12:31am Thursday 21 September 2017

International Experts Publish Consensus Language on Gluten-Related Disorders

Baltimore, Md. An international conference on gluten sensitivity co-chaired by the director of the University of Maryland School of Medicine’s Center for Celiac Research has resulted in the publication of new classification language for related conditions, which may serve as a guide to improve the diagnosis and treatment of gluten-related disorders.  The new consensus has just been published in the peer-reviewed online journal BMC Medicine.

Gluten sensitivity, a condition causing gastrointestinal distress and other clinical symptoms, has been identified by the international panel of experts as a distinct entity on the spectrum of gluten-related disorders that includes wheat allergy and celiac disease. With an estimated six percent of people of European descent affected around the globe, gluten sensitivity could be one of the most common pathologies in the world today.

With gluten sensitivity, we’re standing at the same crossroads that we encountered with celiac disease almost 20 years ago,” says Alessio Fasano, M.D., professor of pediatrics, medicine and physiology and director of the University of Maryland Center for Celiac Research (CFCR) at the University of Maryland School of Medicine. “We’re just beginning to understand how it affects certain individuals and are now in the early stages of discovering its molecular mechanisms. We do know that it’s a different condition from celiac disease, which is what patients have been telling us for some time now. ”

Gluten sensitivity occurs in reaction to gliadin, a protein found in wheat, and similar problematic proteins found in rye and barley. The condition, which does not appear to involve an autoimmune response or the corresponding damage to the small intestine characterized in celiac disease, is now recognized as a distinct pathology on the spectrum of gluten-related disorders. Fifteen experts from seven countries held an international consensus conference in February 2011 to develop a new nomenclature and classification for the condition.  The experts have published their conclusions and recommendations in “Spectrum of Gluten-Related Disorders: Consensus on New Nomenclature and Classification,” which includes a diagnostic roadmap for clinicians.

Dr. Fasano co-chaired the conference along with Carlo Catassi, M.D., M.P.H., co-director of CFCR and professor of pediatrics at the Universita Politecnica delle Marche in Ancona, Italy, and Anna Sapone, M.D., Ph.D., of the Seconda Universita of Naples.

“For the first time, we’ve provided an accurate diagnostic procedure for gluten sensitivity,” says Dr. Catassi. “We’ve confirmed that to correctly diagnose gluten sensitivity, we need to exclude celiac disease and wheat allergy with the appropriate diagnostic tests.”

Dr. Catassi describes the wide-ranging symptoms of gluten sensitivity. “Commonplace symptoms can range from abdominal distress similar to irritable bowel syndrome to light-headedness, fatigue, joint or muscle pain, tingling of the extremities and even depression.” He adds, “Unlike celiac disease, gluten sensitivity does not follow a predictable timetable; the symptoms can become more pronounced or disappear altogether.”

In 2003, the CFCR published the often-cited prevalence study that established the rate of celiac disease at one in 133 people in the United States. “Despite early scientific skepticism, the CFCR played a unique role in demonstrating that celiac disease exists in the United States,” says E. Albert Reece, M.D., Ph.D., M.B.A, vice president for medical affairs, University of Maryland, and John Z. and Akiko K. Bowers Distinguished Professor and dean, University of Maryland School of Medicine. “Now, with the outcomes of the gluten sensitivity consensus conference, the CFCR is leading the global effort to share our knowledge about this emerging condition.”

In celiac disease, complex proteins from wheat, rye and barley trigger the immune system to attack the person’s small intestine. Left undiagnosed and untreated, celiac disease can lead to the development of other autoimmune disorders, as well as osteoporosis, infertility and neurological conditions and, in rare cases, cancer. Unlike celiac disease, gluten sensitivity is not associated with these serious conditions and appears to involve a different immune response. Recent research published in March 2011 by Dr. Fasano’s team uncovered differences in levels of intestinal permeability and the expression of genes regulating the immune response in the gut mucosa in the celiac disease and gluten sensitivity.

“Celiac disease and wheat allergy generate responses from the sophisticated and more modern adaptive immune system,” says Dr. Fasano. “We’ve discovered that reactions in gluten sensitivity appear to be related to the older innate immune system, which generates a more immediate response.”

In celiac disease, the reaction to gluten is mediated by T-cells as the immune system goes awry and attacks its own cells, hence the term autoimmune. Recent research from the CFCR connects gluten sensitivity with the innate immune system, which can result in the more immediate gastrointestinal distress experienced by many people suffering from gluten sensitivity. 
 
Dr. Fasano’s group began researching the condition after patients with negative diagnostic results for celiac disease returned to the CFCR complaining of symptoms similar to celiac disease. Many of the patients responded positively to the gluten-free diet.  “We estimate that 60 to 70 percent of the people coming for treatment actually suffer from gluten sensitivity, not celiac disease,” says Dr. Fasano. He and his team are currently investigating biomarkers for gluten sensitivity that could lead to diagnostic tools for the condition similar to the serological tools used to diagnose celiac disease.

Dr. Sapone notes that until quite recently, “We were dealing with patients whose prescribed symptoms didn’t match any precise indicators. Physicians assumed that patients who improved on a gluten-free diet were benefitting from the placebo effect. Now we know otherwise: patients with gluten sensitivity can greatly benefit from a gluten-free diet.” 

Dr. Fasano is lead author on the review paper, which includes other scientists from the United States and experts from Italy, Slovenia, Argentina, the United Kingdom, Finland and Germany. The Dr. Schär Institute of Burgstall, Italy, hosted the consensus conference.

Founded at the University of Maryland School of Medicine in Baltimore in 1996, the CFCR is a world leader in the treatment, diagnosis, research and education of celiac disease and other gluten-related disorders. Its mission is to promote the awareness of celiac disease and gluten-related disorders to provide better care, better quality of life, and more adequate support for people around the world. Visit www.celiaccenter.org for more information.


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