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  1. Celiac.com 12/21/2018 - For most celiac patients, treatment with the gluten-free diet marks the turning point for their health. It can take a few months for the villi of the small intestine to heal, but eventually the villi are able to absorb the nutrients in their food and the symptoms of celiac disease are alleviated. Unfortunately, there are some celiacs who don’t respond to the gluten-free diet. This is the only current treatment for the disease, resulting in a condition known as refractory celiac disease or nonresponsive celiac disease (NRCD). Although celiac experts have stated that actual refractory celiac disease, wherein damage to the small intestine is irreversible, is rare, a preliminary study reported by Med Page Today suggests that the condition is more common than the medical community once thought. Fortunately, the study also showed that refractory celiac disease patients did respond favorably to medical treatment. Celiac disease, an autoimmune disease caused by gluten, a protein found in wheat, barley, and rye, affects three million Americans, or about 1% of the U.S. population. Patients with refractory celiac disease experience abdominal pain, severe malabsorption of nutrients, and intestinal damage. A single-center preliminary study suggests that “more patients with celiac disease may stop responding to their gluten-free diets,” as reported by Med Page Today. The researchers studied non-responsive celiac patients treated at the University of Virginia Medical Center over the past decade. According to Med Page Today, “Overall, patients were diagnosed with refractive disease a mean of 4.7 years following their initial diagnosis of celiac disease.” Furthermore, diagnoses of refractory celiac seemed to occur more recently, mostly within the last five years and almost half of them within the last six months. The researchers, including Christopher Hammerle, MD, and Sheila Crowe, MD, of the University of Virginia in Charlottesville, found that the refractory celiac disease patients did respond to treatment with thiopurines. “These agents are my treatment-of-choice for refractory celiac disease to avoid long-term steroids,” Hammerle told MedPage Today. According to Shailaja Jamma, MD, and Daniel Leffler, MD, MS, in Real Life with Celiac Disease, there could be many explanations for a failure to respond favorably to the gluten-free diet. In their chapter on NRCD, they write, “you would need to be on a GFD for at least 6 months without significant improvement before we would decide that you were not responding and look for other reasons.” This is due to the fact that recovery times vary from person to person, and as long as patient seems to be improving continually over time, no matter the speed, non-responsive celiac disease is usually an unnecessary label. Jamma and Leffler found that the most common causes—designated “very common’—are gluten exposure and Irritable Bowel Syndrome (IBS). The next most common causes of NRCD, labeled as “somewhat common,” are lactose intolerance or fructose malabsorption, microscopic colitis, and small intestinal bacterial overgrowth. “Rare” causes include actual refractory celiac disease, which can be confirmed with a biopsy of the small intestine, an eating disorder, inflammatory bowel disease, which can also be confirmed with a biopsy as well as imaging studies of the small or large intestine, pancreatic exocrine insufficiency, and motility disturbances, that is, when food moves too quickly or too slowly through the intestine. Finally, food allergy and cancer are “very rare” causes of NCRD. According to the Mayo Clinic, as reported by Celiac.com, “gluten contamination is the leading reason for non-responsive celiac disease,” and estimates that 18% of non-responsive celiac disease cases are due to actual refractory celiac disease. The Mayo Clinic researchers recommend that before making a refractory celiac disease diagnosis, additional diseases as well as gluten contamination should be ruled out as causes. According to Jamma and Leffler, “The first step is often to get confirmation that you do indeed have celiac disease,” since “celiac disease can be mistakenly diagnosed when the true problem is something else.” Med Page Today points out that most of the patients with refractory celiac disease responded favorably to a thiopurine medication rather than the conventional method of treatment for the condition, steroids. This form of treatment doesn’t carry with it the risk of steroid dependence. If you have some concerns regarding your response to the gluten-free diet, it’s recommended that you talk with your doctor about a non-responsive celiac disease evaluation. An evaluation of your diet may very well confirm that you are still ingesting gluten, but if this isn’t the case, other causes can be explored by your doctor. Thiopurine seems promising as a treatment option for those who do, in fact, have actual refractory disease. Resources: 1. About.com: Refractory (Unresponsive) Celiac Disease 2. Celiac.com: Causes of Non-responsive Celiac Disease - More than 50% Continue to Ingest Gluten Unknowingly. 3. Jamma, Shailaja, MD, and Leffler, Daniel A, MD. “Nonresponsive Celiac Disease.” Real Life with Celiac Disease: AGA Press, 2010. 4. Medpage Today: ACG: More Celiac Disease May Be Refractory
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