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  • Jefferson Adams
    Jefferson Adams
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    Can Answering Three Simple Questions Help Diagnose Celiac Disease?

      Can knowing a patient’s age at diagnosis, the manner of presentation, and any added complications help to spot celiac disease? A team of researchers recently set out to develop a simple phenotypic classification for celiac disease.

    Caption: Image: CC--Michael Bär

    Celiac.com 01/23/2019 - In the last decade or so, researchers have learned a great deal about the nature of celiac disease. They have learned that celiac disease can arise at any age, that it can have a myriad of symptoms, or no symptoms at all, and that proper diagnosis and treatment is key to avoiding serious complications later on in life.

    The researchers note that the Oslo definitions establish consensus on celiac disease terminology, but they offer no phenotypic classification for making a composite celiac diagnosis. A team of researchers recently set out to develop a simple phenotypic classification for celiac disease.

    The research team included Ajit Sood, Vandana Midha, Govind Makharia, B. K. Thelma, Shivalingappa S Halli, Varun Mehta, Ramit Mahajan, Vikram Narang, Kriti Sood, and Kirandeep Kaur.

    The team established several factors important for phenotypic classification, including age at diagnosis, age at symptom onset, clinical features, family history, and complications, and they applied these factors to 1,664 patients listed in an existing registry at Dayanand Medical College and Hospital, Ludhiana, India. 

    The researchers evaluated patients below age 15, and below age 18 years, and verified their classifications by using cross tabulations of the existing data. For validation of their process and the results the team solicited review by recognized experts from numerous disciplines.

    Form these results, the research team concludes that their APC classification process, based on age at diagnosis, presentation, complications, offers a simple disease explanatory classification for patients with celiac disease, and can help to provide a composite diagnosis.

    It’s exciting to know that the answers to three simple questions can help doctors to diagnose celiac disease. Stay tuned for more on this and other stories.

    Source:

     

    The researchers are variously affiliated with the Department of Gastroenterology, Dayanand Medical College in Ludhiana, India; the Department of Internal Medicine, Dayanand Medical College, Ludhiana, India; the Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences in New Delhi, India; the Department of Genetics, University of Delhi South Campus in New Delhi, India; the Department of Community Health Sciences, Faculty of Medicine, University of Manitoba in Winnipeg, Canada; the Department of Pathology, Dayanand Medical College, Ludhiana, India; and the Department of Pharmacology, Dayanand Medical College in Ludhiana, India.


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  • About Me

    Jefferson Adams earned his B.A. and M.F.A. at Arizona State University, and has authored more than 2,000 articles on celiac disease. His coursework includes studies in biology, anatomy, medicine, and science. He previously served as Health News Examiner for Examiner.com, and provided health and medical content for Sharecare.com. Jefferson has spoken about celiac disease to the media, including an appearance on the KQED radio show Forum, and is the editor of the book "Cereal Killers" by Scott Adams and Ron Hoggan, Ed.D.

  • Related Articles

    Jefferson Adams
    Kids Can Get Accurate Celiac Diagnosis 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.
    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:
    Gastroenterology. 2017 Jun 15. pii: S0016-5085(17)35736-0. doi: 10.1053/j.gastro.2017.06.002.  
    **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.

    Jefferson Adams
    New Blood Test May Change the Way We Diagnose Celiac Disease
    Celiac.com 08/28/2017 - After 14-day gluten challenge, an HLA-DQ-gluten tetramer blood test provides better detection of celiac disease than biopsy. Can that lead to new disease detection methods in patients who are already on a gluten-free diet?
    Doctors attempting to diagnose celiac disease are often confronted by patients who have already given up gluten. For such patients, diagnostic guidelines currently call for a gluten challenge of at least 14 days, followed by duodenal biopsy. There isn't much good data on how many false-positive results are generated by this method. To get a better picture, a team of researchers recently studied responses to 14-day gluten challenge in subjects with treated celiac disease.
    The research team included Vikas K Sarna, Gry I Skodje, Henrik M Reims, Louise F Risnes, Shiva Dahal-Koirala, Ludvig M Sollid, and Knut E A Lundin. They are variously affiliated with the Department of Immunology and Transfusion Medicine, Oslo University Hospital, Norway; K. G. Jebsen Coeliac Disease Research Centre, University of Oslo, Norway; Department of Clinical Service, Oslo University Hospital, Norway; Department of Pathology, Oslo University Hospital, Norway; Centre for Immune Regulation, University of Oslo and Oslo University Hospital, Norway; and the Department of Gastroenterology, Oslo University Hospital, Norway.
    The research team took a group of 20 patients with biopsy-verified celiac disease, all in confirmed mucosal remission, and presented them with a dietary gluten challenge of 5.7 grams per oral gluten per day for 14 days, then conducted duodenal biopsies. They analyzed blood by multiplex assay for cytokine detection, and by flow cytometry using HLA-DQ:gluten tetramers.
    Nineteen of the twenty participants completed the challenge. Biopsy results showed villous blunting in 5 of those 19 patients. Villous height to crypt depth ratio reduced with at least 0.4 concomitantly with an increase in intraepithelial lymphocyte count of at least 50% in 9 of the 19 patients. Interleukin-8 plasma concentration increased by more than 100% after 4 hours in 7 of 19 subjects. Frequency of blood CD4+effector-memory gut-homing HLA-DQ:gluten tetramer-binding T cells increased by more than 100% on day 6 in 12 of 15 evaluated participants.
    For most celiac patients, a 14-day gluten challenge did not result in sufficient mucosal architectural changes for clear diagnosis (sensitivity ≈25%–50%).
    The team found that an increase in CD4+ effector-memory gut-homing HLA-DQ:gluten tetramer-binding T cells in blood 6 days after gluten challenge is a more sensitive and less invasive biomarker for celiac disease.
    The team is calling for further study. Being able to diagnose celiac disease without biopsy could really help to improve the entire diagnostic process, and could easily lead to an increase in diagnosis.
    Source:
    Gut

    Jefferson Adams
    Are Doctors Following Current Biopsy Guidelines When Diagnosing Celiac Disease?
    Celiac.com 09/21/2017 - Current guidelines by the British Society of Gastroenterology recommend that doctors take at least four duodenal biopsy specimens at the time of upper gastrointestinal (UGI) endoscopy when looking for celiac disease. The practice has been shown to increase celiac diagnoses, and to reduced missed diagnoses.
    The Society recently sought to assess compliance with their own guidelines within their institution. They then sought to apply measures to improve their compliance rate, and to assess the resulting impact on our diagnostic rate for celiac disease.
    The research team included Nilofer Husnoo; Wafaa Ahmed; and Muhammad Hanif Shiwani. They are variously affiliated with the Urology Department, Sheffield Teaching Hospitals NHS Trust, Sheffield, UK, the Gastroenterology Department, Maidstone and Tunbridge Wells NHS Trust, Tunbridge Wells, UK, and the General Surgery Department, Barnsley General Hospital NHS Foundation Trust, Barnsley, UK.
    The team performed a retrospective audit of electronic records for patients with no prior celiac diagnosis, who underwent UGI endoscopy with duodenal biopsies between August 2014 and May 2015. They then used the information to raise awareness among endoscopy users at the Society, and conducted a follow-up audit between February and May 2016.
    They found and registered a total of 924 eligible patients for the first part of the study, and 278 for the second part. The proportion of patients who had ≥4 biopsy specimens submitted increased from 21.9% to 60.8% (p<0.001).
    The study by the BSG suggests that taking less than four duodenal biopsy specimens can result in missed celiac diagnoses. However, a few simple steps can help doctors avoid such missed diagnoses.
    Since atypical symptoms are more common in patients these days, and since the lifetime risk of malignancy, especially intestinal lymphoma and other gastrointestinal cancers, is higher in celiac patients, it's important that doctors conduct a thorough investigation when they suspect celiac disease to avoid missing the diagnosis. For the BSG, that means taking 4 or more biopsy samples.
    Source:
    BMJ Open Gastro. 2017;4(1):e000140

    Jefferson Adams
    Simple Three Point Criteria Can Spot Celiac Disease in Adults Without Biopsy
    Celiac.com 01/07/2019 - Researchers have made progress in spotting celiac disease without biopsy in children with certain parameters. Can the same be done for adults? A team of researchers recently set out to evaluate the accuracy of serology-based criteria in adults with variable pre-test probabilities for celiac disease. The research team included V Fuchs, K Kurppa, H Huhtala, K Laurila, M Mäki, P Collin, T Salmi, L Luostarinen, P Saavalainen, and K Kaukinen.
    New criteria for diagnosing celiac disease in children allow doctors to forgo duodenal biopsies in children who have symptoms, positive blood tests, and celiac disease-associated genes. 
    There’s currently no good data on whether such an approach might work for adults with certain clinical presentations of celiac disease.
    Three study cohorts included 421 adults with high-risk clinical celiac disease suspicion, 2,357 moderate-risk family members of celiac patients, and 2,722 low-risk individuals from the general population. 
    The team collected blood tests and other physical patient data. Their "triple criteria" for celiac disease included transglutaminase 2 antibodies more than ten times the upper limit of normal, positive endomysium antibodies, and appropriate genetics, but required no symptoms. The diagnosis was made by grading the intestinal biopsies.
    In all, 274 patients were diagnosed with celiac disease. Of these, 59 high-risk subjects, 17 moderate-risk subjects, and 14 low-risk subjects fulfilled the "triple criteria.” 
    All had histologically proven celiac disease, giving the criteria a positive predictive value of 100%. Altogether, 90 of the 274 newly diagnosed patients could have avoided biopsy. That’s one in three patients who could have avoided biopsy. In all, 37% of high-risk, 20% of moderate-risk, and 48% of low-risk patients could have avoided biopsy. 
    Biopsies of "triple positive" subjects showed no histological findings other than celiac disease.
    The results of this study are exciting, because it shows that the “triple criteria” can be used by doctors to reliably diagnose celiac disease in adults without using biopsy. 
    Implementing these diagnostic criteria would make diagnosing celiac disease easier in many cases, and will reduce the number of endoscopies by one-third. That’s a winning result all the way around.
    Source:
    Aliment Pharmacol Ther. 2018 Dec 27. doi: 10.1111/apt.15109.  
    The researchers in this article are variously affiliated with the Celiac Disease Research Center, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland; the Tampere Center for Child Health Research, University of Tampere, and Department of Paediatrics, Tampere University Hospital, Tampere, Finland; the Tampere Faculty of Social Sciences, University of Tampere, Tampere, Finland; the Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland; the Department of Dermatology, Tampere University Hospital, Tampere, Finland; the Department of Neurology, Päijät-Häme Central Hospital, Lahti, Finland; the Research Programs Unit, Immunobiology, and Haartman Institute, Department of Medical Genetics, University of Helsinki, Helsinki, Finland; the Department of Internal Medicine, Tampere University Hospital, Tampere, Finland.

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