Study Finds IBD Risk Higher in Children, Adults with AD

The risk for inflammatory bowel disease (IBD) was increased among children and adults with atopic dermatitis (AD), with the risk increasing with AD severity, according to data from a large cohort study published recently in JAMA Dermatology.

The study also found an increased risk for Crohn’s disease (CD) in adults and children with AD, as well as an increased risk for ulcerative colitis (UC) in adults with AD and in children with severe AD, researchers report.

“It is imperative for clinicians to understand atopic dermatitis and the trajectory of our patients with it in order to provide the best standard of care,” senior author Joel M. Gelfand, MD, MSCE, professor in clinical investigation with the Department of Dermatology at the University of Pennsylvania, Philadelphia, said in a news release.

“There are new and better treatments for AD today, and there will likely continue to be more,” continued Gelfand. “But providers have to understand how those treatments could impact other autoimmune diseases. For patients with AD and another autoimmune disease, some currently available medications can exacerbate symptoms of their other disease or can help treat two immune diseases at the same time.”

The study results support the idea that AD and IBD may have some common underlying causes, said Sheilagh Maguiness, MD, pediatric dermatologist and associate professor in the Department of Dermatology at the University of Minnesota, Minneapolis, who was asked to comment on the findings.

“As the pathogenesis of AD is becoming better understood, we are recognizing that, rather than simply a cutaneous disease, the underlying inflammation and immune dysregulation that leads to AD best categorizes it as a systemic inflammatory disease with significant comorbidities,” she told Medscape. “I will be more likely to ask patients and families about GI symptoms, and if positive, may plan to refer to GI more readily than in the past,” added Maguiness, who was not involved in the study.

UK General Practice Cohort

AD has been associated with an increasing number of comorbidities, including IBD, but studies linking AD with IBD, including UC, have had mixed results, the authors write. And few studies have separately examined how AD or AD severity may be linked with UC or CD risk.

To examine the risk for new-onset IBD, UC, and CD in children and adults with atopic dermatitis, the researchers conducted a population-based cohort study using the THIN (The Health Improvement Network) electronic medical record database of patients registered with United Kingdom general practices. They used 21 years of data collected from January 1994 to February 2015.

The researchers matched each patient who had AD with up to five controls based on age, practice, and index date. Because THIN does not capture AD severity, they used treatment exposure assessed by dermatologic referrals and treatments patients received as proxy for severity. The authors used logistic regression to examine the risks for IBD, UC, and CD in children (ages 1-10) with AD, and in adults (ages 30-68) with AD, and they compared their outcomes with the outcomes for controls.

In the pediatric cohort, the team compared 409,431 children who had AD with 1.8 million children without AD. Slightly more than half were boys. In the adult cohort, they compared 625,083 people who had AD with 2.68 million controls, and slightly more than half were women. Data on race or ethnicity were not available, the authors write, but the THIN database is considered to be representative of the UK population.

AD Severity Linked with IBD Risk

The risk for new-onset inflammatory bowel disease appears to be higher in children and adults with AD, and the risk varies based on age, AD severity, and subtype of inflammatory bowel disease, the authors reported.

Overall, AD in children was associated with a 44% increased risk for IBD (adjusted hazard ratio (HR), 1.44; 95% CI, 1.31 – 1.58) compared with controls, the authors report. They found a 74% increased risk for CD in children with AD compared with controls (HR, 1.74; 95% CI, 1.54 – 1.97). More severe AD was linked with increased risk for both IBD and CD.

AD did not appear to increase risk for UC in children, except those with severe AD (HR, 1.65; 95% CI, 1.02 – 2.67).

Overall, adults with AD had a 34% (HR, 1.34; 95% CI, 1.27 – 1.40) increased risk for IBD, a 36% (HR, 1.36; 95% CI, 1.26 – 1.47) increased risk for CD, and a 32% (HR, 1.32; 95% CI, 1.24 – 1.41) increased risk for UC, with risk increasing with increased AD severity.

Robust Data With Cautionary Note

“This study provides the most robust data to date on the association between IBD and AD. It provides clear evidence for an association that most dermatologists or primary care providers are not typically taught in training,” Kelly Scarberry, MD, assistant professor of dermatology at Case Western Reserve University in Cleveland, said by email. “I will be much more likely to pursue diagnostic workup in my AD patients who have GI complaints.”

However, AD severity was measured by proxy, added Scarberry, who was not involved in the study, and the study lacked important racial and ethnic data.

Lindsay C. Strowd, MD, associate professor of dermatology at Wake Forest University, Winston-Salem, North Carolina, also not involved in the study, said that she found the size of the cohort and the longitudinal data to be strengths of the study.

But, she added by email, the “lack of family IBD history, race and ethnicity, and comorbidities, are limitations, as is treatment exposure used as a proxy for disease severity, given that physician treatment practices differ.”

For Steven R. Feldman, MD, PhD, professor of dermatology at Wake Forest, “the most important conclusion, and it is a definitive finding [is] that IBD is uncommon, even in patients with AD.”

“The findings could be misinterpreted,” cautioned Feldman, also not involved in the study. “While there is an increased relative risk, the absolute risk is small.” The study found that “the highest relative risk group is children with severe AD, who have a roughly fivefold increased risk for CD.” However, he added, the incidence rates of CD were only 0.68 per 1000 person-years in children with severe AD and only 0.08 per 1000 person-years in controls.

“Basically, because Crohn disease and IBD don’t happen very often, the modest increase in relative risk the investigators found doesn’t amount to much we’d have to worry about,” he said. “The findings do not show any need to screen patients with atopic dermatitis for IBD any more than we’d need to screen patients without atopic dermatitis.”

The increased relative risk “could be a clue to possible genetic connections between diseases,” he added. “But when we’re making clinical decisions, those decisions should be based on the absolute risk that some event may occur.”

Susan Massick, MD, dermatologist and associate professor at The Ohio State University in Columbus, who was not involved with the study, said, “We are still scratching the surface of the complexity of the immune and inflammatory pathways in AD and IBD.”

“It is important to remember that correlation does not mean causation,” Massick said by email. “It would be premature to draw direct conclusions based on this study alone.”

The authors recommend future related studies in more diverse populations.

The study was supported by Pfizer. Gelfand and two co-authors report relevant financial relationships with Pfizer. Gelfand and three co-authors report relevant financial relationships with other pharmaceutical companies. Maguiness, Scarberry, Strowd, and Massick report no relevant financial relationships. Feldman reports relevant financial relationships with Pfizer and various other pharmaceutical companies.

JAMA Dermatol. Published online August 30, 2023. Abstract

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