Systemic sclerosis and scleroderma are characterized by inflammation and fibrosis of the skin, as well as by vascular abnormalities, visceral damage, and the production of autoantibodies.
Diagnosing the chronic connective tissue disease, which can present in both limited and diffuse forms, can be complicated by the fact that it shares clinical and/or histologic features with a number of "scleroderma mimics," according to Dr. Janet E. Pope.
As with systemic sclerosis, most of these sclerodermalike conditions present with hard skin and tissue fibrosis and should be included in the differential diagnosis, noted Dr. Pope. She offered insight into ways to distinguish sclerodermalike fibrosing skin disorders from systemic sclerosis.
Skin & Allergy News: What are some of the more common "mimics" of systemic sclerosis.
Dr. Pope: Systemic sclerosis can be confused with such sclerodermalike skin disorders as eosinophilic fasciitis (EF), morphea, scleromyxedema, and nephrogenic systemic fibrosis (NSF).
SAN: How can physicians differentiate these from systemic sclerosis?
Dr. Pope: Most of these conditions lack Raynaud's phenomenon, sclerodactyly, and nailfold capillary changes.
Eosinophilic fasciitis (also called Shulman's syndrome) is a rare, localized, fibrosing disorder of subcutaneous tissues. Unlike systemic sclerosis, the overlying skin in EF is flexible enough to be pinched because the pathological disturbance is subcutaneous. This condition is often associated with venous grooving.
Generalized morphea is characterized by cutaneous sclerosis plaques caused by excessive collagen deposition, which leads to thickening of the dermis and/or subcutaneous tissues. Three or more major anatomical regions are affected by plaques in generalized morphea. Studies have shown that morphea often resolves within 2-5 years, but deeper lesions may take longer to resolve and may be accompanied by more disability and damage, depending on where they are located (J. Rheumatol. 1997;24:73-80). Additionally, many patients with morphea have antinuclear antibody and rheumatoid factor autoantibodies.
Scleromyxedema (also called papular mucinosis) is a chronic connective tissue disorder in which mucin deposits cause the skin to become red and raised, and make the movement of affected areas difficult. It tends to involve the head and neck rather than the extremities, and in most cases the sclerodermiform plaques and lichenoid papules are associated with a monoclonal gammopathy.
Finally, nephrogenic systemic fibrosis is a systemic fibrosing condition that occurs in people with kidney disease. NSF affects the skin, muscles, heart, and kidneys. It is strongly associated with exposure to gadolinium-based contrast agents.
Unlike systemic sclerosis, NSF tends to spare the skin of the face, and there is no association with autoantibodies or inflammatory cells.
The predominant histopathologic features of NSF include fibrocytelike cells, histiocytes, dermal dendritic cells, scarlike fibrosis, mucin, edema, calcification, and ossification. Diagnosing NSF requires both histopathologic and clinical findings.
SAN: Have any risk factors for the various conditions been identified?
Dr. Pope: As noted, NSF develops in patients with kidney disease and exposure to gadolinium. Renal failure is a major risk factor. With morphea, many patients who develop the condition are more likely than those without it to have an additional autoimmune disease.
SAN: How are the various conditions treated?
Dr. Pope: Corticosteroids and often methotrexate are used to treat EF, and early, aggressive treatment can minimize damage associated with the disease. Morphea is usually self-limited, and there is no proven treatment, although anecdotal evidence suggests that morphea patients who are being treated with antimalarials often develop new lesions when the treatment is stopped. IV immunoglobulin has been used in scleromyxedema treatment with mixed results.
Finally, there is no single therapeutic agent that has been proved effective for NSF. Anecdotal evidence suggests that extracorporeal photopheresis can lead to some lessening of skin thickening as well as increased mobility. Agents such as pentoxifylline, sodium, thiosulfate, and imatinib mesylate might improve skin fibrosis, but prevention through avoidance of gadolinium exposure in at-risk patients is advocated.
Dr. Pope is an associate professor of medicine in the division of rheumatology at the University of Western Ontario and a rheumatologist at St. Joseph's Health Care, both in London, Ont. She reported having no financial conflicts of interest.