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Case Reports

Abstract

We present the case of a 72-year-old male with a history of arthritis and recurrent pruritic rash present for one year with more recent hand and leg swelling, severe fatigue, weight loss, appetite loss, and headaches. On physical examination, the patient's rash was edematous and erythematous with annular plaques and hyperpigmented macules and plaques involving the trunk, bilateral upper extremities, and neck. Histologic sections of a biopsy specimen demonstrated skin with a perivascular and interstitial mononuclear cell infiltrate with a significant subset of cells exhibiting histiocytoid morphology. By immunohistochemistry, there was a minor but distinct component of MPO-positive, CD163-negative mononuclear cells with a predominant population of CD163-positive histiocytes. A CBC was notable for normocytic hypochromic anemia. A bone marrow biopsy showed dyspoiesis in less than 10% of erythroid cells not meeting threshold for morphologic dysplasia. Peripheral blood next-generation sequencing detected UBA1, DNMT3a, SETBP1, and BCOR mutations with the UBA1 mutation confirming a diagnosis of VEXAS syndrome. VEXAS syndrome is a severe, progressive autoinflammatory condition usually occurring in men above 50 characterized by a mutation in UBA1, a gene on the X-chromosome that encodes E1 enzyme, resulting in impaired ubiquitylation and increased activation of innate immune pathways.  This case highlights MPO-positive mononuclear cells (representing atypical or left-shifted neutrophils) as a helpful histologic finding in cutaneous manifestations of VEXAS syndrome. Recognition of these cells in skin samples from patients with unexplained autoinflammatory symptoms may facilitate earlier diagnosis of this rare syndrome.