Collagen Synthesis by Scleroderma Fibroblasts a

Scleroderma is a disease of connective tissue occurring in a localized and a systemic form.’ Progressive systemic scleroderma (PSS) involves the skin and several internal organs, e.g., the lung, esophagus, kidney, and hea1t.2.~ Several attempts have been made to classify systemic scleroderma on the basis of the clinical picture and the presence of autoantibodies in the serum of patients.’.’ In the acral type of scleroderma, fibrosis usually starts in the extremities and the face and then slowly progresses towards the trunk. Patients with the CREST (calcinosis, Raynaud’s phenomenon, esophagusinvolvement, sclerodactyly, teleangiectasia) syndrome seem to run a more benign course of the disease. A high incidence of internal involvement is characteristic for the diffuse form of scleroderma, which therefore has a serious prognosis. The pathogenesis of scleroderma is poorly understood. A review of the literature suggests at least three hypotheses, which are thought to account for a primary event of the disease: (1) vascular damage and alterations of endothelial cells3“; (2) primary disturbance of collagen metabolism (for review see ref. 9); and (3) an autoimmune response (for review see ref. 10). Nevertheless, regardless of the primary or secondary events, excessive accumulation of connective tissue is generally believed to be responsible for the main clinical symptoms.’ In this review we shall therefore focus on the alterations of connective tissue metabolism in both the systemic and localized form of scleroderma. Fibrosis in scleroderma skin can easily be demonstrated by routine histology (FIGURE 1). Examination of the deep reticular layer of the dermis and of the sub-