JAMA Dermatology

<jats:sec id="ab-doi240018-4"><jats:title>Importance</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec id="ab-doi240018-5"><jats:title>Objective</jats:title><jats:p>To define the spectrum of cutaneous manifestations in VEXAS syndrome and the association of these findings with clinical, genetic, and histological features.</jats:p></jats:sec><jats:sec id="ab-doi240018-6"><jats:title>Design, Setting, and Participants</jats:title><jats:p>This observational cohort study included data from 112 patients who were diagnosed with VEXAS-defining genetic variants in <jats:italic>UBA1</jats:italic> 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.</jats:p></jats:sec><jats:sec id="ab-doi240018-7"><jats:title>Main Outcomes and Measures</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec id="ab-doi240018-8"><jats:title>Results</jats:title><jats:p>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%]).</jats:p></jats:sec><jats:sec id="ab-doi240018-9"><jats:title>Conclusions and Relevance</jats:title><jats:p>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.</jats:p></jats:sec>

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N Engl J Med

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Blood

VEXAS syndrome: an inflammatory and hematologic disease.

Semin Hematol

Estimated prevalence and clinical manifestations of UBA1 variants associated with VEXAS syndrome in a clinical population.

JAMA

Translation of cytoplasmic UBA1 contributes to VEXAS syndrome pathogenesis.

UBA1 variations in neutrophilic dermatosis skin lesions of patients with VEXAS syndrome.

JAMA Dermatol

Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients.

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VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) for the dermatologist.

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Clinical characteristics, disease trajectories and management of vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome: a systematic review.

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Allogeneic stem cell transplantation as a curative therapeutic approach for VEXAS syndrome: a case report.

Clinical and pathological features of cutaneous manifestations in VEXAS syndrome: a multicenter retrospective study of 59 cases.

Histiocytoid Sweet syndrome is more frequently associated with myelodysplastic syndromes than the classical neutrophilic variant: a comparative series of 62 patients.

Medicine (Baltimore)

Sweet syndrome: clinical presentation, malignancy association, autoinflammatory disorders and treatment response in a cohort of 93 patients with long-term follow-up.

Acta Derm Venereol

Vasculitis associated with VEXAS syndrome: a literature review.

Front Med (Lausanne)

VEXAS-defining UBA1 somatic variants in 245,368 diverse individuals in the NIH All Of Us cohort.

Arthritis Rheumatol

Cutaneous involvement in VEXAS syndrome: clinical and histopathologic findings.

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Atypical extensive lupus tumidus-like eruption as an early presentation of VEXAS syndrome.

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.
To define the spectrum of cutaneous manifestations in VEXAS syndrome and the association of these findings with clinical, genetic, and histological features.
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.
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.
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%]).
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.

Skin Manifestations of VEXAS Syndrome and Associated Genotypes.

Skin Manifestations of VEXAS Syndrome and Associated Genotypes

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