Study Highlights Spectrum of Skin Manifestations Among Patients with VEXAS Syndrome

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These data improve existing definitions of the spectrum of cutaneous manifestations reported by patients with VEXAS.

Isabella J. Tan, BS

Credit: LinkedIn

Isabella J. Tan, BS

Credit: LinkedIn

Skin manifestations are an early manifestation commonly seen among those with ‘vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic’ (VEXAS) syndrome, according to new findings, and genetic assessment for VEXAS may require consideration for older males with neutrophilic dermatoses, cutaneous vasculitis, or chondritis.1

These conclusions resulted from a recent study, led by Isabella J. Tan, BS, from Robert Wood Johnson Medical School at Rutgers University in New Jersey. Tan and colleagues sought to better define VEXAS syndrome’s spectrum of cutaneous manifestations and the associated features of the condition.

By doing this research, the investigators hypothesized that the findings could aid in future diagnoses as well as tailoring treatment to specific organs impacted among patients.2

“In this study of a large cohort of patients with VEXAS, we describe the patterns of cutaneous manifestations in VEXAS and the association of skin histopathologic findings with distinct genetic variants,” Tan and colleagues wrote.

Background and Methods

The investigators required that participants display at least a single clinical symptom of VEXAS in order to be included in the research. Additionally, subjects would have to have a somatic mutation in their UBA1 gene, which the investigators would verify.

The participants had been individuals referred between 2019 - 2023 to the National Institutes of Health (NIH) located in Bethesda, Maryland, as the patients had been suspected to have VEXAS syndrome. The research team used an observational cohort study design to assess data from a total of 112 subjects confirmed to have VEXAS-related genetic mutations in their UBA1 gene.

The team looked at demographic data including participants’ ages, ethnicity, sex, race, and specific UBA1 genetic variants. They also recorded several different clinical features linked to VEXAS, some of which included constitutional symptoms such as fever and night sweats as well as manifestations in subjects’ musculoskeletal, hematologic, cutaneous, cardiopulmonary, and other systems.

The NIH had assessed a total of 39 individuals directly, with the other 73 having had their clinical and laboratory reports gathered retrospectively from their medical records. The laboratory information evaluated by the investigators had included C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), hemoglobin, mean corpuscular volume, counts of platelets, and counts of white blood cells.

The investigators determined that the criteria for involvement with organs and hematologic abnormalities connected to VEXAS would be applied to both participant groups as previously established. They also looked at the pattern and distribution of lesions on the skin and their progression over the course of time.

Cutaneous symptom response to therapies was also evaluated subjectively by treating physicians, with clinical photographs taken of subjects with active disease at the time of their NIH assessments.

Findings

The research team found that skin involvement among the 112 subjects, with a median age of 69 and made up of 111 males, had been prevalent among 83%. This had also been identified as the most common initial symptom among 61%.

Among the 64 histopathologic reports of 60 individuals, the main skin histopathologic findings reported by the team included neutrophilic dermatosis, leukocytoclastic vasculitis, and perivascular dermatitis. Links to specific pathogenic genetic variants were shown to exist with particular cutaneous manifestations.

The p.Met41Leu variant was noted by the investigators as most commonly associated with neutrophilic dermal infiltrates, with this often resembling histiocytoid Sweet syndrome. Conversely, the team found that the p.Met41Val variant had been linked with vasculitic lesions with a mixed leukocytic infiltrate.

They added that oral prednisone had led to skin symptom improvement among 67 out of 73 individuals. Those with VEXAS syndrome who had been treated with anakinra often were shown by the team to have developed severe injection-site reactions such as ulceration or formation of abscesses.

“Dermatologists need to be aware of the broad spectrum of cutaneous and histopathologic features in VEXAS syndrome, since skin involvement is both a clinically defining and early feature of the disease,” they wrote.

References

  1. Tan IJ, Ferrada MA, Ahmad S, et al. Skin Manifestations of VEXAS Syndrome and Associated Genotypes. JAMA Dermatol. Published online June 12, 2024. doi:10.1001/jamadermatol.2024.1657.
  2. Sterling D, Duncan ME, Philippidou M, Salisbury JR, Kulasekararaj AG, Basu TN. VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) for the dermatologist. J Am Acad Dermatol. 2023;89(6):1209-1214. doi:10.1016/j.jaad.2022.01.042.
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