Inflammatory bowel diseases and spondyloarthropathies: From pathogenesis to treatment

Abstract

Spondyloarthropathies (SpA) include many different forms of inflammatory arthritis and can affect the spine (axial SpA) and/or peripheral joints (peripheral SpA) with Ankylosing spondylitis (AS) being the prototype of the former. Extra-articular manifestations, like uveitis, psoriasis and inflammatory bowel disease (IBD) are frequently observed in the setting of SpA and are, in fact, part of the SpA classification criteria. Bowel involvement seems to be the most common of these manifestations. Clinically evident IBD is observed in 6%-14% of AS patients, which is significantly more frequent compared to the general population. Besides, it seems that silent microscopic gut inflammation, is evident in around 60% in AS patients. Interestingly, occurrence of IBD has been associated with AS disease activity. For peripheral SpA, two different forms have been proposed with diverse characteristics. Of note, SpA (axial or peripheral) is more commonly observed in Crohn's disease than in ulcerative colitis. The common pathogenetic mechanisms that explain the link between IBD and SpA are still ill-defined. The role of dysregulated microbiome along with migration of T lymphocytes and other cells from gut to the joint ("gut-joint" axis) has been recognized, in the context of a genetic background including associations with alleles inside or outside the human leukocyte antigen system. Various therapeutic modalities are available with monoclonal antibodies against tumour necrosis factor, interleukin-23 and interleukin-17, being the most effective. Both gastroenterologists and rheumatologists should be alert to identify the co-existence of these conditions and ideally follow-up these patients in combined clinics.

Keywords: Ankylosing spondylitis; Axial spondyloarthropathies; Inflammatory bowel disease; Peripheral spondyloarthropathies; Spondyloarthropathies.

Figure 1

Pathogenic mechanisms linking gut and joint inflammation. The pathogenic link between spondyloarthropathies (SpAs) and inflammatory bowel disease (IBD) involves the so-called ‘’gut-synovial axis’’ hypothesis. Various environ mental (gut bacteria-dysbiosis) and host factors (migration of activated gut-T cells and macrophages) leading to initiation of inflammation in genetically predisposed individuals may act as triggers of inflammatory responses against gut and joints components. IBD patients carrying specific human leukocyte antigens (HLA) alleles (such as DRB1 0103 allele, HLA-B27, HLA-B35, HLA-B44) and mutations of the CARD15/NOD2 gene are at higher risk of developing SpAs. Recently, up-regulation of adhesion molecules (E-cadherin, αEβ7 integrin), increased levels of pro-inflammatory cytokines (tumor necrosis factor-α), macrophages expressing CD163 protein, interleukin (IL)-12/IL-23 signaling pathway and signal transducer and activator of transcription 3 protein have also been implicated in the pathophysiology of SpAs in IBD patients. IL: Interleukin; STAT: Signal transducer and activator of transcription; TNF: Tumor necrosis factor; HLA: Human leukocyte antigen; CARD15: Caspase recruitment domain-containing protein 15; NOD: Nucleotide-binding oligomerization domain-containing protein 2.