Immune-mediated Diseases and Risk of Crohn's Disease or Ulcerative Colitis

A Prospective Cohort Study

Chun-Han Lo; Hamed Khalili; Paul Lochhead; Mingyang Song; Emily W. Lopes; Kristin E. Burke; James M. Richter; Andrew T. Chan; Ashwin N. Ananthakrishnan


Aliment Pharmacol Ther. 2021;53(5):598-607. 

In This Article

Abstract and Introduction


Background: Although immune-mediated diseases (IMDs) including inflammatory bowel diseases (IBDs) are known to cluster, to what extent this is due to common environmental influences is unknown.

Aim: To examine the incidence of IBD in individuals with another IMD.

Methods: We used data from the prospective Nurses' Health Study II cohort (1995–2017) to examine the effect of diagnoses of several common IMDs on subsequent risk of Crohn's disease (CD) or ulcerative colitis (UC) using Cox proportional hazards models, adjusting for detailed diet and lifestyle confounders.

Results: We documented 132 cases of CD and 186 cases of UC over 2 016 163 person-years of follow-up (median age at IBD diagnosis 50 years). Compared to participants with no history of IMD, the HRs of CD for those with 1 and ≥ 2 IMDs were 2.57 (95% CI 1.77–3.74) and 2.74 (95% CI 1.36 to 5.49), respectively (P trend < 0.0001). This association was only modestly attenuated by adjustment for environmental risk factors (HR 2.35 and 2.46, respectively). The risk of UC was not increased, with multivariable-adjusted HRs of 1.22 (95% CI 0.85–1.76) and 1.33 (95% CI 0.67–2.65) for those with 1 and ≥ 2 IMDs, respectively, compared to those with none (P trend 0.16) (P heterogeneity comparing CD and UC 0.037). Asthma, atopic dermatitis, psoriasis and rosacea were individually associated with higher risk of CD (HR ranging from 2.15 to 3.39) but not UC.

Conclusions: Individuals with one or more IMDs are at an increased risk for CD but not UC.


Immune-mediated diseases (IMDs), represented by autoimmune and allergic diseases, are a group of disabling medical conditions characterised by acute or chronic inflammation affecting a wide array of organ systems. Increasing in incidence over the past few decades,[1] they affect up to 10% of the Western population[2] and often have protracted courses impairing quality of life and posing significant burden on individuals and the healthcare system.[3] While each IMD differs in the specific underlying pathophysiologic disruption, broadly they arise at the intersection of genetic predisposition and a dysregulated immune response, often to antigens in the external environment or the internal microenvironment, namely the microbiome.[4,5] Genome-wide association studies (GWASs) demonstrate sharing of suspceptibility loci across many IMDs. Such common genetic pathways may account for the clustering of these diseases.[6–8] Supporting this is data from observational studies that suggest frequent co-occurrence of multiple disorders within individuals and families.[9–11] However, an important limitation of the prior studies is the lack of ability to adjust for potential shared environmental influences that could also account for the clustering of IMDs. For example, smoking and obesity are associated with an increased risk of Crohn's disease (CD),[12,13] asthma,[14,15] psoriasis,[16,17] and rheumatoid arthritis (RA).[18,19] Thus, smoking behaviour and body composition could potentially explain, at least in part, the co-occurrence of these diseases.

Inflammatory bowel disease (IBD), comprises CD and ulcerative colitis (UC). These chronic inflammatory disorders of the gut affect an estimated 7 million individuals worldwide.[20] They are characterised by typical onset in early adulthood and progressive bowel damage. Prior studies examining the co-occurrence of CD or UC with other IMDs have been limited by cross-sectional or case-control design,[6–8] and thus unable to present the magnitude of long-term risk of CD or UC in individuals with other IMDs. By relying on administrative health data, many of these studies are subject to ascertainment bias and reliance on billing codes that may lack sufficient accuracy to identify incident diseases. More importantly, they were also limited by inability to adjust for key health behaviours that may be important confounders, such as smoking and diet.

To overcome limitations of these prior studies and to robustly provide an estimate of the absolute incidence of CD or UC in the presence of other IMDs, we utilised data from an ongoing prospective cohort study of women with detailed information on diet and lifestyle to (a) examine the effect of concurrent IMD diagnoses on the incidence of CD or UC after robust adjustment for environmental risk factors; and (b) define the magnitude of risk for several common IMDs.