Joint involvement associated with inflammatory bowel disease

Joint involvement associated with inflammatory bowel disease (IBD) belongs to the concept of spondyloarthritis (SpA) and includes two types of arthritis: a peripheral arthritis characterized by the presence of pauciarticular asymmetrical arthritis affecting preferentially joints of lower extremities and an axial arthropathy including inflammatory back pain, sacroiliitis and ankylosing spondylitis (AS). Treatment of arthritis includes a short-term use of NSAIDs associated with optimized treatment of gut inflammation. Safety concerns mean that long-term treatment with NSAIDs is best avoided if possible. Salazopyrine can be recommended for treatment of peripheral arthritis. Methotrexate and azathioprine are generally ineffective. Finally, efficacy of anti-TNF therapy (infliximab and adalimumab) is well established. However, use of etanercept is not recommended because of the increased risk for intestinal disease relapse. Pathogenesis of gut-joint iteropathy is not elucidated. Both inflammations are tightly related as suggested by human evidence of gut inflammation in patients with other forms of SpA and animal evidence of gut and joint inflammation in HLA-B27/human beta(2)-microglobulin transgenic rat model and TNF(DeltaARE) mice. Several clues for the linkage between gut and joint inflammation have been put forward including an altered recognition and handling of bacterial antigens, an aberrant trafficking of CD8+ T cells with an impaired T-helper type 1 cytokine profile and expression of aEb7 integrin, an altered trafficking of macrophages expressing CD163 and evidence of an increased angiogenesis. A transcriptome analysis of mucosal biopsies identified a set of 95 genes that are differentially expressed in both CD and SpA as compared with healthy controls suggesting common pathways. TNF plays a key role in the pathogenesis of various arthritic diseases and IBD. Mesenchymal/myofibroblast-like cells may represent the local primary targets of TNF in the induction of gut and joint pathology. Selective expression of TNFRI on these cells seems to be sufficient to orchestrate the complete development of SpA-related pathologies at least in TNF(DeltaARE) mice. Finally, genetic susceptibility is probably required to develop these pathologies. Genotyping of AS patients provided evidence for an important overlap between determinants of inherited predisposition to CD and AS. The best documented common association is with an IL-23R polymorphism, although the exact role remains unexplored. In addition, evidence suggests that a number of recently identified CD-susceptibility loci are associated with AS. Clinical, genetical, immunological and therapeutic evidence support the tight junction between gut and joint inflammation in two linked diseases, IBD and SpA, belonging to the 'immune-mediated inflammatory diseases'.