Pathogenesis of Scleroderma

The term "scleroderma" traditionally has been uti l ized to describe the cutaneous changes of a heterogeneous group of disorders involving hardening, tightening, and decreased elasticity of the skin.' Two extreme forms have been identified-localized and diffuse. The localized form, specifically morphea, i s characterized by well-circumscribed, sclerotic plaques with an ivory-colored center and a surrounding violaceous halo. The violaceous halo implies active disease. Visceral involvement is not observed and, therefore, prognosis is generally favorable.2 In sharp contrast is the diffuse type, or progressive systemic sclerosis (PSS), which is correlated with widespread sclerosis, Raynaud's phenomenon, and multisystem invol~ement .~-~ Prognosis is poor, with death often secondary to renal failure or pulmonary fibrosis5 Between these two extremes are intermediate forms, with generalized morphea representing a form of localized scleroderma and acrosclerosis and the CREST syndrome representing a form of PSS.1.6 Formulating a definition of the full spectrum of PSS necessitates an understanding of the etiology and pathogenesis. This, in turn, may clarify the interrelationship between progressive systemic sclerosis, morphea, and the intermediate varieties. According to Lever and Schaumberg-Lever, histologic differentiation of the skin lesions in morphea versus PSS i s usually impossible; however, they identify two stages: (1 1 early inflammatory; and (2 ) !ate sclerotic.' During the early inflammatory stage, the dermis reveals closely packed, thick collagen bundles in conjunction with a