Long-Term Risk of Inflammatory Bowel Disease Explored

Long-Term Risk of Inflammatory Bowel Disease After Endoscopic Biopsy with Normal Mucosa: a Population-Based Sibling-Controlled Cohort Study in Sweden

Background

Although evidence suggests a persistent decreased risk of colorectal cancer for up to 10 years among people with a negative endoscopic biopsy result (i.e., normal mucosa), concerns have been raised about other long-term health outcomes among these people. . In this study, we aimed to explore the long-term risk of inflammatory bowel disease (IBD) after endoscopic biopsy with normal mucosa.

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Normal Gastrointestinal Biopsy Doesn’t Protect Against Later IBD, Study Finds

A study, which followed more than 450,000 people in Sweden after an upper or lower gastrointestinal biopsy, suggests that IBD symptoms may begin significantly before the disease appears on the biopsy

People with a normal gastrointestinal (GI) biopsy still have a higher risk of inflammatory bowel disease (IBD) in the years after that normal biopsy than their population references, according to a new study published February 23 in the journal. journal PLOS Medicine by Dr. Jiangwei Sun of Karolinska Institutet, Sweden, and colleagues.

IBD is a chronic disease of the GI tract and subtypes primarily include Crohn’s disease and ulcerative colitis.

The disease is usually diagnosed with an upper or lower GI biopsy, taken during an endoscopy. In clinical practice, the most common finding on endoscopy is a normal biopsy, and evidence suggests a persistent decreased risk of colorectal cancer up to ten years after a normal biopsy. However, the association between a normal biopsy and a subsequent diagnosis of IBD has not been clear; Some studies have hinted that IBD may have a symptomatic period before diagnosis is possible.

In the new study, researchers used a database of GI biopsy reports from across Sweden from 1965 to 2016 to identify 200,495 people with a normal lower GI biopsy and 257,192 people with a normal upper GI biopsy . They also identified more than 2 million matching population references from the Swedish Total Population Registry, and almost half a million siblings of the biopsied individuals who were alive and had not had their own GI biopsy from the Swedish Multigenerational Registry.

During a median follow-up time of 10 years , 4,853 people (2.4%) with a normal lower GI biopsy developed IBD, compared with 0.4% of population references. This translated to one additional case of IBD for every 37 people over the 30 years after a normal lower GI biopsy.

Individuals with a normal lower GI biopsy had a higher risk of overall IBD (HR=5.56; 95% CI: 5.28-5.85), ulcerative colitis (HR=5.20; 95% CI: 4.85-5 .59) and Crohn’s disease (HR=6.99); 95% CI: 81 6.38-7.66) than the population references. The risks were 3.27 (95% CI: 3.05-3.51) for overall IBD, 3.27 (95% CI: 2.96-3.61) for ulcerative colitis, and 3.77 (95% CI: 2.96-3.61) for overall IBD. %: 3.34-4.26) for Crohn’s disease than their siblings.

A normal upper gastrointestinal biopsy was also associated with an increased risk of Crohn’s disease compared to population references and siblings (HR = 2.93, 95% CI: 2.68-3.21 and HR = 2.39 ; 95% CI: 2.10-2.73). The study was limited by a lack of data on each patient’s indications for biopsy, lifestyle, medical history, and genetics.

HR and 95% CI of IBD as a function of time since biopsy, comparing individuals with a normal mucosal GI biopsy result to their matched population references.

“Endoscopic biopsy with normal mucosa was associated with a high incidence of IBD for at least 30 years. “This may suggest a substantial symptomatic period of IBD and incomplete diagnostic work-ups in patients with early IBD,” the authors say. “Physicians should be aware of the increased long-term risk of IBD in those with symptoms requiring a GI investigation but with a finding of histologically normal mucosa.”

Sun adds: “Endoscopic biopsy with normal mucosa was associated with a high incidence of inflammatory bowel disease for at least 30 years. “This may suggest a substantial symptomatic period before diagnosis of inflammatory bowel disease.”

Conclusions

Endoscopic biopsy with normal mucosa was associated with a high incidence of IBD for at least 30 years. This may suggest a substantial symptomatic period of IBD and incomplete diagnostic examinations in patients with early IBD.

Discussion

In this population-based, sibling-controlled national cohort study, we used 2 different measures (HR and cumulative incidence over time) to explore the temporal association between undergoing a GI diagnostic examination with normal mucosa (no signs of obvious macroscopic or microscopic aberrations) and subsequent IBD. We found a high incidence of IBD for at least 30 years after an endoscopic biopsy with normal mucosa. This is consistent with previous observations of impaired growth in children and adolescents, upregulated inflammatory proteins, dysregulated antibodies and proteins, and increased intestinal permeability years before IBD diagnosis.

Author summary

Why was this study done?

As the most common gastrointestinal (GI) histologic finding at endoscopy, a negative endoscopic result (i.e., normal mucosa) has been associated with a persistently reduced risk of colorectal cancer for up to 10 years. However, concerns have been raised about other long-term health outcomes among these people.

Our objective was to explore the long-term risk of inflammatory bowel disease (IBD) after endoscopic biopsy with normal mucosa.

What did the researchers find?

In this population-based, sibling-controlled cohort study, we identified individuals with a lower (n = 200,495) or upper (n = 257,192) GI biopsy of normal mucosa, their individually matched general population references (n = 989,484 and 1 268,897, respectively), and unexposed full siblings (n = 221,179 and 274,529, respectively).

Compared with population references and unexposed full siblings, individuals with a normal lower gastrointestinal mucosal biopsy had a persistently increased risk of overall IBD (mean HR = 5.56 and 3.27, respectively), ulcerative colitis (UC , average HR = 5.20 and 3.27, respectively) and Crohn’s disease (CD, average HR = 6.99 and 3.77, respectively).

Individuals with a normal upper GI mucosal biopsy also had an increased risk of CD (average HR = 2.93 and 2.39, respectively).

The elevated risk of IBD persisted at least 30 years after a biopsy with normal mucosa.

What do these findings mean?

Our findings suggest a substantial symptomatic period before IBD diagnosis.

Clinicians should be aware of the increased long-term risk of IBD in those with symptoms requiring a GI investigation but with a finding of histologically normal mucosa .