Skin manifestations of VEXAS syndrome associated with specific genotypes
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Key takeaways:
- VEXAS syndrome often has skin manifestations, but these often mimic symptoms of Sweet syndrome or vasculitis.
- Specific pathogenic genetic variants genetic were associated with certain skin manifestations.
Skin manifestations are common in VEXAS syndrome and evaluating their presentations can assist in genotyping the disease and possibly lead to better diagnoses, according to a study.
“VEXAS syndrome can be a diagnostic challenge. Patients may present to a variety of disease specialists depending on their symptoms and providers may not immediately consider a genetic etiology in an older individual,” Edward W. Cowen, MD, MHSc, chief of the dermatology consultation service at the NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases, told Healio. “Although skin involvement occurs in more than 80% of patients, the disease is variable in appearance and may resemble other conditions such as vasculitis and Sweet syndrome.”
VEXAS — which stands for vacuoles, E1 enzyme, X-linked, autoinflammatory and somatic — syndrome is a rarely diagnosed disease caused by pathogenic variants in UBA1 that affects mostly men aged older than 50 years. Its manifestations are wide ranging and can include cytopenia/myelodysplasia, multiorgan systemic inflammation and cutaneous involvement.
In the observational cohort study of 112 patients (median age, 69 years; 99% men) with confirmed UBA1 variations, Cowen and colleagues aimed to define the spectrum of VEXAS syndrome’s cutaneous manifestations and show how they linked to genetic and histologic features of the disease.
Medical record review was conducted for 73 patients, whereas 39 were evaluated at the NIH.
Of the 112 patients included, 93 (83%) had skin involvement, with 68 patients (61%) having skin manifestations as a presenting feature of disease. The face was the most common location for these manifestations with 52 (56%) patients, followed by upper extremity in 41 patients (44%) and the trunk in 42 patients (45%).
Histological reports were available for 60 patients, of which 23 (36%) had leukocytoclastic vasculitis, 22 (34%) had neutrophilic dermatosis and 19 (30%) had perivascular dermatitis.
Specific manifestations were associated with specific pathogenic genetic variants.
Neutrophilic dermal infiltrates were associated with the p.Met41Leu variant, whereas vasculitic lesions with a mixed leukocytic infiltrate were associated with the p.Met41Val variant.
“One striking histologic finding was a distinct pattern of ‘histiocytoid’ dermal neutrophilic inflammation. This pattern can occasionally also be seen in patients with Sweet syndrome unrelated to VEXAS, but was a hallmark feature found in the majority of skin biopsies of patients with VEXAS,” Cowen said. “Together with another pathologic finding, leukocytoclasia, these features can be useful clues to alert the pathologist to a potential diagnosis of VEXAS.”
A VEXAS diagnosis should be considered for any older male patients presenting with neutrophilic dermatitis, particularly histiocytoid Sweet syndrome, vasculitis or leukocytoclasia without vasculitis, he added.