TOPLINE

Skin involvement occurred in 88% of patients with VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome and was among the presenting features in 65%, yet the mean diagnostic delay was 2.7 years in a study.

METHODOLOGY

• Researchers retrospectively reviewed skin manifestations in 43 men with genetically confirmed VEXAS syndrome referred to a multidisciplinary clinic at a tertiary referral center in the United Kingdom from March 2021 to March 2026.
• The mean age at symptom onset was 69 years.
• The most common treatment received was corticosteroids (88%), chemotherapy (73%), and targeted biologic treatment (21%).

TAKEAWAY

• Skin involvement was documented in 38 patients (88%), with skin signs among the presenting features in 28 patients (65%). The mean diagnostic delay was 2.7 years and six patients had died at the last follow-up.
• Most common skin involvements were Sweet syndrome-like neutrophilic dermatosis (40%) and cutaneous vasculitis (21%), with orbital inflammation (37%) and auricular chondritis (26%) as common accompanying findings. The most common hematological associations were underlying myelodysplastic syndrome (67%) and macrocytic anemia (65%), and patients reported weight loss (33%), fever (21%) and arthralgia (51%) as systemic symptoms.
• Skin biopsies classically showed a dense dermal neutrophilic infiltrate, which was histiocytoid in seven cases and "may be misread as a histiocytic or granulomatous process unless myeloperoxidase staining is performed."
• UBA1 variants were identified in blood or bone marrow specimens, with a median variant allele frequency of 64%. The p.Met41Leu variant was associated with neutrophilic dermatosis in 64% of cases, while p.Met41Val was linked to cutaneous vasculitis in 43% and higher mortality.

IN PRACTICE

"The skin is often where VEXAS first declares itself, placing the dermatologist in a key position to recognize it," the authors wrote. "In any older man with a refractory neutrophilic dermatosis, vasculitis, chondritis or orbital inflammation, particularly with unexplained macrocytic anemia or cytopenias, VEXAS should be considered and UBA1 variant analysis undertaken promptly, noting that low-level variants may require sensitive, targeted sequencing."

SOURCE

The study was led by Rachel Blyth, King's College Hospital, London. It was published online on October 3 in the Journal of the European Academy of Dermatology and Venereology.

LIMITATIONS

The retrospective, single-center design and gaps in histologic assessment of the skin lesions limited the findings.

DISCLOSURES

The study did not receive any funding and the authors declared having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.