Erythema multiforme (EM) is an uncommon, immune‐mediated disorder that presents with cutaneous or mucosal lesions or both. In herpes simplex virus (HSV)–associated EM, the findings are thought to ...result from cell‐mediated immune reaction against viral antigen‐positive cells that contain the HSV DNA polymerase gene (pol ). The target lesion, with concentric zones of color change, represents the characteristic cutaneous finding seen in this disorder. Although EM can be induced by various factors, HSV infection continues to be the most common inciting factor. Histopathologic testing and other laboratory investigations may be used to confirm the diagnosis of EM and to differentiate it from other clinical imitators. Imitators of EM include urticaria, Stevens‐Johnson syndrome, fixed drug eruption, bullous pemphigoid, paraneoplastic pemphigus, Sweet's syndrome, Rowell's syndrome, polymorphus light eruption, and cutaneous small‐vessel vasculitis. Because disease severity and mucosal involvement differ among patients, treatment should be tailored to each patient, with careful consideration of treatment risk vs benefit. Mild cutaneous involvement of EM can be managed primarily with a goal of achieving symptomatic improvement; however, patients with HSV‐associated recurrent EM and idiopathic recurrent EM require treatment with antiviral prophylaxis. Inpatient hospitalization may be required for patients with severe mucosal involvement that causes poor oral intake and subsequent fluid and electrolyte imbalance. With this review, we strive to provide guidance to the practicing dermatologist in the evaluation and treatment of a patient with EM.
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Abstract Objective To describe the clinical characteristics, histopathologic features, and outcomes of patients in whom vasculitis developed in association with use of tumor necrosis factor-α (TNF-α) ...inhibitors. Patients and Methods This is a retrospective review of patients evaluated at Mayo Clinic, Rochester, Minnesota, from January 1, 1998, through March 31, 2011, with a diagnosis of vasculitis induced by anti–TNF-α therapy. Results Of 8 patients with vasculitis associated with anti–TNF-α therapy (mean age, 48.5 years), 6 (75%) were female. Four (50%) had rheumatoid arthritis, 1 (13%) had Crohn disease, and 3 (38%) had ulcerative colitis. Five (63%) were treated with infliximab, 2 (25%) with etanercept, and 1 (13%) with adalimumab. The mean duration of treatment before development of vasculitis was 34.5 months. The skin was the predominant organ affected (5 patients 63%), with the most common cutaneous lesion being palpable purpura (4 of 5 80%). Two organs involved in systemic vasculitis were the peripheral nervous system (4 patients 50%) and kidney (1 patient 13%). All cases of vasculitis were histopathologically confirmed. Seven of 8 patients improved with discontinuation of therapy (mean time to resolution, 6.9 months) and adjuvant treatment (all 8 received prednisone; another agent was also used in 7); rechallenge with anti–TNF-α therapy was not attempted in any patient. At last follow-up, no patients had experienced a recurrence of vasculitis after therapy discontinuation. Conclusion Cutaneous small-vessel vasculitis was the most common finding, but systemic vasculitis, including peripheral nerve and renal vasculitis, was also frequently observed.
Pernio or chilblains is characterized by erythema and swelling at acral sites (eg, toes and fingers), typically triggered by cold exposure. Clinical and histopathologic features of pernio are well ...described, but the pathogenesis is not entirely understood; vasospasm and a type I interferon (IFN-I) immune response are likely involved. During the coronavirus disease 2019 (COVID-19) pandemic, dermatologists have observed an increase in pernio-like acral eruptions. Direct causality of pernio due to COVID-19 has not been established in many cases because of inconsistent testing methods (often negative results) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, a form of COVID-19‒associated pernio (also called COVID toes) is probable because of increased occurrence, frequently in young patients with no cold exposure or a history of pernio, and reports of skin biopsies with positive SARS-CoV-2 immunohistochemistry. PubMed was searched between January 1, 2020, and December 31, 2020 for publications using the following keywords: pernio, chilblain, and acral COVID-19. On the basis of our review of the published literature, we speculate that several unifying cutaneous and systemic mechanisms may explain COVID-19‒associated pernio: (1) SARS-CoV-2 cell infection occurs through the cellular receptor angiotensin-converting enzyme 2 mediated by transmembrane protease serine 2, subsequently affecting the renin-angiotensin-aldosterone system with an increase in the vasoconstricting, pro-inflammatory, and prothrombotic angiotensin II pathway. (2) Severe acute respiratory syndrome coronavirus 2 cell infection triggers an immune response with robust IFN-I release in patients predisposed to COVID-19‒associated pernio. (3) Age and sex discrepancies correlated with COVID-19 severity and manifestations, including pernio as a sign of mild disease, are likely explained by age-related immune and vascular differences influenced by sex hormones and genetics, which affect susceptibility to viral cellular infection, the renin-angiotensin-aldosterone system balance, and the IFN-I response.
To determine the population-based incidence of leukocytoclastic vasculitis (LCV).
This is a retrospective population-based study of all Olmsted County, Minnesota, residents with a skin biopsy-proven ...diagnosis of LCV from January 1, 1996, through December 31, 2010.
A total of 84 patients (mean age at diagnosis, 48.3 years) with newly diagnosed skin biopsy-proven LCV (43 women and 41 men) were identified. The incidence rate (age and sex adjusted to the 2000 US white population) was 4.5 per 100,000 person-years (95% CI, 3.5-5.4). The incidence of LCV increased significantly with age at diagnosis (P<.001) and did not differ between female and male patients. Subtypes of LCV were cutaneous small-vessel vasculitis (CSVV), 38 patients (45%); IgA vasculitis, 25 (30%); urticarial vasculitis, 10 (12%); cryoglobulinemic vasculitis, 3 (4%); and antineutrophil cytoplasmic antibody-associated vasculitis, 8 (10%). LCV was idiopathic in 29 of 38 patients with CSVV (76%) and 24 of 25 patients with IgA vasculitis (96%). Thirty-nine of 84 patients (46%) had systemic involvement, with the renal system most commonly involved (17 of 39 44%). Twenty-four of 80 patients (30%) with follow-up data available had recurrent disease. Compared with the Minnesota white population, observed survival in the incident LCV cohort was significantly poorer than expected (P<.001), including the subset of patients with idiopathic CSVV (P=.03).
The incidence of LCV was higher than that reported in previously published studies. Idiopathic LCV was more common in our population-based cohort than that described previously. Overall survival was significantly poorer (P<.001) and should be explored further in future studies.
OBJECTIVE To examine clinical, etiologic, and histologic features of Stevens-Johnson syndrome and to identify possible correlates of clinical disease severity related to etiologic and histopathologic ...findings. PATIENTS AND METHODS This is a retrospective review of patients seen at Mayo Clinic between January 1, 2000, and December 31, 2007. RESULTS Of 27 patients (mean age, 28.1 years), 22 (81%) had involvement of 2 or more mucous membranes, and 19 (70%) had ocular involvement. Medications, most commonly antibiotics and anticonvulsants, were causative in 20 patients. Mycoplasma pneumoniae infection caused 6 of the 27 cases. Corticosteroids were the most common systemic therapy. No patients with mycoplasma-induced Stevens-Johnson syndrome had internal organ involvement or required treatment in the intensive care unit, in contrast to 4 patients each in the drug-induced group. Three patients had chronic ocular sequelae, and 1 died of complications. Biopsy specimens from 13 patients (48%) showed epidermal necrosis (8 patients), basal vacuolar change (10 patients), and subepidermal bullae (10 patients). Biopsy specimens from 11 patients displayed moderate or dense dermal infiltrate. Histologic features in drug-induced cases included individual necrotic keratinocytes, dense dermal infiltrate, red blood cell extravasation, pigment incontinence, parakeratosis, and substantial eosinophils or neutrophils. CONCLUSION Our clinical and etiologic findings corroborate those in previous reports. M pneumoniae —induced Stevens-Johnson syndrome manifested less severely than its drug-induced counterpart. The limited number of biopsies precludes unequivocal demonstration of histopathologic differences between drug-induced and M pneumoniae —induced Stevens-Johnson syndrome.
To further characterize the clinical features, etiologic associations, laboratory findings, and treatment of pernio.
This is a retrospective review of patients with pernio seen at our institution ...between January 1, 2000, and December 31, 2011.
Of 104 patients with pernio (mean age at diagnosis, 38.3 years), 82 (79%) were women. Pernio affected the toes in 85 patients (82%) and the fingers in 31 (30%). Thirty-eight patients (37%) had at least 1 abnormal laboratory test result, and test results were positive for cold agglutinins in 11 (55%) of 20 tested patients. Results were negative for cryoglobulins in all tested patients (n=53). Four patients (4%) had connective tissue disease (nonlupus) associated with pernio; 3 patients (3%) had an associated hematologic malignant disease. Conservative treatments (eg, warming, drying, and smoking cessation) provided complete response in 23 (82%) of 28 patients with follow-up data.
To our knowledge, this study represents one of the largest single-center case series of pernio to date. Most of the patients did not have an underlying systemic association with pernio, although a few patients had pernio in association with connective tissue disease or hematologic malignant disease.
Immune checkpoint inhibitors are approved for select cancer treatment and have shown survival benefit in patients with advanced melanoma. Adverse events, including immune-related adverse events, are ...common and potentially life-threatening. We describe cases of 2 patients with scleroderma (patient 1 had diffuse scleroderma, and patient 2 had limited scleroderma) that developed while they were receiving pembrolizumab therapy for metastatic melanoma. Prompt recognition and treatment of immune-related adverse events may improve tolerance to immune checkpoint inhibitors and contribute to an understanding of the manifesting autoimmune disease.
Monoclonal gammopathy associated with dermatological manifestations are a well-recognized complication. These skin disorders can be associated with infiltration and proliferation of a malignant ...plasma cells or by a deposition of the monoclonal immunoglobulin in a nonmalignant monoclonal gammopathy. These disorders include POEMS syndrome, light chain amyloidosis, Schnitzler syndrome, scleromyxedema and TEMPI syndrome. This article provides a review of clinical manifestations, diagnostics criteria, natural evolution, pathogenesis, and treatment of these cutaneous manifestations.
To report on the survival and the associations of treatments upon survival of patients with calciphylaxis seen at a single center.
Using the International Classification of Diseases, Ninth Revision ...diagnosis code of 275.49 and the keyword "calciphylaxis" in the dismissal narrative, we retrospectively identified 101 patients with calciphylaxis seen at our institution between January 1, 1999, through September 20, 2014, using a predefined, consensus-developed classification scheme.
The average age of patients was 60 years: 81 (80.2%) were women; 68 (68.0%) were obese; 19 (18.8%) had stage 0 to 2 chronic kidney disease (CKD), 19 (18.9%) had stage 3 or 4 CKD; 63 (62.4%) had stage 5 or 5D (dialysis) CKD. Seventy-five patients died during follow-up. Six-month survival was 57%. Lack of surgical debridement was associated with insignificantly lower 6-month survival (hazard ratio HR=1.99; 95% CI, 0.96-4.15; P=.07) and significantly poorer survival for the entire duration of follow-up (HR=1.98; 95% CI, 1.15-3.41; P=.01), which was most pronounced in stage 5 or 5D CKD (HR=1.91; 95% CI, 1.03-3.56; P=.04). Among patients with stage 5/5D CKD, subtotal parathyroidectomy (performed only in patients with hyperparathyroidism) was associated with better 6-month (HR=0.12; 95% CI, 0.02-0.90; P=.04) and overall survival (HR= 0.37; 95% CI, 0.15-0.87; P=.02).
Calciphylaxis is associated with a high mortality rate. Significantly effective treatments included surgical debridement and subtotal parathyroidectomy in patients with stage 5/5D CKD with hyperparathyroidism. Treatments with tissue-plasminogen activator, sodium thiosulfate, and hyperbaric oxygen therapy were not associated with higher mortality.
To prepare a dermatologic addendum to the 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides (CHCC2012) to address vasculitides affecting the skin (D-CHCC). The ...goal was to standardize the names and definitions for cutaneous vasculitis.
A nominal group technique with a facilitator was used to reach consensus on the D-CHCC nomenclature, using multiple face-to-face meetings, e-mail discussions, and teleconferences.
Standardized names, definitions, and descriptions were adopted for cutaneous components of systemic vasculitides (e.g., cutaneous IgA vasculitis as a component of systemic IgA vasculitis), skin-limited variants of systemic vasculitides (e.g., skin-limited IgA vasculitis, drug-induced skin-limited antineutrophil cytoplasmic antibody-associated vasculitis), and cutaneous single-organ vasculitides that have no systemic counterparts (e.g., nodular vasculitis). Cutaneous vasculitides that were not included in the CHCC2012 nomenclature were introduced.
Standardized names and definitions are a prerequisite for developing validated classification and diagnostic criteria for cutaneous vasculitis. Accurate identification of specifically defined variants of systemic and skin-limited vasculitides requires knowledgeable integration of data from clinical, laboratory, and pathologic studies. This proposed nomenclature of vasculitides affecting the skin, the D-CHCC, provides a standard framework both for clinicians and for investigators.
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