Causes of systemic scleroderma

The causes of systemic scleroderma are complex and poorly understood. Multifactorial genesis of the disease is assumed, caused by the interaction of unfavorable exogenous and endogenous factors with a genetic predisposition to the disease. Along with the role of infection (viral and others), cooling, vibration, trauma, stress and endocrine changes, special attention is paid to the trigger action of chemical agents (industrial, household, alimentary) and certain drugs. Some genetic mechanisms of predisposition (predetermination) to systemic scleroderma have been identified, which have been actively studied after the discovery of cases of familial aggregation of the disease. The presence of chromosomal instability in patients with systemic scleroderma has been confirmed. A combination of certain antigens and alleles of the histocompatibility system (HLA) with systemic scleroderma has been established: HLA DQB1, DR1, DR3, DR5, DRU, DRw52, varying in different populations.

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Pathogenesis of systemic scleroderma

The basis of the pathogenesis of systemic scleroderma is the disturbance of immunity, fibrosis formation 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 significance are the established associations between autoantibodies specific for systemic sclerosis, genetic markers and certain clinical characteristics of SSc. Thus, anticentromere antibodies are combined with markers HLA DR1, DR4 and limited skin lesions, pulmonary hypertension and chronic course, and antitopoisomerase antibodies - with DR3, DR5, DQ7, diffuse skin lesions, pulmonary 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 SSc have been proven. In the early stage of the disease, perivascular infiltration of the dermis with CD4 T-lymphocytes, mucoid swelling of the vessel wall, accumulation of fibroblasts and activated mast cells in the perivascular space, and expression of ICAM-1 on endothelial cells are detected. Damage to vessels and the microvasculature 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 microvasculature, and thrombosis are characteristic. Increased collagen formation and fibrosis occupy a major place in the pathogenesis and are the cause of systemic scleroderma, determining the nosological specificity of the disease. Hyperactivity of fibroblasts, possibly genetically determined, leads to excessive production of intercellular matrix components, increased neofibrillogenesis, and generalized fibrosis.