Why are patients with IBD prone to develop an inflammatory arthritis?
The precise pathogenesis of IBD-associated SpA is unknown. However, there is ample clinical evidence supporting that IBD and SpA are along a continuum between pure bowel disease and pure SpA. As noted, ∼25% of patients with IBD develop a form of SpA. Conversely, up to 50% of patients with ankylosing spondylitis have inflammation of the bowel identified on colonoscopy. While many of these are asymptomatic, over time, 6% to 10% of these patients will develop overt symptomatic Crohn’s disease.
There are common findings between the pathophysiology of IBD and SpA that suggest an overlap in the two disease entities. Shared genetic polymorphisms are associated with IBD and ankylosing spondylitis, such as interleukin (IL)-23 receptor, as is microbial dysbiosis (i.e., a substantial alteration of the individual bacterial species compared with unaffected controls). In both diseases, there is a Th17-mediated inflammation characterized by increased IL-6, IL-17a, and IL-23. Finally, gut-derived lymphocytes and macrophages have been identified in circulation and synovial fluid of individuals with SpA; these cells express intestinal markers such as invariant T-cell receptors (mucosal-associated invariant T cells, also called MAIT cells), IL-23R, IL-17a, αEβ7, α4β7, and CD163. What triggers circulation of the gut-derived cells, though, remains unknown but possibly due to microbial signals in the gut and/or increased intestinal permeability due to local inflammation.
