Diffuse rash in a man with paraproteinemia

Scleromyxedema is the generalized form of lichen myxedematosus, which presents with widespread eruption of shiny, firm, dome-shaped or flat-topped papules; these papules do not affect the palms, scalp, or mucous membranes.1,2 Other clinical findings can include the doughnut sign, characterized...

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Scleromyxedema is the generalized form of lichen myxedematosus, which presents with widespread eruption of shiny, firm, dome-shaped or flat-topped papules; these papules do not affect the palms, scalp, or mucous membranes.^1,2 Other clinical findings can include the doughnut sign, characterized by skin thickening with a central depression overlying the proximal interphalangeal joints, and decreased range of motion of the hands, lips, mouth, and extremities.^1,2

There is no sex predilection in scleromyxedema.³ Mean age at onset of the condition is typically the fifth decade of life, but onset can present between the second and seventh decades.^4,5 On average, the condition is diagnosed 3 years after initial onset.⁵

The localized form of lichen myxedematosus is papular mucinosis.¹ Although papular mucinosis is not associated with extracutaneous findings, scleromyxedema has systemic manifestations in up to 77% of patients; in some cases, these manifestations are fatal.^2,5 In a retrospective study of 26 patients with scleromyxedema, gastrointestinal involvement was the most common finding in 60% of patients—specifically, dysphagia due to esophageal dysmotility.^2,5 In another retrospective study of 30 patients with scleromyxedema, other extracutaneous findings included neurologic abnormalities in 30% (eg, carpal tunnel syndrome and dermato-neuro syndrome [fever, seizures, and coma]), rheumatologic abnormalities in 23% (eg, arthralgias with or without arthritis), and cardiac abnormalities in 20% (eg, myocardial ischemia, congestive cardiomyopathy, and inflammatory cardiomyopathy).³ Dyspnea on exertion and myopathy presenting as proximal or generalized weakness is present in approximately 32% and 26% of patients, respectively.⁴

Scleromyxedema is highly associated with hematologic abnormalities, especially monoclonal gammopathy. Up to 88% of patients have a paraproteinemia, most commonly the IgGλ subtype.⁵ Paraproteinemia consisting of the IgGκ, IgMκ, IgAκ, and IgAλ subtypes have also been reported.⁵ Underlying hematologic malignancies include leukemia, multiple myeloma, Hodgkin lymphoma, and non-Hodgkin lymphoma.^3,5 Less common extracutaneous manifestations include renal dysfunction and ocular involvement.^3,4

Several other conditions can present with similar features. The differential diagnosis of scleromyxedema includes primary (limited) cutaneous mucinoses, scleroderma, scleredema, nephrogenic systemic fibrosis, and underlying disorders presenting with leonine facies.^6,7 Limited cutaneous mucinoses are focal and lack systemic features, including paraproteinemia.⁷ Mucinous papules in scleromyxedema classically involve the hands and face, predominantly the glabella and ears, which differentiates the condition from scleroderma and scleredema clinically.⁷ In advanced disease, the central back and digits are typically not involved in scleroderma and scleredema, respectively.⁷ Patients with nephrogenic systemic fibrosis have a history of renal insufficiency and gadolinium exposure, and commonly do not have paraproteinemia or facial involvement.⁸

Characteristic cutaneous, extracutaneous, and histopathologic findings, in addition to monoclonal gammopathy in the absence of thyroid abnormalities, provide a definitive diagnosis of scleromyxedema.^3,7 Biopsy reveals irregularly arranged stellate fibroblasts with collagen deposition and diffuse mucin concentrated primarily in the mid-to-upper dermis.^7,9 Mucin stains with Alcian blue at a pH of 2.5.⁵ Several hypotheses have been proposed regarding the pathogenesis of scleromyxedema; however, its etiology remains elusive.

Treatment is largely based on outcomes from case series and reports secondary to the rarity of the condition. Kaffenberger and Kirby¹⁰ suggest first-line treatments including melphalan, plasmapheresis, intravenous immunoglobulin (IVIG), and systemic corticosteroids. High-dose dexamethasone, in particular, has produced good outcomes.^11,12 Isotretinoin, etretinate, topical calcineurin inhibitors, topical corticosteroids, and intralesional corticosteroids are considered second-line agents.¹⁰ Third-line therapies include various immunosuppressants and chemotherapies (eg, cyclophosphamide, cyclosporine, methotrexate, chlorambucil, bortezomib, and vincristine), as well as interferon α-2b, radiation, psoralen and ultraviolet A radiation, extracorporeal photopheresis, and autologous stem cell transplantation.¹⁰ Regimens incorporating autologous stem cell transplantation have shown promising results; resolution of skin findings and partial to complete remission of the extracutaneous manifestations have been reported in several patients with scleromyxedema.¹³

The patient in our case was initially treated with weekly 40-mg pulse dexamethasone. He had an impressive response as his papules flattened and induration softened. However, this response was short-lived. After 12 weeks of dexamethasone, he started a monthly 5-day cycle of IVIG, 400 mg/kg. Upon completion of cycle seven of IVIG, his skin manifestations have improved. On examination, he had residual papules on his ears and significant decrease in induration of his forehead, glabella, and nose. Although his dysphagia and dyspnea are nearly resolved, his renal function remains impaired. At the time of this writing, the IVIG is being decreased to every other month, with ongoing consideration of autologous stem cell transplantation. 

Matthew M. Wallace, BSc, is a medical student at Virginia Commonwealth University in Richmond, VA, and Alex G. Ortega-Loayza, MD, is an assistant professor of dermatology at  Oregon Health & Science University in Portland, OR.

Acknowledgements

The authors would like to thank the patient for graciously providing permission to publish his case and clinical photos. 

References

1. Rongioletti F, Rebora A. Updated classification of papular mucinosis, lichen myxedematosus, and scleromyxedema. J Am Acad Dermatol. 2001;44:273-281.
2. Cokonis Georgakis CD, Falasca G, Georgakis A, Heymann WR. Scleromyxedema. Clin Dermatol. 2006;24:493-497.
3. Rongioletti F, Merlo G, Cinotti E, et al. Scleromyxedema: a multicenter study of characteristics, comorbidities, course, and therapy in 30 patients. J Am Acad Dermatol. 2013;69:66-72.
4. Gabriel SE, Perry HO, Oleson GB, Bowles CA. Scleromyxedema: a scleroderma-like disorder with systemic manifestations. Medicine (Baltimore). 1988;67:58-65.
5. Dinneen AM, Dicken CH. Scleromyxedema. J Am Acad Dermatol. 1995;33:37-43.
6. Boin F, Hummers LK. Scleroderma-like fibrosing disorders. Rheum Dis Clin North Am. 2008;34:199-220.
7. Hummers LK. Scleromyxedema. Curr Opin Rheumatol. 2014;26:658-662.
8. Cowper SE, Su LD, Bhawan J, Robin HS, LeBoit PE. Nephrogenic fibrosing dermopathy. Am J Dermatopathol. 2001;23:383-393.
9. Rongioletti F, Rebora A. Cutaneous mucinoses: microscopic criteria for diagnosis. Am J Dermatopathol. 2001;23:257-267.
10. Kaffenberger JA, Kirby JS. Lichen myxedematosus. In: Lebwohl MG, Heymann WR, Berth-Jones J, Coulson I, Kaffenberger JA, Kirby JS, eds. Treatment of Skin Disease: Comprehensive Therapeutic Strategies. 4th ed. Philadelphia, PA: Elsevier Saunders; 2014.
11. Horn KB, Horn MA, Swan J, Singhal S, Guitart J. A complete and durable clinical response to high-dose dexamethasone in a patient with scleromyxedema. J Am Acad Dermatol. 2004;51(2 Suppl):S120-S123.
12. Kreuter A, Altmeyer P. High-dose dexamethasone in scleromyxedema: report of 2 additional cases. J Am Acad Dermatol. 2005;53:739-740.
13. Donato ML, Feasel AM, Weber DM, et al. Scleromyxedema: role of high-dose melphalan with autologous stem cell transplantation. Blood. 2006;107:463-466.