{"id":14327,"date":"2023-04-24T15:12:17","date_gmt":"2023-04-24T14:12:17","guid":{"rendered":"https:\/\/touchimmunology.com\/?p=14327"},"modified":"2023-07-18T19:44:24","modified_gmt":"2023-07-18T18:44:24","slug":"managing-inflammatory-bowel-disease-in-spondyloarthritis","status":"publish","type":"post","link":"https:\/\/touchimmunology.com\/axial-spondyloarthritis\/journal-articles\/managing-inflammatory-bowel-disease-in-spondyloarthritis\/","title":{"rendered":"Managing Inflammatory Bowel Disease in Spondyloarthritis"},"content":{"rendered":"
Spondyloarthritides are chronic rheumatic diseases associated with diverse extra-articular manifestations, such as psoriasis, uveitis and\u00a0inflammatory bowel diseases<\/span>\u00a0(IBDs<\/span><\/span>), namely\u00a0Crohn\u2019s disease<\/span>\u00a0(CD<\/span>) and\u00a0ulcerative colitis<\/span>\u00a0(UC<\/span>). Historically,\u00a0spondyloarthritis (SpA)<\/span>\u00a0was divided into several subcategories, namely,\u00a0ankylosing spondylitis<\/span>\u00a0(AS<\/span>), psoriatic arthritis, enteropathic arthritis, reactive arthritis and undifferentiated spondyloarthropathy. Given the possible overlap between these different entities, it is now preferred to use a phenotypic classification, associating the distribution of joint involvement (axial, peripheral or both) with any associated extra-articular manifestations, including IBD.<\/p>\n Clinical SpA occurs in up to\u00a013<\/span>%<\/span>\u00a0of patients with IBD, and CD in particular.1<\/sup><\/span>\u00a0However, in a Canadian cohort, subclinical sacroiliitis was found in\u00a016<\/span>%<\/span>\u00a0of cases, with no difference in prevalence between CD and UC.2<\/sup><\/span>\u00a0On the contrary, up to\u00a060<\/span>%<\/span>\u00a0of patients with SpA have subclinical, histological<\/span>, gastrointestinal inflammation.3<\/sup><\/span>\u00a0IBD seems to be more associated with AS than\u00a0with\u00a0<\/span>psoriatic arthritis<\/span>.4<\/sup><\/span>\u00a0In a large British AS cohort, the prevalence of IBD at diagnosis was 3.7%, which\u00a0was\u00a0<\/span>lower than\u00a0the rate of\u00a0<\/span>acute anterior uveitis\u00a0or<\/span>\u00a0<\/span>psoriasis.5<\/sup><\/span> The incidence rate was 2.4 per 1,<\/span>000<\/span>\u00a0person-years, giving a cumulative incidence at\u00a020<\/span>\u00a0years<\/span>\u00a0of 7.5%, with a higher risk in the first year after diagnosis. High Bath\u00a0Ankylosing Spondylitis<\/span>\u00a0Disease Activity Index\u00a0(<\/span>BASDAI<\/span>)<\/span>\u00a0or Bath\u00a0Ankylosing Spondylitis<\/span>\u00a0Disease Functional Index\u00a0(BASFI)<\/span>\u00a0scores were associated with microscopic gut inflammation, without necessarily having a clinical impact.6<\/sup><\/span>\u00a0<\/span>Interestingly,\u00a0a study of the<\/span>\u00a0British BSRBR-AS cohort\u00a0revealed that, overall,<\/span>\u00a0exposure to anti-tumour necrosis factor (<\/span>TNF)<\/span> therapy was associated with an increased risk of developing IBD compared with unexposed patients;<\/span><\/span>\u00a0<\/span>however,\u00a0<\/span>t<\/span>his\u00a0finding\u00a0<\/span>was\u00a0only replicated in the observational studies and\u00a0<\/span>not in\u00a0the\u00a0<\/span>randomized controlled trials included in the meta-analysis, possibly dye to<\/span>\u00a0u<\/span>nadjusted confounding factors<\/span>.7<\/sup><\/span><\/span><\/p>\n The relationship between SpA and IBD is complex and not yet fully understood. It involves both genetic and immunological mechanisms. Moreover, in recent years, the role of the gut microbiome has been increasingly studied. Genetically,\u00a0human leukocyte antigen B27<\/span>\u00a0(<\/span>HLA-B27)<\/span>\u00a0is the most studied risk factor. Different theories have been formulated regarding its involvement in the pathogenesis of SpA. However, large genetic studies have shown that it is not a risk factor for the occurrence of IBD,8<\/sup><\/span>\u00a0which could suggest different pathophysiological pathways. A clinical study of Caucasian patients with AS showed that HLA-B27-negative patients had more extra-articular manifestations, besides uveitis, than HLA-B27-positive\u00a0<\/span>patients<\/span>.9<\/sup><\/span>\u00a0Conversely, HLA-B27\u00a0wa<\/span>s also associated with gut dysbiosis in patients\u00a0with SpA,\u00a0<\/span>and these effects\u00a0<\/span>were<\/span>\u00a0highly dependent on host genetic background and environment.9<\/sup><\/span>\u00a0On the contrary,\u00a0g<\/span>enome–<\/span>wide association studies have shown common genetic factors between SpA and IBD. The largest\u00a0genome-wide association study<\/span>\u00a0explains\u00a027.8<\/span>%<\/span>\u00a0of the heritability of SpA, which is mostly related to\u00a0m<\/span>ajor\u00a0h<\/span>istocompatibility\u00a0c<\/span>omplex\u00a0<\/span>loci.10<\/sup><\/span>\u00a0Others, such as genes related to type\u00a0<\/span>3<\/span>\u00a0immunity and epithelial barrier integrity are shared risk factors for SpA and IBD. Some variants are associated with only one of the two diseases. Finally, some variants are a risk factor in one disease and protective in the other.3,10<\/sup><\/span><\/p>\n <\/span>Immunologically<\/span>, type\u00a0<\/span>3<\/span>\u00a0immunity, which is involved in the integrity of the intestinal endothelial barrier, seems to play a major<\/span>\u00a0<\/span>role\u00a0in the development of both SpA and IBD<\/span><\/span><\/span>.11<\/sup><\/span>\u00a0Apart from TNF–<\/span>\u03b1<\/span>, the key cytokine in the pathophysiology of IBD is\u00a0interleukin (<\/span>IL)<\/span>-23, whereas in SpA it is IL-17A. IL-23, produced by dendritic cells and macrophages, promotes differentiation and activation of several cell types, including T–<\/span>helper lymphocytes type 17, which in turn produce TNF–<\/span>\u03b1<\/span>\u00a0and IL-17A. There is,<\/span>\u00a0therefore,<\/span>\u00a0an IL-23\/IL-17A axis of inflammation,<\/span>\u00a0but it is not inflexible: treatments directed against IL-23 work well in\u00a0both\u00a0<\/span>IBD and SpA, whereas treatments directed against\u00a0<\/span>IL-17A<\/span><\/span>\u00a0are effective in SpA but not in IBD. This could be explained by different interaction networks and cytokine effects depending on the tissue studied.11<\/sup><\/span><\/p>\n Serum IL–<\/span>17A\u00a0<\/span>is also higher in patients\u00a0with AS\u00a0compared with\u00a0both healthy controls and patients with IBD<\/span><\/span><\/span>,<\/span><\/span>12<\/sup><\/span>\u00a0and small–<\/span>intestine IL–<\/span>23 concentrations\u00a0a<\/span>re\u00a0<\/span>higher in patients with AS and\u00a0<\/span><\/span>CD\u00a0than in healthy controls<\/span><\/span>.13<\/sup><\/span><\/p>\n The gut microbiome\u00a0has been<\/span>\u00a0<\/span>increasingly studied in SpA, but many questions remain unanswered. Several studies have shown variations in the diversity and composition of the gut microbiome in patients, with some bacteria even being associated with disease activity.14,15<\/sup><\/span>\u00a0In particular, an imbalance in the ratio of Firmicutes\/Bacteroidetes could cause AS.16<\/sup><\/span><\/p>\n These three mechanisms\u00a0\u2212\u00a0<\/span><\/span><\/span>genetic, immunological and microbiome\u00a0\u2212<\/span><\/span>\u00a0are strongly linked,\u00a0altering\u00a0<\/span>the epithelial barrier,\u00a0<\/span>causing\u00a0<\/span><\/span>subclinical inflammation,\u00a0and\u00a0<\/span>leading to recruitment of pro-inflammatory cells and cytokines in the axial and peripheral skeleton. It is therefore a real\u00a0<\/span>‘<\/span>gut\u2212<\/span>joint axis‘<\/span><\/span>.3<\/sup><\/span><\/p>\n <\/span>It is important for clinicans, including rheumatologists, to have\u00a0<\/span>good knowledge of the clinical signs and diagnosis of IBD,<\/span>\u00a0to ensure\u00a0<\/span>it is promptly diagnosed and treated<\/span><\/span>. An Italian team proposed a set of criteria\u00a0for<\/span>\u00a0referral to a gastroenterologist: chronic diarrho<\/span>ea, rectal bleeding, perianal abscess\/fistula, chronic abdominal pain and nocturnal symptoms were major criteria (one is sufficient for referral), while oral aphthosis, fever, ana<\/span>emia, a family history of IBD, and weight loss were minor criteria (at least two criteria are necessary for referral).17 <\/sup>T<\/span>hese signs s<\/span>hould be\u00a0assessed\u00a0<\/span>at each follow-up visit.<\/p>\n The diagnostic strategy for IBD in a patient with a history of SpA does not change from\u00a0that for\u00a0<\/span>the general population. As mentioned in the\u00a0European Crohn’s and Colitis Organisation (ECCO)<\/span>\/European Society of Gastrointestinal and Abdominal Radiology<\/span><\/span><\/span>\u00a0recommendations,18<\/sup><\/span>\u00a0no single test is diagnostic of IBD. Instead, diagnosis\u00a0<\/span>is based on a combination of clinical and paraclinical evidence. Fa<\/span>ecal calprotectin is a sensitive marker of intestinal inflammation in IBD. However, its performance as a screening test in the context of SpA may be diminished due to the high prevalence of microscopic inflammation, which may not have a clinical impact.19<\/sup><\/span>\u00a0This marker could also define\u00a0patients\u00a0<\/span>at risk of developing IBD.20<\/sup><\/span>\u00a0An ileocolonoscopy remains mandatory to\u00a0diagnose IBD<\/span>, with two biopsies in the inflamed zone and biopsies in each colonic segment, except in cases of acute severe colitis in which sigmoidoscopy may be sufficient.18<\/sup><\/span>\u00a0There are only\u00a0a\u00a0<\/span>few endoscopic studies in SpA. In a Korean series of\u00a0108<\/span>\u00a0patients<\/span>, lesions were found in\u00a040<\/span>\u00a0cases\u00a0<\/span>(37%)<\/span><\/span>.21<\/sup><\/span>\u00a0Ulceration was the most frequently found lesion, and the terminal ileum was the most frequently affected site.21<\/sup><\/span>\u00a0Small-bowel capsule endoscopy<\/span>\u00a0can also be used. Two studies have evaluated its\u00a0use\u00a0<\/span>in SpA, in comparison with ileocolonoscopy.<\/span>\u00a0Eliakim\u00a0et al<\/span>.\u00a0<\/span><\/span>showed in\u00a02005<\/span>\u00a0that, in 20 patients,<\/span>\u00a0small-bowel capsule endoscopy\u00a0<\/span>uncovered more lesions than ileocolonoscopy\u00a0(30%<\/span>\u00a0versu<\/span>s<\/span>\u00a0<\/span>5%, respectively<\/span>)<\/span>.22<\/sup><\/span>\u00a0Similar results\u00a0(42.2%<\/span>\u00a0versu<\/span>s\u00a0<\/span>10.9%, respectively)\u00a0<\/span><\/span>were found in a prospective study\u00a0of 64 patients<\/span>\u00a0in\u00a02018<\/span><\/span><\/span><\/span><\/span><\/span><\/span>.23<\/sup><\/span><\/p>\n Consideration of IBD is important for the therapeutic management of patients with SpA. Indeed, some treatments are not effective,<\/span>\u00a0or\u00a0are\u00a0<\/span>even contraindicatedEpidemiology<\/h1>\n
Pathophysiology<\/h1>\n
Recognizing\u00a0inflammatory bowel disease\u00a0<\/span>in the context of\u00a0spondylo<\/span>arthritis<\/span><\/h1>\n
Managing\u00a0inflammatory bowel disease\u00a0<\/span>in the context of\u00a0spondyloarthritis<\/span><\/h1>\n