PATHOPHYSIOLOGY OF SCLERODERMA - AN UPDATE

Objectives To review the pathophysiological background of systemic scl erosis in relation to the main components involved: microvascular syst em, immunological system and fibroblasts of the connective tissue. Bac kground Although many particular aspects of the pathophysiology of sys temic sclerosis have been investigated in recent years, the complexity of the pathogenesis and the important links between the components in volved remain unclear. Methods Literature review. Results and conclusi on Scleroderma is a connective tissue disorder resulting in a progress ive fibrosis of skin and internal organs. The genetic background is no t clear. The microvascular system is one of the first targets involved (damage of capillaries, enhanced expression of adhesion molecules int eracting with lymphocytes, perivascular infiltrates as starting points for tissue fibrosis). The immune system is unbalanced (selection of T -cell subpopulations, elevated serum levels of several cytokines, occu rrence of autoantigens to topoisomerase I, centromeric proteins and RN A polymerases). As far as autoimmunity is concerned the triggering aut oantigen is still unknown. Development of connective tissue fibrosis i s prominent (subpopulations of fibroblasts with disturbed regulation o f collagen turnover by TGF-beta, CTGF and collagen receptors (alpha(1) beta(1), alpha(2)beta(1))). Investigation of pathophysiology of sclero derma is effected by monitoring the serum levels for soluble mediators , by cell culture studies of affected and non-affected fibroblasts and EC, by studying environmentally induced forms of scleroderma and by s tudies using animal models. (C) 1998 Elsevier Science B.V. All rights reserved