Abstract

VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a novel, autoinflammatory syndrome that often presents with dermatologic findings. Neutrophilic dermatoses are known cutaneous manifestations of VEXAS syndrome, possibly representing cutaneous infiltration by clonal myeloid cells. However, there is potential for a wide range of dermatologic associations for this newly described condition.

We report the case of a 68-year-old man with VEXAS syndrome with unique clinical and histopathological findings. He presented with pruritic, yellowish annular plaques on the head, neck, arms, and torso. Biopsies showed variable histologic findings with overlapping features of an interstitial granulomatous process and a histiocytic infiltrate, suggestive of non-Langerhans cell histiocytosis. Initial laboratory work-up was unremarkable. Multiple medications were trialed without sustained improvement (hydroxychloroquine, prednisone, methotrexate, mycophenolate, and thalidomide). The rash progressed to subcutaneous nodules on arms and neck along with fatigue, night sweats, fever, and macrocytic anemia. PET/CT scan showed diffuse bone marrow uptake with slight hepatosplenic and nodal uptake. A bone marrow biopsy was performed, showing hypercellular marrow with vacuoles in a subset of myeloid and erythroid precursors. MyeloSeq panel revealed UBA1 gene mutation, confirming a diagnosis of VEXAS. His current treatment regimen is ruxolitinib and prednisone.

Cutaneous manifestations can be the first sign of VEXAS syndrome, highlighting the importance of dermatopathology in diagnosis. This case adds to the literature on this emerging autoinflammatory syndrome, demonstrating a potential, non-neutrophilic dermatologic presentation. In men older than 50 years with an unusual constellation of refractory inflammatory dermatoses and systemic symptoms, VEXAS should be considered.