A recent study found that 83% of VEXAS patients experienced skin involvement, often appearing early in the disease course.

The study elucidates the spectrum of cutaneous manifestations in VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome), a rare genetic disorder characterized by systemic inflammation and progressive bone marrow failure. The study, published in JAMA Dermatology, involved a cohort of 112 patients with VEXAS-defining genetic variants in the UBA1 gene.

Specific genetic variants in UBA1 correlated with distinct cutaneous presentations. Patients with the p.Met41Leu variant frequently exhibited Sweet syndrome–like neutrophilic lesions in 82% of cases, whereas those with the p.Met41Val variant predominantly presented with vasculitic lesions with mixed inflammatory infiltrates, seen in 55% of patients, according to study investigators.

Histopathological analysis supported these genotype-phenotype associations. The predominant skin histological findings included leukocytoclastic vasculitis (36%), neutrophilic dermatosis (34%), and perivascular dermatitis (30%). Oral prednisone was effective in improving skin manifestations in 92% of patients.

The study emphasized the importance of recognizing skin manifestations in the early diagnosis of VEXAS syndrome. Dermatological evaluation and genetic testing for UBA1 variants are recommended in older male patients presenting with cutaneous vasculitis, neutrophilic dermatoses, or chondritis to facilitate timely diagnosis and intervention for this condition.

"Interdisciplinary collaboration among dermatology, hematology, immunology, and rheumatology is vital to comprehensively understand the effect of genotype on the spectrum of clinical disease and survival outcomes," concluded study investigators.

Full disclosures can be found in the original study.