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Background: Hand, foot, and mouth disease is a contagious viral infection usually affecting children. A resurgence of cases in adults, mainly caused by coxsackievirus A6 and with an atypical and more severe presentation, has taken place.Objective: The goal was to examine the clinical, histologic, and immunohistochemical features of this disease in adults.Methods: This is a retrospective study on documented cases of adult hand, foot, and mouth disease from France's Dermatology Department of Strasbourg University Hospital and Bel-Air Hospital in Thionville.Results: Six patients with severe and atypical presentation were included, 4 caused by coxsackievirus A6. The histologic features were: spongiosis, neutrophilic exocytosis, massive keratinocyte necrosis, shadow cells in the upper epidermis, vacuolization of basal cells, necrotic cells in follicles and sweat glands, dense superficial dermal infiltrate of CD3+ lymphocytes, and strong granulysin expression.Limitations: This is a retrospective case series.Conclusion: In adult patients presenting with atypical hand, foot, and mouth disease caused by coxsackievirus A6, biopsy specimens show distinctive changes in the epidermis but also in adnexal structures. The inflammatory infiltrate is made of T cells with a cytotoxic profile, with numerous granulysin-positive cells, as observed in severe drug-induced eruption with necrosis of keratinocytes. [ABSTRACT FROM AUTHOR]

Background: Generalized bullous fixed drug eruption (GBFDE), a particular form of fixed drug eruption (FDE), is characterized by widespread blisters and erosions and can be confused with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Objective: We sought to analyze specific features of GBFDE and differentiate it from SJS/TEN. Methods: We retrospectively studied patients with GBFDE and SJS/TEN during a period of 10 years. GBFDE was defined as typical FDE lesions with blisters involving at least 10% body surface area on at least 3 of 6 different anatomic sites. Clinical presentations; histopathological features; immunohistochemical patterns of cluster-of-differentiation (CD)3, CD4, CD8, CD56, Fas, Fas ligand, granzyme B, perforin, granulysin, and forkhead box P3 (Foxp3); and serum granulysin levels were compared. Results: Twenty-three cases of GBFDE were collected. Patients with GBFDE had shorter latent periods, less mucosal involvement, more eosinophil infiltration, and dermal melanophages. Lesional infiltrates in GBFDE had more dermal CD4+ cells including Foxp3+ regulatory T cells, fewer intraepidermal CD56+ cells, and fewer intraepidermal granulysin+ cells. The serum level of granulysin in GBFDE was also significantly lower than in SJS/TEN. Limitations: The number of cases in this study is small. Conclusion: GBFDE is a distinct disease distinguishable from SJS/TEN by particular features such as granulysin, CD56, and Foxp3 expressions. [Copyright &y& Elsevier]

Background: Life-threatening adverse drug reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) sometimes start with clinical features of ordinary drug-induced skin reactions (ODSRs) and it may be difficult to make a correct diagnosis before severe mucocutaneous erosions occur. We have reported that serum granulysin levels are elevated (cut off: 10 ng/mL) in patients with SJS/TEN before generalized blisters form. Objective: We sought to develop a rapid detection system for elevated serum granulysin to predict the progression from ODSRs. Methods: Serum samples from 5 patients with SJS/TEN at 2 to 4 days before mucocutaneous erosions formed were analyzed. Sera from 24 patients with ODSRs and 31 healthy volunteers were also investigated as control subjects. We developed a rapid immunochromatographic assay for the detection of high levels of serum granulysin using two different antigranulysin monoclonal antibodies. Results: The immunochromatographic test showed positive results for 4 of 5 patients with SJS/TEN but only one patient of 24 with ODSRs. The results correlated closely with those of enzyme-linked immunosorbent assays. Limitations: The validation of the long-time stability in this test strip has not been investigated. Conclusion: This novel test enables the prediction of SJS/TEN occurrence in patients even when only features of ODSRs are noted clinically. [ABSTRACT FROM AUTHOR]

Toxic epidermal necrolysis (TEN) is a life-threatening, typically drug-induced, mucocutaneous disease. TEN has a high mortality rate, making early diagnosis and treatment of paramount importance. New but experimental diagnostic tools that measure serum granulysin and high-mobility group protein B1 (HMGB1) offer the potential to differentiate early TEN from other, less serious drug reactions, but these tests have not been validated and are not readily available. The mainstay of treatment for TEN involves discontinuation of the offending drug, specialized care in an intensive care unit or burn center, and supportive therapy. Pharmacogenetic studies have clearly established a link between human leukocyte antigen allotype and TEN. Human leukocyte antigen testing should be performed on patients of East Asian descent before the initiation of carbamezapine and on all patients before the initiation of abacavir. The effectiveness of systemic steroids, intravenous immunoglobulins, plasmapheresis, cyclosporine, biologics, and other agents is uncertain. [Copyright &y& Elsevier]

Toxic epidermal necrolysis is a life-threatening, typically drug-induced mucocutaneous disease. It is clinically characterized as a widespread sloughing of the skin and mucosa, including both external and internal surfaces. Histologically, the denuded areas show full thickness epidermal necrosis. The pathogenic mechanism involves antigenic moiety/metabolite, peptide-induced T cell activation, leading to keratinocyte apoptosis through soluble Fas ligand, perforin/granzyme B, tumor necrosis factor–alfa, and nitric oxide. Recent studies have implicated granulysin in toxic epidermal necrolysis apoptosis and have suggested that it may be the pivotal mediator of keratinocyte death. [Copyright &y& Elsevier]