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Jefferson Adams posted an article in Celiac Disease Diagnosis, Testing & TreatmentCeliac.com 06/04/2010 - A team of researchers recently set out to assess the positive predictive value of blood test screening for possible cases of celiac disease. The team included Peter Toftedal, Christian Nielsen, Jonas Trolle Madsen, Kjell Titlestad, Steffen Husby, and Søren Thue Lillevang. They are affiliated with the Hans Christian Andersen Children's Hospital, and the Department of Clinical Immunology of Odense University Hospital in Denmark. P. Toftedal and Ch. Nielsen made contributions to the final published article. In deciding which possible celiac disease cases might require duodenal biopsy, doctors rely mainly on tests for celiac disease antibodies, such as immunoglobulin A (IgA) anti-tissue transglutaminase (anti-tTG), IgA endomysium antibody (EMA), IgA and IgG anti-gliadin antibodies (IgA and IgG AGA). For their study, the research team wanted to assess the diagnostic quality of blood testing for possible cases of celiac disease. They did this by performing celiac disease blood tests (IgA and IgG AGA, anti-tTG and EMA) on 11,915 subjects. They then combined the serological data with clinical data and duodenal biopsy results using a unique Danish personal identification number. They found that positive predictive value (PPV) fluctuated in accordance with various combinations of positive celiac disease antibodies. They found the highest predictive value (97.6%) when results for IgA and IgG AGA, anti-tTG and EMA antibodies were all positive. The team used a logistic regression model at initial blood screening to predict the probability of later biopsy-proven celiac disease in relation to concentrations of IgA AGA and anti-tTG. They found that anti-tTG concentrations correlated strongly with EMA positivity, number of additional positive antibodies, and higher PPV. The anti-tTG concentration upon first blood screening for celiac disease was highly informative in relation to EMA positivity, number of additional celiac disease specific antibodies and PPV. Lastly, results for the high-risk patient group showed that anti-tTG and IgA AGA concentrations at initial serological screening accurately predicted probability of future biopsy-proven celiac disease. Source: Clin Chem Lab Med 2010;48:685–91. DOI: 10.1515/CCLM.2010.136
Jefferson Adams posted an article in Celiac Disease & Gluten Intolerance ResearchCeliac.com 04/27/2010 - A team of clinicians recently assessed the diagnostic value of confocal endomicroscopy in celiac disease. Clinicians U. GuÌˆnther, S. Daum, F. Heller, M. Schumann, C. Loddenkemper, M. GruÌˆnbaum, M. Zeitz, and C. Bojarski made up the research team. They are variously affiliated with the Medical Clinic of Gastroenterology, Rheumatology and Infectious Diseases, and with the Department of Pathology, Charité of the Campus Benjamin Franklin of University Medicine Berlin, Germany. Studies by Gutschmidt, by Henker and others have shown that, even in the face of greater awareness and more widespread blood testing, a number of countries suffer from low rates of celiac disease detection. Patchiness of the mucosal and submucosal changes associated with celiac disease impedes proper celiac diagnosis, and contributes to a small, but important sampling error among those assessed. Some clinicians feel that the problem might be resolved somewhat by modifying the endoscopic screening process to include real-time assessment of the duodenal morphology. Better endoscopic and imaging procedures will mean better diagnostic accuracy of biopsy specimens. One early step toward improved gathering of targeted biopsies in celiac disease patients lies in using magnification endoscopy, either alone, or together with high-resolution narrow-band imaging. This method offers better ability to detect patchy villous atrophy sites in the duodenum. However, neither magnification, nor narrow-band imaging techniques can detect increased number of intraepithelial lymphocytes (IELs). Confocal endomicroscopy (CEM) permits live, real-time histology with a 1000x magnification during endoscopy. Recently, a prospective pilot study for the first time showed CEM to enable effective live, real-time diagnosis and evaluation of celiac disease. Researchers compared endomicroscopic findings during live, real-time endoscopy with histological findings graded according to Marsh classification. The research team used CEM to examine twenty-four patients with celiac disease and six patients with refractory celiac disease, all following a gluten-free diet. The team evaluated duodenal mucosa by CEM and by conventional histological analysis for villous atrophy, crypt hyperplasia, and increased numbers of intraepithelial lymphocytes (IELs > 40/100 enterocytes). They then compared the CEM to the histology results for sensitivity, specificity, and inter-observer variability using Marsh classification scores. As control subjects, the team used thirty patients without celiac disease, but who were undergoing routine upper gastrointestinal endoscopy. Using conventional histology on the 30 patients with celiac disease, the team found 23 cases with villous atrophy and crypt hyperplasia, and 27 cases of increased IELs. Using CEM, the team found 17 cases of villous atrophy, 12 cases of crypt hyperplasia, and 22 cases of increased IELs. The CEM results compared favorably to those of conventional histology for villous atrophy, for which CEM showed a sensitivity of 74%, and for increased numbers of IELs, for which CEM showed a sensitivity of 81%. However, the CEM results were lacking for detecting crypt hyperplasia, for which CEM showed a sensitivity of 52%. The Îº values for determination of inter-observer variability were 0.90 for villous atrophy, 1.00 for crypt hyperplasia, and 0.84 for IEL detection. For the 30 control patients, both traditional histology and CEM revealed normal duodenal architecture with overall specificity of 100%. From these results, the team concluded that the assessment of duodenal histology by CEM in patients with celiac disease is sensitive and specific in determining increased numbers of IELs and villous atrophy, but inadequate for detecting crypt hyperplasia. Until improvements are made, CEM is not suitable for use in diagnosing celiac disease. SOURCE: Endoscopy 2010; 42:197–202.
Vijay Kumar, M.D., Research Associate Professor at the University of Buffalo and President and Director of IMMCO Diagnostics: Not really. It is not true that the serological methods have lower predictive value in children less than two years of age. In all the studies that we did, there was 100% correlation of the EMA to the disease activity irrespective of the age. Karoly Horvath, M.D., Ph.D., Associate Professor of Pediatrics; Director, Peds GI & Nutrition Laboratory; University of Maryland at Baltimore: There are age dependent changes in several blood parameters during childhood. It is well known that immunoglobulin levels depend on the age of children. E.g. the IgA class immunoglobulins reach the adult level only by 16 years of age, and the blood level of IgA immunoglobulins is only 1/5th of adult value below two years of age. A large study from Europe (Brgin-Wollf et al. Arch Dis Child 1991;66:941-947) showed that the endomysium antibody test is less specific and sensitive in children below two years of age. They found that the sensitivity of the EmA test decreased from 98% to 88% in children younger than 2 years of age. It means that 12% of their patients with celiac disease, who were younger than two years of age, did not have an increase in their endomysium antibody levels.