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MOM, F.R.C.M. (Fellow of the Royal College of Mothers)
Dr. Ron Hoggan, Ed.D. posted an article in Summer 2003 Issue
Celiac.com 12/24/2022 - My doctor is a nice guy. He is also very bright and has an impressive memory for many things. He couldn’t have gotten through medical school—he couldn’t even have gotten acceptance into medical school without being pretty capable. But he can’t know as much about me as I do. Neither has he observed my children for as long or with as much concern as I have. If we are ever to achieve balanced relationships with physicians, we must all acknowledge our own, and each others’ expertise. The history of the discovery of the gluten-free diet is really a story that should improve doctor-patient collaboration if the facts ever become widely known. World War II Grain Shortages or Concerned Mom? Not long ago I listened to a speaker, once again, crediting World War II grain shortages in The Netherlands for Dr. Dicke’s discovery of the gluten-free diet as the treatment of choice for patients with celiac disease. This is a myth that has been perpetuated for far too long. This faulty tale sullies the memory of a great scientist, Dr. Willem Karel Dicke, and robs a concerned mother of the credit she richly deserves. The facts are available in Dr. Dicke’s Ph. D. thesis. Dr. Chris Mulder has generously provided an English translation of Dr. Dicke’s thesis. In his thesis, Dr. Dicke clearly states that the insight came from a 1932 meeting with two colleagues and a discussion of their observations of a child with celiac disease. This was long before World War II even began, and the grain shortages actually occurred late in the war. Further, in the follow-up commentary at the end of the translation, Dr. Mulder reveals that the idea, which led to these 1932 insights, originated with a concerned mother’s observations of her own child, and her comments to Dicke’s colleagues. The myth about World War II grain shortages simply does not jibe with the facts. It seems far more likely that a concerned mom, not a busy pediatrician, would notice what a child ate and how that affected his bowel movements. To my ears, this latter explanation has the ring of truth. The question of who deserves the credit for this pivotal insight may not appear very important. However, our increasingly specialized society pressures us to place more and more trust in the specialist, whether lawyer, doctor, or auto mechanic. When we are placing our own and our children’s health and safety in the hands of another person, we may reasonably expect these specialists get their facts straight on simple historical issues that can easily be investigated. Investigating a Mother's Hypothesis Dr. Dicke’s important role, as a physician and a man of science, was to investigate this concerned mother’s hypothesis. His memory is enhanced by the recognition he freely rendered to the originators of the idea. We not only violate his memory, we insult his stature as a scientific investigator, when we perpetuate the false claim that the chance occurrence of WW II grain shortages led to the discovery of the treatment value of a gluten-free diet. More importantly, this question speaks to the importance of trusting ourselves, our own observations, and our own assessments—our own gut, if you will, in our quest for health. Dr. Dicke’s work was extremely important and it constituted a huge contribution to Humanity. His research has already saved countless lives and will continue to do so. But we need to remember that the original insight that identified the trigger for celiac disease came from an observant mother. In remembering this, many of us will feel empowered to collaborate with our physicians, rather than blindly accepting yet another useless prescription. And that is the pivotal importance of publicly recognizing where the idea of a gluten-free diet originated. We need to recognize that the physician’s expertise is only one important element in the diagnostic and treatment process. We may often defer to doctors’ superior knowledge of medical issues. However, our own expertise, as the occupants of our bodies, or as parents, must also contribute to this process and our subsequent healing. We need to trust our own observations and judgement. Dismissal or denigration of our unique expertise bespeaks a competitive spirit; not a collaborative one. Such a competitive attitude may weaken the diagnostic process and hinder our recovery. -
Celiac.com 04/25/2012 - In my experience growing up with undiagnosed celiac disease, I had to deal with several symptoms that my doctors had no answers for. One of the most frustrating of these was my skin troubles—dermatitis herpetiformis. After my experiences with misdiagnoses, and finally more recently, learning how to effectively get rid of dermatitis herpetiformis, I encourage parents to be particularly watchful for signs of dermatitis herpetiformis in their children, and I have some useful advice for those—children and adults—who have already been diagnosed with this annoying and sometimes quite troublesome rash. Since dermatitis herpetiformis occurs in 15 to 20% of celiacs, it’s worth any celiac’s time to learn more about this condition. By definition, dermatitis herpetiformis is a blistering and extremely itchy skin rash. It’s usually symmetrical in shape and is most commonly located on the elbows, knees, buttocks, and upper back. It’s common for people with dermatitis herpetiformis to have rashes appear in the same spot, and they can either be consistent or come and go. People can experience the rash on other parts of the body, and severity of symptoms can vary. Dermatitis herpetiformis is sometimes called the “gluten rash” or “celiac disease rash” because it occurs in people with a gluten intolerance or celiac disease. It is commonly misdiagnosed as eczema. Gluten is a protein found in wheat, barley, and rye. In people who have celiac disease, gluten causes an autoimmune response which results in the immune system attacking the lining of the small intestine—specifically the villi, the absorptive hair-like structures of the lining. With dermatitis herpetiformis, outbreaks are also triggered by gluten. Interestingly, unlike celiac disease which appears more in women than men, dermatitis herpetiformis is more commonly found in men by a ratio of about two-to-one. It is rarely seen in children under ten and first appears in the teenage years or even in one’s twenties or thirties. It may come and go, even if you’re eating a gluten-containing diet. Diagnosis is done with a skin biopsy. In most cases, a dermatitis herpetiformis diagnosis means celiac disease as well, even if you’re not obviously suffering from the characteristic intestinal symptoms of this disease. No matter what, the treatment is the same: a strict gluten-free diet. Dermatitis herpetiformis rashes are treated in two main ways--the gluten-free diet, of course, and antibiotics such as dapsone or sulfapyridine for those who aren’t able to tolerate dapsone. A truly gluten-free diet can eliminate dermatitis herpetiformis, but in my experience and according to the National Institutes of Health, a dermatitis herpetiformis rash responds dramatically to dapsone, within 48 to 72 hours. To treat the underlying cause of dermatitis herpetiformis, which is celiac disease, a strict gluten-free diet must be followed, but according to the National Institutes of Health, “Even with a gluten-free diet, dapsone or sulfapyridine therapy may need to be continued for 1–2 years to prevent further dermatitis herpetiformis outbreaks.” As a celiac with dermatitis herpetiformis, completely eliminating gluten from my diet has been the only lasting solution for dermatitis herpetiformis, but unfortunately I can accidentally ingest gluten from time to time, especially when I travel. In my most recent outbreak, I decided to get a prescription for dapsone. Although dapsone is a very strong drug with side effects and should be used sparingly, I was in need of something fast-acting. I followed the instructions exactly, and not only did it relieve the pain but within three days, I could see a remarkable change in the appearance of the dermatitis herpetiformis. After reexperiencing the painful and frustrating symptoms of dermatitis herpetiformis and the relief that came with proper treatment, I knew I had to address this topic to help others. I encourage everyone to get the word out about dermatitis herpetiformis so more and more people dealing with this misdiagnosed condition can get help just as I did. Resources: About.com: Dermatitis Herpetiformis, The ‘Gluten Rash’. Celiac Disease Awareness Campaign: Dermatitis Herpetiformis. eMedecine.Medscape.com: Dermatitis herpetiformis. -
Celiac.com 09/27/2017 - Patients who have clinical, genetic and histological signs of celiac disease, but no serological markers, present a challenge when it comes to making a diagnosis. If the patient doesn't have elevated antibodies, what signs do doctors look for? What's the best way to evaluate the patient's natural history and response to a gluten-free diet? A team of researchers recently set out to outline a specific profile, and to evaluate the natural history and response to a gluten-free diet of patients with seronegative celiac disease. The research team included Maria Pina Dore; Giovanni Mario Pes; Ivana Dettori; Vincenzo Villanacci; Alessandra Manca and Giuseppe Realdi. They are variously affiliated with the Internal Medicine Section, Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy, with the Baylor College of Medicine, Michael E. DeBakey VAMC, Houston, TX, USA, the Pathology Section, Department of Molecular and Translational Medicine, Spedali Civili and University of Brescia, Brescia, Italy, and with the Pathology Section, Department of Clinical and Experimental Medicine, University of Sassari in Sassari, Italy. Patients with duodenal mucosa damage Marsh I, II and III stages, HLA DQ2/DQ8 haplotype and clinical features suggestive of celiac disease, but with negative celiac serology, were defined as seronegative celiac patients. The team excluded other common causes of duodenal mucosa damage. They the compared HLA–DR and DQ genotype/haplotype between all Marsh stages of patients with seronegative and seropositive celiac disease. They then assessed clinical features, lab tests and histological findings after a gluten-free diet and a gluten re-challenge. The group provided the team with a long follow-up period to gather data. The researchers enrolled a total of 48 patients who fulfilled diagnostic criteria over a 4-year period. Patients with seronegative and seropositive celiac disease showed similar clinical phenotype and HLA−DR and DQ frequencies. However, Marsh I stage was seen in 42% of seronegative patients (42% vs 22%; p<0.05). After a 1-year gluten-free diet trial, clinical symptoms, histological features and laboratory testing improved in 40 patients and worsened in those who underwent a 6-months gluten challenge. Five patients with seronegative celiac disease (25%) experienced the occurrence of autoimmune diseases during an average follow-up of about 11 years. Patients with seronegative celiac disease did not show any specific profile, but they did see benefits from a gluten-free diet similar to seropositive patients. In the absence of more sensitive serological markers, diagnosing seronegative celiac disease remains an often confusing and challenging process of excluding various other possibilities. Source: BMJ Open Gastro. 2017;4(1):e000159 -
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 -
Celiac.com 04/04/2017 - From 2009 to 2014, the number of people with celiac disease in the United States held steady, while the number of undiagnosed individuals fell by about half. Mayo Clinic researchers, reviewing information from National Health and Nutrition Examination Surveys, say the increase in diagnosis likely stems from better detection, better celiac disease awareness, and/or possibly from the rising popularity of gluten-free diets. The research team reviewed blood test results of more than 22,000 people over age of six years of age. Interestingly, while rates of celiac disease ready held steady, the number of people following a gluten-free diet without a celiac diagnosis more than tripled, to an estimated 3.1 million people. Source: AllergicLiving.com -
Celiac.com 07/11/2013 - A team of researchers wanted to better understand screening practices for celiac disease in patients with type 1 diabetes across North America. One question they sought to answer was whether diabetes centers screen for celiac disease in type 1 diabetes more frequently than other facilities. The research team included S.M. Simpson, E.J. Ciaccio, S. Case, N. Jaffe, S. Mahadov, B. Lebwohl, P.H. Green. All except Case are affiliated with the Celiac Disease Center at Columbia University, New York, USA. Shelley Case runs her own nutrition consulting business in Regina, Saskatchewan. For their study, the team conducted a survey with 27 questions on screening practices for celiac disease in patients with type 1 diabetes. The questions were compiled by experts in celiac disease and diabetes. The team sent surveys by email to diabetes educators and dietitians throughout the United States and Canada between December 2010 and May 2011. They received 514 responses from 484 endocrine clinics, diabetes clinics, private practices, community nutrition centers, and inpatient centers. Thirty-five percent of these locations screened for celiac disease, with endocrine clinics reporting screening at the highest rate of eighty percent. Not surprisingly, the most common test celiac disease test was tissue transglutaminase, while the most frequently recommended treatment of confirmed celiac disease was a gluten-free diet. However, only 365 respondents (71%) recommended biopsy in patients with positive blood results. More than half of those responding (55.3%) reported that patient symptoms improved once they adopted a gluten-free diet. Staff at endocrine clinics were most likely to suggest celiac disease testing for patients with type 1 diabetes. Due to low screening frequency as well as inconsistency in management of positive celiac disease blood tests, the research team is calling for increased education regarding celiac disease in patients with type 1 diabetes, along with the adoption of uniform protocols. Source: Diabetes Educ. 2013 May 14. -
Celiac.com 08/12/2011 - Although serological analysis is used in diagnosing celiac disease, histopathology is regarded as most reliable. A team of researchers set out to assess the clinical, pathological and serological spectrum of celiac disease in a general population via prospective study (Kalixanda study). The research team included Marjorie M. Walker, Joseph A. Murray, Jukka Ronkainen, Pertti Aro, Tom Storskrubb, Mauro D’Amato, Brian Lahr, Nicholas J. Talley, and Lars Agreus. For their study, the team evaluated a random sample of 1000 adults from the general population by upper endoscopy, duodenal biopsy, and serological analysis of tissue transglutaminase (tTg) levels. They screened samples that were tTg+ for endomysial antibody (EMA) levels. The baseline value for celiac diagnosis was villous atrophy with 40 intraepithelial lymphocytes (IELs)/100 enterocytes (ECs). The team found 33 subjects with tTg+ and 16 with EMA+. Their histological analysis showed 7/1000 subjects (0.7%) with celiac disease, all of whom showed tTg+ and 6 of 7 of whom showed EMA+. Another 26 subjects showed tTg+, 7 of 26 showing EMA+. The team then addressed these cases with a second quantitative pathology study, this one a nested case-control design, that used a celiac diagnosis baseline of 25 IELS/100 ECs. Under this criteria, all 13 samples that were tTg+ and EMA+ had more than 25 IELs/100ECs. A total of 16 subjects (1.6%) showed serological and histological evidence of gluten-sensitive enteropathy. The team quantified IELs in duodenal biopsy samples from 500 seronegative individuals. A total of 19 (3.8%) of those subjects had >25 IELs and lymphocytic duodenosis (LD). A celiac diagnosis level of ≥25 IELs/100 ECs was strongly associated with serological indicators of celiac disease, while a higher IEL threshold missed half of cases. Quantification of tTg is a sensitive test for celiac disease, and diagnosis can be confirmed by observation of ≥25 IELs/100ECs in duodenal biopsy. Lymphocytic enteropathy in the form of both celiac disease and Lymphocytic duodenitis, is common, occurring in about 5.4% of the general population. Source: Gastroenterology doi: 10.1053/j.gastro.2010.04.007
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Celiac.com 04/06/2012 - The first step in diagnosing celiac is serological testing, looking for the presence of anti-tTg antibodies. But in adults at least a duodenal biopsy is still the gold standard of diagnosis, partially because of the risk of false positive anti-tTg results. Yet serum anti-tTg levels positively correlate with the severity of small intestinal histopathology. This prompted researchers in Italy to wonder if those patients with the highest ant-tTg levels could be spared an endoscopy, and if so, how high their anti-tTg levels had to be. They conclude, in their words, that "tissue-transglutaminase antibody level 5-folds the upper limit of normal is 100% specific for duodenal atrophy and using this cut-off biopsy could by avoided in 1/3 of patients. Diagnostic criteria of celiac disease in adults need revision." They retrospectively looked at 945 patients who came to their center because of suspected celiac disease. Three different commercially available methods were used to assess anti-tTg levels, which were then correlated with duodenal histology. By all serological methods used, anti-tTg levels increased in parallel with increasing severity of intestinal damage. As noted above, a cut off of five times the upper limit of normal ant-tTg included all of the patients with significant levels of villous atrophy. Celiac disease was confirmed in these patients by the presence of antiendomysial antibodies (EMS) and by their positive response to a gluten free diet. The use of serological results alone had previously been suggested as diagnostic guidelines for children, but these authors suggest that many adults could be spared an endoscopy as well. They also note this strategy is already being implemented in primary care, with people adopting a gluten free diet solely on the basis of blood work; this study is valuable in that it validates that approach. Source: Zanini B, Magni A, Caselani F, Lanzarotto F, Carabellese N, Villanacci V, Ricci C, Lanzini A. High tissue-transglutaminase antibody level predicts small intestinal villous atrophy in adult patients at high risk of celiac disease. Dig Liver Dis. 2012 Apr; 44(4):280-5. Epub 2011 Nov 25. -
Celiac.com 01/02/2013 - Doctors use capsule endoscopy to assess the small bowel in a number of intestinal diseases, including celiac disease. The main advantage of capsule endoscopy is that it allows for complete visualization of the intestinal mucosal surface. A team of researchers recently set out to investigate whether capsule endoscopy can predict the severity of celiac disease, and detect celiac disease complications. The research team included M. Barret, G. Malamut, G. Rahmi, E. Samaha, J. Edery, V. Verkarre, E. Macintyre, E. Lenain, G. Chatellier, N. Cerf-Bensussan, and C. Cellier. They are affiliated with the Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges-Pompidou, Service d'Hépato-gastro-entérologie, and the Université Paris Descartes, Sorbonne Paris Cité, Faculté de médecine, both in Paris, France. For their study, the team reviewed medical files for nine patients with symptomatic celiac disease, eleven patients with refractory celiac disease type I (RCDI), 18 patients with refractory celiac disease type II (RCDII), and 45 patients without celiac disease who received both capsule endoscopy and upper endoscopy or enteroscopy. To properly diagnose the type of celiac disease in the patients, the researchers used a centralized histological review, flow cytometry analysis of intraepithelial lymphocytes, and the analysis of T-cell receptor rearrangement by multiplex polymerase chain reaction. A total of 47 capsule endoscopies were administered for the 38 celiac patients: ten for the patients with symptomatic celiac disease; eleven for patients with RCDI; and 26 for RCDII patients. Another 47 capsule endoscopies were administered for the 45 non-celiac patients were retrospectively reviewed. They found that patients with celiac disease had more villous atrophy, and more numerous, or distally located ulcers than the control subjects. They also found that, in celiac disease patients, capsule endoscopy was of acceptable quality in 96% of cases and was complete in 62% of cases. Moreover, the concordance of capsule endoscopy with histology for villous atrophy was better than that of optic endoscopy (κ coefficient =0.45 vs. 0.24, P<0.001). Extensive mucosal damage on capsule endocscopy was associated with low serum albumin (P=0.003) and the RCDII form (P=0.02). The also detected three cases of overt lymphoma by capsule endoscopy during the follow-up. Overall, the results show that capsule endoscopy provides a sufficient match with histology and nutritional status in patients with symptomatic or refractory celiac disease. Lastly, capsule endoscopy may predict the type of RCD and enable the early detection of overt lymphoma. Source: Am J Gastroenterol. 2012 Oct;107(10):1546-53. doi: 10.1038/ajg.2012.199. Epub 2012 Sep 11.
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Celiac.com 12/13/2010 - Driven by the high prevalence of celiac disease, a team of researchers based in Italy to assess a new, noninvasive disease screening strategy that would allow them to make an early diagnosis of celiac disease in 6- to 8-year-old children. Timely diagnosis will help doctors to initiate a gluten-free diet in willing patients, achieve growth targets, and prevent celiac disease complications. For the study, the research team recruited 5000 subjects, and ultimately tested 4048 saliva samples for anti-tissue transglutaminase (tTG) and immunoglobulin (Ig)A using fluid-phase radioimmunoprecipitation. For children with positive samples, the team arranged follow-up screening by serum radioimmunoassay tTG IgA, enzyme-linked immunosorbent assay tTG IgA, and anti-endomysium IgA. Children with positive serum assays underwent endoscopy with duodenal biopsies, and researchers advised those diagnosed with celiac disease to start a gluten-free diet. The team gained screening consent from 4242 parents (84.8%), and obtained usable saliva samples from a total of 4048 children (95.4%). Thirty-two children showed positive salivary tTG IgA, with another nine showing borderline autoantibody results. Thirty-one of the 32 tTG IgA-positive subjects, and three of the nine borderline subjects also had positive blood screens. Intestinal biopsy showed twenty-eight children with villous atrophy, while one child showed Marsh 1 lesions. The research team recommended a gluten-free diet to three children without performing endoscopy. This makes for a celiac disease rate of 1.16% in the study population, including 19 known cases of celiac disease. The results show that screening detected three cases of celiac disease for every two cases diagnosed before screening was 3:2. The ratio between symptomatic and asymptomatic patients was 1:1.6. The study shows that saliva screens for celiac disease can be effective in identifying celiac disease early in childhood. Also, for this study at least, the data shows full compliance with gluten-free diet in the children diagnosed with celiac disease. Source: Journal of Pediatric Gastroenterology & Nutrition 3 November 2010. doi: 10.1097/MPG.0b013e3181e6f2d0 -
Celiac.com 08/16/2012 - Tests for blood antibodies against native gliadin (anti-nGli) are still often assumed to perform better in the diagnosis of celiac disease in young children than tests for antibodies to deamidated gliadin (anti-dGli), tissue transglutaminase (anti-tTG), and endomysium (EmA). A team of researchers recently set out to determine whether testing IgG and IgA antibodies Against native gliadin was best for diagnosing celiac disease in children under 2-years old. Specifically they wanted to compare the performance of assays for anti-nGli, anti-dGli, anti-tTG, and EmA in this age group. The research team included T. Richter, X. Bossuyt, P. Vermeersch, H.H. Uhlig, M. Stern, A. Hauer, K.P. Zimmer, L. Mearin, J.H. Roo, C. Dähnrich, and T. Mothes. They are affiliated with the University Children's Hospital, the Children's Hospital of the Clinical Centre, "Sankt Georg," and the Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics at University Hospital in Leipzig, Germany; with the Department Laboratory Medicine of University Hospital in Leuven, Belgium, the University Children's Hospital in Tübingen, Germany, the University Children's Hospital in Graz, Austria, the University Children's Hospital in Giessen, Germany, the Department of Paediatrics at Leiden University Medical Centre in Leiden, The Netherlands, and with EUROIMMUN Medizinische Labordiagnostika GmbH in Lübeck, Germany. For their study, they conducted a retrospective analysis of 184 children. The study group included 42 children with celiac disease under normal diet, and a control group of 142 children up to 2 years of age. The team measured immunoglobulin (Ig) A- and IgG-anti-dGli, IgA- and IgG-anti-nGli, IgA- and IgG-anti-tTG, and IgA-EmA in blood samples. They calculated areas under receiver operating characteristics curves, sensitivities, specificities, positive and negative predictive values, positive and negative likelihood ratios, as well as diagnostic odds ratios. When all the data was complete, they found that only tests for IgG-anti-dGli, IgA-anti-tTG, and IgA-EmA had high specificity (≥0.96) connected with high sensitivity (≥0.86), with high positive predictive values (≥0.52 and ≥0.69 at pretest probabilities of 0.05 and 0.1, respectively) and negative predictive values (≥0.99 and ≥0.98 at pretest probabilities of 0.05 and 0.1, respectively). These tests also showed high positive likelihood ratio (≥24) at low negative likelihood ratio (≤0.15) and high diagnostic odds ratios (≥136). From their data, the team concluded that using anti-nGli tests to diagnose celiac disease in young children was not helpful. They maintain that IgA-anti-tTG, IgA-EmA, and IgG-anti-dGli provided much more reliable results than anti-nGli in diagnosing celiac disease in young children. Source: J Pediatr Gastroenterol Nutr. 2012 Jul;55(1):21-25.
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Celiac.com 06/15/2012 - Diagnosing celiac disease can be challenging for doctors if a patient has already started a gluten-free diet, and/or when test results are inconsistent. A research team set out to evaluate the in vitro gliadin challenge in such patients. Researchers included Raffaella Tortora MD; Ilaria Russo PhD; Giovanni D De Palma MD; Alessandro Luciani PhD; Antonio Rispo MD; Fabiana Zingone MD; Paola Iovino MD; Pietro Capone MD; and Carolina Ciacci MD They are variously affiliated with the Department of Clinical and Experimental Medicine at Federico II University of Naples in Naples, Italy; the Department of Surgery, Endoscopy Unit at Federico II University of Naples in Naples, Italy; the Institute of Pediatrics at the University of Foggia in Foggia, Italy; and the University of Salerno, School of Medicine, Gastroenterology at Campus di Baronissi in Salerno, Italy. For their study, the team included 57 patients without celiac disease (negative controls), 166 patients with untreated celiac disease and 55 patients with celiac disease following a gluten-free diet (positive controls), and 59 patients with difficult diagnosis. The team conducted duodenal biopsies on all patients which provided the data for diagnosing the celiac disease and for the in vitro evaluation of the gliadin-induced mucosal expression of seven inflammatory markers: PY99, ICAM-1 (intercellular cell adhesion molecule), HLA-DR, CD3, CD25, CD69, and transglutaminase 2 IgA. As part of their diagnostic work-up for celiac disease, the team included a test for specific serum antibodies. The team asked patients in the difficult diagnosis group to discontinue their gluten-free diets to that they could test for antibodies under untreated conditions. To maintain statistical accuracy, the team used the area under the receptor-operated curve (ROC) to analyze the results. They found that HLA-DR was most accurate in diagnosing celiac disease on negative controls and positive controls, excluding patients on a gluten-free diet (area under ROC=0.99). Test accuracy did not increase by combining HLA-DR data with data of other markers. The results were similar in the 39 patients of the difficult diagnosis group who underwent the test for celiac disease-specific antibodies under untreated conditions. Finally, the results showed that in vitro response of mucosal HLA-DR to gliadin is an accurate tool for diagnosing celiac disease, including in patients with difficult diagnosis. Source: The American Journal of Gastroenterology. 2012;107(1):111-117.
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Celiac.com 01/02/2012 - To properly diagnose celiac disease doctors must observe classic histological changes to small bowel mucosa. Success rates can vary among clinics and practitioners. A clinical team recently compared biopsy interpretation between different pathology practice types. A research team recently assessed variability in small bowel histopathology reporting between different pathology practice settings, and its impact celiac disease diagnosis. The researchers included Carolina Arguelles-Grande, Christina A. Tennyson, Suzanne K. Lewis, Peter H. R. Green, and Govind Bhagat. The team used a pathologist to blindly assessed biopsies from community hospitals (n=46), university hospitals (n=18) and commercial laboratories (n=38) for differences in histopathology reporting and agreement in diagnosis of celiac disease and degree of villous atrophy (VA) by k analysis. Data showed very good agreement for primary diagnosis between the authors and university hospitals (k=0.888), but only moderate agreement compared with community hospitals (k=0.465) or commercial labs (k=0.419). The review showed that diagnosis varied in 26 (25%) cases, leading to a 20% increase in celiac disease diagnosis after review. The 49 patients diagnosed with celiac disease by both institutions showed fair agreement in degree of VA (k=0.292), with moderate agreement between the authors and commercial laboratories (k=0.500) and fair agreement with university hospitals (k=0.290) or community hospitals (k=0.211). In 27% of cases, the degree of VA was upgraded, while VA was downgraded in just 2% of cases. Data also showed poor agreement for Marsh score categories 1 and 2 (k<0.0316), with both missed at other centers, and just fair or moderate agreement for Marsh scores 3a and 3b. They found that data on the degree of VA and intraepithelial lymphocytosis were lacking in 26% and 86% of reports, while non-quantifiable descriptors, such as ‘blunting’ or ‘marked atrophy’ were common. The data show that community-based hospitals and commercial pathology labs are under-diagnosing celiac disease-related histological changes. To combat variations in biopsy interpretation and reduce under-diagnosis of celiac disease, the team calls for greater celiac disease awareness and uniformity in small bowel biopsy reporting among pathologists. Source: Journal of Clinical Pathology (2011). doi:10.1136/jclinpath-2011-200372
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Celiac.com 07/14/2010 - Intestinal biopsy is considered the the gold standard for celiac disease testing. However, biopsy is an invasive procedure and most people would be happy to avoid biopsy all together. Based solely on serology, a new diagnostic standard has been proposed that would no longer require intestinal biopsy for celiac disease diagnosis in some patients. Researchers performed duodenal biopsy and serology in six-hundred and seventy-nine adults who were at high risk and low risk for celiac disease. They tested blood samples to detect antibodies to tissue transglutaminase (tTG) and deamidated gliadin peptide (DGP). The goal of researchers was to establish the diagnostic performance of various serological tests for diagnosing celiac disease in patients with varying pretest results. In this study, they hope to find potential serological algorithms to decrease the requirement for biopsy. One-hundred and sixty-one consecutive adults with undiagnosed, but suspected intestinal disorders were selected as the high-risk group to be evaluated for celiac disease. Five-hundred and eighteen patients who had been referred for routine upper gastrointestinal endoscopy due to non-specific symptoms such as indigestion, were randomly selected for the low-risk group. Prevalence of celiac disease was found in 39.1% of the high-risk group, and 3.3% of the low-risk group. Of the high-risk patients, all individual assays demonstrated a high diagnostic efficacy, while the low-risk group demonstrated a lower diagnostic efficacy. The serological findings of this study demonstrated that the algorithm used for individual assays allows patients to avoid biopsy with a negative serology; and positive serology results would require a patient to undergo biopsy. The DGF/tTG Screen assay may very well be recognized as the best preliminary test for celiac disease. The combination of two tests which include a DGP/tTG screening, may have the ability to identify celiac disease correctly in various clinical situations, which would allow biopsy to be avoided in the vast majority of cases. Although the findings were significant for this study, small bowel histology is still deemed the gold standard for accurate celiac disease diagnosis. Further validation of the algorithms is necessary to confirm the findings of this study before new diagnostic guidelines can be considered. Source: World J Gastroenterol. 2010 Jul 7;16(25):3144-52. -
Diagnosing Celiac Disease is Far from Straightforward
Diana Gitig Ph.D. posted an article in Latest Research
Celiac.com 05/25/2011 - Perhaps because celiac disease presents clinically in such a variety of ways, diagnosing it often takes an inordinately long time. A serological test positive 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 symptoms, and that patients should be spared it; others claim that the onset of celiac disease can predate the occurrence of villous atrophy, yielding a falsely negative misinterpretation of biopsy results. To lend some clarity, a group of researchers in Romania analyzed the significance of genetic tests. It has been estimated that 98% of people with celiac disease have the DQ2 and DQ8 HLA haplotypes. But because these alleles are found in as many as 40% of the general population, they are considered more a prerequisite for developing celiac than a true positive indicator. However, they have high negative predictive value: their absence has traditionally been used to rule out a diagnosis of celiac. Samasca et al. looked at the HLA types of thirty-seven children with celiac disease confirmed by duodenal biopsy. Some also had confounding conditions like malabsorption syndromes, type I diabetes, and juvenile rheumatoid arthritis. Nine of the children were negative for the HLA DQ2 and DQ8 haplotypes. Of these nine, only two tested positive for the presence of anti tissue transglutaminase antibodies. One of them, a four year old boy, improved on a gluten free diet; the other, a 9 year old girl, did not comply with her gluten free diet, making it difficult to draw conclusions from her symptoms (notably an unsatisfying weight curve). Based on these meager data, the authors conclude that the absence of DQ2 and DQ8 should not be used to exclude a diagnosis of celiac disease. Yet another, more plausible explanation might be that the few children in their study who lack these haplotypes as well as antibodies against tissue transglutaminase but still exhibit unspecified "changes on duodenal biopsy" might be suffering from gluten intolerance, which is mediated by an immune pathway less defined than the one leading to celiac disease. Still, their point that diagnosing celiac disease can be a complicated business is certainly a valid one. Source: Samasca et al. Controversies in the laboratory diagnosis of celiac disease in children; new haplotypes discovered. Romanina Archives of Microbiology and Immunology 69(3): 119-124, 2010. -
Celiac.com 10/01/2009 - Antibodies to deamidated gliadin offer a promising new tool in the diagnosis of celiac disease. A team of researchers recently set out of examine serodiagnosis of childhood celiac disease assay of antibodies against deamidated gliadin. The research team was made up of Christian Prause, Thomas Richter, Sibylle Koletzko, H. Holm Uhlig, Almuthe C. Hauer, Martin Stern, Klaus-Peter Zimmer, Martin W. Laass, Christian Probst, Wolfgang Schlumberger, and Thomas Mothes. Their results show that the ELISA for gauging IgG antibodies to deamidated gliadin-analogous fusion peptides (GAF3X) performs better in children than does the ELISA for gauging antibodies against native gliadin, and compares favorably to results for IgA antibodies against tissue transglutaminase (IgA-anti-tTG). By combining investigations of IgG antibodies to GAF3X (IgG-anti-GAF3X) with IgA-anti-tTG, a significantly higher number of children were positively confirmed to have celiac disease, or to be free of celiac disease. The new IgG-anti-GAF3X ELISA detected three instances of IgA deficienc, along with two cases of silent celiac disease, in addition to improving diagnosis of children under 2 years of age. It will be interesting to see where these enhanced approaches for diagnosing celiac disease will take us. Much research certainly supports the benefits of early diagnosis and treatment, especially with respect to the development of conditions associated with untreated and/or latent celiac disease. Even the ability to diagnose a new category of gluten intolerant individuals might gain steam from more refined screening techniques. Source: Annals of the New York Academy of Sciences - Volume 1173 Issue Contemporary Challenges in Autoimmunity, Pages 28 - 35
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Celiac.com 10/16/2008 - When faced with possible cases of celiac disease, it is known that testing for tissue transglutaminase (TTG) antibodies and newly developed deamidated gliadin peptide (DGP) antibodies offers greater accuracy than testing for native gliadin antibodies. But what is the best overall test for TTG and DGP? A research team recently set out to compare multiplex immunoassay (MIA) testing for antibodies against enzyme-linked immunosorbent assay (ELISA) testing for antibodies in biopsy-proven celiac patients and control subjects, and to determine the helpfulness of using the two tests in combination for making diagnosis of celiac disease. The research team was made up of doctors S. Rashtak, M. W. Ettore, H. A. Homburger & J. A. Murray. Doctors Rashtak and Murray are with the Mayo Clinic in Rochester, Minnesota. The team compared sensitivity, specificity and accuracy of MIA and ELISA testing methods for TTG and DGP antibodies in 92 adults with untreated celiac disease, and 124 healthy control subjects. For every test, except TTG IgG, the results showed strong agreement and a significant correlation between the results of MIA and ELISA methods (j > 0.8, r > 0.7). For TTG IgG, both showed low sensitivity (MIA-13.0% vs. ELISA-28.3%), high specificity (MIA-100.0% vs. ELISA-96.8%), and about the same levels of overall accuracy (MIA-63.0% vs. ELISA-67.6%). They found no significant differences between diagnosis accuracy made using the MIA method compared to diagnosis made using ELISA, or between either of those against a combination of the two methods. Compared to using either test alone, using both tests together made for a slight increase in overall test sensitivity where any one of the tests was positive, and an increase in specificity when all tests were positive. The team determined that MIA testing for antibodies is as accurate as ELISA for celiac disease diagnosis and offers practical advantages over ELISA method. MIA testing measures multiple antibodies simultaneously, provides a complete antibody phenotype, and offers a quicker turnaround time and lower cost. They further noted that carefully targeted combination testing can help identify patients who require intestinal biopsy, which may reduce unnecessary biopsies. Aliment Pharmacol Ther 28, 805–813
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Celiac.com 04/08/2009 - A study published in Journal of Insurance Medicine has delineated clear economic benefits to diagnosing celiac disease on a national level using a managed-care approach. A team of researchers based at Columbia University Medical Center's Celiac Disease Center recently set out to estimate the rate of celiac disease diagnosis and assess the economic benefits of diagnosis by reviewing retrospective cohort studies from a national managed-care-population database. The research team was made up of Peter H. R. Green, Alfred I. Neugut, Afzal J. Naiyer, Z. Collette Edwards, Susan Gabinelle, and Vijit Chinburapa. Using the data, the team isolated cases of newly diagnosed with celiac disease. They also isolated 3 control groups that included people without a diagnosis of celiac disease, but who showed 1, 2, or 3 or more symptoms common to the disease. They used claim, incident, and eligibility information from 10.2 million managed care individuals across America from January 1999 and December 2003. They quantified and compared direct standardized relative value based (RVU) medical cost and use of medical services across the whole of the 4 study base. What they found was that the rate of newly diagnosed cases of celiac disease had increased more than 100% over the study period. The celiac disease group showed substantial overall shrinkage in direct standardized medical costs compared with the control subjects. RVU-based medical costs for the celiac subjects were 24%, 33%, and 27% below cohort 1 (p,0.05), 29.0%, 38%, and 24% below cohort 2 (p,0.05), and 38%, 33%, and 31% below cohort 3 (p,0.01) for the 12-month, 24-month and 36-month post-diagnosis periods, respectively. The reduced costs correlated with a reduction in office visits, lab, diagnostic, imaging, and endoscopy procedures compared to the 3 other cohorts over the 3-year follow-up period. The researchers found increased rates of celiac disease diagnosis, which was tied directly to a substantial reduction in direct standardized RVU-based medical costs and use of selected health care services over the period of the study. Journal of Insurance Medicine 2008;40:218–228
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Celiac.com 07/30/2007 - A study published in the journal Clinical Gastroenterology and Hepatology suggests that a newly proposed system of classifying duodenal pathology on celiac disease provides an improved inter-observation than the less Marsh-Oberhuber classification, and offers an advance towards making a simpler, better, more valid diagnosis of celiac disease. Celiac disease is presently classified according to the Marsh-Oberhuber system of classifying duodenal lesions. Recently, a more elementary method has been suggested. That method is based on three villous morphologies—non-atrophic, atrophic with villous crypto ratio <3:1, and atrophic, villi idnetectable—combined with intraepithelial counts of >25/100 enterocytes. The study team chose a group of sixty people to be part of the study. Of the 60 patients the team studied, 46 were female and 14 were male. The average age was 28.2 years with a mean range of 1-78 years. 10 people had celiac disease, 13 had celiac disease with normal villi, but a pathological increase in epithelial lymphocytes >25/100 & hyperplastic crypts. 37 patients had celiac disease with villous aptrophy. Patients were given biopsies, with at least 4 biopsies were taken from the second part of the duodenum. Biopsies were fixed in formalin and processed according to standard procedures, with cuts at six levels, and stained with hematoxylin resin. The slides were sent randomly to 6 pathologists who were blind to one another. The results showed that this new method of classification yielded better inter-observer agreement and more accurate diagnosis that the more difficult Marsh-Oberhuber system. Clinical Gastroenterology and Hepatology 2007;5:838–843 health writer who lives in San Francisco and is a frequent author of articles for Celiac.com.
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Celiac.com 10/30/2007 - A recent study published in the August issue of American Journal of Gastroenterology suggest that villous atrophy in suspected cases of celiac disease can be reliably detected by video capsule enteroscopy (VCE). Reliable diagnosis presently demands the identification of tell-tale lesions in the mucosa of the small bowel. Accomplishing such identification requires an endoscopy of the upper gastrointestinal tract, and multiple duodenal biopsies. A team of Italian researchers evaluated the effectiveness of Video Capsule Enteroscopy against the standard endoscopy of the upper GI with biopsies of the second portion of the duodenum in patients suspected of having celiac disease. The research team included Emanuele Rondonotti, M.D.; Cristiano Spada, M.D.; David Cave, M.D.; Marco Pennazio, M.D.; Maria E. Riccioni, M.D.; Italo De Vitis, M.D.; David Schneider, M.D.; Tatiana Sprujevnik, M.D.; Federica Villa, M.D.; Jennifer Langelier, M.D.; Arrigo Arrigoni, M.D.; Guido Costamagna, M.D.; Roberto de Franchis, M.D. The research team tested a total of 43 patients. In 41 patients, VCE reached the ileocecal valve during the reading time. 32 patients were found to exhibit diagnostic histology. Of those, 28 were diagnosed with celiac disease using capsule enteroscopy, for a total sensitivity of 87.5%. Overall, for diagnosing celiac disease, VCE was shown to be 90.9% specific, 96.5% predictive, 71.4% negative predictive, with positive and negative likelihood ratios of 9.6% and 0.14% respectively. Four patients showed normal VCE findings, but were still diagnosed with celiac disease. Of these patients, three had Marsh grade III lesions, and one had Marsh grade I lesions. The ability of VCE to offer high-quality images of small bowel mucosa including high-resolution of the individual villi led the team to conclude the VCE may offer an effective alternative to duodenal biopsy among some patients. As VCE is also far less invasive than the endoscopy/biopsy approach, it may also generate greater patient acceptance. Also, unlike conventional endoscopy/biopsy, VCE offers exploration of the entire small intestine, and may lead to the discovery of damaged villi beyond those areas accessible via endoscopy. Because of the small number of the test subjects, the results, though encouraging, invite a larger and more comprehensive study before VCE becomes an acceptable alternative to conventional endoscopy/biopsy method for diagnosing celiac disease. American Journal of Gastroenterology 2007; 102(8): 1624-1631
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Celiac.com 09/28/2007 - Figures concerning the diagnostic accuracy of various serologic test and HLA-DQ typing for diagnosing celiac disease have largely come from case–control studies. A team of doctors recently set out to assess the performance of serologic testing and HLA-DQ typing in the diagnosis of celiac disease. Results of their study were published recently in the Annals of Internal Medicine. The team was made up of Muhammed Hadithi, MD; B. Mary E. von Blomberg, PhD; J. Bart A. Crusius, PhD; Elisabeth Bloemena, MD, PhD; Pieter J. Kostense, PhD; Jos W.R. Meijer, MD, PhD; Chris J.J. Mulder, MD, PhD; Coen D.A. Stehouwer, MD, PhD; and Amado S. Peña, MD, PhD Their study looked at patients who had been referred for small bowel biopsy to determine weather they had celiac disease, and evaluated the effectiveness of serologic testing for celiac disease, specifically of antigliadin antibodies (AGA), antitransglutaminase antibodies (TGA), and anti-endomysium antibodies (EMA) and HLA-DQ typing. Data was measured by comparing the performance of serologic testing and HLA-DQ against a reference baseline of abnormal histologic findings and clinical resolution after a gluten-free diet. Of 463 participants, sixteen had celiac disease (prevalence = 3.46% [95% CI, 1.99% to 5.55%]). Testing positive on both TGA and EMA showed a corresponding sensitivity of 81% (CI, 54% to 95.9%), specificity of 99.3% (CI, 98.0% to 99.9%), and negative predictive value of 99.3% (CI, 98.0% to 99.9%). A positive test for either HLA-DQ type increased both sensitivity (100% [CI, 79% to 100%]) and negative predictive value (100% [CI, 98.6% to 100%]), while testing negative for both minimized the negative likelihood ratio (0.00 [CI, 0.00 to 0.40]) and post-test probability (0% [CI, 0% to 1.4%]). Adding HLA-DQ typing to TGA and EMA testing, and adding serologic testing to HLA-DQ typing, saw no corresponding difference in test performance compared with either testing strategy alone. Overall results show TGA and EMA testing were the most sensitive serum antibody tests and a negative HLA-DQ type excluded the celiac disease from the diagnosis. However, the addition of HLA-DQ typing to TGA and EMA testing, and the addition of serologic testing to HLA-DQ typing, provided no change of test performance compared with either form of testing alone. Finally, the findings were somewhat limited, as low number of overall cases of celiac disease rule out meaningful comparisons of testing strategies. Annals of Internal Medicine (volume 147, pages 294-302)
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Celiac.com 04/10/2007 - Celiac disease is one of the most common chronic health disorders in western countries. Yet, due largely to poor awareness of celiac disease by primary care physicians, most celiac cases in North America go undiagnosed. A recent study published in the American Journal of Gastroenterology suggests that the North American diagnostic rate for celiac disease can be improved through the use of active case-finding strategies in the primary care setting. The study set out to determine the most common celiac symptoms faced by clinicians, and to determine how effective an active case-finding strategy might be in raising the levels of diagnosis. The study drew from a large pool of individuals who attended one of three participating North American clinical practices. 737 women and 239 men with symptoms or conditions known to be associated with celiac disease were tested for immunoglobulin A anti-transglutaminase (tTG) antibodies, and those with elevated anti-tTG were then tested for IgA anti-endomysial antibodies (EMA). Those who tested positive for EMA were encouraged to undergo an intestinal biopsy and HLA typing. The median age for those tested was 54.3 years. Of 976 subjects tested, 30 showed a positive anti-tTG test (3.07%, 95% CI 1.98–4.16). 22 patients (18 women, 4 men) were diagnosed with celiac. In these 22 cases, the most frequent reasons for celiac disease screening were bloating (12/22), thyroid disease (11/22), irritable bowel syndrome (7/22), unexplained chronic diarrhea (6/22), chronic fatigue (5/22), and constipation (4/22). The prevalence of celiac disease in the serologically screened sample was 2.25% (95% CI 1.32–3.18). According to the study, active screening implementation substantially increased diagnostic rates from a baseline low of 0.27 cases per thousand visits (95% CI 0.13–0.41), to a rate of 11.6 per thousand visits (95% CI 6.8–16.4, P < 0.001). The study concludes that the implementation of active strategies in primary care settings is likely to improve the diagnostic rate of celiac disease in North America. Am J Gastroenterol 2007; 102:1–7 health writer who lives in San Francisco and is a frequent author of articles for Celiac.com.
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Am J Gastroenterol. 2005 Jan;100(1):177-85 Celiac.com 06/30/2005 – In order to determine whether celiac disease mucosal lesions may have a patchy distribution that would require more than one biopsy sample to make an accurate celiac disease diagnosis, Italian researchers closely examined the detailed biopsies taken from 112 consecutively diagnosed children. All of the children in the study had positive anti-endomysium (EMA) or anti-tissue transglutaminase (tTGA) antibodies, and each underwent an upper GI endoscopy in which 4-5 biopsies were taken from Treitz and/or distal duodenum, intermediate duodenum, proximal duodenum, and the duodenal bulb. All biopsies were then classified according to the Marsh criteria. The researchers diagnosed 110 or the 112 patients with celiac disease, and none of the biopsies taken from these children appeared normal. All those diagnosed were positive for HLA-DQ2 or DQ8 genetic markers. The researchers conclude that: “Mucosal atrophy is present in 85% of patients with celiac disease and total villous atrophy is significantly more frequent in distal duodenum or proximal jejunum. Fifty percent of patients have identical villous atrophy throughout the duodenum and no duodenal areas are histologically normal. In genetically susceptible children with positive serology, a diagnosis of celiac disease can reliably be made even if biopsies are not taken from the distal duodenum or jejunum.” -
Better Methods for Diagnosing People with Latent Celiac Disease
Scott Adams posted an article in Latest Research
Troncone R, Greco L, Mayer M, Mazzarella G, et. al. Gastroenterology, 1996; 111: 318-324 The final paragraph says: In conclusion, our data show that approximately half of the siblings of patients with celiac disease show signs of sensitization to gluten as they mount an inflammatory local response to rectal gluten challenge. The genetic background and the clinical meaning of such gluten sensitivity need to be established. Further studies, particularly at the jejunal level, are necessary before deciding if any action is to be taken in this subset of first-degree relatives.
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