Dermatopathologist accuracy in classifying angioinvasive fungal infections using virtual microscopy.

BACKGROUND: Due to perceived difficulty in the categorization of angioinvasive fungal infections based on histopathology, variation exists in dermatopathology reporting. METHODS: This study characterized the diagnosis of angioinvasive fungal infections by light microscopy at a single academic institution over an 11-year period. Subsequently, the accuracy of blinded reclassification by virtual microscopy was measured. RESULTS: Seventy-six specimens with hematoxylin-eosin slides were obtained from 33 patients. The mean diagnostic accuracy of dermatopathologists in differentiating mucormycosis, hyalohyphomycosis, and phaeohyphomycosis based on blinded reclassification via virtual microscopy was 74%, with a range of 65%-91%. CONCLUSIONS: While there was a range in diagnostic accuracy, the highest score of 91% and the identification of common sources of error suggest that histopathologic categorization of angioinvasive fungal infections can frequently be performed. However, accurate identification is not always possible given common pitfalls in diagnosis. In addition, standardized and clinically useful reporting should be considered.

Cutaneous Necrosis of the Skin Secondary to Methicillin-Resistant Staphylococcus aureus (MRSA) and Bacteroides With Superimposed Herpes Simplex Virus Type II (HSV-II) in the Setting of Infective Endocarditis.

Herpes simplex virus type II (HSV-II) with superimposed bacterial skin infection is an uncommon presentation of cutaneous necrosis in the setting of infective endocarditis. This case reflects a unique presentation of an immunosuppressed patient with infective endocarditis complicated by septic emboli and cutaneous skin lesions attributable to HSV-II and superimposed bacterial skin infection. The patient presented from an outside hospital with symptoms consistent with acute onset heart failure and skin lesions. Transthoracic and transesophageal echocardiography performed there demonstrated focal thickening of the anterior mitral valve leaflet with severe mitral regurgitation. The patient then underwent extensive infectious work-up and was put on broad-spectrum antibiotics. Further work-up demonstrated greater than three DUKE minor criteria and reiterated the focal thickening of the anterior leaflet of the mitral valve, making infective endocarditis the most likely etiology. Biopsies of the skin lesions were performed which stained positive for HSV-II and grew methicillin-resistant Staphylococcus aureus and Bacteroides fragilis. The cardiothoracic surgery service ultimately decided not to perform any surgical intervention to the mitral valve during her hospitalization as she was deemed to be too high of a risk due to her thrombocytopenia and significant comorbidities. She was later discharged in hemodynamically stable condition on long-term intravenous antibiotics with repeat echocardiography demonstrating significant reduction in the mitral regurgitation and the focal thickening of the anterior leaflet of the mitral valve.

Myeloid Dendritic Cells Are Major Producers of IFN-ß in Dermatomyositis and May Contribute to Hydroxychloroquine Refractoriness.

Dermatomyositis pathogenesis remains incompletely understood; however, recent work suggests a predominant IFN-1 response. We explored dermatomyositis pathogenesis by quantifying the inflammatory cells in the skin, comparing myeloid with plasmacytoid dendritic cell release of IFN-ß, and assessing myeloid dendritic cell (mDC) contribution to hydroxychloroquine refractoriness. Immunohistochemistry was performed to assess cell-type expression in lesional skin biopsies from 12 patients with moderate-to-severe cutaneous dermatomyositis. Immunofluorescence, laser-capture microdissection, and flow cytometry were used to assess mDC release of IFN-ß in lesional skin biopsies and blood of patients with dermatomyositis. Immunohistochemistry was utilized to determine whether myeloid or plasmacytoid dendritic cells were increased in hydroxychloroquine nonresponders. CD4+, CD11c+, and CD69+ cells were more populous in lesional skin of patients with dermatomyositis. mDCs colocalized with IFN-ß by immunofluorescence and laser-capture microdissection revealed increased IFN-ß mRNA expression by mDCs in lesional skin of patients with dermatomyositis. In blood, both mDCs and plasmacytoid dendritic cells were major producers of IFN-ß in patients with dermatomyositis, whereas plasmacytoid dendritic cells predominately released IFN-ß in healthy controls (P < 0.01). mDCs were significantly increased in the skin of hydroxychloroquine nonresponders compared with that in the skin of responders (P < 0.05). mDCs cells appear to play an important role in dermatomyositis pathogenesis and IFN-ß production.

Increased MxA protein expression and dendritic cells in spongiotic dermatitis differentiates dermatomyositis from eczema in a single-center case-control study.

BACKGROUND: Dermatomyositis (DM) is conventionally characterized by interface dermatitis (ID) on skin histopathology. A subset of DM patients has skin biopsies showing spongiotic dermatitis (SD), a histopathology more commonly seen in eczema. In this study, we aimed to (a) identify the percentage of clinically diagnosed DM patients with SD skin biopsies, (b) identify cytokine and cell markers that can help determine if a SD skin biopsy is consistent with DM. METHODS: In this case-control study, biopsy specimens from ten DM patients with SD (DM-SD) were compared to specimens from ten healthy controls, ten patients with eczema, and 12 patients with DM with ID (DM-ID). Specimens were stained by immunohistochemistry for MxA, IFN-ß, CD11c, and BDCA2. One-way ANOVA with Bonferroni's multiple comparison test was used to compare protein expression between groups. RESULTS: Eleven of 164 (6.7%) patients with a clinical diagnosis of DM at our tertiary care center were identified as having SD. MxA, IFN-ß, CD11c, and BDCA2 protein expression was significantly higher in DM-SD compared to eczema and healthy controls. Expressions of MxA, IFN-ß, and BDCA2 were not significantly different between DM-SD and DM-ID. CONCLUSION: Increased MxA, IFN-ß, CD11c, and BDCA2 protein expression may aid in distinguishing between DM-SD and eczema and warrants further investigation.

Applicability of EULAR/ACR classification criteria for dermatomyositis to amyopathic disease.

BACKGROUND: Existing classification systems for idiopathic inflammatory myopathies (IIMs) fail to permit classification and/or diagnosis of amyopathic dermatomyositis (ADM) in patients. OBJECTIVE: In light of the new European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for IIM, we evaluated the likelihood of the skin variables included in the EULAR/ACR criteria (Gottron's sign, Gottron's papules, and heliotrope rash) to give a high probability of classifying patients with ADM. METHODS: This retrospective study evaluated 211 adult patients with dermatomyositis at the University of Pennsylvania. The EULAR/ACR criteria were used to determine the probability of classification for patients with ADM. RESULTS: Of patients with ADM, 73.7% would be classified as having a reasonable probability of dermatomyositis on the new EULAR/ACR criteria and 26.3% would not meet the suggested 55% minimum probability cutoff to be classified as having it on the basis of the EULAR/ACR criteria. LIMITATIONS: This study was conducted with a retrospective design at a tertiary academic medical center. CONCLUSIONS: The 3 skin variables included in the EULAR/ACR classification criteria for IIM improve on previous criteria but miss classifying some patients with ADM. It is important to consider additional variables such as skin biopsy results to encompass more of these patients and prevent the inclusion of any skin diseases mimicking ADM.