Celiac disease patients with ongoing intestine damage at lymphoma risk

August 5, 2013
This is a biopsy of small intestine showing normal villi. Credit: Govind Bhagat, Columbia University Medical Center.

Patients with celiac disease who had persistent intestine damage (identified with repeat biopsy) had a higher risk of lymphoma than patients whose intestines healed, according to findings published in the August 6, 2013, issue of Annals of Internal Medicine.

Celiac disease is a common autoimmune disease, affecting approximately one percent of individuals in Western nations. It is characterized by damage to the lining of the that over time reduces the body's ability to absorb components of common foods. The damage is due to a reaction to eating gluten, which is found in wheat, barley, and rye.

When a patient with is initially diagnosed, shows flattening of villi, the long, fingerlike projections that normally absorb nutrients and fluid. Symptoms of celiac disease, which include diarrhea, weight loss, and iron-deficiency anemia, result from damaged villi. Though not a universal practice, a follow-up biopsy is often done several months to several years after diagnosis, to monitor the effects of and treatment on intestinal healing.

"After the diagnosis is made and the patient starts a gluten-free diet, we expect to see recovery of the villi," said Peter Green, MD, professor of medicine and director of the Celiac Disease Center at Columbia University Medical Center (CUMC), a gastroenterologist at NewYork-Presbyterian/Columbia, and a co-author of the study. "Physicians and patients alike see healing as a goal, but until now there was no confirmed link between healing on intestinal biopsy and clinical risk factors."

This is a biopsy of small intestine showing villous atrophy, i.e., flat villi. Credit: Image courtesy of Govind Bhagat, Columbia University Medical Center.

"We have known for many years that patients with celiac disease have an increased risk of lymphoma, but we did not know whether intestinal healing and its timing affect that risk," said study first author Benjamin Lebwohl, MD, MS, assistant professor of medicine, member of the Celiac Disease Center, and assistant professor of epidemiology at the Mailman School of Public Health, at CUMC, and a gastroenterologist at NewYork-Presbyterian/Columbia. "Our study shows that celiac patients with persistent villous atrophy—as seen on follow-up biopsy—have an increased risk of lymphoma, while those with healed intestines have a risk that is significantly lower, approaching that of the general population."

A type of blood cancer, lymphoma occurs when white blood cells called lymphocytes, which help protect the body from infection and disease as part of the immune system, divide faster than normal or surpass their typical life expectancy. Lymphoma may develop in the blood or bone marrow, as well as in the lymph nodes, spleen, and other organs; eventually, it may form tumors.

"Guidelines about routine follow-up biopsy are inconclusive, but this study may convince physicians that the follow-up biopsy can carry important prognostic information," said Dr. Lebwohl.

One reason this link was not previously seen was a lack of data on the broad spectrum of patients with celiac disease, rather than just those seeking specialized care. Over the past decade, Jonas Ludvigsson, MD, PhD, a pediatrician and professor of clinical epidemiology at the Karolinska Institutet in Stockholm, established a large population-based database using biopsy results from 28 pathology departments in Sweden. "It is only now that we are able to quantify the risk of persistent villous atrophy, which is likely to mirror poor dietary adherence," said Dr. Ludvigsson, senior author of the study.

In this study, researchers identified patients with celiac disease who underwent a follow-up biopsy between 6 months and 5 years after their initial diagnosis; the median duration between celiac disease diagnosis and follow-up biopsy was 1.3 years. The patients were then followed for an average of 8.9 years after their follow-up biopsy. Of 7,625 patients with celiac disease, 4,317 (57 percent) had healed on the follow-up biopsy, while the remaining 3,308 patients (43 percent) had persistent villous atrophy.

The investigators found that overall, patients with celiac disease had an annual lymphoma risk of 67.9 per 100,000, a 2.81-fold increase compared with the general population risk of 24.2 per 100,000. Those with persistent villous atrophy had a larger annual risk: 102.4 per 100,000, compared with those with healed intestines, whose risk was 31.5 per 100,000. According to the authors, these findings support the end-point of mucosal healing as a goal for patients with celiac so as to reduce lymphoma risk.

Why some patients heal while others do not is unclear. "We know from prior studies that healing is more likely among patients who report strict adherence to the gluten-free diet, compared with those who admit to less-than-strict dietary habits," said Dr. Lebwohl. Since persistent villous damage was seen even in the face of strict dietary adherence, there are likely other, as-yet-unidentified, factors that affect healing. "Our findings linking the follow-up biopsy result to lymphoma risk will lead us to redouble our efforts to better understand intestinal healing and how to achieve it," said Dr. Lebwohl.

Explore further: New study finds low rates of biopsy contribute to celiac disease underdiagnosis in US

Related Stories

New study finds low rates of biopsy contribute to celiac disease underdiagnosis in US

June 29, 2012
Under-performance of small bowel biopsy during endoscopy may be a major reason that celiac disease remains underdiagnosed in the United States, according to a new study published online recently in Gastrointestinal Endoscopy. ...

Low adherence to biopsy guidelines affects celiac disease diagnosis in the United States

July 7, 2011
A new study has found that most patients undergoing biopsy of the small intestine do not have the recommended number of samples to diagnose celiac disease. The study, published in the July 2011 issue of Gastrointestinal ...

Medical follow-up in celiac disease is less than optimal

July 25, 2012
Follow-up exams for patients with celiac disease are often inadequate and highly variable, according to a new study in Clinical Gastroenterology and Hepatology, the official clinical practice journal of the American Gastroenterological ...

Celiac 'epidemics' link to infections early in life

December 18, 2012
Celiac disease affects about one percent of the population but occasional 'epidemics' have been noticed along with a seasonal variation in number of cases diagnosed. New research published in BioMed Central's open access ...

Recommended for you

Google searches can be used to track dengue in underdeveloped countries

July 20, 2017
An analytical tool that combines Google search data with government-provided clinical data can quickly and accurately track dengue fever in less-developed countries, according to new research published in PLOS Computational ...

MRSA emerged years before methicillin was even discovered

July 19, 2017
Methicillin resistant Staphylococcus aureus (MRSA) emerged long before the introduction of the antibiotic methicillin into clinical practice, according to a study published in the open access journal Genome Biology. It was ...

New test distinguishes Zika from similar viral infections

July 18, 2017
A new test is the best-to-date in differentiating Zika virus infections from infections caused by similar viruses. The antibody-based assay, developed by researchers at UC Berkeley and Humabs BioMed, a private biotechnology ...

'Superbugs' study reveals complex picture of E. coli bloodstream infections

July 18, 2017
The first large-scale genetic study of Escherichia coli (E. coli) cultured from patients with bloodstream infections in England showed that drug resistant 'superbugs' are not always out-competing other strains. Research by ...

Ebola virus can persist in monkeys that survived disease, even after symptoms disappear

July 17, 2017
Ebola virus infection can be detected in rhesus monkeys that survive the disease and no longer show symptoms, according to research published by Army scientists in today's online edition of the journal Nature Microbiology. ...

Mountain gorillas have herpes virus similar to that found in humans

July 13, 2017
Scientists from the University of California, Davis, have detected a herpes virus in wild mountain gorillas that is very similar to the Epstein-Barr virus in humans, according to a study published today in the journal Scientific ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.