reactive peptide level was 0.49 mg/dL (to convert to nanomoles per liter, multiply by 9.524), and platelet count was 270 ×103/µL (to convert to ×109/L, multiply by 1).A, Fundus photograph shows a normal left optic disc with an adjacent arc-shaped patch of retinal whitening and no other macular pathology. B, Optical coherence tomography through the retinal lesion reveals abnormal thickening and hyperreflectivity of the retinal nerve fiber and ganglion cell layers (arrowhead), producing shadowing over an otherwise normal outer retina.Perform diagnostic vitreous paracentesis and intravitreal antibiotic injectionStart systemic corticosteroids and biopsy the superficial temporal artery What Would You Do Next?

Observe and recommend smoking cessation

Obtain a hypercoagulable laboratory workup

Perform diagnostic vitreous paracentesis and intravitreal antibiotic injection

Start systemic corticosteroids and biopsy the superficial temporal artery

Isolated nerve fiber layer infarct secondary to giant cell arteritis

D

Start systemic corticosteroids and biopsy the superficial temporal artery

While smoking may accelerate progression of age-related macular degeneration or hypertensive retinopathy, smoking alone does not cause visible retinopathy. Hypercoagulable workup may be helpful in atypical cases of retinal vein occlusion but would likely not be useful in evaluating an isolated nerve fiber layer (NFL) infarct. The retinal whitening in this case localized to the innermost retinal layers, making endogenous endophthalmitis unlikely. Although serum inflammatory markers were normal, the combination of retinal ischemia, patient age, and jaw claudication raised sufficient suspicion for giant cell arteritis (GCA) to justify prompt initiation of oral corticosteroids to reduce the risk of additional ischemic events until definitive diagnosis via temporal artery biopsy. Histopathologic analysis of the left superficial temporal artery demonstrated internal elastic lamina disruption and granulomatous mural inflammation with giant cells, diagnostic of GCA (Figure 2).The artery exhibits marked luminal stenosis (90%). There is neovascularization of the tunica media and intima, areas of medial disruption, and inflammatory cells throughout the arterial wall. The inset shows a multinucleated giant cell adjacent to and engulfing internal elastic lamina (hematoxylin-eosin).Nerve fiber layer infarcts (“cotton-wool spots”) result when occlusion of small retinal arterioles produces focal inner retinal ischemia. The white, fluffy appearance of NFL infarcts reflects axoplasmic stasis, ie, accumulation of cellular debris in retinal ganglion cell axons.1 Whereas some NFL infarcts may be asymptomatic, others can produce focal absolute scotomas from loss of underlying retinal ganglion cells or relative arcuate scotomas from axonal damage to retinal ganglion cell nerve fiber bundles coursing through ischemic or infarcted areas.2While frequently seen in diabetic or hypertensive retinopathy, NFL infarcts may occur with other retinovascular diseases including retinal vein occlusion, radiation retinopathy, and human immunodeficiency virus retinopathy.3 Isolated NFL infarcts without associated microvasculopathy may be a manifestation of thromboembolic disease, GCA, collagen vascular disease, or hematologic malignancies.3 Although isolated NFL infarcts are an uncommon presentation of GCA,4,5 they may herald severe irreversible vision loss from ischemic optic neuropathy, central retinal artery occlusion, cilioretinal artery occlusion, or choroidal infarction. It is therefore essential to query GCA symptoms such as temporal headache, jaw claudication, scalp tenderness, fever, weight loss, and proximal muscle weakness suggestive of polymyalgia rheumatica. Laboratory evaluation of erythrocyte sedimentation rate, C-reactive peptide, and platelet count should be performed in patients older than 50 years. Although very rare (<1% of cases), it is possible for both erythrocyte sedimentation rate and C-reactive peptide to be normal in patients with GCA.6This patient posed a particular diagnostic challenge owing to the rare combination of normal serum biomarkers, and a solitary NFL infarct as the only ophthalmic manifestation of GCA. This case nicely illustrates potential benefits of a thorough review of systems and recognizing NFL infarcts as a possible marker of systemic disease.The patient was prescribed oral prednisone (initially 1 mg/kg daily) and cotreated with rheumatology. She reported substantial improvement in the paracentral scotoma, without further episodes of ocular ischemia.

Ophthalmology

A 66-year-old white woman presented with a 2-month history of a “cloudy spot” in her left eye. She denied eye pain, transient vision loss, photophobia, or photopsias but reported right-sided jaw pain migrating to include both temples, ears, neck, and left shoulder. The jaw became more painful and fatigued with chewing, associated with an 3.6-kg weight loss over 3 months. A mouth guard prescribed by her dentist for temporomandibular joint disease had provided substantial relief over the past 2 months. She denied any history of hypertension, hyperlipidemia, type 2 diabetes, or human immunodeficiency virus exposure but had a 20 pack/year cigarette smoking history.Uncorrected visual acuity was 20/25 OU. Automated perimetry revealed a small paracentral relative scotoma in the left eye. Superficial temporal artery pulses were palpable without tenderness, and anterior segment examination was unremarkable in both eyes. Fundus examination revealed healthy-appearing optic discs in both eyes and an arc-shaped area of retinal whitening in the nasal macula concentric to the optic disc in the left eye (Figure 1, A). No intra-arterial plaques were noted. Optical coherence tomography through the lesion showed localized hyperreflectivity and thickening of the retinal nerve fiber and ganglion cell layers (Figure 1, B). Fluorescein angiography revealed normal choroidal and retinal arterial perfusion. Erythrocyte sedimentation rate was 2 mm/h, C-reactive peptide level was 0.49 mg/dL (to convert to nanomoles per liter, multiply by 9.524), and platelet count was 270 ×103/µL (to convert to ×109/L, multiply by 1).A, Fundus photograph shows a normal left optic disc with an adjacent arc-shaped patch of retinal whitening and no other macular pathology. B, Optical coherence tomography through the retinal lesion reveals abnormal thickening and hyperreflectivity of the retinal nerve fiber and ganglion cell layers (arrowhead), producing shadowing over an otherwise normal outer retina.Perform diagnostic vitreous paracentesis and intravitreal antibiotic injectionStart systemic corticosteroids and biopsy the superficial temporal artery

what would you do next?

What would you do next?

Start systemic corticosteroids and biopsy the superficial temporal artery

Perform diagnostic vitreous paracentesis and intravitreal antibiotic injection

Obtain a hypercoagulable laboratory workup

Observe and recommend smoking cessation

a

female

61-70

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2633462

A woman in her 40s was referred to her local university for ophthalmic examination. She had been receiving care for dry eye syndrome, hyperopia, and presbyopia by another eye care clinician, and on routine examination a circumscribed elevation of her right iris was found. She noted intermittent shooting pain responsive to artificial tears in this eye; otherwise, she was without ophthalmic symptoms. She did not have any significant medical or family history, and review of symptoms was unremarkable.On examination, corrected distance Snellen acuity was 20/20 OU. Intraocular pressures were 12 mm Hg OD and 10 mm Hg OS. Slitlamp examination revealed a circumscribed elevation of the right iris inferotemporally (Figure, A). Her iris was uniformly pigmented, and gonioscopy revealed an iridocorneal angle open to scleral spur with a circumscribed area of iris insertion anterior to the Schwalbe line inferotemporally, not deepening on compression. Her lens was clear, and no iridociliary lesions were appreciated after pupillary dilation. The optic nerve and fundus appeared normal. The left eye appeared healthy with a uniformly deep anterior chamber.A, Low-powered slitlamp examination of the right eye showing irregularity of the posterior light reflection inferotemporally, indicating iris elevation. B, High-frequency ultrasound biomicroscopy of the inferotemporal quadrant of the right eye showing a circumscribed ciliary lesion with overlying closure of the iridocorneal angle.Ultrasound biomicroscopy of the right eye was performed, showing an inferotemporal lesion (Figure, B), with few similar-appearing lesions located in other quadrants.Attempt lesion rupture with neodymium-doped yttrium aluminum garnet laser What Would You Do Next?

Observe and repeat imaging in 6 months

Lesion biopsy

Systemic workup for occult malignancy

Attempt lesion rupture with neodymium-doped yttrium aluminum garnet laser

Ciliary body cysts

A

Observe and repeat imaging in 6 months

Contemporary imaging modalities for anterior segment tumors include optical coherence tomography and high-frequency ultrasound biomicroscopy. When considering lesions posterior to the iris pigmented epithelium, ultrasound biomicroscopy has been shown to be superior with regards to lesion visualization and resolution.1Ultrasound biomicroscopy in this patient showed a round lesion with a thin hyperechoic wall and a hypoechoic interior, suggestive of an epithelial-lined ciliary body cyst. Smaller, similar lesions were also found in this eye, supporting this diagnosis.Primary ciliary body cysts were recognized in histopathologic studies during the early 20th century. Although their etiology is unknown, embryonic developmental abnormalities and zonular tension with separation of ciliary epithelial layers has been suggested to be causatory.2 Secondary cysts have also been reported with inflammation, topical parasympathomimetics, parasitic infection, metastasis, and penetrating trauma, with ingrowth of surface epithelium.3 Ciliary body cysts may be appreciated after pupillary dilation and typically appear translucent with transillumination or reddish-brown owing to underlying uveal tissue. If in contact with the lens, they may cause a sectoral cataract. They may also cause anterior projection of the iris root and a pseudoplateau iris configuration, with or without iridocorneal angle closure.In a study by Marigo et al,3 primary iris and ciliary body cysts constituted most anterior segment lesions sent to a tertiary referral center for diagnostic evaluation. Their most common location included the iridociliary junction (74.2%) followed by the pars plicata (14.0%), pars plana (6.8%), and iris (5.0%). Three or fewer cysts were found in 62.2% of eyes, while 13.3% of patients had cysts affecting more than 180° of the ciliary body.3Although ciliary body cysts occur more commonly than other lesions such as medulloepithelioma, melanoctyoma, adenoma of the pigment epithelium, or melanoma, they must be differentiated for prognostic purposes. According to a report by Lois et al,4 a very thin wall with hypoechoic center is a distinguishing echographic feature of cysts. Rarely, ciliary body melanomas can mimic cysts if cavitation occurs with imbalance of blood supply and tumor growth, leading to necrosis and tissue reabsorption; these lesions typically have thick walls with medium reflectivity, septation (bands of solid tissue within the cavity), and hyperechoic inner contents corresponding to exudate, cellular debris, and pigment-lade macrophages. Medulloepitheliomas can also contain cystoid spaces but typically occur in children and are associated with a lens notch, retrolental membrane, or areas of intralesional cartilage. Finally, melanocytomas and adenomas of the ciliary pigment epithelium may resemble cavitated melanomas ultrasonographically.4Ciliary body cysts may often be monitored unless there is significant closure of the iridocorneal angle and rise in intraocular pressure, irritation of ciliary nerves, opacification of the lens, or other ocular compromise. In these instances, treatment options include neodymium-doped yttrium aluminum garnet laser cystotomy or argon laser peripheral iridoplasty for pseudoplateau iris configuration. Cystotomy requires adequate visualization of the cyst and may lead to pigment dispersion and inflammation; the cyst may still recur.5Based on ultrasound biomicroscopy, a diagnosis of ciliary body cysts was made and no further diagnostic evaluation was made. There was not significant compromise of her iridocorneal angle, and the lesions were therefore monitored. She returned to the clinic 6 months later, and intraocular pressure was 16 mm Hg OD and 15 mm Hg OS. Gonioscopy of the right eye revealed stable angle anatomy, and the optic nerve appeared healthy. Ultrasound biomicroscopy showed stable cyst sizes. The bilateral change in intraocular pressure was thought to be owing to diurnal variation, and the patient was asked to return to clinic in 1 year for subsequent examination.

Ophthalmology

A woman in her 40s was referred to her local university for ophthalmic examination. She had been receiving care for dry eye syndrome, hyperopia, and presbyopia by another eye care clinician, and on routine examination a circumscribed elevation of her right iris was found. She noted intermittent shooting pain responsive to artificial tears in this eye; otherwise, she was without ophthalmic symptoms. She did not have any significant medical or family history, and review of symptoms was unremarkable.On examination, corrected distance Snellen acuity was 20/20 OU. Intraocular pressures were 12 mm Hg OD and 10 mm Hg OS. Slitlamp examination revealed a circumscribed elevation of the right iris inferotemporally (Figure, A). Her iris was uniformly pigmented, and gonioscopy revealed an iridocorneal angle open to scleral spur with a circumscribed area of iris insertion anterior to the Schwalbe line inferotemporally, not deepening on compression. Her lens was clear, and no iridociliary lesions were appreciated after pupillary dilation. The optic nerve and fundus appeared normal. The left eye appeared healthy with a uniformly deep anterior chamber.A, Low-powered slitlamp examination of the right eye showing irregularity of the posterior light reflection inferotemporally, indicating iris elevation. B, High-frequency ultrasound biomicroscopy of the inferotemporal quadrant of the right eye showing a circumscribed ciliary lesion with overlying closure of the iridocorneal angle.Ultrasound biomicroscopy of the right eye was performed, showing an inferotemporal lesion (Figure, B), with few similar-appearing lesions located in other quadrants.Attempt lesion rupture with neodymium-doped yttrium aluminum garnet laser

what would you do next?

What would you do next?

Lesion biopsy

Observe and repeat imaging in 6 months

Attempt lesion rupture with neodymium-doped yttrium aluminum garnet laser

Systemic workup for occult malignancy

b

female

41-50

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2635058

A 39-year-old man with a history of Osler-Weber-Rendu syndrome presented with double vision after scuba diving. When he descended to 35 ft during his dive, the patient experienced blurred vision in the right eye and sharp pain in the right temporal area. At 50 ft of depth, vision in the right eye went completely black. He ascended back to the surface at an appropriate speed and his vision recovered, but he was left with a mild residual blur. This was associated with a pain and pressure sensation in the right eye lasting 30 minutes and noticeable bruising on the right upper eyelid. After this episode, he noticed constant, binocular, diagonal diplopia in all gazes that was worse in upgaze.He was seen in our ophthalmology clinic the next day. His visual blur had resolved, but double vision persisted. On examination, visual acuity was 20/20 OU. There was no relative afferent pupillary defect. Color vision tested with Ishihara pseudoisochromatic plates was normal. Confrontation visual fields were full in both eyes. He had restricted supraduction and proptosis of 2.5 mm in the right eye. Intraocular pressure was 10 mm Hg OU. There was ecchymosis of the right upper eyelid. Results of dilated eye examination were unremarkable. 24-2 Humphrey visual fields were normal in both eyes. Magnetic resonance angiography of the head showed no vascular abnormalities. Magnetic resonance imaging of the orbits showed a fusiform heterogeneous peripherally enhancing extraconal mass within the superior orbit on the right, resulting in proptosis with downward displacement of the right globe (Figure).T1-weighted magnetic resonance imaging of orbit with contrast shows a fusiform heterogeneous peripherally enhancing extraconal mass within the superior orbit on the right (arrowhead), resulting in proptosis with downward displacement of the right globe. What Would You Do Next?

Observe

Perform canthotomy and cantholysis

Perform fine-needle aspiration

Perform a surgical drainage of the collection

Subperiosteal hemorrhage of the superior right orbit

A

Observe

The magnetic resonance imaging and clinical findings are consistent with a subperiosteal hemorrhage that occurred while scuba diving. Failure to equalize pressure in the face mask during a dive can lead to barotrauma and rupture of the small vessels in the subperiosteal space.1 Barotrauma from failure to equalize face mask pressure can be exacerbated by Valsalva maneuvers. Nontraumatic subperiosteal hemorrhage can present with acute pain, a decrease in vision, double vision, eyelid swelling, and ecchymosis. Signs include proptosis, globe displacement, reduced acuity, limitation of motility, resistance to retropulsion, and signs of optic nerve compromise.Trauma is the most common cause of subperiosteal hemorrhage.2 Other causes of nontraumatic subperiosteal hemorrhage include vomiting, straining during child birth, bleeding disorders, paranasal sinus infections or mucocele, general anesthesia, sickle cell crises, and vitamin C deficiency.The clinical presentation and imaging of the orbits can be key to the diagnosis of subperiosteal hemorrhage. On computed tomography, the hematoma appears as a fusiform mass, most often in the superior orbit displacing the adjacent tissues inferiorly. Magnetic resonance imaging can confirm the presence of blood and shows more detail of the surrounding soft tissue. It is important to exclude any underlying vascular abnormalities with angiography, especially in this patient because of his underlying history of Osler-Weber-Rendu syndrome.3 While it is possible the magnetic resonance angiography missed some small telangiectatic vessels that may have contributed to the subperiosteal hemorrhage, barotrauma-induced hemorrhage from diving has been previously reported in normal individuals.3When optic nerve function is not compromised, as in this patient, a conservative approach is recommended, as the blood will resolve spontaneously with time.4,5 In patients with intraorbital hemorrhage occurring with vascular malformations, a conservative approach is also favored unless vision is significantly compromised. If there are signs of orbital compartment syndrome, canthotomy and cantholysis might be necessary. In patients with vision loss and optic nerve compromise, urgent drainage of the hematoma is preferred, although improvement after delayed evacuation has been reported.6,7 Needle aspiration has also been suggested as an alternative surgical method in cases of optic nerve compromise.2Because the patient did not demonstrate optic nerve compromise, he was managed nonoperatively. He had complete resolution of symptoms after 2 weeks.

Ophthalmology

A 39-year-old man with a history of Osler-Weber-Rendu syndrome presented with double vision after scuba diving. When he descended to 35 ft during his dive, the patient experienced blurred vision in the right eye and sharp pain in the right temporal area. At 50 ft of depth, vision in the right eye went completely black. He ascended back to the surface at an appropriate speed and his vision recovered, but he was left with a mild residual blur. This was associated with a pain and pressure sensation in the right eye lasting 30 minutes and noticeable bruising on the right upper eyelid. After this episode, he noticed constant, binocular, diagonal diplopia in all gazes that was worse in upgaze.He was seen in our ophthalmology clinic the next day. His visual blur had resolved, but double vision persisted. On examination, visual acuity was 20/20 OU. There was no relative afferent pupillary defect. Color vision tested with Ishihara pseudoisochromatic plates was normal. Confrontation visual fields were full in both eyes. He had restricted supraduction and proptosis of 2.5 mm in the right eye. Intraocular pressure was 10 mm Hg OU. There was ecchymosis of the right upper eyelid. Results of dilated eye examination were unremarkable. 24-2 Humphrey visual fields were normal in both eyes. Magnetic resonance angiography of the head showed no vascular abnormalities. Magnetic resonance imaging of the orbits showed a fusiform heterogeneous peripherally enhancing extraconal mass within the superior orbit on the right, resulting in proptosis with downward displacement of the right globe (Figure).T1-weighted magnetic resonance imaging of orbit with contrast shows a fusiform heterogeneous peripherally enhancing extraconal mass within the superior orbit on the right (arrowhead), resulting in proptosis with downward displacement of the right globe.

what would you do next?

What would you do next?

Perform canthotomy and cantholysis

Observe

Perform a surgical drainage of the collection

Perform fine-needle aspiration

b

male

31-40

Black

original

https://jamanetwork.com/journals/jamacardiology/fullarticle/2643987

A 35-year-old woman with a history of hypertension and chronic lymphocytic leukemia who underwent allogenic bone marrow transplant approximately 9 months prior presented to the emergency department with concern of shortness of breath and productive cough for a week. Her bone marrow transplant had been complicated with severe graft-versus-host disease (GVHD) of skin and liver, diagnosed by biopsies 1 month after her transplant. In the emergency department, chest radiography showed multifocal airspace consolidations involving both lungs. Because of respiratory distress, she was admitted to the intensive care unit. She was subsequently diagnosed as having methicillin-resistant Staphylococcus aureus pneumonia. Respiratory failure developed, and the patient was intubated and treated with vasopressors. After 3 days in the intensive care unit, vasopressors were weaned off, and she was extubated. On hospital day 5, she was noted to have generalized erythematous skin with mild elevated liver enzyme, suggesting acute flare of chronic GVHD. Skin biopsy confirmed the diagnosis. Her hospital course was complicated with diffuse alveolar hemorrhage, possibly from pulmonary GVHD. Steroid and immunosuppressive medication doses were increased, and pulse methylprednisolone was started. At 48 hours after her skin lesions flared up, a change in her rhythm was noted on telemetry: her baseline sinus rhythm with heart rate of 90 beats per minute (bpm) was changed to bradycardia. A 12-lead electrocardiogram (ECG) is shown in the Figure. Her baseline ECG obtained a day earlier showed normal sinus rhythm with first-degree atrioventricular (AV) block (PR interval of 240 milliseconds). The patient denied symptoms associated with bradycardia. What Would You Do Next?

Place a dual chamber pacemaker

Observe and continue treatment for GVHD

Place an emergent transvenous temporary pacemaker

Place an emergent transcutaneous pacemaker

Complete heart block in association with an exacerbation of GVHD

B

Observe and continue treatment for GVHD

The ECG in the Figure demonstrates sinus tachycardia with the heart rate of 106 bpm with complete AV block and junctional escape with a heart rate of 45 bpm. Generalized low voltage was also noted. The patient was asymptomatic. Therefore, the emergent pacemaker was not indicated.Well-known manifestations of GVHD include dermatologic, gastrointestinal, hepatic, pulmonary, musculoskeletal, and hematologic manifestations and sicca syndrome.1-3 Cardiac manifestations have rarely been reported to be a target of GVHD and can present as bradycardia, coronary artery disease, sudden cardiac death, or cardiomyolysis.1-3 Bradyarrhythmia has been reported to occur with acute GVHD or with an acute flare of chronic GVHD in the form of sinus node dysfunction or AV block.1,3,4 These findings appear to be secondary to immunologic reaction or cytokines released during GVHD.1,5 In previous case reports, most patients had resolution of bradycardia within 2 to 16 days.1,2 One patient with complete heart block required a permanent pacemaker implantation.4Given the complicated and multifactorial problems after bone marrow transplant in adult patients, possible coexisting common cardiac disorders, such as coronary artery disease, sick sinus syndrome, and degeneration of AV conduction system, should be excluded. To exclude coronary artery diseases, serial ECG and troponin were obtained in this case. There were no ST-T changes, and test results for cardiac enzymes were negative. Echocardiography was performed and showed left ventricular ejection fraction of 60% and no segmental wall abnormalities. The patient denied history of bradycardia or syncopal episodes.Another important differential diagnosis of bradyarrhythmia in patients with GVHD is drug toxicity. The rapid infusion of high-dose pulse steroids (reported for 500-2000 mg intravenously over 20 seconds to 20 minutes) is noted to be associated with bradyarrhythmias, with incidence rates of 1% to 82%.6 Arrhythmias from high-dose steroids are reported in the form of atrial fibrillation/flutter, ventricular tachycardia, idioventricular rhythm, sinus bradycardia, and complete AV block.7 Other symptoms associated with bradyarrhythmias include flushing, sweating, and loss of consciousness. The patient received methylprednisolone, which was started 1 day before complete heart block was noted and remained asymptomatic through the course.The patient continued to receive treatment for GVHD including increased doses of tacrolimus, mycophenolate mofetil, and steroid. Her skin rash improved, and her liver function test results normalized. She remained in complete heart block for 5 days before her rhythm converted back to sinus tachycardia (heart rate, 101 bpm) with first-degree AV block. A temporary pacing wire was not placed because she remained asymptomatic and hemodynamically stable. The increased dose of steroid was not likely to be the cause of her bradycardia because the bradycardia resolved despite continuing the same steroid dose.

Cardiology

A 35-year-old woman with a history of hypertension and chronic lymphocytic leukemia who underwent allogenic bone marrow transplant approximately 9 months prior presented to the emergency department with concern of shortness of breath and productive cough for a week. Her bone marrow transplant had been complicated with severe graft-versus-host disease (GVHD) of skin and liver, diagnosed by biopsies 1 month after her transplant. In the emergency department, chest radiography showed multifocal airspace consolidations involving both lungs. Because of respiratory distress, she was admitted to the intensive care unit. She was subsequently diagnosed as having methicillin-resistant Staphylococcus aureus pneumonia. Respiratory failure developed, and the patient was intubated and treated with vasopressors. After 3 days in the intensive care unit, vasopressors were weaned off, and she was extubated. On hospital day 5, she was noted to have generalized erythematous skin with mild elevated liver enzyme, suggesting acute flare of chronic GVHD. Skin biopsy confirmed the diagnosis. Her hospital course was complicated with diffuse alveolar hemorrhage, possibly from pulmonary GVHD. Steroid and immunosuppressive medication doses were increased, and pulse methylprednisolone was started. At 48 hours after her skin lesions flared up, a change in her rhythm was noted on telemetry: her baseline sinus rhythm with heart rate of 90 beats per minute (bpm) was changed to bradycardia. A 12-lead electrocardiogram (ECG) is shown in the Figure. Her baseline ECG obtained a day earlier showed normal sinus rhythm with first-degree atrioventricular (AV) block (PR interval of 240 milliseconds). The patient denied symptoms associated with bradycardia.

what would you do next?

What would you do next?

Observe and continue treatment for GVHD

Place a dual chamber pacemaker

Place an emergent transvenous temporary pacemaker

Place an emergent transcutaneous pacemaker

a

female

31-40

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2636590

A man in his 60s presented with progressive onset of nocturnal dyspnea, dysphonia, dysphagia, and noisy breathing over the previous year. In addition, he reported a 22.7-kg weight loss. He also had a medical history significant for obstructive sleep apnea, gastroesophageal reflux disease with Barrett esophagitis, diabetes, and degenerative joint disease. Findings from his head and neck physical examination were normal except for the laryngeal examination. Laryngeal endoscopy revealed a large, well-mucosalized mass emanating from the left pyriform sinus, with mass effect on the larynx (Figure, A). The bilateral true vocal folds (TVFs) were visualized and were normal, but the full range of mobility of the left TVF could not be assessed owing to mass effect. A computed tomographic scan with contrast of the neck was obtained and revealed a 5 × 6-cm, nonenhancing, well-circumscribed laryngeal mass (Figure, B). The tumor was originating from the left pyriform sinus and did not appear to be locally invasive. Given these findings, the patient underwent direct laryngoscopy for transoral carbon dioxide laser–assisted excision without complications. Microscopic examination of the mass demonstrated polygonal cells with peripherally placed nuclei and eosinophilic cytoplasm containing cross-striations (Figure, C). Postoperatively, the patient reported improvement in dysphagia, voice quality, sleep, and breathing patterns.A, A large left pyriform sinus mass with mass effect on the larynx. B, Preoperative computerized tomography scan showing a large laryngeal mass without local invasion. C, Polygonal cells with peripherally placed nuclei and eosinophilic cytoplasm containing cross-striations (hematoxylin-eosin, original magnification ×40). What Is Your Diagnosis?

Rhabdomyoma

Granular cell tumor

Paraganglioma

Hibernoma

A. Rhabdomyoma

A

Rhabdomyoma

Rhabdomyoma is a rare, benign, mesenchymal tumor that comprises an estimated 2% of striated muscle tumors1 and is categorized as cardiac or extracardiac, based on the anatomical location. Cardiac rhabdomyomas predominantly occur in children in association with genetic disorders, including tuberous sclerosis, congenital heart disease, or glycogen storage diseases.2 These growths are believed to be hamartomas, as opposed to true neoplasms, owing to their well-differentiated histological appearance and high association with tuberous sclerosis. In contrast to cardiac rhabdomyomas, extracardiac rhabdomyomas (ECRMs) are uncommon and are generally regarded as true neoplasms with no discernable association to tuberous sclerosis.Adult ECRMs are slow-growing tumors with an estimated 93% of cases in the head and neck region, and a male to female ratio of 3:1.3,4 The median age of diagnosis is 60 years, with a range of 33 to 80 years.5 Specific sites of origin include the pharyngeal constrictor muscles, the floor of mouth, and occasionally the pharynx or the larynx. As such, these tumors can compress local aerodigestive structures and variably present with an airway obstruction, dysphagia, odynophagia, and/or hoarseness. Unlike their cardiac counterparts, ECRMs are typically solitary (in 70% of cases), although cases of multinodular (25%) and multifocal (5%) growths have been observed.6,7 There are no reported cases of malignant transformation.Extracardiac rhabdomyomas involving the head and neck region are generally classified as either adult or fetal.3 Adult ECRMs show mature skeletal muscle differentiation, whereas fetal ECRMs display features of immature muscle differentiation. Adult ECRMs have a characteristic histological appearance secondary to this skeletal muscle differentiation. They consist of polygonal-shaped cells with abundant granular eosinophilic cytoplasm, often contain recognizable cross-striations, and have peripherally located nuclei.5,6 When performed, electron microscopy demonstrates numerous mitochondria, myofilaments, and structures typical of striated muscle. Adult ECRMs express skeletal-muscle markers (eg, actin, desmin, and myoglobin) and are negative for epithelial markers (eg, AE1/AE3, EMA), neuroendocrine markers (eg, chromogranin, synaptophysin), glial fibrillary acidic protein, and CD68.5,6In regard to radiologic studies, magnetic resonance imaging is the preferred modality. Typically, adult ECRMs appear hyperintense or isointense to muscle on T1- and T2-weighted magnetic resonance imaging and demonstrates mild enhancement with gadolinium.8 Other features that point to this diagnosis are submucosal location and absence of invasion into surrounding tissues.3Unlike cardiac rhabdomyomas, ECRMs do not spontaneously regress.2 The main treatment modality is complete surgical resection. Reported recurrence rates have been as high as 42%,5 presumably owing to incomplete resection, highlighting the importance of complete primary resection. However, some cases of “recurrence” may actually represent a second primary, because additional ECRMs may be found many years following initial treatment.9The 2 most commonly used approaches for resection are either transcervical or transoral. The transcervical approach is preferred for large tumors in the inferior portion of the parapharyngeal space owing to its direct access to this region and adequate exposure of neurovascular structures.2 Restricted by a smaller operative window, the transoral approach is limited to tumors with radiographic evidence of small size, well-defined borders from surrounding tissue, and nonhypervascularity.10 Given that this patient had a well-circumscribed mass without evidence of local invasion, the transoral approach was selected.This case demonstrates presentation of a rare upper airway tumor, adult ECRM, in the setting of obstructive and compressive symptoms. Diagnosis is based on clinical examination and imaging and is confirmed with final pathologic findings showing mature skeletal muscle differentiation that consists of cross-striation and polygonal-shaped cells with granular eosinophilic cytoplasm. Management of ECRMs should include complete resection, via either the transcervical or the transoral approach, to prevent recurrence.

General

A man in his 60s presented with progressive onset of nocturnal dyspnea, dysphonia, dysphagia, and noisy breathing over the previous year. In addition, he reported a 22.7-kg weight loss. He also had a medical history significant for obstructive sleep apnea, gastroesophageal reflux disease with Barrett esophagitis, diabetes, and degenerative joint disease. Findings from his head and neck physical examination were normal except for the laryngeal examination. Laryngeal endoscopy revealed a large, well-mucosalized mass emanating from the left pyriform sinus, with mass effect on the larynx (Figure, A). The bilateral true vocal folds (TVFs) were visualized and were normal, but the full range of mobility of the left TVF could not be assessed owing to mass effect. A computed tomographic scan with contrast of the neck was obtained and revealed a 5 × 6-cm, nonenhancing, well-circumscribed laryngeal mass (Figure, B). The tumor was originating from the left pyriform sinus and did not appear to be locally invasive. Given these findings, the patient underwent direct laryngoscopy for transoral carbon dioxide laser–assisted excision without complications. Microscopic examination of the mass demonstrated polygonal cells with peripherally placed nuclei and eosinophilic cytoplasm containing cross-striations (Figure, C). Postoperatively, the patient reported improvement in dysphagia, voice quality, sleep, and breathing patterns.A, A large left pyriform sinus mass with mass effect on the larynx. B, Preoperative computerized tomography scan showing a large laryngeal mass without local invasion. C, Polygonal cells with peripherally placed nuclei and eosinophilic cytoplasm containing cross-striations (hematoxylin-eosin, original magnification ×40).

what is your diagnosis?

What is your diagnosis?

Paraganglioma

Rhabdomyoma

Hibernoma

Granular cell tumor

b

male

61-70

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2627415

A man in his 40s with newly diagnosed acute myelogenous leukemia (AML) arising from myelodysplasia presented with fever, cough, abdominal pain, difficulty swallowing, and 1 month of neutropenia. He had abruptly developed a painful eruption on his scalp, face, and left leg 24 hours prior to presentation after being scratched in these areas by his pet cat. The patient had not received any chemotherapy or antimicrobial prophylaxis. Physical examination revealed an ill-appearing, diaphoretic, thin man with multiple erythematous to violaceous, tender, edematous, targetoid nodules and plaques with central dusky appearance on the left forearm and right upper thigh (Figure, A). Vital signs included temperature of 39.7° C, blood pressure of 141/69 mm Hg, and pulse of 122 bpm. His white blood cell count was 1.8 × 103/µL (reference range, 4.5-11 × 103/µL; to convert to ×109/L, multiply by .001), and absolute neutrophil count was 246 cells/µL (reference range, 1520-6370 cells/µL). Other laboratory values were remarkable for a red blood cell count of 2.13 × 106/µL (reference range, 3.9-5.5 × 106/µL; to convert to ×1012/L, multiply by 1), hemoglobin of 6.1 g/dL (reference range, 14-17.5 g/dL; to convert to g/L, multiply by 10), and platelet count of 14 × 103/µL (reference range 150-350 × 103/µL, to convert to ×109/L, multiply 1). Cellular cytogenetics of his AML were notable for a 5q deletion and p53 mutation. Punch biopsy specimens from the right arm and left thigh were performed for histopathologic evaluation and tissue culture. A brisk neutrophilic infiltrate was seen on histopathology (Figure, B).A, 1.5 cm-long, edematous plaque with dusky central erythema on upper thigh. B, Punch biopsy specimen with hematoxylin-eosin staining (original magnification ×40); arrowhead indicates brisk dermal neutrophilic infiltrate. What Is Your Diagnosis?

Fusarium species infection

Bartonella henselae infection

Leukemia cutis

Sweet syndrome

D. Sweet syndrome

D

Sweet syndrome

Histopathologic analysis demonstrated spongiosis with mild papillary dermal edema and a subjacent brisk, predominantly neutrophilic infiltrate admixed with scattered lymphocytes, occasional histiocytes, and numerous extravasated erythrocytes. Gram, Gomori methenamine silver (GMS), AFB stains, and corresponding tissue cultures returned negative results. Overall, the clinical and histopathological presentation was consistent with Sweet syndrome (acute febrile neutrophilic dermatosis).Sweet syndrome is a reactive process classically diagnosed by the abrupt development of painful erythematous papules, plaques or nodules in the setting of neutrophilia, fever, and malaise.1 There is a visually diverse spectrum of lesions from ulcerated vesicles to subcutaneous nodules, most commonly on the head, neck, and extremities.1,2 Sweet syndrome requires clinical correlation, histopathology, and tissue cultures to exclude other diagnoses, because it can clinically mimic infections and cutaneous metastases.Sweet syndrome can be broken into the subgroups of classical, drug-induced, and malignancy-associated disease. In malignancy-associated Sweet syndrome, the cutaneous eruption may occur as a paraneoplastic herald of disease, and concomitantly with active disease.2 Because neutrophilia may be absent in these cases, it is still important to consider a diagnosis of Sweet syndrome in the setting of neutropenia.2 Malignancy-associated disease is most commonly found with hematologic malignant diseases, with AML being the most closely associated.3 Review of cytological features in patients with AML found increased rates of Sweet syndrome in AML with myelodysplastic-related features, 5q deletion, and FLT3 mutations.3 This patient had both a 5q deletion and p53 mutation, which may have contributed to the development of Sweet syndrome.In contrast to Sweet syndrome, angioinvasive fungal infections typically present as violaceous plaques or papules with central necrosis.4 Genera commonly associated with angioinvasion include Fusarium, Scedosporium, Candida, Aspergillus, and the Mucorales.4,5 Given the dark, dusky erythematous plaques present on this immunocompromised patient, an angioinvasive fungal infection was initially clinically favored. Immunosuppression, neutropenia, and hematological malignant disease, especially AML, as in this patient, are strong risk factors for fungal infection and dissemination, which can quickly become a medical emergency.5-7 Skin biopsies for histologic analysis and tissue culture in immunocompromised patients are essential to make the diagnosis. Histopathologic analysis in this case demonstrated papillary dermal edema with hemorrhage and diffuse neutrophilic infiltrate. Importantly, no organisms were observed and tissue culture results were negative.Bartonella henselae lesions characteristically present at the site of inoculation with an erythematous papule or crusted pustule and tender lymphadenopathy, and can occur secondary to exposure to cats. Histologically, lymph nodes and skin lesions may show central necrosis with surrounding histiocytes and lymphocytes. Although the patient did recall cat scratches, his clinical presentation and histological findings were not consistent with Bartonella infection. Of note, Sweet syndrome lesions have been found to display pathergy with lesion development at sites of cutaneous injury.2 Leukemia cutis also can present with purpuric papules, nodules, and plaques, and also may have numerous neutrophils on histopathologic analysis; however, malignant immature leukocytes would be present in the dermal infiltrate.2After histopathologic confirmation and no growth on tissue cultures, the patient was treated with topical triamcinolone ointment (0.1%) as well as oral prednisone (0.5 mg/kg/d) with clinical resolution of his lesions and gastrointestinal symptoms. This is characteristic of Sweet syndrome, which typically shows an excellent response to systemic corticosteroids. A patient is typically given 0.5 to 1 mg/kg per day orally until the lesions improve, before tapering to 10 mg daily over 4 to 6 weeks.2This case is notable for the unusual presentation of Sweet syndrome, clinically mimicking an angioinvasive fungal infection, in the setting of AML. Given the wide differential diagnosis in these patients and the disparity of treatment options, this case highlights the importance of histologic analysis and tissue culture to make an accurate diagnosis in an immunocompromised patient, and the importance of making a timely diagnosis.

Oncology

A man in his 40s with newly diagnosed acute myelogenous leukemia (AML) arising from myelodysplasia presented with fever, cough, abdominal pain, difficulty swallowing, and 1 month of neutropenia. He had abruptly developed a painful eruption on his scalp, face, and left leg 24 hours prior to presentation after being scratched in these areas by his pet cat. The patient had not received any chemotherapy or antimicrobial prophylaxis. Physical examination revealed an ill-appearing, diaphoretic, thin man with multiple erythematous to violaceous, tender, edematous, targetoid nodules and plaques with central dusky appearance on the left forearm and right upper thigh (Figure, A). Vital signs included temperature of 39.7° C, blood pressure of 141/69 mm Hg, and pulse of 122 bpm. His white blood cell count was 1.8 × 103/µL (reference range, 4.5-11 × 103/µL; to convert to ×109/L, multiply by .001), and absolute neutrophil count was 246 cells/µL (reference range, 1520-6370 cells/µL). Other laboratory values were remarkable for a red blood cell count of 2.13 × 106/µL (reference range, 3.9-5.5 × 106/µL; to convert to ×1012/L, multiply by 1), hemoglobin of 6.1 g/dL (reference range, 14-17.5 g/dL; to convert to g/L, multiply by 10), and platelet count of 14 × 103/µL (reference range 150-350 × 103/µL, to convert to ×109/L, multiply 1). Cellular cytogenetics of his AML were notable for a 5q deletion and p53 mutation. Punch biopsy specimens from the right arm and left thigh were performed for histopathologic evaluation and tissue culture. A brisk neutrophilic infiltrate was seen on histopathology (Figure, B).A, 1.5 cm-long, edematous plaque with dusky central erythema on upper thigh. B, Punch biopsy specimen with hematoxylin-eosin staining (original magnification ×40); arrowhead indicates brisk dermal neutrophilic infiltrate.

what is your diagnosis?

What is your diagnosis?

Fusarium species infection

Leukemia cutis

Sweet syndrome

Bartonella henselae infection

c

male

41-50

White

original

https://jamanetwork.com/journals/jama/fullarticle/2649161

A 57-year-old man with a history of HIV disease, hyperlipidemia, and major depressive disorder presented to his primary care physician with depression and insomnia. His mood had been controlled with bupropion, 300 mg/d, for the past several years; however, the recent death of his husband led to increased hopelessness, insomnia, and decreased energy. Results of laboratory studies (thyroid-stimulating hormone, complete blood cell count, and metabolic profile) were unremarkable. His total score on the Patient Health Questionnaire 9 (PHQ-9) was 16 (Table 1).The patient has depressive symptoms of at least moderate severity. How Would You Interpret These Test Results?

The patient has major depressive disorder.

The patient has dysthymic disorder.

The patient has depressive symptoms of at least moderate severity.

The patient does not have bipolar disorder.

C

The patient has depressive symptoms of at least moderate severity.

Depression is present in approximately 14% of patients in primary care settings but is often not diagnosed. When standardized screening instruments are not used, general practitioners correctly identify depression in approximately 47% of patients with depression.1 The PHQ-9 is a self-report form based on symptoms experienced over the past 2 weeks that consists of 9 items (0 = not at all, 1 = several days, 2 = more than half the days, 3 = nearly every day), which are summed to yield a score ranging from 0 through 27. Scores of 5-9 represent mild depressive symptoms; 10-14, moderate; 15-19, moderately severe; and 20 or more, severe depressive symptoms.2 A 3- to 5-point change in PHQ-9 score is clinically meaningful.2In primary care settings, a total score of 10 or higher has an estimated sensitivity of 81.3% (95% CI, 71.6%-89.3%), specificity of 85.3% (95% CI, 81.0%-89.1%), positive predictive value (PPV) of 44.2% (95% CI, 41.9%-46.6%), and positive likelihood ratio (LR+) of 6.9 (95% CI, 6.4-7.4) for major depressive disorder (MDD).3 A higher threshold score (PHQ-9 score ≥14) has a lower sensitivity (56.0%) but higher specificity (96.6%), PPV (73.4%), and LR+ (16.5).3 Advantages of the publicly accessible PHQ-9 include its self-report format, rapid scoring and interpretation, availability in multiple languages, suitability for remote administration (eg, via telehealth), and sensitivity to treatment-associated change.2This patient’s PHQ-9 score indicates depressive symptoms of at least moderate severity. His symptoms, previously in remission, were likely exacerbated by the recent death of his husband. In addition, his history supports (but does not confirm) a diagnosis of MDD; patients with dysthymic disorder or subthreshold depression would typically have PHQ-9 scores lower than 16. Because the PHQ-9 does not screen for bipolar disorder, elevated PHQ-9 scores should prompt additional questions to exclude bipolar depression, including asking about a sustained period of grandiosity, decreased need for sleep, or pressured speech. Importantly, the patient was screened for and denied suicidal ideation (item 9, Table 1). For patients with a positive response for item 9, the P4 screener asks 4 questions (regarding suicidal past history, plan, probability, and preventive factors) that stratify patients into “minimal,” “lower,” and “higher” suicide risk levels.4Because anxiety co-exists in 30% to 50% of depressed patients, screening for anxiety with a measure such as the generalized anxiety disorder 7-item (GAD-7) scale is also reasonable.2 Additionally, inquiry about alcohol and other substance use disorders is warranted. When screening for depression in patients with physical illness, concern has been raised about whether the 4 somatically focused items (fatigue, weight/appetite changes, sleep disturbance, and psychomotor symptoms) are specific to MDD. However, a study of 235 patients with diabetes or cardiopulmonary disease and 204 without these conditions found that only fatigue was significantly more common in patients with physical illness and that all 4 somatic symptoms showed similar improvement with depression treatment in patients with and without comorbidity.5Many guidelines, including those of the US Preventive Services Task Force,6 recommend routine screening for depression among adults and reference the PHQ-9 as one of the preferred instruments. The US Preventive Services Task Force also recommends the Geriatric Depression Scale, Edinburgh Postnatal Depression Scale, and Hospital Anxiety and Depression Scale, which are specific to defined populations of patients (Table 2). The PHQ-9 is also validated for depression screening in older adults.9 Multiple depression scales exist, and a conversion tool has been developed to cross-calibrate scores between the PHQ-9 and other scales.10 Instead of using a screening tool, clinicians may interview patients for DSM-5 symptoms of MDD during history-taking. However, this unstructured assessment typically requires more time, and the 9 symptoms of MDD are measured by the PHQ-9 items. A PHQ-9 score of 10 or higher should prompt a more thorough evaluation, which is required to establish a diagnosis of MDD.10The patient was referred to a psychiatrist. Bupropion was increased to 450 mg/d and his symptoms improved. Approximately a year later, his PHQ-9 score had decreased to 4.The PHQ-9 is a short, publicly available, self-report form that screens for and tracks clinically significant depressive symptoms.Patients with a PHQ-9 score of 10 or higher should be evaluated for clinical depression and comorbid psychiatric conditions by either a primary care or mental health clinician (eg, psychologist or psychiatrist) before initiating treatment.The presence of suicidal ideation (item 9) should prompt a thorough self-harm assessment; several follow-up questions are suggested (eg, the P4 suicidality screener).

Diagnostic

A 57-year-old man with a history of HIV disease, hyperlipidemia, and major depressive disorder presented to his primary care physician with depression and insomnia. His mood had been controlled with bupropion, 300 mg/d, for the past several years; however, the recent death of his husband led to increased hopelessness, insomnia, and decreased energy. Results of laboratory studies (thyroid-stimulating hormone, complete blood cell count, and metabolic profile) were unremarkable. His total score on the Patient Health Questionnaire 9 (PHQ-9) was 16 (Table 1).The patient has depressive symptoms of at least moderate severity.

how would you interpret these test results?

How do you interpret these results?

The patient has dysthymic disorder.

The patient has major depressive disorder.

The patient does not have bipolar disorder.

The patient has depressive symptoms of at least moderate severity.

d

male

51-60

original

https://jamanetwork.com/journals/jama/fullarticle/2647853

A 30-year-old woman presented with widespread, erythematous, purpuric macules and papules on the abdomen and extremities. The eruption had been present for approximately 8 months and consisted of asymptomatic, self-resolving, and continuously appearing macules and papules. Her medical history was significant for chronic hepatitis B infection, for which tenofovir was initiated 4 months ago. Review of systems was positive only for occasional arthralgias in her knees and ankles. She was not taking any other medications.The patient was in no acute distress, and her vital signs were within normal limits. On physical examination, there were purpuric, erythematous macules coalescing into patches on the upper extremities, abdomen, and lower extremities (Figure). She had no oral or genital involvement and no joint effusions or deformities. A skin punch biopsy showed extravasated erythrocytes, a neutrophilic infiltrate, fibrinoid necrosis, and broken-down neutrophils releasing nuclear debris, consistent with leukocytoclastic vasculitis (Figure). A second skin punch biopsy was performed for direct immunofluorescence, which was negative. Results of a complete blood cell count and comprehensive metabolic panel were unremarkable.Physical examination of the lower extremities. Dotted areas indicate areas of the skin that were biopsied. Inset, Photomicrograph from first skin punch biopsy (hematoxylin-eosin, original magnification ×200). What Would You Do Next?

Prescribe prednisone

Evaluate for systemic vasculitis

Prescribe a topical glucocorticoid

Provide reassurance and observe patient

Cutaneous small-vessel vasculitis (CSVV)

B

Evaluate for systemic vasculitis

The keys to the correct diagnosis are the physical examination and biopsy results. CSVV has a variable clinical appearance including purpuric papules, purpuric macules, urticaria-like lesions, petechiae, and ulcers.1-4 A distribution predominantly involving dependent areas in a nonretiform pattern is also clinically consistent with CSVV.1,2 In the case of suspected CSVV, it is important to establish the diagnosis and to assess for other end-organ involvement.CSVV is a vasculitis involving postcapillary venules in the skin. The condition most commonly manifests as palpable purpura on the bilateral lower extremities. The incidence of CSVV is between 39.6 and 59.8 cases per million people annually.1 A skin biopsy is used to confirm the diagnosis, and histopathology shows leukocytoclastic vasculitis with extravasated erythrocytes, a neutrophilic infiltrate, fibrinoid necrosis, and broken-down neutrophils releasing nuclear debris (leukocytoclasis). A second biopsy should be obtained for direct immunofluorescence whenever possible, to evaluate for IgA-related CSVV. Importantly, for accurate direct immunofluorescence results, the newest lesion or a lesion that appeared within the past 24 to 48 hours should be sampled.Workup for systemic involvement should be the first step in evaluation of patients with CSVV.1-5 A thorough history and physical examination including a full review of systems is essential. Systemic involvement occurs in approximately 20% of cases of CSVV, and paresthesias, fever, and lack of painful lesions are identified risk factors. Laboratory workup generally includes a complete blood cell count with white blood cell differential, basic metabolic panel, liver function tests, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Given that renal and gastrointestinal involvement are common internal manifestations of CSVV,1-4 urinalysis to assess for hematuria and a fecal occult blood test are also recommended.Etiologies of CSVV include infections (bacterial or viral), autoimmune connective tissue diseases (such as systemic lupus erythematosus or rheumatoid arthritis), inflammatory conditions (including inflammatory bowel disease or cryoglobulinemia), medications (such as antibiotics), neoplasms (including hematologic malignancies or solid-organ carcinomas), and idiopathic disease. Infections and medications are the most common etiologies. Although a specific etiology is identified in only about one-half to two-thirds of cases, an expanded etiologic workup is required in cases with extensive cutaneous involvement or systemic involvement, as well as in patients with recurrent episodes or a suspected systemic trigger.1-3 This extended workup can include testing for streptococcal antibodies; hepatitis B and C serologic evaluation; testing for human immunodeficiency virus; antinuclear antibody panel, including anti-Ro and anti-La; rheumatoid factor level; complement (C3 and C4) levels; complement activity (CH50); testing for perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) and cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA); cryoglobulin levels, and serum protein electrophoresis with immunofixation. Additional laboratory, radiographic, or endoscopic workup may sometimes be necessary.1,4Treatment of CSVV is determined by the extent of involvement and the underlying etiology. If a clear etiology can be identified, treatment of the underlying cause or discontinuation of the causative agent is the best approach. In limited CSVV involving the lower extremities, treatment includes rest, leg elevation, compression, and sometimes potent topical corticosteroids. Occasionally, short tapering courses of oral corticosteroids are required. Individuals with chronic CSVV without a clear precipitant may benefit from colchicine and dapsone, either alone or in combination. Cases resistant to colchicine and dapsone may require systemic immunomodulators such as hydroxychloroquine, methotrexate, mycophenolate mofetil, azathioprine, a longer course of oral corticosteroids, intravenous immunoglobulin, cyclosporine, rituximab, or plasmapheresis.1,4 In recalcitrant cases, it is paramount to continue workup for an underlying etiology.In this patient, laboratory workup revealed an elevated ESR (60 mm/h) and CRP level (3.56 mg/L). Findings from urinalysis and stool guaiac testing were normal. Given the patient’s occasional arthralgias, a rheumatologic workup was initiated and revealed results positive for antinuclear antibody (1:640, homogeneous pattern), anti–double-stranded DNA antibody (298 IU/mL), antihistone antibody (2.1 units), and rheumatoid factor (803 IU/mL). C3 and C4 levels were normal, and results for anti-Ro, anti-La, anticyclic citrullinated peptide, cryofibrinogen, cryoglobulin, p-ANCA, c-ANCA, anti-Smith, antiribonuclear protein, anticentromere, and anti-Scl 70 were all negative. The hepatitis B viral load was 113 000 000 IU/mL. Results of hepatitis C testing were negative. While these results were suggestive of a diagnosis of systemic lupus erythematosus, the American College of Rheumatology criteria for systemic lupus erythematosus were not met.6 Furthermore, the observed serology findings (ANA, anti-dsDNA, and rheumatoid factor) may be seen in the setting of chronic hepatitis B infection.7-10 Thus, hepatitis B was thought to be the most likely etiology of CSVV in this patient.The patient continued tenofovir and started colchicine, with improvement in skin symptoms. Repeat laboratory testing showed reduction in CRP level to 0.64 mg/L and reduction in hepatitis B viral load to 2350 IU/mL 13 months after starting tenofovir.

General

A 30-year-old woman presented with widespread, erythematous, purpuric macules and papules on the abdomen and extremities. The eruption had been present for approximately 8 months and consisted of asymptomatic, self-resolving, and continuously appearing macules and papules. Her medical history was significant for chronic hepatitis B infection, for which tenofovir was initiated 4 months ago. Review of systems was positive only for occasional arthralgias in her knees and ankles. She was not taking any other medications.The patient was in no acute distress, and her vital signs were within normal limits. On physical examination, there were purpuric, erythematous macules coalescing into patches on the upper extremities, abdomen, and lower extremities (Figure). She had no oral or genital involvement and no joint effusions or deformities. A skin punch biopsy showed extravasated erythrocytes, a neutrophilic infiltrate, fibrinoid necrosis, and broken-down neutrophils releasing nuclear debris, consistent with leukocytoclastic vasculitis (Figure). A second skin punch biopsy was performed for direct immunofluorescence, which was negative. Results of a complete blood cell count and comprehensive metabolic panel were unremarkable.Physical examination of the lower extremities. Dotted areas indicate areas of the skin that were biopsied. Inset, Photomicrograph from first skin punch biopsy (hematoxylin-eosin, original magnification ×200).

what would you do next?

What would you do next?

Provide reassurance and observe patient

Prescribe a topical glucocorticoid

Evaluate for systemic vasculitis

Prescribe prednisone

c

female

21-30

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2606656

A man in his 30s presented with reticulate hyperpigmentation, progressive since early childhood, overlying the trunk and extremities (Figure, A and B). Physical examination revealed normal fingernails and toenails, dermatoglyphics, and dentition. Additionally, there was no evidence of alopecia or keratoderma. Review of systems was remarkable for hypohidrosis, photophobia, and a history of recurrent sinopulmonary infections, including pneumonia, requiring hospitalization. Family history was notable for similarly affected men on the patient’s mother’s side. A punch biopsy specimen was obtained (Figure, C and D).A, Reticulate hyperpigmentation involving the lower and upper distal extremities, including the dorsal surface of the hand. B, Diffuse reticulate hyperpigmentation of the trunk and flexures, including the posterior neck and axilla. C, Hematoxlyn-eosin stain (original magnification ×200). D, Congo red stain (original magnification ×200). What Is Your Diagnosis?

Dermatopathia pigmentosa reticularis

Dowling-Degos disease

Dyskeratosis congenita

X-linked reticulate pigmentary disorder

D. X-linked reticulate pigmentary disorder

D

X-linked reticulate pigmentary disorder

Histopathologic examination demonstrated deposits of amyloid within the papillary dermis along with basilar hyperpigmentation and pigment incontinence with melanophages (Figure, C). The amyloid deposits were strongly highlighted with a Congo red stain (Figure, D). Based on clinicopathologic correlation, the diagnosis of X-linked reticulate pigmentary disorder (XLRPD) was made. Due to financial limitations, the patient was unable to pursue the recommended genetic testing for the POLA1 mutation.X-linked reticulate pigmentary disorder is a multisystem disease with characteristic cutaneous findings. Pedigrees affected by XLRPD were initially described in the late 1970s and 1980s.1,2 During early childhood, affected men develop diffuse, asymptomatic reticulate hyperpigmentation, intermingled with hypomelanotic macules. Pigmentation begins in the flexures and spreads to the buttocks, trunk, extremities and sometimes face. Distinctive facies, characterized by an upswept frontal hairline and arched eyebrows, may be present. Coarse hair is sometimes reported.3,4 Hypohidrosis is common, but dental anomalies and onychodystrophy are variable.4,5 Histopathology demonstrates findings of macular amyloidosis: amyloid deposition within the papillary dermis, along with pigment incontinence, basilar hyperpigmentation, and necrotic keratinocytes in affected adults, but not children. This suggests that amyloid deposition in XLRPD is an age-dependent and secondary phenomenon.2,3Multisystem involvement in XLRPD is common. Gastrointestinal disease includes gastroenteritis, diarrhea, failure to thrive, and colitis. Neurologic abnormalities may present with seizures, hemiplegia, and developmental delay. Ocular symptoms are described as photophobia and visual impairment owing to corneal dyskeratosis and amyloid deposition. Urogenital involvement has been reported, including urethral strictures and nephrolithiasis. Pulmonary involvement is present in all affected men; recurrent (and sometimes fatal) pneumonia and pulmonary fibrosis are common.1-4,6 In contrast to men, affected (mosaic) women do not demonstrate systemic involvement, and the only cutaneous finding is streaky pigmentation along the lines of Blaschko, simulating the clinical appearance of the third stage of incontinentia pigmenti.7It was recently discovered that XLRPD is caused by an intronic mutation in the POLA1 gene, located within the interval Xp22.11-p21.3, which encodes the catalytic subunit of DNA polymerase-α. A dominant mode of inheritance has been suggested. This mutation results in the missplicing of POLA1 and its deficient expression; downstream effects include enhanced expression of IRF (interferon regulatory factor) and NF-κB (nuclear factor κ-light-chain-enhancer of activated B cells)–dependent gene expression and reduced cytosolic RNA:DNA primers. Consequently, patients with XLRPD display increased type-I interferon activity and reduced levels of interferon-γ and interleukin-17A, changes that are linked with autoinflammation, immunodeficiency, and recurrent infections.8,9Several genodermatoses are characterized by reticulate hyperpigmentation but can be distinguished from XLRPD based on the age of onset, systemic involvement, mode of inheritance, and histopathology. Dermatopathia pigmentosa reticularis (DPR) demonstrates a similar age of onset to that of XLRPD and sweating abnormalities are common (hypohidrosis or hyperhidrosis). However, DPR is also associated with adermatoglyphia, palmoplantar keratoderma, nonscarring alopecia, and autosomal dominant inheritance—features absent in XLRPD. Dermatopathia pigmentosa reticularis is caused by mutations in keratin 14, and systemic involvement is not described. In contrast to XLRPD, Dowling-Degos disease is an autosomal dominant genodermatosis with onset in the third or fourth decades of life, absence of systemic disease, and histopathology with reticulated, antlerlike projections arising from the epidermis along with basilar hyperpigmentation. Dowling-Degos disease is due to a mutation in keratin 5. Like XLRPD, dyskeratosis congenita (DKC) is characterized by multisystem involvement, X-linked recessive (most commonly) inheritance, and onset in childhood. However, premalignant leukoplakia and hematologic dyscrasia, including leukemia and Hodgkin lymphoma, are common features of DKC that are absent in XLRPD. The X-linked recessive form of DKC is caused by mutations in DKC1. Importantly, DPR, Dowling-Degos disease, and DKC do not demonstrate amyloid deposition on histopathology.5

Dermatology

A man in his 30s presented with reticulate hyperpigmentation, progressive since early childhood, overlying the trunk and extremities (Figure, A and B). Physical examination revealed normal fingernails and toenails, dermatoglyphics, and dentition. Additionally, there was no evidence of alopecia or keratoderma. Review of systems was remarkable for hypohidrosis, photophobia, and a history of recurrent sinopulmonary infections, including pneumonia, requiring hospitalization. Family history was notable for similarly affected men on the patient’s mother’s side. A punch biopsy specimen was obtained (Figure, C and D).A, Reticulate hyperpigmentation involving the lower and upper distal extremities, including the dorsal surface of the hand. B, Diffuse reticulate hyperpigmentation of the trunk and flexures, including the posterior neck and axilla. C, Hematoxlyn-eosin stain (original magnification ×200). D, Congo red stain (original magnification ×200).

what is your diagnosis?

What is your diagnosis?

Dowling-Degos disease

Dyskeratosis congenita

X-linked reticulate pigmentary disorder

Dermatopathia pigmentosa reticularis

c

male

31-40

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2607373

A woman in her early 20s presented with 1 year of discrete asymptomatic brown lesions distributed over her lower extremities. She denied any history of trauma or prior lesions at these sites and could not pinpoint any exacerbating or alleviating factors. She denied fever, arthralgias, myalgias, or constitutional symptoms. She had no significant past medical history and took no medications or supplements. A physical examination revealed several 2-mm to 4-mm round, hyperpigmented macules symmetrically distributed over the lower extremities and dorsal feet (Figure, A). No prior treatments had been attempted. A skin biopsy was performed (Figure, B-D). What is your diagnosis? What Is Your Diagnosis?

Lichen planus pigmentosus

Leukocytoclastic vasculitis

Macular lymphocytic arteritis

Erythema dyschromicum perstans

C. Macular lymphocytic arteritis

C

Macular lymphocytic arteritis

A punch biopsy revealed mononuclear inflammation and fibrosis around vessels at the junction of the deep dermis and subcutis (Figure, B). The vessel lumen was narrowed by pink fibrous material (Figure, C), and a Verhoeff-van Gieson stain revealed an intact elastic lamina (Figure, D). Histologic and clinical features were consistent with macular lymphocytic arteritis. Laboratory workup revealed a normal complete blood count, and the patient tested negatively for hepatitis B and C and human immunodeficiency virus (HIV). Antinuclear antibody and antineutrophil cytoplasmic antibody laboratory results were within normal limits; Complement C4 was in a low-normal range and was accompanied by a normal complement C3. After biopsy specimen analysis and initial laboratory work, the patient was lost to follow-up and therefore has not yet started an adequate trial of therapy. To the authors’ knowledge, she has developed no systemic symptoms and no ulceration or spread of her cutaneous lesions.Macular lymphocytic arteritis (MLA), also known as lymphocytic thrombophilic arteritis, is a newly described entity first reported in 2003 by Fein et al.1 The condition tends to affect women in the third to fifth decades of life. Clinically, patients tend to present with erythematous to hyperpigmented macules or livedo racemosa with a predilection for the lower extremities.A definitive diagnosis can only be made with a classic histological pattern. Histology of the deep dermis and subcutis reveals a predominantly lymphohistiocytic perivascular infiltrate and a concentric hyalinized fibrin ring located intraluminally2 or intramurally.3 It has been postulated that this fibrin ring may represent a localized thrombophilia caused by a lymphocytic endovasculitis.2 Neutrophils and eosinophils are typically sparse or absent.Patients with macular lymphocytic arteritis may show elevated erythrocyte sedimentation rate and antinuclear antibody titers. Anticardiolipin antibodies, factor V Leiden mutations, and prothrombin gene mutations have also been described.2,3 The clinical significance of these anomalies has yet to be determined. Although serologic testing may reveal antiphospholipid antibodies, patients generally do not meet the full criteria for antiphospholipid antibody syndrome.2 Nevertheless, patients with this presentation should be screened for the presence of an underlying prothrombotic state. Recently, a case of MLA was described in a patient with concurrent HIV and hepatitis B infections.4The lesions are typically asymptomatic and tend to follow an indolent course. Scarring and atrophie blanche are typically not seen after resolution. Long-term follow-up generally shows no progression to systemic involvement.1,5There is significant debate as to whether macular lymphocytic arteritis represents an entirely new entity or an indolent form of cutaneous polyarteritis nodosa (cPAN).6 Both represent medium vessel vasculitides that can present with hyperpigmented patches, livedo, and an absence of systemic symptoms. In contrast to MLA, early cPAN histology shows neutrophilic inflammation. Subacute cPAN does involve lymphocytes and fibrinoid necrosis but with added disruption of the vascular media and internal elastic lamina not classically seen in MLA.7 However, these differences are subtle, and many believe MLA to represent a phase of cPAN. Given the overlap in clinical presentations and subtle differences histologically, it is reasonable to consider MLA and cPAN as 2 ends of the same disease spectrum. Over time, further research may clarify the relationship between these 2 conditions.Most patients with macular lymphocytic arteritis are concerned with the cosmetic appearance of the lesions, and treatment has proven to be difficult. Topical corticosteroids provide little relief.8 Oral corticosteroids have shown promising temporary results but without long-lasting benefit.2 A course of dapsone followed by doxycycline provided significant cutaneous improvement in a single case.9 Many authors have chosen to begin antiplatelet or anticoagulation therapy in patients with abnormal laboratory results, but the long-term benefit of these treatments is yet to be determined. Warfarin, aspirin, clopidogrel, and nifedipine have all been tried with little change in cutaneous manifestations.2 Where cosmetic treatment is not desired, watchful waiting is a reasonable course of action.

Dermatology

A woman in her early 20s presented with 1 year of discrete asymptomatic brown lesions distributed over her lower extremities. She denied any history of trauma or prior lesions at these sites and could not pinpoint any exacerbating or alleviating factors. She denied fever, arthralgias, myalgias, or constitutional symptoms. She had no significant past medical history and took no medications or supplements. A physical examination revealed several 2-mm to 4-mm round, hyperpigmented macules symmetrically distributed over the lower extremities and dorsal feet (Figure, A). No prior treatments had been attempted. A skin biopsy was performed (Figure, B-D). What is your diagnosis?

what is your diagnosis?

What is your diagnosis?

Erythema dyschromicum perstans

Lichen planus pigmentosus

Leukocytoclastic vasculitis

Macular lymphocytic arteritis

d

female

21-30

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2617869

A woman in her 20s presented with numerous grouped yellow-brown and red-brown papules on the upper eyelids, infraorbital rims, bilateral axillae, inframammary creases, lower back, buttocks, hips, inguinal folds, and proximal thighs (Figure, A and B). The lesions first appeared in her right axilla 6 months prior and were asymptomatic. The patient also noted a 3-month history of polyuria, polydipsia, and nocturia. Review of symptoms was otherwise negative. She had no notable medical or family history. On physical examination there were no other sites of involvement including mucosal surfaces. Shave biopsies were obtained from the right (Figure, C) and left axillae (Figure, D) and sent for histopathological examination.A, Clinical images show punctate yellow-brown papules on the upper eyelids and infraorbital rims; B, numerous red-brown papules in the right axilla. C, Histopathology of a shave biopsy sample from the right axilla (original magnification ×200). D, Histopathology of a shave biopsy sample taken from the left axilla (original magnification ×200). What Is Your Diagnosis?

Xanthogranuloma

Erdheim-Chester disease

Xanthoma disseminatum

Generalized eruptive histiocytoma

C. Xanthoma disseminatum

C

Xanthoma disseminatum

The skin biopsy specimens revealed a collection of foamy histiocytes, lymphocytes, and scattered eosinophils in the superficial dermis. There were multinucleated giant cells including Touton-type forms (Figure, C). The histiocytes stained strongly with cluster of differentiation (CD) 68 (Figure, D) and were negative for S100 and CD1a. Complete blood cell count and metabolic panel were within normal limits. A lipid panel showed an elevated high-density lipoprotein cholesterol (73 mg/dL; normal range, 40-59 mg/dL [to convert to mmol/L, multiply by 0.0259]) but was otherwise within normal limits. Serum protein electrophoresis and immunofixation electrophoresis showed normal patterns. Urine osmolality (180 mOsm/kg; normal range, 50-800 mOsm/kg) and serum osmolality (288 mOsm/kg; normal range, 280-303 mOsm/kg) were within normal limits with normal findings on water deprivation test. Antidiuretic hormone level was normal (<0.5 pg/mL; normal range, 0-6.9 pg/mL), as were thyroid-stimulating hormone, luteinizing hormone, follicle-stimulating hormone, prolactin, and growth hormone. Magnetic resonance imaging (MRI) of the brain revealed prominent abnormal thickening of the pituitary infundibulum. Bone survey did not reveal any lesions. Treatment options were discussed, but the patient declined.Xanthoma disseminatum (XD) is a rare, normolipemic, benign non-Langerhans cell histiocytosis of unknown etiology with mucocutaneous and pituitary involvement.1,2 Patients with XD present with an eruption of numerous, symmetrically distributed yellow-brown and red-brown papules on the face, trunk, proximal extremities, and flexural and intertriginous areas.1 Some patients also have involvement of the conjunctivae, oral mucosa, and upper respiratory tract.1 Associated pituitary involvement typically presents with mild, transient diabetes insipidus, but hyperprolactinemia and various degrees of hypopituitarism may also be seen.1,3 Involvement of the central nervous system outside of the pituitary gland is rare, but carries a poor prognosis.1,4 Plasma cell dyscrasias have been reported in association with XD.5In early lesions of XD, mononuclear histiocytes predominate the infiltrate.6 However, in more established lesions, multinucleated cells, including Touton cells and other inflammatory cells, are present. As a non-Langerhans cell histiocytosis, immunohistochemical staining is characterized by positive CD68 and factor XIIIa tests, and negative S100 and CD1a tests.6Xanthoma disseminatum may be difficult to differentiate from other non-Langerhans cell histiocytoses. While the presence of Touton giant cells makes it easy to confuse XD with xanthogranuloma, pituitary involvement on history and MRI is more consistent with XD.6,7 Erdheim-Chester disease (ECD) may present with cutaneous lesions and pituitary involvement similar to those seen in XD; however, as ECD is primarily a disease of the long bones, with cutaneous involvement seen in only 30% of cases, a skeletal survey can be used to differentiate these diseases.8 Additionally, BRAF mutations have been found in ECD but not in XD.7 Generalized eruptive histiocytoma presents with cutaneous lesions very similar to XD. However, histologically, xanthoma cells and giant cells are typically absent, and pituitary or other systemic involvement is not seen.6 Evolution from generalized eruptive histiocytoma to XD has been reported.9 Multicentric reticulohistiocytosis is another non-Langerhans cell histiocytosis that can have cutaneous lesions similar to XD but is associated with severe destructive arthropathy.6Three clinical courses have been suggested for XD: (1) a common, persistent form with lesions that may never resolve; (2) a rare, self-healing form with spontaneous resolution of lesions; and (3) a very rare, progressive form with organ dysfunction and central nervous system involvement.2 Treatment options for XD include surgical excision, electrocoagulation, cryotherapy, carbon dioxide laser, radiation, lipid-lowering agents, systemic glucocorticoids, and chemotherapeutic agents.1,10 Recently, anakinra, an interleukin-1 receptor antagonist, has been reported to be effective in the treatment of XD.7 Associated diabetes insipidus may remit spontaneously, but desmopressin may be required in some patients.1,2

Dermatology

A woman in her 20s presented with numerous grouped yellow-brown and red-brown papules on the upper eyelids, infraorbital rims, bilateral axillae, inframammary creases, lower back, buttocks, hips, inguinal folds, and proximal thighs (Figure, A and B). The lesions first appeared in her right axilla 6 months prior and were asymptomatic. The patient also noted a 3-month history of polyuria, polydipsia, and nocturia. Review of symptoms was otherwise negative. She had no notable medical or family history. On physical examination there were no other sites of involvement including mucosal surfaces. Shave biopsies were obtained from the right (Figure, C) and left axillae (Figure, D) and sent for histopathological examination.A, Clinical images show punctate yellow-brown papules on the upper eyelids and infraorbital rims; B, numerous red-brown papules in the right axilla. C, Histopathology of a shave biopsy sample from the right axilla (original magnification ×200). D, Histopathology of a shave biopsy sample taken from the left axilla (original magnification ×200).

what is your diagnosis?

What is your diagnosis?

Generalized eruptive histiocytoma

Erdheim-Chester disease

Xanthogranuloma

Xanthoma disseminatum

d

female

21-30

original

https://jamanetwork.com/journals/jamapediatrics/fullarticle/2631763

A young girl presented to the pediatric emergency department for evaluation of blisters on both of her hands. Three weeks prior, she had returned from school with 2 itchy papules on her right hand. The papules continued to enlarge over the course of the day and progressed to form blisters. The following day, she noticed similar lesions appearing on her left hand. She was evaluated by her pediatrician, who prescribed oral cefdinir and hydrocortisone, 2.5%, cream, but there was no substantive improvement. On further questioning, she recalled similar itchy papules appearing on her feet without progression to blisters. Her medical history was significant for atopic dermatitis that was well controlled with topical triamcinolone, 0.1%, cream. Physical examination demonstrated numerous skin-colored tense bullae on her bilateral hands (Figure 1, A). Xerosis was on the trunk and extremities. On her dorsal and plantar feet, there were macerated, erosive plaques without vesicles or bullae (Figure 1, B). Results of herpes simplex virus polymerase chain reaction, bacterial culture, potassium hydroxide preparation, mineral oil preparation, and direct immunofluorescence were negative.A, Bilateral palms with at least 20 tense, white-gold bullae, several with violaceous borders and overlying tapioca-like appearance, present diffusely but concentrated on the palmar surfaces. B, Bilateral dorsal feet with macerated, erosive plaques. No active vesicles or bullae present. What Is Your Diagnosis?

Childhood bullous pemphigoid

Dyshidrotic eczema

Bullous tinea

Distal blistering dactylitis

B. Dyshidrotic eczema

B

Dyshidrotic eczema

Punch biopsy revealed subacute spongiotic dermatitis with eosinophils and prominent intraepidermal vesicle formation. These findings were consistent with dyshidrotic eczema. The patient started topical mometasone, 0.1%, ointment, but owing to lack of improvement, oral prednisone 1 mg/kg/d was added to her regimen. At her 3-week follow-up, no new blisters were seen, and all previous lesions were healing (Figure 2). Postprednisone treatment. Bilateral palmar surfaces with areas of erythema and mild desquamation at locations of previous lesions.Dyshidrotic eczema is a vesiculobullous disease of the palms and soles. It can be idiopathic or related exposure to contact allergens.1 Dyshidrotic eruptions are a known adverse effect of intravenous immunoglobulin therapy. It can be exacerbated by hyperhidrosis. Dyshidrotic eczema can present as a severe, sudden outbreak of intensely pruritic deep-seated vesicles.2 The lesions resemble “tapioca” but may coalesce to form bullae. The eruption typically presents symmetrically on the lateral aspects of the fingers as well as the palms and soles.2 In chronic cases, lesions may appear hyperkeratotic and fissured. Most patients experience flares throughout their life; however, decreased frequency and severity may occur with age. Relapses are more common in those with atopy, sweat gland disorderes, or occupational exposure to triggers. Flares can range in intensity from mild to severe, occur at variable intervals, and persist for several weeks.2Diagnosis is often clinical; however, an appropriate initial workup must be performed to exclude processes that can cause a similar clinical presentation such as bullous tinea, bacterial infection, autoimmune bullous disease, and allergic contact dermatitis.2 Skin scraping with potassium hydroxide can be performed to look for fungal hyphae seen in bullous tinea. Exudative bacterial culture swab should be performed because bacterial superinfection can distort typical clinical presentations of other disease entities or be the primary cause of bulla, as seen in distal blistering dactylitis. In cases with diagnostic uncertainty, a tissue biopsy with direct immunofluorescence can be performed to rule out autoimmune bullous disease.2 Patch testing is considered if allergic contact dermatitis is suspected.Adequate treatment for dyshidrotic eczema is not only important for functionality and quality of life but also to restore the skin’s barrier function and prevent complications such as bacterial and viral superinfections. First-line therapy includes a topical corticosteroid. Mometasone furoate has been shown to be safe and effective, where most patients noted resolution of their flare within 9 weeks and had continued remission when used as maintenance.3Alternate options for topical therapy include other superpotent or potent topical corticosteroids and calcineurin inhibitors (eg, tacrolimus or pimecrolimus), both of which have produced beneficial results comparable with mometasone treatment in 1 study.4 Calcineurin inhibitors have the benefit of not causing similar adverse effects as seen with corticosteroids and can be used for rotational therapy with topical corticosteroids.4In more severe cases warranting oral therapy, such as this one, systemic glucocorticoids can be administered with a gradual taper initiated once blisters resolve.2 If lesions are recalcitrant, steroid-sparing agents, such as methotrexate, azathioprine, or mycophenolate mofetil, can be used to induce and maintain remission.2,5-7 Lastly, phototherapy, using high-dose ultraviolet A light, soak or cream psoralen-ultraviolet-light, or oral psoralen-ultraviolet-light may be indicated for appropriate patients.8 Diagnosis and treatment of dyshidrotic eczema can lead to significantly improved quality of life, as seen in this patient. Dyshidrotic eczema eruptions can have a variety of presentations and should be considered in the differential diagnosis for any patient presenting with an acral vesiculobullous eruption.

Pediatrics

A young girl presented to the pediatric emergency department for evaluation of blisters on both of her hands. Three weeks prior, she had returned from school with 2 itchy papules on her right hand. The papules continued to enlarge over the course of the day and progressed to form blisters. The following day, she noticed similar lesions appearing on her left hand. She was evaluated by her pediatrician, who prescribed oral cefdinir and hydrocortisone, 2.5%, cream, but there was no substantive improvement. On further questioning, she recalled similar itchy papules appearing on her feet without progression to blisters. Her medical history was significant for atopic dermatitis that was well controlled with topical triamcinolone, 0.1%, cream. Physical examination demonstrated numerous skin-colored tense bullae on her bilateral hands (Figure 1, A). Xerosis was on the trunk and extremities. On her dorsal and plantar feet, there were macerated, erosive plaques without vesicles or bullae (Figure 1, B). Results of herpes simplex virus polymerase chain reaction, bacterial culture, potassium hydroxide preparation, mineral oil preparation, and direct immunofluorescence were negative.A, Bilateral palms with at least 20 tense, white-gold bullae, several with violaceous borders and overlying tapioca-like appearance, present diffusely but concentrated on the palmar surfaces. B, Bilateral dorsal feet with macerated, erosive plaques. No active vesicles or bullae present.

what is your diagnosis?

What is your diagnosis?

Bullous tinea

Distal blistering dactylitis

Dyshidrotic eczema

Childhood bullous pemphigoid

c

female

11-20

White

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2629724

A 60-year-old woman was referred to the emergency department with a history of abdominal discomfort and a palpable mass in the right iliac fossa. She denied any change in her bowel habits or having experienced rectal bleeding. She had a normal appetite and had no history of weight loss. Before this admission, she was healthy, with no previous medical problems. On examination, her vital signs were within normal limits. She was mildly tender in the right iliac fossa and there was a large mobile mass, at least 10 cm in diameter, that was easily palpable in the right iliac fossa. She was initially investigated with a computed tomography (CT) scan of the abdomen (Figure 1). She underwent a colonoscopy that showed no intraluminal mucosal abnormalities or masses, but evidence of external compression at the cecum was noted.Coronal (A) and transverse (B) computed tomographic images show a large intra-abdominal cystic mass in the right iliac fossa. What Is Your Diagnosis?

Appendix abscess

Cecal carcinoma

Mucocele of the appendix

Neuroendocrine tumor

C. Mucocele of the appendix

C

Mucocele of the appendix

The CT scan demonstrated a large right-sided cystic mass arising from the appendix. Based on these findings, the clinical diagnosis of mucocele of the appendix was made and a surgical resection was planned. The normal colonoscopy results excluded cecal carcinoma. Neuroendocrine tumors arising from the appendix usually present with symptoms of acute appendicitis.1 The CT scan appearances are not consistent with that of an appendix abscess.Mucocele of the appendix is an obstructive dilatation of the appendix caused by an intraluminal accumulation of mucoid material, secondary to 1 of the following processes: retention cyst, mucosal hyperplasia, mucinous cystadenoma, or mucinous cystadenocarcinoma.2 Mucoceles are found in 0.2% to 0.3% of all appendectomy specimens.3 Around 50% of patients are asymptomatic at the time of presentation when the mucocele is found as an incidental finding. Other patients may present with abdominal pain, abdominal mass, weight loss, or acute appendicitis.4 The presence of symptoms is associated with a higher incidence of cystadenocarcinoma.The diagnosis is usually confirmed with a CT scan, which characteristically shows a well-encapsulated cystic mass that is usually in the right lower quadrant. Curvilinear mural calcification is seen in 50% of cases.5 Cystadenomas and cystadenocarcinomas are typically larger and are associated with a 20% incidence of perforation. Perforation is indicated by the presence of ascites in the pelvis and the right upper quadrant.When a mucocele perforates, it releases mucoid material into the peritoneal cavity. This material may be acellular or may contain dysplastic cells. Patients with a spillage of mucus into the peritoneal cavity containing epithelial cells have a different prognosis than those with intact mucoceles, and a specimen of the fluid should be sent for analysis.5 In cases with epithelial cell contamination, patients may progress to developing pseudomyxoma peritonei, peritoneal carcinomatosis, or peritoneal tumors, which is why it is important to keep mucoceles intact during excisions. Peritoneal carcinomatosis may be treated with a combination of cytoreductive surgery and intraperitoneal chemotherapy, and patients should be referred to a peritoneal carcinomatosis treatment center for this definitive treatment.6 If a large mucocele is found during laparoscopy, conversion to laparotomy is safer, as it allows the specimen to be removed without rupturing and also allows for an exploration for mucoid fluid.7Excising a mucocele does not have to extend to the right hemicolectomy, unless there is an involvement of the appendiceal or ileocolic lymph nodes, although this is unusual. If a frozen section of the appendix shows a spread of tumor cells longitudinally, this would also require a right hemicolectomy to allow for an adequate removal.8The patient underwent a laparotomy during which a huge cystic lesion occupying much of the right side of the abdomen was found (Figure 2). Medial and lateral adhesions were divided to mobilize the mass. A limited right hemicolectomy was performed to remove the bowel and lesion en masse. The histology of the specimen confirmed a mucinous cystadenoma originating from the appendix. Following the operation, she made an uneventful recovery, required no further treatment, and is doing well.At laparotomy, a large cystic mass (black arrowhead) was found arising from the cecum (white arrowhead). After mobilizing the right colon, a limited right hemicolectomy with primary anastomosis was performed and the tumor was removed en masse.

Surgery

A 60-year-old woman was referred to the emergency department with a history of abdominal discomfort and a palpable mass in the right iliac fossa. She denied any change in her bowel habits or having experienced rectal bleeding. She had a normal appetite and had no history of weight loss. Before this admission, she was healthy, with no previous medical problems. On examination, her vital signs were within normal limits. She was mildly tender in the right iliac fossa and there was a large mobile mass, at least 10 cm in diameter, that was easily palpable in the right iliac fossa. She was initially investigated with a computed tomography (CT) scan of the abdomen (Figure 1). She underwent a colonoscopy that showed no intraluminal mucosal abnormalities or masses, but evidence of external compression at the cecum was noted.Coronal (A) and transverse (B) computed tomographic images show a large intra-abdominal cystic mass in the right iliac fossa.

what is your diagnosis?

What is your diagnosis?

Appendix abscess

Mucocele of the appendix

Neuroendocrine tumor

Cecal carcinoma

b

female

51-60

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2631753

A man in his 70s with history of pancreatic adenocarcinoma who had undergone a Whipple procedure 2 years prior to presentation came to the emergency department with a 1-day history of waxing and waning sharp abdominal pain radiating to his back. He admitted to nausea but no vomiting, fevers, or chills. He reported having normal bowel movements and passing flatus without difficulty. On examination, he was afebrile and not tachycardic. He had a well-healed abdominal midline wound. His abdomen was soft, not distended, and mildly tender diffusely, worse in the epigastrium, without rebound, guarding, or any palpable masses. His bloodwork revealed an elevated lipase level of 2842 U/L (to convert to microkatals per liter, multiply by 0.0167) without leukocytosis or any electrolyte abnormalities. Liver function test results were within normal limits. Given a history of pancreaticoduodenectomy, the patient underwent computed tomography of the abdomen and pelvis with oral and intravenous contrast for further evaluation (Figure).A, Axial cross-section of patient's computed tomographic scan of his abdomen and pelvis after a Whipple procedure. The stomach is distended with oral contrast and an air fluid level. A tubular solid structure can be seen within the body of the stomach. B, Coronal view demonstrating the tubular solid mass within the distended stomach. What Is Your Diagnosis?

Tumor recurrence

Marginal ulcer

Afferent loop syndrome

Internal hernia

C. Afferent loop syndrome

C

Afferent loop syndrome

The computed tomographic scan demonstrated a distended stomach, with intussusception of the afferent limb of the gastrojejunostomy from the patient’s Whipple procedure into the stomach with an air fluid level. Given the patient’s elevated lipase level and symptoms of epigastric pain radiating to the back, the patient was diagnosed with pancreatitis secondary to afferent loop syndrome from intussusception of the gastrojejunostomy into the stomach.Afferent loop syndrome, or mechanical obstruction of the afferent limb instigating pancreatobiliary issues, is a well-known delayed complication after gastrointestinal bypass surgery.1 The obstruction can be caused by kinking or compression of the afferent limb by postoperative adhesions, internal hernias, volvulus, or intussusception. Other causes include stenosis or obstruction at the gastrojejunostomy site from ulceration, radiation enteritis, tumor recurrence, bezoars, or foreign bodies.2 In a retrospective study of 186 patients who underwent pancreaticoduodenectomy and adjuvant therapy for pancreatic cancer, afferent loop syndrome was found in approximately 13% of long-term survivors (>2 years after surgery).3 The most common clinical signs and symptoms include abdominal pain, nausea, or vomiting. Interestingly, this study found that 2-year survival was the only independent predictor for the development of afferent limb syndrome after controlling for other factors such as age, sex, type of surgery, and adjuvant chemoradiation. Malignant obstruction from cancer recurrence was seen in 33% of the patients, while radiation enteropathy was found to be the cause in 38%.Patients with a surgical history of gastric bypass who present with pancreaticobiliary problems, such as obstructive jaundice, cholangitis, or pancreatitis, should be evaluated for afferent loop syndrome. Computed tomographic imaging is the diagnostic study of choice. Acute or complete obstruction of the afferent limb is a surgical emergency. If the obstruction is benign, surgery would include adhesiolysis and reconstruction; however, if the obstruction is malignant, then bypass or excision and reconstruction should be performed. Several studies favor endoscopic stenting or transhepatic percutaneous stenting; however, results are limited because these minimally invasive procedures are very technically difficult to do given the altered anatomy.4-6After fluid resuscitation and placement of a nasogastric tube, this patient underwent emergent exploratory laparotomy with manual evaluation of the intussusception. There was no evidence of bowel ischemia nor obvious tumor at the lead point. We converted the Billroth II type gastrojejunal anastomosis to a Roux-en-Y by performing a small-bowel resection followed by a side-to-side jejunojejunostomy. No other acute abdominal pathology nor recurrence of his cancer was identified.

Surgery

A man in his 70s with history of pancreatic adenocarcinoma who had undergone a Whipple procedure 2 years prior to presentation came to the emergency department with a 1-day history of waxing and waning sharp abdominal pain radiating to his back. He admitted to nausea but no vomiting, fevers, or chills. He reported having normal bowel movements and passing flatus without difficulty. On examination, he was afebrile and not tachycardic. He had a well-healed abdominal midline wound. His abdomen was soft, not distended, and mildly tender diffusely, worse in the epigastrium, without rebound, guarding, or any palpable masses. His bloodwork revealed an elevated lipase level of 2842 U/L (to convert to microkatals per liter, multiply by 0.0167) without leukocytosis or any electrolyte abnormalities. Liver function test results were within normal limits. Given a history of pancreaticoduodenectomy, the patient underwent computed tomography of the abdomen and pelvis with oral and intravenous contrast for further evaluation (Figure).A, Axial cross-section of patient's computed tomographic scan of his abdomen and pelvis after a Whipple procedure. The stomach is distended with oral contrast and an air fluid level. A tubular solid structure can be seen within the body of the stomach. B, Coronal view demonstrating the tubular solid mass within the distended stomach.

what is your diagnosis?

What is your diagnosis?

Marginal ulcer

Tumor recurrence

Internal hernia

Afferent loop syndrome

d

male

71-80

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2627270

A 67-year-old man presented with intermittent ocular irritation, discharge, and blurry vision in his left eye. He had a history of chronic lymphocytic leukemia for which he had received allogeneic bone marrow transplantation; his course was complicated by extensive graft-vs-host disease including ocular manifestations. His graft-vs-host disease was treated with systemic tacrolimus. He also had a history of herpes simplex keratitis with fungal infection in the right eye that led to corneal perforation requiring penetrating keratoplasty. His best-corrected visual acuities were 20/125 OD and 20/60 OS. Slitlamp examination of the right eye revealed eyelid margin hyperemia, penetrating keratoplasty graft in place, a deep and quiet anterior chamber, a normal iris, and posterior chamber intraocular lens. Examination of the left eye revealed eyelid margin hyperemia, an apparent soft tissue lesion on the palpebral conjunctiva of the left lower eyelid, inferior bulbar conjunctival injection, a small paracentral anterior stromal scar, a deep and quiet anterior chamber, a normal iris, and posterior chamber intraocular lens. The conjunctival lesion had vascular and papilliform elements (Figure) and had not been noted on a routine examination 6 months prior.Clinical photograph showing a soft-tissue lesion on the palpebral conjunctiva of the left lower eyelid, accompanied by inferior bulbar conjunctival injection. What Would You Do Next?

Perform time-domain anterior segment optical coherence tomography