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    A Systematic Review of Diagnostic Testing for Celiac Disease Among Patients With Abdominal Symptoms


    Jefferson Adams

    Celiac.com 06/03/2010 - Clinical presentation of celiac disease can vary considerably from patient to patient. Most patients with celiac disease present atypical symptoms. Moreover, most patients who present abdominal symptoms in primary care do not have celiac disease, and so diagnostic tests for celiac disease are not necessary and should be avoided.


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    A team of researchers recently conducted a systematic review of diagnostic testing for celiac disease among patients with abdominal symptoms.

    The team included Daniëlle A. W. M. van der Windt, PhD; Petra Jellema, PhD; Chris J. Mulder, MD, PhD; C. M. Frank Kneepkens, MD, PhD; and Henriëtte E. van der Horst, MD, PhD. Their article appears in the Journal of the American Medical Association.

    The goal of the research was to review and summarize evidence on the performance of diagnostic tests for spotting celiac disease in adults who present abdominal symptoms in primary care or similar settings.

    To obtain initial data, the team search MEDLINE (from January 1966  through December 2009, and EMBASE from January 1947 through December 2009. They also conducted a physical search of references for additional relevant studies.

    The team chose cohort or nested case-control diagnostic studies which included adults presenting non-acute abdominal symptoms, which featured celiac disease prevalence of 15% or less, and in which the tests included gastrointestinal symptoms or serum antibody screens.

    Two independent reviewers conducted studies tool and data extraction. They then calculated sensitivities and specificities for each study and computed pooled estimates using bivariate analysis where there was clinical and statistical homogeneity.

    In all, the team included sixteen studies encompassing 6085 cases in their review.

    Specificity, sensitivity, and confidence intervals for predicting celiac disease varied with abdominal symptoms.  For patients presenting with classic diarrhea, for example, predictive sensitivity ranged from 0.27 to 0.86, while specificity ranged from 0.21 to 0.86.

    Pool estimates for 8 studies on IgA antiendomysial antibodies were 0.90, with a 95% confidence interval [CI] (0.80-0.95) for sensitivity and 0.99, with a 95% CI (0.98-1.00) for specificity, with a positive likelihood ratio [LR] of 171 and negative LR of 0.11.

    Pool estimates for IgA antitissue transglutaminase antibodies (7 studies) were 0.89, with a 95% CI (0.82-0.94) and 0.98 at 95% CI (0.95-0.99), respectively, with a positive LR of 37.7 and negative LR of 0.11.

    IgA and IgG antigliadin antibodies showed variable results, especially for sensitivity, which ranged from 0.46-0.87 for IgA, and from 0.25-0.93 for IgG.

    One recent study using deamidated gliadin peptides showed good specificity (0.94), but the target population offered limited supporting evidence.

    For adults who present abdominal symptoms in primary care or other unscreened settings, IgA antitissue transglutaminase antibodies and IgA antiendomysial antibodies offer high sensitivity and specificity for diagnosing celiac disease.

    SOURCE:  JAMA. 2010;303(17):1738-1746. doi:10.1001/jama.2010.549

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    Guest Craig J Brown

    Posted

    I see lots of patients that have severe gluten sensitivity and family histories of celiac and positive genetics that fail their criteria, who find a gluten-free diet life changing. Another recent study took 36 of these "negatives" gave them a high gluten challenge for a month.

     

    1/3 nothing happened

    1/3 suddenly had classic lesions on biopsy

    1/3 were still negative but so sick that they embraced a gluten-free diet afterward.

     

    The error here is that they will only diagnose celiac Disease if the biopsy is positive. Europe is moving past that stumbling block, the US has not, yet.

     

     

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    In May of 2010 I found myself being admitted to the hospital for severe abdominal cramping and pain, blood in my stool, and blood in my stomach bile when I was throwing up. After a week, in the hosp and a colonoscopy, the Dr. said I had mild/severe colitis, and to avoid all fresh fruits and veggies, especially anything that would encourage gas and bloating. I followed his advice and instead of getting better it got worse. Having moved from the area, and husband having lost his job, and our having no money, having lost my sister to a liver cancer (whole other story there) I was becoming very afraid when my symptoms began to get worse.(I never ever really felt 'good'. I decided to keep a food journal. After doing some online research, I decided to go gluten-free, and by the second day, the change was shocking. It has been 3 months, and tho I am still learning, I feel SO much better! I still have occasional issues, but that is usually when I find myself using dairy. So maybe I will discover I am lactose intolerant as well. Discovering that I may not have to go back to gluten to verify whether I have celiac or not worries me, but after reading this, I may not have to. I am glad I have this comprehensive site that helps me make decisions.

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  • Related Articles

    Scott Adams
    Celiac.com 2/13/2003 - This new study emphasizes the importance of following a strict gluten-free diet, and getting regular follow-up biopsies after your diagnosis. It also speaks to the need to discover whether or not you may have additional food intolerance, such as to cows milk (casein), soy, corn, etc., as some of these can also cause intestinal damage similar to that of celiac disease. -Scott Adams

    Lee SK, Lo W, Memeo L, Rotterdam H, Green PH.
    Gastrointest Endosc 2003 Feb;57(2):187-91
    Current affiliations: Department of Surgical Pathology and Medicine, Columbia University College of Physicians and Surgeons, New York, New York.
    BACKGROUND: The diagnosis of celiac disease requires characteristic histopathological changes in an intestinal biopsy with clinical improvement in response to a gluten-free diet. Endoscopy with procurement of biopsy specimens is often performed to document response to the diet, but there are little data on the appearance of treated celiac disease. This study examined the endoscopic and histopathological appearance of the duodenum of patients with celiac disease whose diet was gluten-free.
    METHODS: A cohort of 39 adult patients (mean age 52 years, range 20-74 years) with biopsy-proven celiac disease was retrospectively reviewed. All had responded clinically to a gluten-free diet that they had maintained for a mean of 8.5 years (range 1-45 years). The endoscopic and histopathological appearances of the duodenal mucosa were reviewed. Blinded review of the diagnostic (initial) and post-treatment biopsy specimens was also performed to assess response of individual patients to the diet.
    RESULTS: The endoscopic appearance was normal in 23%, reduced duodenal folds were present in 46%, scalloping of folds in 33%, mucosal fissures in 44%, and nodularity in 33%. There was more than 1 abnormality present in 46%. Histology was normal in only 21%. The remainder had villous atrophy (69% partial, 10% total). Paired (diagnostic and follow-up) biopsy specimens were reviewed blindly for 12 patients. The mean (SD) intraepithelial lymphocyte count fell from 61 (22) to 38 (17) (normal
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    PMID: 12556782

    Scott Adams
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    Objective:
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    Participants: Coded stool samples from 20 children with newly diagnosed celiac disease and 64 controls. Six children with celiac disease had stool tests every two weeks for three months after starting a gluten-free diet.
    Main Outcome Measures: Secretory IgA antibodies against gliadin and human tissue transglutaminase in stool samples, determined in duplicate by using recommended cut-off limits.
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    Dr. Kenneth Fine Comments on this Study:
    Dont Throw the Baby Out With the Bath Water!
    Letter to the Editor BMJ
    Kamran Rostami, M.D., Ph.D. Department of Medicine, Gloucestershire Royal Hospital Gloucester, UK
    Kenneth Fine, M.D. The Intestinal Health Institute, Dallas, Texas, USA
    We have read with interest the article by Kappler et al recently published in your journal (1) and feel several issues deserve mention. This article is very timely in light of the growing worldwide awareness of immunologic sensitivity to dietary gluten and celiac disease, as well as appreciation of its high prevalence; these facts are driving the need for more widely available, low cost, non-invasive screening tests. Stool testing for these disorders holds great promise for screening because it does not require any invasion of body tissues, is of relatively low cost, and could be widely available combining medical care delivery of such tests with home testing.
    While our first criticism of this study is its small cohort size (20 patients), the results are intriguing, but in our opinion have been misinterpreted by the authors. First, there is a potential methodological flaw in this study whereby a serologic method was apparently transferred intact to analyze stool. The aspects of a serologic ELISA method possibly requiring modification for use in stool include but are not limited to: degree to which the sample is diluted prior to analysis; technique and amount of washing of plates during ELISA analysis (because of greater solid contaminant of fecal fluid vs. serum); mathematical conversion of detected optical density to a Unit; and how that calculated Unit is interpreted relative to a normal vs. abnormal cutoff. Utilizing fecal antigliadin and antitissuetransglutaminase IgA antibody testing in this way were reported to be very insensitive (6-10%) but highly specific (97-98%) for celiac disease. Such results should be interpreted as possibly possessing either a misassigned cutoff value (i.e., one that was too high), or possibly introduction of an artificial element that drove fecal antibody concentrations down (such as over-diluting the stool, improper handling or storage of specimens allowing ex vivo destruction of antibody, or centrifuging the stool at the wrong speed driving antibody into the pellet; the authors mentioned destruction of antibody during transit within the GI tract, but antibody is very stable within the GI tract, and has been detected in stool by many authors). Nevertheless, as performed in this study, such a highly specific stool test for celiac disease could be used as a pre-screening test of sorts, able to specifically and non-invasively detect celiac disease, perhaps with a home collected stool specimen. At the worst, 6-10% of celiac patients could be identified even before presenting to a medical institution.
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    References:
    1. Kappler M, Krauss-Etschmann S, Diehl V, Zeilhofer H, Koletzko S. Detection of secretory IgA antibodies against gliadin and human tissue transglutaminase in stool to screen for celiac disease in children: validation study. BMJ. 2006 January 28; 332(7535): 213-14.
    2. Rostami K, Kerckhaert J, Tiemessen R, von Blomberg BM, Meijer JW, Mulder CJ. Sensitivity of antiendomysium and antigliadin antibodies in untreated celiac disease: disappointing in clinical practice. Am J Gastroenterol. 1999 Apr;94(4):888-94.
    3. Ferguson A, Arranz E, OMahony S. Clinical and pathological spectrum of celiac disease--active, silent, latent, potential. Gut. 1993 Feb;34(2):150-1.
    4. Arranz E, Ferguson A. Jejunal fluid antibodies and mucosal gamma/delta IEL in latent and potential celiac disease. Adv Exp Med Biol. 1995;371B:1345-8.

    Jefferson Adams
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    Jefferson Adams
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    Source:
    British Journal of Nutrition (2009), 102, 882–887


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    Sources:
    1. Toft M, Dietrichs E. Aggravated stuttering following subthalamic deep brain stimulation in Parkinson’s disease--two cases. BMC Neurol. 2011 Apr 8;11:44.
    2. Tani T, Sakai Y. Stuttering after right cerebellar infarction: a case study. J Fluency Disord. 2010 Jun;35(2):141-5. Epub 2010 Mar 15.
    3. Lundgren K, Helm-Estabrooks N, Klein R. Stuttering Following Acquired Brain Damage: A Review of the Literature. J Neurolinguistics. 2010 Sep 1;23(5):447-454.
    4. Jäncke L, Hänggi J, Steinmetz H. Morphological brain differences between adult stutterers and non-stutterers. BMC Neurol. 2004 Dec 10;4(1):23.
    5. Kell CA, Neumann K, von Kriegstein K, Posenenske C, von Gudenberg AW, Euler H, Giraud AL. How the brain repairs stuttering. Brain. 2009 Oct;132(Pt 10):2747-60. Epub 2009 Aug 26.
    6. Galantucci S, Tartaglia MC, Wilson SM, Henry ML, Filippi M, Agosta F, Dronkers NF, Henry RG, Ogar JM, Miller BL, Gorno-Tempini ML. White matter damage in primary progressive aphasias: a diffusion tensor tractography study. Brain. 2011 Jun 11.
    7. Lundgren K, Helm-Estabrooks N, Klein R. Stuttering Following Acquired Brain Damage: A Review of the Literature. J Neurolinguistics. 2010 Sep 1;23(5):447-454.
    8. [No authors listed] Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 43-1988. A 52-year-old man with persistent watery diarrhea and aphasia. N Engl J Med. 1988 Oct 27;319(17):1139-48
    9. Molteni N, Bardella MT, Baldassarri AR, Bianchi PA. Celiac disease associated with epilepsy and intracranial calcifications: report of two patients. Am J Gastroenterol. 1988 Sep;83(9):992-4.
    10. http://ezinearticles.com/?Food-Allergy-and-Stuttering-Link&id=1235725 
    11. http://www.craig.copperleife.com/health/stuttering_allergies.htm 
    12. https://www.celiac.com/forums/topic/73362-any-help-is-appreciated/
    13. Ford RP. The gluten syndrome: a neurological disease. Med Hypotheses. 2009 Sep;73(3):438-40. Epub 2009 Apr 29.
    14. Hadjivassiliou M, Gibson A, Davies-Jones GA, Lobo AJ, Stephenson TJ, Milford-Ward A. Does cryptic gluten sensitivity play a part in neurological illness? Lancet. 1996 Feb 10;347(8998):369-71.

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    Journal of Clinical Pathologyhttp://dx.doi.org/10.1136/jclinpath-2018-205023

    Jefferson Adams
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    Alimentary Pharmacology & Therapeutics

    Jefferson Adams
    Celiac.com 06/12/2018 - A life-long gluten-free diet is the only proven treatment for celiac disease. However, current methods for assessing gluten-free diet compliance are lack the sensitivity to detect occasional dietary transgressions that may cause gut mucosal damage. So, basically, there’s currently no good way to tell if celiac patients are suffering gut damage from low-level gluten contamination.
    A team of researchers recently set out to develop a method to determine gluten intake and monitor gluten-free dietary compliance in patients with celiac disease, and to determine its correlation with mucosal damage. The research team included ML Moreno, Á Cebolla, A Muñoz-Suano, C Carrillo-Carrion, I Comino, Á Pizarro, F León, A Rodríguez-Herrera, and C Sousa. They are variously affiliated with Facultad de Farmacia, Departamento de Microbiología y Parasitología, Universidad de Sevilla, Sevilla, Spain; Biomedal S.L., Sevilla, Spain; Unidad Clínica de Aparato Digestivo, Hospital Universitario Virgen del Rocío, Sevilla, Spain; Celimmune, Bethesda, Maryland, USA; and the Unidad de Gastroenterología y Nutrición, Instituto Hispalense de Pediatría, Sevilla, Spain.
    For their study, the team collected urine samples from 76 healthy subjects and 58 patients with celiac disease subjected to different gluten dietary conditions. To quantify gluten immunogenic peptides in solid-phase extracted urines, the team used a lateral flow test (LFT) with the highly sensitive and specific G12 monoclonal antibody for the most dominant GIPs and an LFT reader. 
    They detected GIPs in concentrated urines from healthy individuals previously subjected to gluten-free diet as early as 4-6 h after single gluten intake, and for 1-2 days afterward. The urine test showed gluten ingestion in about 50% of patients. Biopsy analysis showed that nearly 9 out of 10 celiac patients with no villous atrophy had no detectable GIP in urine, while all patients with quantifiable GIP in urine showed signs of gut damage.
    The ability to use GIP in urine to reveal gluten consumption will likely help lead to new and non-invasive methods for monitoring gluten-free diet compliance. The test is sensitive, specific and simple enough for clinical monitoring of celiac patients, as well as for basic and clinical research applications including drug development.
    Source:
    Gut. 2017 Feb;66(2):250-257.  doi: 10.1136/gutjnl-2015-310148.