Abstract

VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a recently described adult autoinflammatory syndrome characterized by acquired somatic mutations within the X-chromosomal UBA1 gene. To our knowledge, 141 cases have been reported in the literature, 126 of which demonstrated cutaneous manifestations with only 19% of cases showing “Sweet’s-like” features. Herein, we report a case of a 73-year-old male with a history of monoclonal gammopathy of undetermined significance (MGUS) who presented with indurated, erythematous papules on the trunk and extremities. Biopsy demonstrated an unremarkable epidermis overlying a marked superficial-to-deep dermal infiltrate composed of neutrophils, scattered lymphocytes, and numerous cells with eccentrically “C-shaped” nuclei. Additionally, many mononuclear cells were present, morphologically resembling histiocytes. Focal areas of karyorrhectic debris were identified, without overt signs of endothelial damage. Immunohistochemical studies were performed which demonstrated reactivity with MPO, CD163, and CD33 within the lesional cells of interest. CD3 demonstrated admixed T-cells while CD20, CD30, CD1a, CD117, TdT, and CD34 were negative. Given the morphologic and immunophenotypic findings, a diagnosis of histiocytoid Sweet’s syndrome (HSS) was rendered. Due to clinical suspicion for VEXAS syndrome, Sanger sequencing was performed which demonstrated a single variant (c.121A>C) in the UBA1 gene, a known missense variant observed in VEXAS syndrome. On follow-up, the patient is doing well, showing response to steroid therapy. We aim to increase awareness of the rare entity, VEXAS syndrome, highlighting a unique cutaneous manifestation of HSS in a patient with underlying MGUS.

Financial Disclosure:
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