Comment on Donato et al, page 463

In this issue of Blood, Donato and colleagues demonstrate the value of high-dose chemotherapy with stem cell reconstitution for patients with scleromyxedema.

There are 2 types of skin disorders that are specifically associated with monoclonal gammopathies. In one, protein deposits directly into the skin. Examples are amyloidosis and cryoglobulinemia. A second group of skin disorders is associated with an M component, but no proteinaceous deposits are found in the skin. Pyoderma gangrenosum is an ulcerative disease of the skin that is associated with a monoclonal protein. Necrobiotic xanthogranuloma is associated with an IgG monoclonal gammopathy in 73% of patients. Other examples include Schnitzler syndrome and scleromyxedema.1 

Scleromyxedema, also known as papular mucinosis and lichen myxedematosus, is associated with a monoclonal G lambda protein. The association between the skin disorder and the monoclonal protein remains unknown. Scleromyxedema on biopsy demonstrates papular mucinous deposits, dermal fibroblast proliferation, and fibrosis. Clinical findings include waxy papules on the fingers and face and deep thickened furrows on the forehead and the back.2 

Often patients with dermatologic disorders are not considered candidates for systemic chemotherapy since the toxicity of the treatment often exceeds the long-term morbidity associated with the disorder. Scleromyxedema is an exception as it exhibits a number of life-threatening extracutaneous manifestations. The most common is dysphagia, due to esophageal dysmotility, leading to chronic aspiration. Peripheral neuropathy, myopathy, and encephalopathy are reported. Dyspnea on exertion is seen due to progressive lung fibrosis. Pulmonary function tests demonstrate restrictive physiology.

Numerous modalities have been used in the treatment of scleromyxedema including retinoids, corticosteroids, plasmapheresis, electron beam therapy, and psoralen plus ultraviolet A light. Shortly after the introduction of oral melphalan/prednisone for the treatment of multiple myeloma, its use in scleromyxedema was reported.3  In the initial report, one patient died of myelodysplasia related to melphalan. The treatment of scleromyxedema has followed the treatment of multiple myeloma as it has evolved over the years. High-dose dexamethasone has been reported to be successful.4  The dermatologic remission was complete and was not associated with a complete hematologic response. Thalidomide has led to marked improvement of the skin lesions and joint mobility within 2 months.5  In all 3 patients, the monoclonal protein level fell.

In 2001, Feasel et al reported on their first patient who underwent stem cell transplantation, demonstrating a complete response of scleromyxedema.6  In this issue of Blood, the authors have expanded their experience to 8 patients (7 IgG-lambda, 1 IgG-kappa), with 5 complete responses and 2 partial responses. There was no correlation between a clinical response in the skin and hematologic response. Unfortunately, immunoglobulin free light chain values were not measured. No grades 3 to 4 nonhematologic toxicity was seen, and no deaths occurred. Extracutaneous manifestations including gastrointestinal, central nervous system, and pulmonary manifestations completely resolved. Pulmonary function testing showed significant improvement in 2. Donato and colleagues further extend the therapeutic options for this recalcitrant disorder. Stem cell transplantation could be considered as initial therapy or for those patients in whom an initial trial of dexamethasone or thalidomide/dexamethasone fails to provide benefit. ▪

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