RESUMO
Purpose: Heterozygous missense STAT1 mutations leading to a gain of function (GOF) are the most frequent genetic cause of chronic mucocutaneous candidiasis (CMC). We describe the case of a patient presenting a new GOF mutation of STAT1 with the clinical symptoms of CMC, recurrent pneumonia, and persistent central erythema with papulopustules with ocular involvement related to rosacea-like demodicosis. Methods: Genetic analysis via targeted next-generation sequencing (NGS; NGS panel DIPAI v.1) exploring the 98 genes most frequently involved in primary immunodeficiencies, including STAT1, was performed to identify an underlying genetic defect. Results: NGS identified a novel variant of STAT1, c.884C>A (exon 10), p.T295Y, not previously described. This variant was found to be gain of function using an in vitro luciferase reporter assay. Rosacea-like demodicosis was confirmed by substantial Demodex proliferation observed via the microscopic examination of a cutaneous sample. A review of literature retrieved 20 other cases of STAT1 GOF mutations associated with early-onset rosacea-like demodicosis, most with ocular involvement. Conclusion: We describe a new STAT1 GOF mutation associated with a phenotype of CMC and rosacea-like demodicosis. Rosacea-like demodicosis appears as a novel and important clinical phenotype among patients with STAT1 GOF mutation.
Assuntos
Candidíase Mucocutânea Crônica/genética , Infestações por Ácaros/genética , Rosácea/genética , Fator de Transcrição STAT1/genética , Adulto , Candidíase Mucocutânea Crônica/patologia , Feminino , Mutação com Ganho de Função , Humanos , Infestações por Ácaros/patologia , Rosácea/patologia , Pele/patologiaAssuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Rinofima/epidemiologia , Rinofima/etiologia , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Estudos de Casos e Controles , Intervalos de Confiança , Progressão da Doença , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Prevalência , Prognóstico , Estudos Retrospectivos , Rinofima/fisiopatologia , Medição de Risco , Índice de Gravidade de Doença , Distribuição por SexoRESUMO
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.
