Causes of systemic scleroderma

The causes of systemic scleroderma are complex and insufficiently studied. Multifactorial genesis of the disease due to the interaction of unfavorable exogenous and endogenous factors with a genetic predisposition to the disease is suggested. Along with the role of infection (viral, etc.), cooling, vibration, trauma, stress and endocrine disruptions, special attention is paid to the trigger action of chemical agents (industrial, domestic, alimentary) and individual medicines. Some genetic mechanisms of predisposition (predetermination) to systemic scleroderma have been identified, which were actively studied after detection of cases of familial aggregation of the disease. The presence of chromosomal instability in patients with systemic scleroderma was confirmed. A combination of certain antigens and alleles of the histocompatibility system (HLA) with systemic scleroderma was established: HLA DQB1, DR1, DR3, DR5, DRU, DRw52, varying in different populations.

[1], [2], [3], [4]

Pathogenesis of systemic scleroderma

The basis of the pathogenesis of systemic scleroderma is violations of immunity, fibrosis and microcirculation interacting at the level of cellular (immunocompetent cells - fibroblasts - endothelial blood cells) and receptor-ligand systems (adhesion molecules, growth factors, interleukins, etc.).

Of great scientific and practical importance are the established associations between specific for systemic scleroderma autoantibodies, genetic markers and certain clinical characteristics of the SSD. So, antitsentromernye antibodies combined with markers HLA DR1, DR4 and limited skin lesions, pulmonary hypertension and chronic course and antitopoizomeraznye antibodies - with DR3, DR5, DQ7, diffuse lesion of the skin, lung fibrosis and rapidly progressive course of systemic sclerosis. The pathogenetic role of T-cell disorders, their participation in the development of vascular pathology and fibrosis in the SDS have been proved. In the early stage of the disease, periclavicular infiltration of the dermis from CD4-T-lymphocytes is detected, mucoid swelling of the vessel wall, accumulation of fibroblasts and activated mast cells in the perivascular space, expression of ICAM-1 on endothelial cells. The defeat of the vessels and microcirculatory bed is the most important link in the pathogenesis and morphogenesis of systemic scleroderma. Signs of activation and destruction of the endothelium, proliferation of smooth muscle cells, thickening of the intima and narrowing of the lumen of the microcirculatory bed, thromboses are characteristic. Increased collagen formation and fibrosis occupy the main place in pathogenesis and is the cause of systemic sclerosis, determining the nosological specificity of the disease. Hyperactivity of fibroblasts, possibly genetically determined, leads to excessive production of intercellular matrix components, an increase in neofibrilogenesis and generalized fibrosis.