by
Contributing Writer
Expert Critique: Bradley W. Anderson, MD
Gastroenterology and Hepatology Fellow
Mayo Clinic
Rochester, MN
Inflammatory bowel disease (IBD), which includes both Crohn’s disease and ulcerative colitis, is unique among gastrointestinal conditions given the breadth of preventative measures needed to promote and maintain patient health and safety. Such measures account for a heightened susceptibility for communicative disease (which may be further augmented in the setting of immunosuppressant therapy), nutritional deficiencies, anxiety/depression, and malignancy, among others. The following article highlights the findings of several recent studies which have examined both common and previously under-recognized IBD co-morbidities and acknowledges that the interaction between IBD and these related conditions, while unknown, is likely complex and multifactorial. Although an understanding of contributing pathophysiologic mechanisms remains to be established, this article serves to remind the reader as to the variety of organ systems that may potentially be affected by a chronic inflammatory process and underscores the clinical attentiveness demanded by this disease process.
Inflammatory bowel disease (IBD) has long been associated with an elevated risk of colon cancer. But the chronic inflammation of IBD is increasingly linked with other cancers and other conditions, and IBD therapies that alter the immune system and are often used for long periods may promote carcinogenesis. Therefore, as the IBD population ages and has longer exposure to inflammation and immunosuppression, the risk of cancer and other conditions may increase.
“A larger number of older IBD patients are at risk for different comorbidities just because of their age, and this is an important consideration in treatment,” Ashwin N. Ananthakrishnan, MD, of Massachusetts General Hospital and Harvard Medical School in Boston, told the Reading Room. “Cancer, chronic obstructive pulmonary disease, cardiovascular disease, and diabetes are the most relevant and common comorbidities that challenge the management of IBD patients. I think there should be more emphasis on coexisting conditions in gastroenterology training.”
Cancers
A 2016 review in the World Journal of Gastroenterology by Jordan Axelrad, MD, MPH, and associates reported the following standardized incidence ratios of cancers secondary to chronic intestinal inflammation:
- Colorectal cancer — 5.7
- Small bowel adenocarcinoma — 27.1
- Intestinal lymphoma — 15.51
- Cholangiocarcinoma — 916.63
“Gastroenterologists and oncologists caring for patients with IBD and cancer are increasingly confronted with questions regarding the management of IBD after a diagnosis of cancer, and conversely, the management of cancer in patients with IBD,” Axelrad and co-authors wrote. Despite these efforts, much remains unknown regarding the interaction between IBD, IBD medications, and cancer treatment, and the risk of cancer recurrence in patients with IBD and a history of cancer.
“Understanding the effects of chemotherapy, hormonal therapies, radiation, and surgery for cancer on IBD may help identify patients at the highest risk for disease exacerbation during and after specific cancer treatments, especially in those who may require re-initiation of immunosuppressive therapies for IBD,” the team said.
A recent study by Jacob Burns, MD, and colleagues in European Urology reported an increased risk of prostate cancer versus age- and race-matched controls in a study of 1,033 cases of IBD. The 10-year incidence of prostate cancer was 4.4% among IBD patients compared with 0.65% among controls, for a hazard ratio (HR) of 4.84, and a clinically significant cancer incidence at 10 years of 2.4% in the IBD group versus 0.42% for controls (HR 4.04). In addition, prostate-specific antigen values were higher in IBD patients after age 60.
A 2018 case-control study by Lihong Cao suggested that IBD patients had up to three times the risk of papillary thyroid cancer compared with a control group. And in a linked meta-analysis of pooled results of studies involving more than 330,000 IBD patients, an elevated risk ranging from 45% to 100% emerged for IBD overall, with a 20-100% risk for ulcerative colitis. Race or ethnicity did not appear to affect the risk.
Myocardial Infarction
Also in 2018, Muhammad Panhwar, MD, and colleagues reported findings at the American College of Cardiology’s annual meeting from a large healthcare database showing an elevated risk of myocardial infarction (MI) in IBD patients, especially those who were female and younger. MI occurred approximately twice as often in adults with IBD as in controls, at 3.9% versus 1.65%, for a relative risk of 2.4. The risk remained elevated after adjustment for age, race, sex, and classical cardiovascular risk factors, for an adjusted OR of 1.21.
IBD patients were more likely than controls to have the following cardiovascular disease risk factors, the researchers reported:
- Diabetes, 8.9% versus 15.9%
- Hypertension, 21.9% versus 33.6%
- Dyslipidemia, 18.3% versus 27.8%
- Smoking, 12.0% versus 20.7%
The relative risk of MI was highest among patients ages 20 to 25, relative risk (RR) 20.5, but decreased with age, dropping to 1.81 in those ages 60 to 64. “These findings emphasize the need for aggressive risk-factor reduction in IBD,” Panhwar and co-authors wrote. IBD alters the proteome of the protective high-density lipoprotein in the cholesterol molecule. A resulting loss of anti-inflammatory proteins and a gain in pro-inflammatory proteins carried in the high-density lipoprotein particle impair its cholesterol efflux capacity, rendering it less cardioprotective, the team explained.
Parkinson’s Disease
In another large U.S. health database study from 2018, Inga Peter, PhD, and colleagues reported in JAMA Neurology that IBD patients had a 28% greater likelihood of developing Parkinson’s disease (PD) than unaffected matched controls. Those treated with tumor-necrosis factor inhibition had a 78% reduction in PD incidence rates compared with those unexposed to anti-TNF.
The IBD-PD findings were in line with those of a 2016 Taiwanese population analysisshowing a 35% adjusted increased incidence of PD among IBD patients and underscored the need for these clinicians and patients to be aware of this heightened susceptibility.
Immune-mediated Diseases
A 2017 overview by Morten Halling, et al. reported that IBD patients in a large Danish national registry were more at risk compared with matched controls for a range of immune-mediated diseases (IMDs). A total of 20 different IMDs were found to be significantly more frequent in the IBD group, with odds ratios ranging from 1.3 for polymyalgia rheumatica to 126.7 for primary sclerosing cholangitis. IBD patients also had six times the risk of celiac disease.
Overall, ulcerative colitis (UC) patients were more vulnerable, having 16 UC-associated conditions versus 12 of their Crohn’s disease (CD) counterparts. In both IBD subtypes, ORs were significantly increased across a range of conditions, including primary sclerosing cholangitis, celiac disease, type 1 diabetes, sarcoidosis, asthma, iridocyclitis, psoriasis, pyoderma gangrenosum, rheumatoid arthritis, and ankylosing spondylitis.
IMDs restricted to UC were autoimmune hepatitis, primary biliary cholangitis, Grave’s disease, polymyalgia rheumatica, temporal arteritis, and atrophic gastritis.
IMDs affecting only CD patients were psoriatic arthritis and episcleritis, while those restricted to women with UC were atrophic gastritis, rheumatoid arthritis, temporal arteritis, and polymyalgia rheumatica, while conditions restricted to female CD patients were episcleritis, rheumatoid arthritis, and psoriatic arthritis.
“The findings support the hypothesis that shared pathogenic pathways among IMDs could exist,” the authors noted.