Comorbidity Before and After a Diagnosis of Inflammatory Bowel Disease

Charles N. Bernstein; Zoann Nugent; Seth Shaffer; Harminder Singh; Ruth Ann Marrie


Aliment Pharmacol Ther. 2021;54(5):637-651. 

In This Article

Abstract and Introduction


Background: Comorbidity is an important predictor of how disease course in inflammatory bowel (IBD) evolves.

Aims: To determine pre-diagnosis relative rates (RR) and post-diagnosis hazard ratios (HR) of component diseases of the Charlson Comorbidity Index (CCI) in a cohort study of persons with IBD.

Methods: The University of Manitoba IBD Epidemiology Database includes all Manitobans with IBD from 1 April 1984 through 31 March 2018 and matched controls. All outpatient physician claims and hospital discharge abstracts were searched for diagnostic codes for CCI component diseases. Some diseases were collapsed into one group such that we assessed 12 conditions. We report the RR of these conditions prior to IBD and the incidence of these diagnoses after IBD. Using Cox proportional hazards regression we report post-diagnosis HR. Confidence intervals were adjusted for Bonferroni correction.

Results: The RR of cardiovascular diseases, peripheral vascular diseases, chronic pulmonary diseases, connective tissue disease/rheumatic diseases, renal disease, liver diseases, peptic ulcer disease, and cancer were all increased prior to diagnoses of IBD compared to controls. All comorbidities were increased post IBD diagnosis. The increased HR for dementia in persons with Crohn's disease was a concerning novel finding. The increased association with paraplegia/hemiplegia was unexpected. For all comorbidities, except diabetes, the age at diagnosis was younger in IBD than controls.

Conclusions: Persons with IBD have a higher comorbidity burden than persons without IBD. Optimal care plans for persons with IBD should include an assessment for other comorbidities that include just about every other organ system.


Several well-described inflammatory extra-intestinal diseases are comorbid with inflammatory bowel diseases (IBD).[1–3] These range from inflammatory arthritides like seronegative spondyloarthropathies, to inflammatory skin diseases such as pyoderma gangrenosum and erythema nodosum, to primary sclerosing cholangitis and inflammatory ocular diseases like uveitis. Psychiatric disorders such as depression and anxiety,[4] osteoporosis[5] and venous thromboembolic diseases[6] are also significantly more common in IBD than in the general population; and attention to the possibility that these conditions may emerge during the course of IBD is considered a necessary metric in quality IBD care.

Comorbidity is an important predictor of how disease course in IBD evolves and is a growing concern given that the incidence and prevalence of IBD is rising amongst the elderly and comorbidity increases with age. Most studies of individuals with elderly-onset IBD fail to acknowledge the importance of comorbidity when assessing patients' treatment outcomes. In one study age of diagnosis was not a factor that restricted the use of immunomodulators, but comorbidity delayed the initiation of immunomodulator therapy.[7] In that study, as in most comorbidity studies, Charlson Comorbidity Index (CCI) was the comorbidity measure. Comorbidity can also increase the likelihood of drug-to-drug interaction.[8] In another study, the postoperative complication rate in an elderly cohort was found to be similar to that of younger patients, but postoperative complications were predicted by the CCI.[9]

When comorbidity is measured in epidemiological studies of IBD the CCI is commonly used. The CCI is a weighted index that was initially developed to predict 1-year mortality and includes 11 serious diseases. The original Index was developed with 19 conditions[10] but was modified in one commonly used adaptation to 17 conditions[11] for application to administrative health data.

These diseases including chronic pulmonary disease, renal disease, ischemic heart disease and congestive heart failure, cerebrovascular disease, peripheral vascular disease, dementia, rheumatological disease, human immunodeficiency virus (HIV), mild liver disease and moderate to severe liver disease (often grouped into one liver disease category), peptic ulcer disease, diabetes with or without chronic complications, hemiplegia or paraplegia, and metastatic solid tumours or any cancer (often grouped into cancer category). The CCI is commonly used for assessing comorbidity, especially when using large administrative datasets. Most such studies typically report that persons with IBD have higher CCI than matched controls.[12,13] However, less attention focuses on the occurrence of the individual conditions, limiting the ability to understand their incidence, prevalence and individual effects on IBD outcomes.

We aimed to explore whether the incidence of diseases that make up the CCI is increased in people diagnosed with IBD either before or after IBD diagnosis.