The Arthritis Connection to Inflammatory Bowel Disease (IBD): Why Has It Taken So Long to Understand It?

Inflammatory bowel disease (IBD) associated arthritis is a subgroup of spondyloarthritis (SpA) that has suffered from lack of recognition in rheumatology clinical and research circles for over 100 years. Although clinically distinguishable from rheumatoid arthritis and ankylosing spondylitis, it took advances in detection systems in the middle of the last century (rheumatoid factor, HLA-B27) to convincingly make the final separations. We now know that significant numbers of patients with SpA have associated clinical IBD and almost half of them show subclinical gut inflammation, yet the connection between the gut and the musculoskeletal system has remained a vexing problem. Two publications from Nathan Zvaifler (one in 1960, the other in 1975) presciently described the relationship between the gut and the spine/peripheral joints heralding much of the work present today in laboratories around the world trying to examine basic mechanisms for the connections (there are likely to be many) between the gut, the environment (presumably our intestinal flora) and the downstream effect on the musculoskeletal system. The role of dysregulated microbiome along with microbiome-driven T helper 17 cell expansion and immune cell migration to the joints has been recognised, all of which occur in the appropriate context of genetic background inside and outside of the human leucocyte antigen system. Moreover, different adhesion molecules that mediate immune cells homing to the gut and joints have been noted. In this review, we studied the origins and evolution of IBD-arthritis, proposed pathogenic mechanisms and the current gaps that need to be filled for a complete understanding of IBD-arthritis.