Systematic review and meta-analysis: the impact of co-occurring immune-mediated inflammatory diseases on the disease localization and behavior of Crohn’s disease

Abstract

Background: Patients with Crohn’s disease (CD) are at increased risk of co-occurring immune-mediated inflammatory diseases (IMIDs). As discrepancy exists regarding the phenotypic presentation of CD among patients with such co-occurring IMIDs, we aimed to conduct a systematic review with meta-analysis characterizing the phenotype of CD among this subgroup of patients. Methods: PubMed, Embase, and Scopus were searched from their earliest records to October 2019 for studies reporting the behavior and localization of CD according to the Vienna or Montreal Classifications and CD-related surgery in patients with co-occurring IMIDs. These studies were the subject of a random effect meta-analysis. Results: After reviewing 24,413 studies, we identified a total of 23 studies comprising 1572 and 35,043 CD patients with and without co-occurring IMIDs, respectively, that fulfilled our inclusion criteria. Overall, patients with co-occurring IMIDs were more likely to have upper gastrointestinal inflammation than were patients without co-occurring IMIDs [relative risk (RR) = 1.49 (95% confidence interval (CI) 1.09–2.04), p = 0.01, I2 = 7%]. In addition, presence of primary sclerosing cholangitis (PSC) was associated with a lower occurrence of ileal affection [RR = 0.44 (95% CI 0.24–0.81), p < 0.01, I2 = 32%], increased occurrence of colonic affection [RR = 1.78 (95% CI 1.33–2.38), p < 0.01, I2 = 32%] and an increased likelihood of non-stricturing and non-penetrating behavior [RR = 1.43 (95% CI 0.97–2.11), p = 0.07, I2 = 86%]. The latter reached significance when cumulating different IMIDs [RR = 1.30 (95% CI 1.09–1.55), p < 0.01, I2 = 88%]. CD patients with PSC also underwent fewer CD-related surgeries [RR = 0.55 (95% CI 0.34–0.88), p = 0.01, I2 = 0%], irrespective of CD location or behavior. Conclusion: This study emphasizes that CD patients with co-existing PSC are likely to have a unique inflammatory distribution primarily confined to the colon, while patients with IMIDs in general have higher likelihood of affection of upper gastrointestinal tract and a non-stricturing and non-penetrating behavior. As such a phenotype of CD is typically associated with a milder disease course; future studies are needed to confirm these results.

Characteristics of inflammatory bowel diseases in patients with concurrent immune-mediated inflammatory diseases

“…Another recent systematic review and meta-analysis found that CD patients with concurrent IMIDs were more likely to have upper gastrointestinal involvement and nonstricturing and nonpenetrating phenotypes than those without IMIDs. Given that this meta-analysis suggests that CD patients with concurrent IMIDs may have a milder disease course, which contradicts the findings of the previous meta-analysis, more research is needed to better understand CD patients’ behaviors if they develop other IMIDs and require medication[ 35 ].…”

“…Patients with “extensive UC” had a higher prevalence of PSC than those with left-sided colitis. PSC was more common in CD patients with ileocolonic or colonic involvement than in those with ileal involvement[ 35 , 41 ]. PSC-IBD patients have a predilection for more severe right-sided colitis according to several studies[ 42 , 43 ].…”

“…Previous studies found that PSC-IBD patients had fewer or no symptoms[ 44 ] and were less likely to require immunosuppressants such as steroids, thiopurines, hospitalization[ 45 ], and surgery than IBD patients without PSC[ 46 ]. In addition, patients with PSC-CD had a higher risk of nonstricturing and nonpenetrating behavior than those without PSC, as well as being less likely to undergo CD-related surgeries, according to a recent meta-analysis[ 35 ]. All of these findings suggest that PSC-IBD patients may have better IBD outcomes, suggesting that PSC-IBD is a distinct disease phenotype from IBD phenotypes in patients with other IMIDs (Table 1 ).…”