Published: 06-08-2013 00:00 | Updated: 29-10-2014 10:58

Intestinal biopsy can reveal the risk of lymphoma for gluten-intolerant individuals

Coeliac disease (gluten intolerance) sufferers who have residual inflammation of the intestinal mucosa several years after diagnosis have a higher risk of contracting cancer of the lymphatic system  lymphoma  than those patients whose intestinal mucosa have healed. These are the findings of a new study led by researchers from Karolinska Institutet, published in the journal Annals of Internal Medicine.

When a patient is diagnosed with gluten intolerance, biopsies of the small intestine show that the long finger-like projections that absorb nutrients and moisture from the food we eat – the intestinal villi – have flattened out. Damaged villi can lead to diarrhoea, weight loss and iron deficiency, which are common symptoms of gluten intolerance. Once the patient has been diagnosed and starts to eat a gluten-free diet, the damage to the intestinal mucosa is expected to heal so that the villi recover. However, in some cases the intestine does not heal. Poor healing is observed if the patient fails to follow a gluten-free diet, but also occurs in some patients who do follow such a diet.

It was already known that gluten-intolerant individuals are at a greater risk of contracting lymphoma, but until now it has not been known whether this risk is affected if the intestine heals. One reason for being unable to make this connection is that insufficient data has been available. However, over the course of the last ten years, Jonas F Ludvigsson, Professor of Clinical Epidemiology at Karolinska Institutet, and his colleagues at the Department of Medical Epidemiology and Biostatistics have compiled a database containing the results of intestinal biopsies from around 29,000 patients at all Swedish pathology departments.

"This study shows that a control biopsy can be used after the patient has started a gluten-free diet to show whether the patient has a high or low risk of lymphoma in the future," explains Professor Ludvigsson. "The new blood tests (antibodies) that are now available, and that are used increasingly often in the diagnosis of coeliac disease, can help healthcare professionals to diagnose the disease and to monitor patients, but are no replacement for a small intestine biopsy."

The study involved researchers identifying gluten-intolerant patients who underwent an intestinal biopsy between six months and five years after their diagnosis. These patients were then monitored for an average of eight to nine years after taking the biopsy. Of a total of 7,625 gluten-intolerant patients, the intestine had healed in 4,317 patients (57 percent) by the time of the biopsy, while the remaining 3,308 patients (43 percent) still had damaged villi when the biopsy was taken.

The study also showed that, on average, gluten-intolerant individuals are 2.81 times more likely than others to suffer from lymphoma. However, those patients whose intestines did not heal were 3.78 times more likely to contract lymphoma, whereas those whose intestines did heal were 1.5 times more likely. According to the researchers, it is therefore important that the intestine heals in order to reduce the risk of these patients developing lymphoma.

The study is the result of collaboration between Columbia University, Mayo Clinic and Karolinska Institutet, and has been financed by the American-Scandinavian Foundation, the Celiac Sprue Association, the National Center for Advancing Translational Sciences and the National Institutes of Health. Jonas Ludvigsson is also a Pediatrician at Örebro University Hospital.


Mucosal healing and risk for lymphoproliferative malignancy in celiac disease: a population-based cohort study.
Lebwohl B, Granath F, Ekbom A, Smedby K, Murray J, Neugut A, et al
Ann. Intern. Med. 2013 Aug;159(3):169-75