Scleroderma

Scleroderma (systemic sclerosis) is a complex disease in which extensive fibrosis, vascular alterations, and autoantibodies against various cellular antigens are among the principal features (Fig. 1 and 2).1 There are two major subgroups in the commonly accepted classification of scleroderma: limited cutaneous scleroderma and diffuse cutaneous scleroderma.2 In limited cutaneous scleroderma, fibrosis is mainly restricted to the hands, arms, and face. Raynaud’s phenomenon is present for several years before fibrosis appears, pulmonary hypertension is frequent, and anticentromere antibodies occur in 50 to 90% of patients. Diffuse cutaneous scleroderma is a rapidly progressing disorder that affects a large area of the skin and compromises one or more internal organs. We believe that the acronym CREST (calcinosis, Raynaud’s phenomenon, esophageal motility dysfunction, sclerodactyly, and telangiectasia) is obsolete, since it cannot be assigned to only one subgroup of patients with the disease and does not sufficiently indicate the burden of internal-organ involvement. In rare cases, patients with scleroderma have no obvious skin involvement. Patients with scleroderma plus evidence of systemic lupus erythematosus, rheumatoid arthritis, polymyositis, or Sjögren’s syndrome are considered to have an overlap syndrome. This classification can be useful, but none of the proposed classifications sufficiently reflect the heterogeneity of the clinical manifestations of scleroderma. Scleroderma can lead to severe dysfunction and failure of almost any internal organ. Here, too, there is considerable heterogeneity (Table 1). Involvement of visceral organs is a major factor in determining the prognosis. The kidneys, esophagus, heart, and lungs are the most frequent targets. Renal involvement can be controlled by angiotensin-converting–enzyme inhibitors. Severely debilitating esophageal dysfunction is the most common visceral complication, and lung involvement is the leading cause of death. The mechanisms underlying visceral involvement in scleroderma are unclear, despite progress in the treatment of these complications. Relevant data on mechanisms are limited, since most of the available information is derived from crosssectional studies and from patients in various stages of the disease, often after treatment; moreover, there are no satisfactory animal models of scleroderma. Nevertheless, a critical evaluation of the available experimental and clinical data will help reduce ambiguity and may provide the basis for future studies of scleroderma.