Scleromyxedema is a rare disease characterized by mucin deposition in skin and other organs and the production of a monoclonal IgG protein. Herein we describe our experience with a series of patients with this condition and specifically focus on the use of intravenous immunoglobulin (IVIG) for long-term management. We retrospectively reviewed the clinical manifestations of 10 patients evaluated at our center, highlighting the potential organ involvement. We found that systemic manifestations of the disease are common and often mimic those seen in systemic sclerosis. Eight of the 10 patients were treated with IVIG with a 100% complete or partial response rate. Treatment was initiated at a dose of 2 g/kg (total dose, divided over 2-5 days) for 6 months of initial therapy. In each case where IVIG was used, maintenance infusions are required to preserve disease control. We highlight the long-term use of this medication in several cases. We discuss the potential therapeutic benefit of IVIG in this condition, where the pathophysiology of the disease is poorly understood, and underscore new data on the potential mechanism of action of IVIG therapy.