Skin Manifestations of VEXAS Syndrome and Associated Genotypes.

Autor:	Tan IJ; Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey., Ferrada MA; University of Maryland School of Medicine, Baltimore., Ahmad S; Cleveland Clinic Children's, Cleveland, Ohio., Fike A; Vasculitis Translational Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland., Quinn KA; Vasculitis Translational Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland., Groarke EM; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland., Beck DB; Department of Medicine and Center for Human Genetics and Genomics, NYU Grossman School of Medicine, New York University, New York., Allbritton J; The Joint Pathology Center, Silver Spring, Maryland., Castelo-Soccio L; Dermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland., Young NS; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland., Patel BA; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland., Grayson PC; Vasculitis Translational Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland., Cowen EW; Dermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland.
Jazyk:	angličtina
Zdroj:	JAMA dermatology [JAMA Dermatol] 2024 Aug 01; Vol. 160 (8), pp. 822-829.
DOI:	10.1001/jamadermatol.2024.1657
Abstrakt:	Importance: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly defined genetic disease with an estimated prevalence of 1 in 4269 men older than 50 years and is marked by systemic inflammation, progressive bone marrow failure, and inflammatory cutaneous manifestations. Objective: To define the spectrum of cutaneous manifestations in VEXAS syndrome and the association of these findings with clinical, genetic, and histological features. Design, Setting, and Participants: This observational cohort study included data from 112 patients who were diagnosed with VEXAS-defining genetic variants in UBA1 between 2019 and 2023. Data were collected from medical record review or from patients with VEXAS directly evaluated at the National Institutes of Health in Bethesda, Maryland. Main Outcomes and Measures: To define the spectrum of cutaneous manifestations in VEXAS in association with genetic, histological, and other clinical findings. A secondary outcome was cutaneous response to treatment in VEXAS. Results: Among the 112 patients (median [range] age, 69 [39-79] years; 111 [99%] male), skin involvement was common (93 [83%]), and the most frequent presenting feature of disease (68 [61%]). Of 64 histopathologic reports available from 60 patients, predominant skin histopathologic findings were leukocytoclastic vasculitis (23 [36%]), neutrophilic dermatosis (22 [34%]), and perivascular dermatitis (19 [30%]). Distinct pathogenic genetic variants were associated with specific cutaneous manifestations. The p.Met41Leu variant was most frequently associated with neutrophilic dermal infiltrates (14 of 17 patients [82%]), often resembling histiocytoid Sweet syndrome. In contrast, the p.Met41Val variant was associated with vasculitic lesions (11 of 20 patients [55%]) with a mixed leukocytic infiltrate (17 of 20 patients [85%]). Oral prednisone improved skin manifestations in 67 of 73 patients (92%). Patients with VEXAS treated with anakinra frequently developed severe injection-site reactions (12 of 16 [75%]), including ulceration (2 of 12 [17%]) and abscess formation (1 of 12 [8%]). Conclusions and Relevance: Results of this cohort study show that skin manifestations are a common and early manifestation of VEXAS syndrome. Genetic evaluation for VEXAS should be considered in older male patients with cutaneous vasculitis, neutrophilic dermatoses, or chondritis. Awareness of VEXAS among dermatologists is critical to facilitate early diagnosis.
Databáze:	MEDLINE
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