EXTRAINTESTINAL SIGNS, PATHOGENESIS AND GENETIC PREDICTORS OF ULCERATIVE COLITIS

Abstract

Ulcerative colitis (UC) is a systemic disease that involves not only the intestine but the whole organism, in which extraintestinal manifestations (EIM) are frequent and in some cases appear before the intestinal symptoms. This article covers the spectrum of EIM in UC (musculoskeletal system, eyes, skin, hepatobiliary system) and modern views on their pathogenesis. Immunological mechanisms - T-cell dysregulation, molecular mimicry, the cytokine flow (TNF-α, IL-1, IL-6) and bacterial translocation associated with disruption of the intestinal barrier - play a leading role in the development of EIM. Genetic predictors include the HLA complex (among them HLA-B27, HLA-DRB10103, HLA-B8/DR3) and HLA-independent loci, as well as the familial concordances reported in GWAS studies. Clinically, UC is noted to be accompanied by peripheral and axial arthritis, enthesitis, osteopenia/osteoporosis and steroid-induced myopathy; ophthalmological complications (episcleritis, uveitis); skin changes (erythema nodosum, pyoderma gangrenosum, Sweet's syndrome), as well as hepatobiliary lesions (primary sclerosing cholangitis, autoimmune hepatitis). The fact that EIM are sometimes independent of intestinal activity complicates diagnosis and treatment. The article demonstrates the importance of multidisciplinary vigilance, early screening, and individualized therapy based on the genetic and clinical phenotype (choice of biological agents). This approach serves to reduce complications and to improve the patient's long-term outcomes.