Dupilumab improves itch, but not fibrosis, in a patient with scleromyxedema: A case report.

Scleromyxedema is a rare, chronic mucinosis characterized by widespread skin fibrosis and an associated monoclonal gammopathy. Therapeutic options remain limited. We present the case of a male in his 50s with biopsy-confirmed scleromyxedema and IgG λ monoclonal gammopathy who initially responded to intravenous immunoglobulin but later progressed despite full-dose maintenance. Due to severe pruritus and recent evidence implicating Type 2 cytokines in scleromyxedema pathogenesis, dupilumab was added to ongoing intravenous immunoglobulin. Pruritus improved within 4 months, but fibrosis remained unchanged and M-protein levels continued to rise, reaching 35.3 g/L by month 12. Dupilumab was discontinued due to lack of disease modification. Bone marrow biopsy confirmed smoldering multiple myeloma. The patient subsequently responded well to daratumumab, cyclophosphamide, bortezomib, and dexamethasone chemotherapy and autologous stem cell transplant. This case illustrates the potential for IL-4Rα blockade to control symptoms such as pruritus in scleromyxedema, but underscores the need for plasma cell-directed therapy to address the underlying disease process.