ABSTRACT Multiple myeloma (MM) is a malignant plasma cell disorder that primarily presents with CRAB symptoms (calcium elevation, renal failure, anemia, and bone abnormalities). In rare cases, MM manifests with systemic complications like skin ulcers, which present management challenges. Here, we report a 78‐year‐old Japanese man with MM and refractory severe skin ulcers. Despite the absence of CRAB symptoms, the patient developed painful, necrotic ulcers on his lower extremities. Initial treatment with antibiotics and prednisolone provided no improvement. Pathological findings indicated venous congestion and vasculopathy due to microthrombosis associated with hypergammaglobulinemia. Plasma exchange (PE) was performed to reduce M‐protein levels, leading to granulation and partial healing. However, ulcers recurred after PE cessation. Two years post‐diagnosis, symptomatic MM with anemia necessitated chemotherapy. Given the patient's advanced age and high infection risk, lenalidomide‐dexamethasone (Ld) therapy was initiated. This approach achieved complete epithelialization within 1 year, with no ulcer recurrence. Over 5 years, maintenance Ld therapy maintained low serum immunoglobulin G levels without systemic side effects or further relapses. This case highlights the utility of PE for temporary symptom relief and Ld therapy for long‐term management of MM‐associated skin ulcers. While the exact etiology of ulcers in this case remains unclear, elevated M‐protein levels and microthrombosis likely contributed. This case emphasizes the importance of individualized treatment strategies in MM patients with non‐CRAB complications like skin ulcers. Ld therapy alone may be a viable option for elderly MM patients with severe ulcers, even in the absence of CRAB symptoms. Further research is warranted to clarify ulcer pathophysiology and optimize treatment.
Hattori et al. (2026) studied this question.