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Scleromyxedema is a rare clinical variant of primary cutaneous mucinosis. It is defined by a generalized papular and sclerodermoid eruption associated with monoclonal gammopathy. No specific definitive treatment is known and those tried have inconsistent results. The first‐line treatment is intravenous immunoglobulin infusions with variable response and frequent relapse. We describe, here, a patient with scleromyxedema with lambda monoclonal gammopathy treated effectively with low‐dose lenalidomide and dexamethasone. There was no clinical or biological relapse after 3 years of follow‐up. In our opinion, agents targeting the abnormal plasma cell clone like lenalidomide are the most promising in the treatment of scleromyxedema.
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