Man With Progressive Induration of the Skin and Pruritus

April 1, 2006

A disorder similar to scleromyxedema, nephrogenic fibrosing dermatopathy, has been reported in patients receiving renal dialysis. Lichen myxedematosus, an atypical form of papular mucinosis, is not associated with sclerosis and paraproteinemia; however, it may represent an early presentation of scleromyxedema.

A 53-year-old man presents with progressive induration of the skin and pruritus of the abdomen, upper chest, and arms of 3 months' duration (Figure 1). He also reports that pain and swelling of his hands developed after he handled halogenated hydrocarbons at work (Figure 2).

The patient has a history of hypertension and gastroesophageal reflux disease; he takes metoprolol, aspirin, and acetaminophen. Recently, he underwent surgery for bilateral carpal tunnel syndrome. The operation relieved the numbness in his hands.

Close examination of the skin reveals small, densely packed, waxy papules on the hands and forearms, abdomen, upper trunk, face, and neck. Other physical examination findings are normal.

The results of routine laboratory studies-including the erythrocyte sedimentation rate and an antinuclear antibody test-are normal. However, a small spike in the M protein level (0.2 g/dL) is noted on serum protein electrophoresis.

Biopsy specimens from the thickened skin on the right arm and abdomen reveal an increased number of fibroblasts in the papillary dermis. The increased cellularity and absence of markedly thickened collagen bundles rule out progressive systemic sclerosis (Figures 3 and 4). Increased mucin is noted; a colloidal iron stain highlights the increased acid mucopolysaccharide deposition (Figure 5). The cause is scleromyxedema.

Additional serologic studies reveal an underlying IgG γ paraproteinemia. A bone marrow biopsy specimen shows a slightly hypercellular marrow with scattered immature plasma cells; there is no evidence of underlying lymphoma or leukemia.

The patient subsequently becomes hoarse and dyspneic.Therapy with melphalan is started. After a few weeks, the pruritus, swelling, and "tightness" of his skin subside. The therapy also alleviates the pain and swelling of his hands as well as his dyspnea and hoarseness.

SCLEROMYXEDEMA: AN OVERVIEW

Scleromyxedema is characterized by 2- to 3-mm waxy papules and progressive induration of the skin, particularly on the hands, forearms, face, neck, and upper trunk.1,2 Other features of this rare disorder include3:

  • Paraproteinemia.

  • Dysphagia.

  • Muscle weakness.

  • Lung involvement (dyspnea, hoarseness).

  • CNS involvement (seizures, aphasia).

  • Peripheral neuropathy (eg, carpal tunnel syndrome).

  • Arthritis.

  • Renal involvement.

In addition, scleromyxedema has been associated with hepatitis C and HIV infection.

DIAGNOSIS

A biopsy of skin lesions is required for diagnosis of scleromyxedema. The results show increased mucin deposition; however, the increase in mucin may not always be apparent in the skin and CNS.4 Scleromyxedema must be differentiated from progressive systemic sclerosis, which is characterized by fibrosis in the dermis without an increase in dermal mucin and fibroblasts.5,6 A bone marrow biopsy is necessary to rule out associated conditions, such as multiple myeloma, Hodgkin disease, non-Hodgkin lymphoma, leukemia, and Waldenström macroglobulinemia.

A disorder similar to scleromyxedema, nephrogenic fibrosing dermatopathy, has been reported in patients receiving renal dialysis.7 Lichen myxedematosus, an atypical form of papular mucinosis, is not associated with sclerosis and paraproteinemia; however, it may represent an early presentation of scleromyxedema.1 Careful monitoring of patients with lichen myxedematosus is advised, since prompt treatment may lead to remission in some patients.

MANAGEMENT

Scleromyxedema is usually progressive and refractory to treatment.2 The Table lists various options.8-14 Response to these therapies varies. Although treatment with alkylating agents may be beneficial, it may be associated with lymphoproliferative disease. Thus, patients receiving this therapy must be closely monitored.9

Table - Therapeutic options for scleromyxedema

Alkylating agents (melphalan) Cytotoxic agents (chlorambucil, cyclophosphamide) Corticosteroids (dexamethasone) Electron beam therapy Extracorporeal photophoresis Grenz ray therapy Plasmapheresis Psoralen and UV-A photochemotherapy Retinoids Thalidomide Topical dimethyl sulfoxide

References:

REFERENCES:

1.

Rongioletti F, Rebora A. Updated classification of papular mucinosis, lichen myxedematosus, and scleromyxedema.

J Am Acad Dermatol.

2001;44: 273-281.

2.

Godby A, Bergstresser PR, Chaker B, Pandya AG. Fatal scleromyxedema: report of a case and review of the literature.

J Am Acad Dermatol.

1998;38 (2 pt 2):289-294.

3.

Berger JR, Dobbs MR, Terhune MH, Maragos WF.The neurologic complications of scleromyxedema.

Medicine (Baltimore).

2001;80:313-319.

4.

Clark BJ, Mowat A, Fallowfield ME, Lee FD. Papular mucinosis: is the inflammatory cell infiltrate neoplastic? The presence of a monotypic plasma cell population demonstrated by in situ hybridization.

Br J Dermatol.

1996;135:467-470.

5.

Fudman EJ, Golbus J, Ike RW. Scleromyxedema with systemic involvement mimics rheumatic diseases.

Arthritis Rheum.

1986;29:913-917.

6.

Yaron M, Yaron I, Yust I, Brenner S. Lichen myxedematosus (scleromyxedema) serum stimulates hyaluronic acid and prostaglandin E production by human fibroblasts.

J Rheumatol.

1985;12:171-175.

7.

Mackay-Wiggan JM, Cohen DJ, Hardy MA, et al. Nephrogenic fibrosing dermopathy (scleromyxedema-like illness of renal disease).

J Am Acad Dermatol.

2003;48:55-60.

8.

Tschen JA, Chang JR. Scleromyxedema: treatment with interferon alfa.

J Am Acad Dermatol.

1999;40(2 pt 2):303-307.

9.

Krasagakis K, Zouboulis CC, Owsianowski M, et al. Remission of scleromyxedema following treatment with extracorporeal photophoresis.

Br J Dermatol.

1996;135:463-466.

10.

Helm F, Helm TN. Iatrogenic myelomonocytic leukemia following melphalan treatment of scleromyxedema.

Cutis.

1987;39:219-223.

11.

Caradonna S, Jacobe H. Thalidomide as a potential treatment for scleromyxedema.

Arch Dermatol.

2004;140:277-280.

12.

Davis LS, Sanal S, Sangueza OP. Treatment of scleromyxedema with 2-chlorodeoxyadenosine.

J Am Acad Dermatol.

1996;35(2 pt 2):288-290.

13.

Bonnetblanc JM, Bedane C. Regression of scleromyxedema with topical betamethasone and dimethyl sulfoxide: a 30-month follow-up.

Arch Dermatol.

1991;127:1733-1734.

14.

Lister RK, Jolles S, Whittaker S, et al. Scleromyxedema: response to high-dose intravenous immunoglobulin (hdIVIg).

J Am Acad Dermatol.

2000; 43(2 pt 2):403-408.