Vexed by VEXAS: A Case Report

Summary: Introduction: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a late-onset, acquired disease with both autoinflammatory and hematologic manifestations secondary to acquired UBA1 gene mutation. VEXAS affects various systems including the skin, eyes, lungs, bone marrow, and vasculature. VEXAS vascular dysfunction may meet diagnostic criteria for known vasculitides like Polyarteritis Nodosa (PAN). Cutaneous PAN may manifest as purpura, erythematous nodules, livedo reticularis, and ulcers – herein we describe an atypical presentation of PAN in a patient with VEXAS. Case presentation: A 64-year-old male with 2-year history of pulmonary hypertension, sinusitis periorbital edema, pancytopenia and palpable purpura presented with progressive dyspnea and weight loss. Physical exam showed linear hyperpigmentation overlying vasculature with palpable cord-like induration. Histology displayed leukocytoclastic vasculitis plus intimal vasculitis of a medium artery, suggesting PAN. Next-Generation Sequencing following bone marrow biopsy indicated UBA1 gene mutation. Clinical correlation suggested VEXAS syndrome. Treatment with prednisone improved symptoms. Conclusion: The clinical constellation of fatigue, weight loss, symmetrical palpable purpura raised concern for vasculitis. Pulmonary parenchymal symptoms, sinusitis, inflammatory orbital disease, and pancytopenia in an adult male past the fifth decade raises concern for VEXAS syndrome. Cordlike, hyperpigmented and indurated vascular streaking is an atypical presentation of both PAN and VEXAS.