Reflecting on the immunopathology of arthritis associated with inflammatory bowel disease: what do we know and what should we know?

Abstract

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is clinically closely associated with arthritis. Three major arthritis clinical subtypes have been described, peripheral arthritis type 1 (PeA1), peripheral arthritis type 2 (PeA2), and axial spondyloarthritis (axSpA). While genetic overlaps between IBD and arthritis have been defined, detailed pathophysiology for these three major subtypes of arthritis in patients with IBD has only recently begun to be established. The genetic and molecular mechanisms distinguishing axial and peripheral arthropathies in patients with UC and CD need to be better described. Understanding the pathophysiology for PeA1, PeA2, and axSpA in the settings of both UC and CD is necessary to provide the fundamental biology underlying the clinical phenotypes in IBD arthritis. This has been attempted for CD-associated spondyloarthritis, differentiating this from both CD and axSpA, while observing unique peripheral blood mononuclear cells linking gut inflammation to joint disease. We should know more about the processes by which immune cells are perturbed in these disorders, how they translocate to joints, how they are activated, what other molecules and mediators are involved, and how gut microbes and microbial products damage joints. Information from such studies are needed to elucidate whether distinctions between IBD-related peripheral and axSpA are clinically meaningful. IBD-related peripheral and axSpA studies are needed to elucidate whether distinctions between peripheral and axSpA are clinically meaningful, to better understand immunopathogenesis, and to develop novel targeted therapies.