Thalidomide as a potential treatment for scleromyxedema.

A 39-year-old African American woman was referred in April 1995 with a 1-year history of skin thickening. The process began on her hands and progressed to involve her arms, face, neck, shoulders, chest, and proximal extremities. Her only systemic complaints were limited mobility of her joints, particularly her hands and wrists. Physical examination findings revealed leonine facies. The skin of the neck, shoulders, and chest exhibited 1to 2-mm coalescent linear papules. The skin of the hands, forearms, upper arms, and trunk was sclerotic. Skin biopsy results showed marked dermal thickening, displacement of collagen bundles by mucin, and numerous spindled fibroblasts, consistent with scleromyxedema. The results of laboratory tests, including a complete blood cell count, chemistry tests, liver function tests, an antinuclear antibody panel, an extractable nuclear antigen panel, and thyroid function tests, were normal. Immunoglobulins were obtained, and the following levels were revealed: IgM, 92 mg/dL (reference range, 25-210 mg/ dL); IgA, 152 mg/dL (reference range, 40-390 mg/dL); and IgG, 1490 mg/dL (reference range, 525-1650 mg/ dL), with a light chain monoclonal gammopathy. Hematologic evaluations, including serum and urine protein electrophoresis, immunoelectrophoresis, a bone marrow examination, and radiography of the head and chest, produced no evidence of multiple myeloma. Because of significant restriction of joint mobility, the patient underwent treatment with cytotoxic agents. She was initially treated with melphalan, 16 mg/d orally (PO), plus prednisone, 100 mg/d PO, for 4 days at a time in 1-month intervals for 4 cycles from June 1995 to September 1995, with little response. She was then treated with cyclophosphamide, 75 mg/d PO, plus prednisone, 100 mg/d PO, for 21 days at 1-month intervals for 6 cycles from October 1995 to March 1996, with minimal improvement. The patient was then administered prednisone, 40 mg every other day, from April 1996 to June 1996, again with no improvement. A trial of cladribine, 0.1 mg/kg, was instituted for 5 days at 1-month intervals for 5 cycles from September 1995 to January 1997, and was unsuccessful. The patient then received supportive therapy, including topical corticosteroids and emollients, and underwent physical therapy. In February 1998, the patient developed status epilepticus, fever, and hypotension, requiring admission to the intensive care unit and mechanical ventilation. The findings of an examination for a cause of the patient’s illness, including computed tomography, magnetic resonance imaging, and magnetic resonance angiography of the head, and of a complete infectious disease workup were negative. Because an organic brain syndrome was previously reported in association with scleromyxedema and there was no obvious other cause, this episode was attributed to scleromyxedema. The patient returned to her baseline level of function and was administered phenytoin (Dilantin), topical corticosteroids, and emollients. She declined further chemotherapy because of the lack of efficacy and intolerable adverse effects. The patient’s disease progressed to her lower extremities. She had difficulty walking and could no longer perform activities of daily living. She developed significant alopecia. The patient was regularly assessed for progression to multiple myeloma. Despite the persistence of the monoclonal gammopathy, she never developed marrow plasmacytosis, lytic bone lesions, or other signs of multiple myeloma. Even with obvious disease progression, further treatment with cytotoxic agents was abandoned because of lack of response and risk of a secondary malignancy.