09/12/2016 11:32 GMT | Updated 10/12/2017 05:12 GMT

One In Five Children With Celiac Disease May Not Respond To A Gluten-Free Diet

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Celiac disease is an autoimmune disease caused by the ingestion of gluten containing grains (wheat, rye, and barley) that develops in genetically predisposed individuals. Patients with celiac disease may present with gastrointestinal complaints such as abdominal pain, bloating, diarrhea or constipation and/ or a variety of signs and symptoms outside of the gastrointestinal tract including fatigue, joint pain, or headache. The diagnosis of celiac disease is confirmed when a small intestinal tissue sample, known as a biopsy, shows the classic sign of the disease which is blunting of the intestinal villi. Unlike multiple sclerosis or type one diabetes which are also autoimmune diseases, celiac disease is unique in that it is the only autoimmune disease for which we know the trigger. Complete, lifelong removal of the trigger, gluten, is the only current treatment. Its removal, in the form of adherence to the gluten-free diet, leads to the resolution of the small intestinal damage that is present at diagnosis as well as the associated signs and symptoms.

Thirty years ago, patients underwent three small intestinal biopsies before a diagnosis of celiac disease was confirmed. The first took place when celiac disease was suspected, a second occurred once a patient was on a gluten free diet, and a third was then done to confirm that intestinal damage returned after the patient was reintroduced to gluten. Later, the development of accurate, non-invasive screening blood tests for celiac disease in the 1990's revolutionized how physicians diagnose and manage celiac disease. Instead of three small intestinal biopsies to confirm the diagnosis, the general and recommended practice became screening patients with a blood test and confirming the diagnosis with small intestinal biopsy at the initial presentation. At the same time, management guidelines for children and adults with celiac disease were altered such that practitioners were advised to serially follow the serology tests until they normalized. This shift in guidelines of clinical practice was due to the belief that serology tests, which were highly sensitive and specific at initial diagnosis, also served as biomarkers of intestinal inflammation and measures of adherence to the gluten free diet. However, these tests were not studied or therefore validated for these specific purposes. Despite the fact that studies have shown more than one-third of adults diagnosed with celiac disease to have persistent small intestinal damage, irrespective of their blood test results after two years on a gluten free diet, it was thought that children heal more quickly and more completely.

The frequency with which children achieve mucosal recovery, or normalization of their small intestine, has not been studied in depth. Our recently published study examined the charts of approximately 100 children with celiac disease on treatment with strict gluten free diet for over two years and found that 1 in 5 had persistent small intestinal damage. A particularly worrisome aspect of our results was that neither the presence of symptoms nor the results of the serology tests, suggested as a marker of mucosal recovery, could predict which children had persistent damage to the intestine. Our concern is that this persistent damage could interfere with a child's potential growth during a very important developmental period, in addition to other possible complications. Additional studies are necessary before the management of celiac disease is universally altered but for now, physicians should have a low threshold to repeat an endoscopy with small intestinal biopsies for children with celiac disease. Future studies should aim to evaluate the frequency of persistent enteropathy in children and aim to identify non-invasive biomarkers in the blood, urine, or poop that can accurately measure mucosal recovery. While in the past only the only available treatment for celiac disease was a gluten free diet there are novel therapeutics in development that may one day be useful for children and adults who continue to sustain damage to the small intestine despite maintaining a gluten free diet.

Maureen Leonard, MD MMSc

Clinical Director, Center for Celiac Research and Treatment

Instructor in Pediatrics, Massachusetts General Hospital for Children | Pediatric Gastroenterology & Nutrition