Are You Confident of the Diagnosis?
Characteristic findings on physical examination
Scleredema typically presents as nonpitting, skin-colored induration of the skin, usually with no surface changes. There is usually no sharp demarcation between the involved and non-involved skin. The face, neck, and trunk, particularly the upper back, are the sites of predilection (Figure 1, Figure 2). Symptoms vary depending on the site and extent of the skin involvement. Patients with limited disease are usually asymptomatic, but those with extensive disease may experience stiffness and functional impairment (eg, extensive facial involvement may lead to difficulty in mastication).
Although it may present spontaneously, scleredema frequently presents in association with the following three disease states:
– Febrile illness
– Monoclonal gammopathy
– Diabetes mellitus
Febrile illness-associated scleredema
Scleredema may develop after a bout of febrile illness, especially after a streptococcal pharyringitis, but the condition may develop after other bacterial and viral infections. The condition usually develops a few days to a few weeks after the infection. Onset of the disease is usually rapid with resolution over the subsequent 6 to 24 months. For some, however, the disease may be persistent. Treatment with oral antibiotics in those patients with streptococcal infection-associated scleredema has not shown to improve the affected skin.
Monoclonal gammopathy-associated scleredema
Scleredema may develop in association with monoclonal gammopathy, usually in the setting of multiple myeloma. In this setting, scleredema is more insidious in onset, persistent, and extensive compared with scleredema occurring in other settings. Usually, the onset precedes the diagnosis of monoclonal gammopathy by several years, but it may present simultaneously. Treatment of the underlying disease may result in resolution of the associated skin disease.
Diabetes-mellitus-associated scleredema represents the most common form of scleredema. Most present with subtle elevated indurated skin involving the upper back. Rarely, patients may present with more diffuse and widespread areas of involvement. Typically, there is longstanding history of DM, usually type I, in contrast to monoclonal gammopathy-associated scleredema in which scleredema usually precedes the associated disease. Well controlled DM has not consistently led to improvement of the skin.
A variety of other conditions have been reported to occur in association with scleredema. There are case reports of gall bladder carcinoma, sarcoidosis, carcinoid tumor, scabies, and infliximab associated with scleredema. Whether these isolated cases represent true association requires further investigation and validation.
Expected results of diagnostic studies
For DM and febrile illness associated scleredema, the diagnosis can usually be established with confidence based on the history and clinical findings alone. A biopsy may be performed to confirm the diagnosis, but it is not necessary. Blood tests are not indicated in these instances. If there is no history of any of the associated diseases, screening for DM and monoclonal gammopathy as well as a biopsy should be performed. Because scleredema usually precedes the diagnosis of monoclonal gammopathy by several years, it may be necessary to continue to monitor and screen for the gammopathy in those who have progressive disease.
Clinical differential diagnosis of scleredema includes other clinical entities with indurated skin, namely morphea, systemic sclerosis, nephrogenic systemic sclerosis, scleromyxedema, and thyroid dermopathy. Although these entities have some overlapping clinical morphologic features with scleredema, history, distribution and consistency of the lesions, and a biopsy should readily differentiate these entities from scleredema.
A punch biopsy of the affected area shows a markedly expanded dermis (“never ending dermis”) that appears relatively normal. The expansion of the dermis is due to primarily an increase in space between collagen bundles throughout the dermis, which may be subtle to marked depending on the amount of mucin deposition (Figure 3, Figure 4). The presence of hyaluronic acid may be appreciated on H&E and may be highlighted by a colloidal iron stain and any of the three “blue” stains-alcian blue, methylene blue, and toluidine blue.
In scleredema, there is no appreciable increase in the number of fibroblasts or amount of collagen in contrast to the other entities in the clinical differential diagnosis. In morphea and systemic sclerosis, there are thickened collagen bundles with decrease in space between them. In nephrogenic system sclerosis and thyroid dermopathy, there is a significant increase in the number of fibrocytes associated with increase in the amount of mucin.
Who is at Risk for Developing this Disease?
The condition occurs in all age and ethnic groups. Both the pediatric and adult populations are affected in febrile illness and DM- associated scleredema. In monoclonal gammopathy-associated scleredema, the majority of cases have been in the elderly population.
What is the Cause of the Disease?
The pathogenesis of scleredema is poorly understood. Although the nature of the association between scleredema and the associated diseases has not been elucidated, it is hypothesized that there is an unknown circulating factor that stimulates the fibroblasts of the skin to become more active.
Considered to be one of the cutaneous mucinoses, an affected lesion in scleredema shows an increased amount of glycoseaminoglycans (mucin), namely in the form of hyaluronic acid. No appreciable increase in number of fibroblasts or amount of collagen is observed. Rather, it is presumed that the existing fiboblasts through an unknown signaling mechanism produce more mucin, primarily hyaluronic acid.
Systemic Implications and Complications
Rarely, scleredema may involve soft tissue and visceral organs. In extreme cases, deaths have been reported due to involvement of vital organs. When patients present with widespread disease, possible symptoms and signs of other organ involvement should be sought. Additional workup may be necessary that includes imaging studies and recruitment of subspecialists to treat affected organs. For example, scleredema involving the heart muscles may lead to cardiomyopathy resulting in congestive heart failure.
Treatment options for scleredema are summarized in Table I.
|Medical Treatment||Physical Modality|
|Immunosuppressive agents||Narrowband UVB|
|cyclosporine||Psoralen + UVA|
Optimal Therapeutic Approach for this Disease
Patients with limited disease require no therapeutic intervention as they are usually asymptomatic. Those with extensive disease with symptoms may require treatment. No treatment has been proven to be consistently effective, however. A variety of treatment modalities have been reported to be successful in the treatment of scleredema, but they consist of mostly case reports and a few case series. Therefore a therapeutic ladder is difficult to establish.
UVA1 treatment appears promising, but the UVA1 units are only available in a handful of institutions around the world. Radiation therapy is time consuming and costly. Thus, topical steroid, systemic steroid, or phototherapy other than UVA1 as monotherapy or in combination may be better suited as first-line therapy and immunosuppressive agents and radiation therapy reserved as second-line therapy. In symptomatic extensive disease, immunosuppressive agents or radiation therapy may be indicated as the first line of therapy.
Additional treatments that have been reported to be effective include pentoxyphylline, prostaglandin E1, penicillamine, extracorporeal photophoresis, high-dose penicillin, and factor XIII.
As there is no consistently proven or Food and Drug Administration-approved treatment for scleredema, the risk and benefits should be carefully discussed with the patient when systemic agents and physical modalities are recommended. The end goal should be to restore functional deficits affected by the disease, but it may not be achievable in all cases. Specialists should be consulted if there is evidence of internal involvement.
Unusual Clinical Scenarios to Consider in Patient Management
See Systemic Implications and Complications.
What is the Evidence?
Venencie, PY, Powell, FC, Su, WP, Perry, HO. “Scleredema: a review of thirty-three cases”. J Am Acad Dermatol. vol. 11. 1984. pp. 128-34.
Sansom, JE, Sheehan, AL, Kennedy, CT, Delaney, TJ. “A fatal case of scleredema of Buschke”. Br J Dermatol. vol. 130. 1994. pp. 669-70. (This case report highlights the fact that extensive widespread disease may rarely result in death.)
Pujol, JA, Bueno, M, Fuertes, MA, Gimenez, H, Carapeto, FJ. “Improvement of scleredema associated with IgA multiple myeloma after chemotherapy”. Clin Exp Dermatol. vol. 20. 1995. pp. 149-52. (A well-documented case of multiple myeloma-associated scleredema is presented in this case report accompanied by a table that consists of 23 previously reported cases. In patients with monoclongal gammopathy- or multiple myeloma-associated scleredema, the skin disease usually precedes the plasma-cell dyscrasia.)
Tate, BJ, Kelly, JW, Rotstein, H. “Scleredema of Buschke: a report of seven cases”. Australas J Dermatol. vol. 37. 1996. pp. 139-42. (This case series consists of patient with diabetes-associated scleredema. In this case series, the patients had long-standing diabetes mellitus and extensive skin disease. Diabetes mellitus preceded the diagnosis of scleredema in these patients.)
Santos-Juanes, J, Osuna, CG, Iglesias, JR, De Quiros, JF, del Rio, JS. “Treatment with chemotherapy of scleredema associated with IgA myeloma”. Int J Dermatol. vol. 40. 2001. pp. 720-1. (This is a rare case report of scleredema that improved by treating the underlying disease with melphalan and prednisone. In contrast to diabetes-mellitus-associated scleredema, monoclonal gammopathy- or multiple myeloma-associated scleredema may respond to treatment if the associated disease is treated aggressively.)
Bowen, AR, Smith, L, Zone, JJ. “Scleredema adultorum of Buschke treated with radiation”. Arch Dermatol. vol. 139. 2003. pp. 780-4. (Three patients with extensive, symptomatic diabetes-mellitus-associated scleredema were treated with electron-beam radiation therapy. Partial response was observed in all three patients, which was not durable. Radiation therapy could be considered in those patients with severe restrictive disease.)
Breuckmann, F, Appelhans, C, Harati, A, Rotterdam, S, Altmeyer, P, Kreuter, A. “Failure of low-dose methotrexate in the treatment of scleredema diabeticorum in seven cases”. Dermatol. vol. 211. 2005. pp. 299-301. (In this report of seven cases of diabetes-mellitus-associated scleredema, methotrexate did very little to improve the skin induration based on clinical examinations. Patients, however, had subjective improvement of symptoms. The case series highlights the treatment-resistant nature of the disease.)
Lewerenz, V, Ruzicka, T. “Scleredema adultorum associated with type 2 diabetes mellitus: a report of three cases”. J Eur Acad Dermatol Venereol. vol. 21. 2007. pp. 560-1. (In these patients with diabetes mellitus type I= associated scleredema, the patients had unpredictable treatment outcome. The first patient was successfully treated with UVA-1 therapy and physiotherapy while the second patient failed to respond to UVA-1 therapy. The third patient had transient scleredema that resolved after administration of intravenous penicillin.)
Kroft, EB, de Jong, EM. “Scleredema diabeticorum case series: successful treatment with UV-A1”. Arch Dermatol. vol. 144. 2008. pp. 947-8. (This small case series of three patients showed objective improvement of the disease after being treated with UVA-1 therapy.)
Bray, SM, Varghese, S. “Ultrasonic massage and physical therapy for scleredema: improving activities of daily living”. Arch Dermatol. vol. 146. 2010. pp. 453-4. (This case report highlights the importance of adjunctive therapy, including physical therapy, to improve the quality of life in severely affected patients.)
(As one of the largest case series of scleredema patients in the English medical literature, the authors highlight the clinical characteristics of scleredema patients. They emphasize the protracted course that is usually not amenable to therapy and asymptomatic nature of the disease with only a few having symptoms of the skin and visceral organs.)
Copyright © 2017, 2013 Decision Support in Medicine, LLC. All rights reserved.
No sponsor or advertiser has participated in, approved or paid for the content provided by Decision Support in Medicine LLC. The Licensed Content is the property of and copyrighted by DSM.