Abstract:

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently typified adult-onset autoinflammatory syndrome due to somatic mutations affecting UBA1 (gene encoding the ubiquitin-activating enzyme 1). Given that up to 88% of patients have cutaneous afflictions, the objectives of this report are to heighten awareness of this condition and its related dermatological manifestations, and to feature a novel association with Kikuchi-Fujimoto Disease (KFD). A healthy 69-year-old ethnic Chinese male presented with periodic fevers, urticarial eruption, cervical lymphadenitis, arthralgia, macrocytic anemia and raised acute-phase reactants. Bone marrow examination was conclusive for secondary myelodysplasia. Thorough evaluation for infection, connective tissue disease and malignancy was unyielding. Skin biopsy of a representative urticarial lesion was consistent with histiocytoid Sweet syndrome (HSS), while cervical lymph node biopsy demonstrated necrotizing lymphadenitis. Subsequently, the patient developed relapsing polychondritis, a papulonodular eruption and an unprovoked deep vein thrombosis with pulmonary embolism, all whilst on systemic corticosteroids and methotrexate. Skin biopsy findings of the new rash was compatible with KFD. Sanger sequencing of the patient’s blood revealed c.121A→C sequence alteration in the UBA1 gene that engendered a p.Met41Leu missense mutation, confirming the diagnosis of VEXAS syndrome. This case allows for the various possible dermatoses of VEXAS syndrome to be highlighted. In addition, the challenge in distinguishing KFD and HSS histopathologically is discussed, given that both entities have a superficial and deep perivascular and interstitial inflammatory pattern, nuclear dust, mononuclear cells bearing crescentic nuclei and histiocytes that are CD68/CD163/myeloperoxidase positive.

Financial Disclosure: No current or relevant financial relationships exist.

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Joel Lim, MD