[Connective tissue diseases: development predictors, multimorbidity variants, physical treatment methods. (Literature...

Connective tissue diseases, such as systemic lupus erythematosus, systemic scleroderma and dermatomyositis are heterogeneous autoimmune diseases with damage to the skin, vessels and internal organs, immune dysregulation, fibrosis.

The relevance of their study is due to high multimorbidity, including cardiovascular, oncological and neuropsychiatric complications (pulmonary hypertension develops in 30-40% of patients with scleroderma, paraneoplastic syndromes are recorded in 40% of patients with dermatomyositis). Increase in knowledge of genetic and epigenetic factors triggering debut of connective tissue diseases emphasizes the need for an interdisciplinary approach and personalization of therapy.

To analyze the modern data on pathogenesis, genetic predictors, clinical complications and comorbid conditions, methods of treatment of the connective tissue diseases, as well as to evaluate the promising research directions for improving diagnosis and therapy.

A review of scientific publications and clinical studies presented in international abstract databases for the period from 2013 to 2025 involving more than 700 thousand patients was carried out. Data on genetic biomarkers, epidemiological factors, effectiveness of physical methods of treatment of the connective tissue diseases and innovative approaches were systematized.

Key genetic (polymorphisms of HLA class II, TRAF1-C5, TNFSF4, antibodies to MDA5) and epigenetic risk factors (insolation, smoking, vitamin D deficiency) of the connective tissue diseases have been identified. Effectiveness of physical therapy for improvement of the function of joints and lungs, phototherapy for correction of skin manifestations has been proven. Autologous stem cell transplantation has shown effectiveness in refractory forms. Personalization of biomarker-based therapy improves patients' quality of life. The main challenges have been established: resistance to therapy, risk of infections during immunosuppression. The investigation of gut microbiome and development of targeted drugs inhibiting TGF-β and interleukin-6 have been recognized as promising directions.

Connective tissue diseases require early diagnosis, interdisciplinary strategy and integration of pharmacological and non-drug methods. Physical treatment methods demonstrate proven effectiveness in the context of a comprehensive approach to therapy. Physical therapy with a high level of evidence (I, A) improves the function of joints and lungs, as well as contributes to the reduction of fibrosis severity. UVA-1 phototherapy is a method of choice for improving the skin elasticity in scleroderma and skin forms of the connective tissue diseases by inhibiting TGF-β and collagen synthesis. Ultrasound therapy in combination with hyaluronidase, high-intensity dye laser therapy are indicated for reduction of the vascular disorders in tissues. Cryotherapy (whole-body and local), electrophoresis with corticosteroids have a local anti-inflammatory effect, complement the range of non-drug interventions, improving the quality of life of patients, but require individualization of parameters. Personalization of treatment based on genetic markers, as well as the introduction of innovative methods (targeted therapy) can reduce the risk of complications, but problems of resistance and iatrogenic effects remain. Further research should be aimed at the study of the role of microbiome and development of pathogenetically substantiated drugs.