Abstract

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly identified autoinflammatory disorder caused by somatic variants in the UBA1 gene, affecting the E1 ubiquitin-activating enzyme. It presents with diverse clinical features, including fever, polychondritis, and cutaneous lesions, particularly neutrophilic dermatitis and vasculitis. Therapeutic responses to biologics vary, with few post-treatment biopsies reported. We present the pre- and post-treatment skin biopsy findings of an 83-year-old male with sequencing-proven VEXAS syndrome, treated with canakinumab and prednisone. The patient initially developed a non-itchy rash on the face, trunk, and upper extremities, with fevers and fatigue after contracting COVID-19 infection. After two months with no response of rash to topical steroids, left arm punch biopsy revealed superficial dermal neutrophilic infiltrate, vascular ectasia, and leukocytoclasia. Rheumatology evaluation and extensive work up showed systemic inflammation with exclusion of underlying infection and malignancies. Subsequent finding of left ear chondritis led to identification of UBA1 gene somatic mutation and diagnosis of VEXAS syndrome. Treatment with canakinumab 150 mg subcutaneously every four weeks and prednisone taper resulted in significant improvement in fatigue and rash, although pink papules with minimal scale recurred during tapering. A new biopsy of recurrent lesions on the upper back showed superficial and deep perivascular and periadnexal lymphohistiocytic infiltrate. Neutrophils were not appreciated, although rare nuclear fragments were seen which could represent neutrophilic remnants. This case underscores the importance of recognizing the evolving histopathological features in VEXAS syndrome, particularly in response to treatment, to ensure accurate diagnosis and guide therapeutic strategies.