Romosozumab‐Associated Recurrent Erythema Nodosum in Mixed Connective Tissue Disease

OBJECTIVE: The aim of this study was to describe recurrent erythema nodosum (EN) temporally associated with romosozumab in a patient with mixed connective tissue disease and to examine the biologic plausibility of this association in the context of Wnt/β-catenin-mediated immune regulation. METHODS: We evaluated a patient with mixed connective tissue disease and osteoporosis who developed EN following romosozumab exposure. Clinical assessment included detailed medication reconciliation, infectious evaluation, markers of inflammation, response to glucocorticoids, and recurrence upon re-exposure. A focused literature review was conducted to assess prior reports and mechanistic relevance. RESULTS: A 71-year-old woman developed EN approximately one month after her first dose of romosozumab, with complete remission following prednisone therapy. Within days of the second dose, she experienced a more extensive recurrence involving the hands, thighs, and right calf, which resolved after a glucocorticoid taper. Infectious evaluation was negative, markers of inflammation were normal, and medication reconciliation did not identify alternative pharmacologic triggers. Romosozumab was discontinued, and no recurrence occurred during follow-up before transition to denosumab. CONCLUSION: This case supports a probable association between romosozumab and recurrent EN. Rechallenge, exclusion of alternative etiologies, and emerging evidence on Wnt-mediated immune regulation suggest a mechanistic link between sclerostin inhibition and panniculitic hypersensitivity reactions.