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      Frequently Asked Questions About Celiac Disease   04/07/2018

      This Celiac.com FAQ on celiac disease will guide you to all of the basic information you will need to know about the disease, its diagnosis, testing methods, a gluten-free diet, etc.   Subscribe to Celiac.com's FREE weekly eNewsletter   What are the major symptoms of celiac disease? Celiac Disease Symptoms What testing is available for celiac disease?  Celiac Disease Screening Interpretation of Celiac Disease Blood Test Results Can I be tested even though I am eating gluten free? How long must gluten be taken for the serological tests to be meaningful? The Gluten-Free Diet 101 - A Beginner's Guide to Going Gluten-Free Is celiac inherited? Should my children be tested? Ten Facts About Celiac Disease Genetic Testing Is there a link between celiac and other autoimmune diseases? Celiac Disease Research: Associated Diseases and Disorders Is there a list of gluten foods to avoid? Unsafe Gluten-Free Food List (Unsafe Ingredients) Is there a list of gluten free foods? Safe Gluten-Free Food List (Safe Ingredients) Gluten-Free Alcoholic Beverages Distilled Spirits (Grain Alcohols) and Vinegar: Are they Gluten-Free? Where does gluten hide? Additional Things to Beware of to Maintain a 100% Gluten-Free Diet What if my doctor won't listen to me? An Open Letter to Skeptical Health Care Practitioners Gluten-Free recipes: Gluten-Free Recipes
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    KIDS CAN GET ACCURATE CELIAC DIAGNOSIS WITHOUT BIOPSY


    Jefferson Adams


    • Can doctors diagnose celiac disease correctly at least 99 times out of 100 in the office without biopsy?


    Celiac.com 08/07/2017 - The guidelines of the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition allow for diagnosis of celiac disease without biopsies in children with symptoms and levels of immunoglobulin A against tissue-transglutaminase (TGA-IgA) 10-fold or more the upper limit of normal (ULN), confirmed by detection of endomysium antibodies (EMA) and positivity for HLA-DQ2/DQ8.


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    To validate this approach, a team of researchers recently performed a large, international prospective study. The primary goal was to see if the non-biopsy approach can identify children with celiac disease with a positive predictive value (PPV) above 99% in clinical practice. That means they want to make sure doctors can get it right at least 99 times out of 100 in the office. They also wanted to compare the performance of different serological tests and to see if the suggested criteria can be simplified.

    The research team included KJ Werkstetter, IR Korponay-Szabó, A Popp, V Villanacci, M Salemme, G Heilig, ST Lillevang, ML Mearin, C Ribes-Koninckx, A Thomas, R Troncone, B Filipiak, M Mäki, J Gyimesi, M Najafi, J Dolinšek, S Dydensborg Sander, R Auricchio, A Papadopoulou, A Vécsei, P Szitanyi, E Donat, R Nenna, P Alliet, F Penagini, H Garnier-Lengliné, G Castillejo, K Kurppa, R Shamir, AC Hauer, F Smets, S Corujeira, M van Winckel, S Buderus, S Chong, S Husby, S Koletzko; ProCeDE study group, P Socha, Bozena Cukrowska, H Szajewska, J Wyhowski, N Brown, G Batra, Z Misak, S Seiwerth, Y Dmitrieva, D Abramov, Y Vandenplas, A Goossens, MW Schaart, VTHBM Smit, N Kalach, P Gosset, JB Kovács, A Nagy, I Lellei, R KÅ‘bányai, K Khatami, M Monajemzadeh, K Dimakou, A Patereli, T Plato Hansen, R Kavalar, M Bolonio, H Kogler, G Amann, R Kosova, M Maglio, E Janssens, R Achten, P Frűhauf, H Skálová, T Kirchner, L Petrarca, FM Magliocca, F Martínez, V Morente, S Thanner-Lechner, M Ratschek, M Gasparetto, L Hook, D Canioni, C Wanty, A Mourin, K Laurila, M Vornane, V Nachmias Friedler, SL Morgenstern, J Amil Dias, F Carneiro, S Van Biervliet, S Vande Velde, H Banoub, S Sampson, AM Müller, A Ene, M Rafeey, and IAT Eftekhar Sadat. See the team’s individual affiliations below.**

    For their study, the team gathered data from consecutive pediatric patients 18 years or younger from 33 pediatric gastroenterology units in 21 countries. Patients all tested positive for TGA-IgA from November 2011 through May 2014, and all patients were on a gluten-containing diet. Local centers recorded patient symptoms, including measurements of total IgA, TGA, and EMA, and biopsy findings. The team recorded malabsorption when the children had chronic diarrhea, weight loss or insufficient gain, growth failure, or anemia.

    They directly compared central findings from 16 antibody tests (8 for TGA-IgA, 1 for TGA-IgG, 6 for IgG against deamidated gliadin peptides, and 1 for EMA, from 5 different manufacturers) 2 HLA-DQ2/DQ8 tests from 2 manufacturers, and histopathology findings from the reference pathologist. They based final diagnoses on local and central results. When all local and central results agreed for celiac disease, the team recorded those cases as proven celiac disease. Patients with TGA-IgA levels that were 3-fold or less below the ULN, but otherwise showed no indications of celiac disease, were classified as no celiac disease.

    The team conducted central histo-morphometry analysis on all other biopsies, and the cases were given a blind review. Inconclusive cases were regarded as not having celiac disease for better diagnostic accuracy and recruited 803 children for the study. They excluded 96 due to incomplete data, low level of IgA, or poor-quality biopsies, leaving 707 children, of whom 645 were diagnosed with celiac disease, 46 were found not to have celiac disease, and 16 had inconclusive results. The group was 65.1% female, and patients averaged 6.2 years old.

    Results from local laboratories of TGA-IgA 10-fold or more above ULN, a positive EMA result, and any one symptom identified children with celiac disease (n=399) with a PPV of 99.75 (95% CI, 98.61-99.99). The PPV was 100.00 (95% CI, 98.68-100.00) in 278 patients when only malabsorption symptoms were used instead of any one symptom.

    Inclusion of HLA analyses did not increase accuracy.

    Findings from central laboratories differed greatly for patients with lower levels of antibodies, but when levels of TGA-IgA were 10-fold or more the ULN, PPVs ranged from 99.63 (95% CI, 98.67-99.96) to 100.00 (95% CI, 99.23-100.00).

    This study confirms that children can be accurately diagnosed with celiac disease without biopsy. Diagnosis based on level of TGA-IgA 10-fold or more the ULN, a positive result from the EMA tests in a second blood sample, and the presence of at least 1 symptom could avoid risks and costs of endoscopy for more than half the children with celiac disease worldwide.

    HLA analysis is not required for accurate diagnosis.

    Source:

     

    **The members of the research team are variously affiliated with the Dr. von Hauner Children’s Hospital, Ludwig-Maximilian’s University Munich, Celiac Disease Center Heim Pál Children’s Hospital, Budapest and Dept. of Pediatrics, University of Debrecen, Hungary, University of Medicine and Pharmacy “Carol Davila” and National Institute for Mother and Child Health “Alessandrescu-Rusescu”, Bucharest, Romania, Institute of Pathology, Spedali Civili, Bresci, Italy, Dept. of Clinical Immunology, Odense University Hospital, Denmark, Dept. of Pediatrics, Leiden University Medical Center, the Netherlands, Dept. of Pediatric Gastroenterology and Hepatology, La Fe University Hospital, Valencia, Spain, Dept. of Pediatric Gastroenterology, Royal Manchester Children's Hospital, Manchester, United Kingdom, Dept. of Translational Medical Sciences & European Laboratory for the Investigation of Food-Induced Diseases, University Federico II, Naples, Italy, Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland, Dept. of Pediatric Gastroenterology & Hepatology, Children Medical Center, Tehran University of Medical Sciences, Iran, Dept. of Pediatrics, University Medical center (UMC) Maribor, Slovenia, Hans Christian Andersen Children's Hospital, Odense University Hospital, Denmark, Division of Gastroenterology, Hepatology and Nutrition, First Dept. of Pediatrics, Children's Hospitals "Agia Sophia", University of Athens, Athens, Greece, Gastroenterology Outpatient Clinic, St. Anna Children's Hospital, Medical University Vienna, Vienna, Austria, Dept. of Pediatrics, First Faculty of Medicine and General Teaching Hospital, Charles University, Prague, Czech Republic, Dept. of Pediatrics, Sapienza University of Rome, Italy, Dept. of Pediatrics, Jessa Hospital, Hasselt, Belgium, Dept. of Pediatric Gastroenterology, Addenbrookes Hospital, Cambridge, United Kingdom, Dept. of Pediatric Gastroenterology, Hepatology and Nutrition, Hôpital Necker-Enfants Malades, Paris, France, Dept. of Pediatric Gastroenterology and Nutrition, Hospital Universitari Sant Joan, Reus, Spain, Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel, Sackler faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, Dept of Pediatrics, Medical University of Graz, Graz, Austria, Université Catholique de Louvain, IREC, PEDI, Cliniques universitaires Saint Luc, Brussels, Belgium, Dept. of Pediatric Gastroenterology, Hospital S. João, Porto, Portugal, Dept. of Pediatric Gastroenterology, Hepatology and Nutrition, Ghent University Hospital, Ghent, Belgium, Dept. of Pediatrics, St. Marien Hospital, Bonn, Germany, Queen Mary's Hospital for Children, Carshalton, United Kingdom, Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, Pathology Department, Children's Memorial Health Institute, Warsaw, Poland, Pediatrics, Medical University of Warsaw, Pathomorphology, Pediatric University Hospital, Warsaw, Poland, Royal Manchester Children’s Hospital, Manchester, UK, Referral Center for Pediatric Gastroenterology and Nutrition, Children’s Hospital Zagreb, Institute of Pathology, Medical School University of Zagreb, Zagreb, Croatia, Russian Medical Academy of Continuing Postgraduate Education, Pathology, Kidz Health Castle, UZ Brusses, Brussel, Belgium, Pediatrics, Pathology, Leiden University Medical Center (LUMC), Hôpital Saint Vincent de Paul, Catholic University, Gastroenterology & Nephrology, Pathology, Heim Pál Children's Hospital, Budapest, Pediatric Gastroenterology, Hepatology &Nutrition, Children Medical Center, Tehran University of Medical Science and Mofid Children Hospital, Shahid Beheshti University of Medical Sciences, Pathology Unit, Children Medical Center Hospital Tehran, Division of Gastroenterology and Hepatology, First Department of Pediatrics, Children’s hospital «Agia Sofia», University of Athens, Clinical Pathology, Odense University Hospital, Department of Pathology, University Medical Center Maribor, Maribor, Slovenia, Pediatric Gastroenterology & Hepatlogy and David Ramos, Pathology Unit, La Fe University Hospital Valencia, St. Anna Children's Hospital, Department of Pathology, Medical University Vienna, Dept. of Translational Medical Sciences & European Laboratory for the Investigation of Food-Induced Diseases, University Federico II, Naples Italy, Pediatrics, Pathology, Jessa Hospital, Hasselt, Pediatrics and Adolescent Medicine, pathologist, Institute of Pathology, First Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic, Institute of Pathology, Ludwig Maximilian's University Munich, Munich, Germany, Pediatrics and Infantile Neuropsychiatry, Radiology, Oncology and Human Pathology, “Sapienza” University, Rome, Italy, Gastroenterology Unit, Pathology Unit, Hospital Universitari de Sant Joan de Reus, IISPV, URV, Pediatrics, Institute for Pathology, Medical University of Graz, Austria, Pediatric Gastroenterology, Hepatology & Nutrition, Pathology, Cambridge University NHS Foundation Trust, Addenbrookes Hospital, Cambridge, UK, Anatomo-Pathology, Hôpital Necker-Enfants Malades, Paris, France, Pediatric Gastroenterology, Pathology Unit, Université Catholique de Louvain, Cliniques universitaires Saint Luc, Brussels, Belgium, Centre for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland, Institute of Gastroenterology, Nutrition & Liver Diseases, Schneider Children's Medical Center, Department of Pathology, Rabin Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Israel, Hospital S. João, Porto, Portugal, Dept. of Pediatric Gastroenterology, Hepatology and Nutrition, Ghent University Hospital, Gent, Belgium, Queen Mary's Hospital for Children, Dept of Pathology, Epsom & St Helier University NHS Trust, Carshalton, UK, Department of Pathology, University of Bonn, Bonn, Germany, Histology Department National Institute for Mother and Child Health, Bucharest, Romania, and with the Liver & Gastrointestinal Research Center, Pathology Unit, Tabriz University of Medical Sciences.


    Image Caption: Can doctors diagnose celiac disease correctly in the office without biopsy? Photo: CC--Enokson
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    WHAT IS CELIAC DISEASE?
    Celiac disease is an autoimmune condition that affects around 1% of the population. People with celiac disease suffer an autoimmune reaction when they consume wheat, rye or barley. The immune reaction is triggered by certain proteins in the wheat, rye, or barley, and, left untreated, causes damage to the small, finger-like structures, called villi, that line the gut. The damage occurs as shortening and villous flattening in the lamina propria and crypt regions of the intestines. The damage to these villi then leads to numerous other issues that commonly plague people with untreated celiac disease, including poor nutritional uptake, fatigue, and myriad other problems.
    Celiac disease mostly affects people of Northern European descent, but recent studies show that it also affects large numbers of people in Italy, China, Iran, India, and numerous other places thought to have few or no cases.
    Celiac disease is most often uncovered because people experience symptoms that lead them to get tests for antibodies to gluten. If these tests are positive, then the people usually get biopsy confirmation of their celiac disease. Once they adopt a gluten-free diet, they usually see gut healing, and major improvements in their symptoms. 
    CLASSIC CELIAC DISEASE SYMPTOMS
    Symptoms of celiac disease can range from the classic features, such as diarrhea, upset stomach, bloating, gas, weight loss, and malnutrition, among others.
    LESS OBVIOUS SYMPTOMS
    Celiac disease can often less obvious symptoms, such fatigue, vitamin and nutrient deficiencies, anemia, to name a few. Often, these symptoms are regarded as less obvious because they are not gastrointestinal in nature. You got that right, it is not uncommon for people with celiac disease to have few or no gastrointestinal symptoms. That makes spotting and connecting these seemingly unrelated and unclear celiac symptoms so important.
    NO SYMPTOMS
    Currently, most people diagnosed with celiac disease do not show symptoms, but are diagnosed on the basis of referral for elevated risk factors. 

    CELIAC DISEASE VS. GLUTEN INTOLERANCE
    Gluten intolerance is a generic term for people who have some sort of sensitivity to gluten. These people may or may not have celiac disease. Researchers generally agree that there is a condition called non-celiac gluten sensitivity. That term has largely replaced the term gluten-intolerance. What’s the difference between celiac disease and non-celiac gluten-sensitivity? 
    CELIAC DISEASE VS. NON-CELIAC GLUTEN SENSITIVITY (NCGS)
    Gluten triggers symptoms and immune reactions in people with celiac disease. Gluten can also trigger symptoms in some people with NCGS, but the similarities largely end there.

    There are four main differences between celiac disease and non-celiac gluten sensitivity:
    No Hereditary Link in NCGS
    Researchers know for certain that genetic heredity plays a major role in celiac disease. If a first-degree relative has celiac disease, then you have a statistically higher risk of carrying genetic markers DQ2 and/or DQ8, and of developing celiac disease yourself. NCGS is not known to be hereditary. Some research has shown certain genetic associations, such as some NCGS patients, but there is no proof that NCGS is hereditary. No Connection with Celiac-related Disorders
    Unlike celiac disease, NCGS is so far not associated with malabsorption, nutritional deficiencies, or a higher risk of autoimmune disorders or intestinal malignancies. No Immunological or Serological Markers
    People with celiac disease nearly always test positive for antibodies to gluten proteins. Researchers have, as yet, identified no such antobodies or serologic markers for NCGS. That means that, unlike with celiac disease, there are no telltale screening tests that can point to NCGS. Absence of Celiac Disease or Wheat Allergy
    Doctors diagnose NCGS only by excluding both celiac disease, an IgE-mediated allergy to wheat, and by the noting ongoing adverse symptoms associated with gluten consumption. WHAT ABOUT IRRITABLE BOWEL SYNDROME (IBS) AND IRRITABLE BOWEL DISEASE (IBD)?
    IBS and IBD are usually diagnosed in part by ruling out celiac disease. Many patients with irritable bowel syndrome are sensitive to gluten. Many experience celiac disease-like symptoms in reaction to wheat. However, patients with IBS generally show no gut damage, and do not test positive for antibodies to gliadin and other proteins as do people with celiac disease. Some IBS patients also suffer from NCGS.

    To add more confusion, many cases of IBS are, in fact, celiac disease in disguise.

    That said, people with IBS generally react to more than just wheat. People with NCGS generally react to wheat and not to other things, but that’s not always the case. Doctors generally try to rule out celiac disease before making a diagnosis of IBS or NCGS. 
    Crohn’s Disease and celiac disease share many common symptoms, though causes are different.  In Crohn’s disease, the immune system can cause disruption anywhere along the gastrointestinal tract, and a diagnosis of Crohn’s disease typically requires more diagnostic testing than does a celiac diagnosis.  
    Crohn’s treatment consists of changes to diet and possible surgery.  Up to 10% of Crohn's patients can have both of conditions, which suggests a genetic connection, and researchers continue to examine that connection.
    Is There a Connection Between Celiac Disease, Non-Celiac Gluten Sensitivity and Irritable Bowel Syndrome? Large Number of Irritable Bowel Syndrome Patients Sensitive To Gluten Some IBD Patients also Suffer from Non-Celiac Gluten Sensitivity Many Cases of IBS and Fibromyalgia Actually Celiac Disease in Disguise CELIAC DISEASE DIAGNOSIS
    Diagnosis of celiac disease can be difficult. 

    Perhaps because celiac disease presents clinically in such a variety of ways, proper diagnosis often takes years. A positive serological test for antibodies against tissue transglutaminase is considered a very strong diagnostic indicator, and a duodenal biopsy revealing villous atrophy is still considered by many to be the diagnostic gold standard. 
    But this idea is being questioned; some think the biopsy is unnecessary in the face of clear serological tests and obvious symptoms. Also, researchers are developing accurate and reliable ways to test for celiac disease even when patients are already avoiding wheat. In the past, patients needed to be consuming wheat to get an accurate test result. 
    Celiac disease can have numerous vague, or confusing symptoms that can make diagnosis difficult.  Celiac disease is commonly misdiagnosed by doctors. Read a Personal Story About Celiac Disease Diagnosis from the Founder of Celiac.com Currently, testing and biopsy still form the cornerstone of celiac diagnosis.
    TESTING
    There are several serologic (blood) tests available that screen for celiac disease antibodies, but the most commonly used is called a tTG-IgA test. If blood test results suggest celiac disease, your physician will recommend a biopsy of your small intestine to confirm the diagnosis.
    Testing is fairly simple and involves screening the patients blood for antigliadin (AGA) and endomysium antibodies (EmA), and/or doing a biopsy on the areas of the intestines mentioned above, which is still the standard for a formal diagnosis. Also, it is now possible to test people for celiac disease without making them concume wheat products.

    BIOPSY
    Until recently, biopsy confirmation of a positive gluten antibody test was the gold standard for celiac diagnosis. It still is, but things are changing fairly quickly. Children can now be accurately diagnosed for celiac disease without biopsy. Diagnosis based on level of TGA-IgA 10-fold or more the ULN, a positive result from the EMA tests in a second blood sample, and the presence of at least 1 symptom could avoid risks and costs of endoscopy for more than half the children with celiac disease worldwide.

    WHY A GLUTEN-FREE DIET?
    Currently the only effective, medically approved treatment for celiac disease is a strict gluten-free diet. Following a gluten-free diet relieves symptoms, promotes gut healing, and prevents nearly all celiac-related complications. 
    A gluten-free diet means avoiding all products that contain wheat, rye and barley, or any of their derivatives. This is a difficult task as there are many hidden sources of gluten found in the ingredients of many processed foods. Still, with effort, most people with celiac disease manage to make the transition. The vast majority of celiac disease patients who follow a gluten-free diet see symptom relief and experience gut healing within two years.
    For these reasons, a gluten-free diet remains the only effective, medically proven treatment for celiac disease.
    WHAT ABOUT ENZYMES, VACCINES, ETC.?
    There is currently no enzyme or vaccine that can replace a gluten-free diet for people with celiac disease.
    There are enzyme supplements currently available, such as AN-PEP, Latiglutetenase, GluteGuard, and KumaMax, which may help to mitigate accidental gluten ingestion by celiacs. KumaMax, has been shown to survive the stomach, and to break down gluten in the small intestine. Latiglutenase, formerly known as ALV003, is an enzyme therapy designed to be taken with meals. GluteGuard has been shown to significantly protect celiac patients from the serious symptoms they would normally experience after gluten ingestion. There are other enzymes, including those based on papaya enzymes.

    Additionally, there are many celiac disease drugs, enzymes, and therapies in various stages of development by pharmaceutical companies, including at least one vaccine that has received financial backing. At some point in the not too distant future there will likely be new treatments available for those who seek an alternative to a lifelong gluten-free diet. 

    For now though, there are no products on the market that can take the place of a gluten-free diet. Any enzyme or other treatment for celiac disease is intended to be used in conjunction with a gluten-free diet, not as a replacement.

    ASSOCIATED DISEASES
    The most common disorders associated with celiac disease are thyroid disease and Type 1 Diabetes, however, celiac disease is associated with many other conditions, including but not limited to the following autoimmune conditions:
    Type 1 Diabetes Mellitus: 2.4-16.4% Multiple Sclerosis (MS): 11% Hashimoto’s thyroiditis: 4-6% Autoimmune hepatitis: 6-15% Addison disease: 6% Arthritis: 1.5-7.5% Sjögren’s syndrome: 2-15% Idiopathic dilated cardiomyopathy: 5.7% IgA Nephropathy (Berger’s Disease): 3.6% Other celiac co-morditities include:
    Crohn’s Disease; Inflammatory Bowel Disease Chronic Pancreatitis Down Syndrome Irritable Bowel Syndrome (IBS) Lupus Multiple Sclerosis Primary Biliary Cirrhosis Primary Sclerosing Cholangitis Psoriasis Rheumatoid Arthritis Scleroderma Turner Syndrome Ulcerative Colitis; Inflammatory Bowel Disease Williams Syndrome Cancers:
    Non-Hodgkin lymphoma (intestinal and extra-intestinal, T- and B-cell types) Small intestinal adenocarcinoma Esophageal carcinoma Papillary thyroid cancer Melanoma CELIAC DISEASE REFERENCES:
    Celiac Disease Center, Columbia University
    Gluten Intolerance Group
    National Institutes of Health
    U.S. National Library of Medicine
    Mayo Clinic
    University of Chicago Celiac Disease Center