From the Ronald O. Perelman Department of Dermatology, New York University
A 72-year-old man with diabetes-associated scleredema is presented. The patient had a long history of diabetes mellitus that had been difficult to control with complications of retinopathy, nephropathy, and arteriosclerosis leading to myocardial infarcts and stroke. The scleredema has remained stable with 4 months of topical clobetasol ointment twice daily and biweekly physical therapy. Diseases associated with scleredema and therapeutic options are summarized.
History.A 72-year-old man presented with a 1-year history of thickening of the skin on the posterior neck and upper back. He first noted hardening and tightness of the skin over his posterior neck and upper back approximately 1 year ago. He was seen in the Charles C. Harris Skin and Cancer Pavilion where a 4-mm punch biopsy was obtained in August 2001. He was initially treated with 10 percent urea lotion, but this preparation was discontinued after the patient developed skin irritation and blisters. He is currently applying clobetasol ointment twice daily and has noted no change in his skin condition. He also attends physical therapy twice a week.
Medical history includes poorly-controlled type II diabetes mellitus with glycosolated hemoglobin values of 9-20 percent over the past 5 years. The diabetes mellitus is complicated by diabetic retinopathy and blindness, chronic renal insufficiency with a creatinine of 2.0 mg/dl, hypoglycemic seizures secondary to insulin therapy, and arteriosclerosis, which has resulted in three myocardial infarcts and a stroke. He also has a history of hypertension, congestive heart failure, degenerative joint disease, and carcinoma in situ of the bladder.
Physical examination.The skin over the posterior neck and upper back was thick and firm to the touch. No surface changes were present.
Laboratory data.A complete blood count was normal. A basic metabolic panel showed an elevated glucose level of 339 mg/dl, creatinine 2.0 mg/dl, and blood urea nitrogen 41 mg/dl. A serum protein electrophoresis showed an elevated gamma immunoglobulin 1.69 gm/dl (normal range = 0.5 to 1.6 gm/dl).
Histopathology.Hematoxylin and eosin stained sections show a thick reticular dermis with thick collagen bundles separated by clear spaces. Basophilic myxoid material is focally present within some of these spaces. A colloidal iron stain shows that this myxoid material is mucin. The overlying epidermis is unremarkable.
Scleredema is characterized by hard and thick skin. Approximately one-third of cases are associated with type II diabetes mellitus, particularly diabetes that has been difficult to control and has resulted in complications, such as retinopathy, neuropathy, nephropathy, and arteriosclerosis. In these diabetes-associated cases, the onset is gradual. Men outnumber women 10 to 1. The neck, upper back, and shoulders are the usual sites of involvement. Characteristically there is an abrupt step-off between the normal and involved skin although this is difficult to discern in our patient. Diabetes-associated scleredema is refractory to therapy, is slowly progressive, and can lead to restriction of range of motion of the upper back and shoulders.
Approximately one-fourth of scleredema cases are abrupt in onset and occur shortly after an infection, usually streptococcal pharyngitis. Other infections that have been reported in association with acute-onset scleredema include influenza, measles, mumps, and varicella. In these infection-associated cases, patients tend to be younger, and women outnumber men 2 to 1. The lesions usually begin on the face and/or neck and spread to the arms, shoulders, back, and chest. There is no clear demarcation between involved and normal skin. A masklike expression may develop from skin tightening on the face. The tongue and esophagus may be involved leading to dysphagia. Cardiac involvement, which includes arrhythmias, carditis, and heart failure; paraproteinemias (usually IgG-κ); and multiple myeloma have been reported. Although the disease is refractory to treatment, approximately 50 percent of infection-associated cases are self-limited and resolve over months to years .
The etiology of scleredema is unknown although increased deposition of collagen and mucin are seen. The propeptide of type 1 collagen is increased in suction blister fluid aspirates obtained from scleredema skin as compared to normal control skin. The α 1 subunits of procollagens I and III mRNA and fibronectin mRNA were elevated in fibroblasts cultured from scleredema skin as compared to fibroblasts from patients with normal skin . In addition to the associations with diabetes mellitus, infection, paraproteinemias, and myeloma, cases have been reported in association with other diseases that include Waldenstrom macroglobulinemia, anaphylactoid purpura, malignant insulinoma, rheumatoid arthritis, Sjögren syndrome, primary hyperparathyroidism, polyserositis, localized myositis, primary biliary cirrhosis, IgA deficiency, dermatomyositis, and exposure to organic solvents.
Although generally refractory to treatment, several therapeutic modalities have been attempted with some success. These include extracorporeal photopheresis (for patients with paraproteinemia) , radiotherapy, electron beam radiation , PUVA photochemotherapy , prostaglandin E1 , cyclosporin , and high-dose penicillin. Physical therapy is recommended to prevent limitations in range of motion. However, no trials have been performed to evaluate the benefit of physical therapy.
References1. Venencie PY, et al. Scleredema: review of 33 cases. J Am Acad Dermatol 1984;11:1984.
2. Varga J, et al. Scleredema adultorum: case report and demonstration of abnormal expression of extracellular matrix genes in skin fibroblasts in vivo and in vitro. Br J Dermatol 1995;132:992.
3. Stables GI, et al. Scleredema associated with paraproteinemia treated by extracorporeal photopheresis. Br J Dermatol 2000;142:781.
4. Lee MW, et al. Electron beam therapy in patients with scleredema. Acta Dermatol Venereol (Stockh) 2000;80:307.
5. Grundmann-Kolloman M, et al. Cream PUVA therapy for scleredema adultorum. Br J Dermatol 2000;142:1058.
6. Ikeda Y, et al. Severe diabetic scleredema with extension to the extremities and effective treatment using prostaglandin E1. Int Med 1998;37:861.
7. Mattheou-Vakali G, et al. Cyclosporin in scleredema. J Am Acad Dermatol 1996;35:990.
© 2003 Dermatology Online Journal