RESUMO
ABSTRACT Gain-of-function mutations in the STAT1 gene have been initially associated with chronic mucocutaneous candidiasis. However, further research has shown that STAT1 GOF variants may increase susceptibility to infection by other intracellular pathogens. This report describes the first case of disseminated leishmaniasis associated with a STAT1 GOF mutation in a pediatric patient who did not have chronic mucocutaneous candidiasis. The patient was a four-year-old boy presenting with fever, severe asthenia, hepatosplenomegaly, pancytopenia, and liver failure. Bone marrow aspirate revealed hemophagocytosis and Leishmania parasites. Treatment consisted primarily of liposomal amphotericin B, as per the Hemophagocytic Lymphohistiocytosis 2004 protocol. After eight weeks of treatment, the patient did not improve and was submitted to diagnostic splenectomy. Activated macrophages and nodular spleen necrosis secondary to the visceral leishmaniasis were detected. Unfortunately, the patient died in the second week after splenectomy due to overwhelming systemic infection. DNA sequencing revealed a pathogenic (p. R274Q) GOF mutation in STAT1.
RESUMO
Introdução: A dermatite atópica é uma doença inflamatória crônica da pele que nas suas formas moderadas e graves afeta profundamente a qualidade de vida dos seus portadores e familiares. O metotrexato tem sido indicado off-label para casos graves e refratários em crianças e adolescentes, pois é uma opção terapêutica acessível e de baixo custo. Existe uma escassez de publicações envolvendo a medicação, sobretudo na faixa etária pediátrica. Objetivo e método: O presente estudo busca avaliar as características clínicas das crianças e adolescentes em uso atual ou prévio de metotrexato para tratamento de dermatite atópica moderada ou grave. Foram incluídos 10 pacientes, 60% do gênero masculino, mediana de idade no início do metotrexato de 14 anos (variando de 3 a 18 anos), e mediana do tempo de evolução da dermatite atópica de 14 anos (variando de 3 a 17 anos). Rinite alérgica e asma em 100% e 50% casos, respectivamente, e transtornos psíquicos em 60%. Resultados: Seis pacientes obtiveram melhora clínica com mediana de tempo de 9 meses (variando de 4 a 14 meses) e mediana do Scoring Atopic Dermatitis inicial de 50,5 (IIQ 13,8) e de 32,5 (IIQ 24,3) após 12 a 15 meses de tratamento. Efeitos adversos foram observados em 20% dos casos, e suspensão do metotrexato em apenas um paciente. Conclusão: Nesta série de casos com dez pacientes houve melhora clínica em seis, com poucos efeitos adversos, sendo uma alternativa terapêutica válida.
Introduction: Atopic dermatitis is a chronic inflammatory disease of the skin that in its moderate and severe forms profoundly affects the quality of life of patients and their families. Methotrexate has been used off-label for severe and refractory cases in children and adolescents, as it is an affordable and low-cost therapeutic option. There is a lack of publications addressing this medication, especially in the pediatric age group. Objective and method: The present study seeks to evaluate the clinical characteristics of children and adolescents in current or previous use of methotrexate for the treatment of moderate or severe atopic dermatitis. Ten patients were included, 60% were male, median age at the beginning of methotrexate use was 14 years (ranging from 3 to 18 years), and median time of course of atopic dermatitis was 14 years (ranging from 3 to 17 years). Allergic rhinitis and asthma were found in 100% and 50% of cases, respectively, and mental disorders in 60%. Results: Six patients achieved clinical improvement with a median time of 9 months (ranging from 4 to 14 months) and a median score in the initial Scoring Atopic Dermatitis of 50.5 (interquartile range, 13.8) and 32.5 (interquartile range, 24.3) after 12 to 15 months of treatment. Adverse effects were reported in 20% of cases, and methotrexate discontinuation in only one patient. Conclusion: In this case series of ten patients, methotrexate led to clinical improvement in six patients with few adverse effects, thus being a valid therapeutic alternative.