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    Do We Really Need Biopsies to Diagnose Celiac Disease?


    Jefferson Adams


    • Can celiac disease be accurately detected without a biopsy?


    Image Caption: Can blood tests alone accurately diagnose celiac disease? Photo: CC--Garland Cannon

    Celiac.com 07/13/2017 - Until recently, duodenal biopsy was considered the gold standard for diagnosing celiac disease, but that is changing.


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    A number of studies have shown that celiac disease can be diagnosed using serological tests alone, but many clinicians have yet to embrace this approach.

    In both retrospective and prospective studies, one research team showed that certain IgA-tissue transglutaminase antibodies levels can predict celiac disease in adults 100% of the time.

    After making some adjustments to the analytical method for measuring the antibody, a team of researchers recently set out to to determine whether such serum tests can reliably diagnose celiac disease in large numbers adult patients without the need for small bowel biopsy.

    The research team included GKT Holmes, JM Forsyth, S Knowles, H Seddon, PG Hill, and AS Austin.

    They are variously associated with the Royal Derby Hospital, the Department of Pathology, and the Derby Digestive Diseases Centre at the Royal Derby Hospital in Derby, UK.

    For their study, the team conducted a retrospective analysis in an unselected series of 270 adult patients who underwent small bowel biopsies and the measurement of serum IgA-tissue transglutaminase antibody levels from 2009 to 2014.

    At an IgA-tissue transglutaminase antibody cut-off greater than 45 U/ml (>8×upper limit of normal+2SDs) the positive predictive value for celiac disease in this cohort was 100%; 40% of cases were above this cut-off.

    The team found that they could use IgA-tissue transglutaminase antibody levels to reliably diagnose celiac disease in a high proportion of these adult patients.

    This study adds to the growing body of evidence that supports the diagnosis of celiac disease without a mandatory small bowel biopsy.

    As a realist of these findings, the study team has changed the diagnostic guidelines for their center, and will now make celiac diagnosis based on cut-off levels of IgA-tissue transglutaminase.

    This is exciting news. For many, many years, the biopsy was considered the gold standard for diagnosing celiac disease.

    By eliminating biopsies in favor of IgA-tissue transglutaminase levels, diagnosing celiac disease could become much easier and even cheaper.

    Do you have celiac disease? Did you receive a biopsy for diagnosis? How do you feel about celiac diagnosis without biopsy? Share your thoughts below.

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    Guest Lois Bemis

    Posted

    My teenage daughter was diagnosed by a genetic test.

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    Guest Tracy Hintz

    Posted

    My daughter was diagnosed in 2006 by colonoscopy. She has the blood test in 2005 and after a negative result on her blood test and suffering another six months until a colonoscopy was finally done. The GI specialist didn't even need to wait for biopsies because of the damage, but of course the biopsies were positive as well. I'm dubious about relying on blood work alone, at least in children. I´d hate to be the patient or the family member or a patient suffering who was told it was negative based on blood alone. We were told because she was vomiting and had diarrhea daily that they suspect the blood test was negative because so little was being absorbed in her system.

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    Guest Clair C.

    Posted

    I was tested after a trip to Brazil pointed out to my doctor that I might be celiac. He did just the celiac test and I so conclusively "failed it" that he declared me celiac after 10 to 15 years of not knowing what was wrong with me. There is no question that I am celiac after so many symptoms and so many years of eating gluten free (about 9 years and counting).

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    Guest cgil7

    Posted

    I was also diagnosed by genetic testing. I did not know anything about celiac disease when I was young and having all kinds of stomach issues. I went gluten free because I thought maybe I had a sensitivity to wheat and felt so much better. I later found out about celiac disease and asked my doctor to test me for it and he refused, saying it was very rare and I had IBS which is common in women. I had genetic testing done many years later and all markers were positive, in fact the counselor I talked to said she had been in the field for over 30 years and had never seen anyone with positive markers end up NOT having celiac disease but my Dr. at the time said they would not diagnose me with celiac unless I went back on gluten for a month or so and then had a biopsy. I was not willing to do that because I had been so sick before on gluten that I could not work or do much of anything. It took over 15 years before I finally got properly diagnosed and found doctors that were educated and knowledgeable about the disease.

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    Guest Joe Hurley

    Posted

    My blood tests were all negative, but the biopsy showed damage to the small intestine. Does this mean I don't have celiac disease?

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    Guest Kristy

    Posted

    I had the biopsy. The blood work was "borderline" yet I already had serious blunting. My concern is that it might get missed in some cases.

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    Guest Allie

    Posted

    I was diagnosed by lab work. I have been gluten free since my diagnosis in 2011.

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    Guest Elisabeth

    Posted

    This would be great; I had a biopsy that didn't show celiac disease, because my physician had the test done after 3 months of gluten free diet! The advise was to skip the gluten free diet and come back for another biopsy after three months! After so many years with pain I just couldn't do that again. So now the physician doesn't believe me. But I am pain free!

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    Guest Cecelia Brothwell

    Posted

    I was not tested for celiac disease when I first went to a doctor - tested for a multitude of other things and all negative. Went 3 more years until seeking second opinion. Positive with endoscopy to confirm at which time 3 areas of metaphylasia (sp) were found. One year later on celiac diet, repeat scoping, all areas gone. Now having 3 year scoping as follow up. All pediatricians have this as part of grandchildren's family health history.

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    Guest Patricia

    Posted

    Excellent informative article. Am 75 and have had some scary episodes from anesthesia in the past. I will now no longer do the duodenal biopsy. Had unsymptomatic celiac diagnosed one year ago in a blood test.

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    I think that the biopsy is actually not as accurate as physicians would have us believe. In a lecture by Dr. Fasano I attended he admitted that celiac disease is "patchy" and the biopsy may not reach the affected area. If a blood test comes back positive the person has a problem with gluten regardless of the level of damage (Marsh score) and should not eat it.

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    Guest Mindy

    Posted

    12 years ago I had low bone density. Endocrinologist did one test. tTg. Normal was 1-19 mine was 181. Proved part of why my bone density was not good at age 50. I tried to eat well but gluten was in tiny amounts in many places. I didn't know I was celiac, but never ate sandwich or pizza instinctively. I refused the "gold standard" biopsy. I don't see a need for invasive tests when I can change behavior. I am gluten-free. I don't eat gluten-free junk either. I am much better. Still work as I was undiagnosed for so long and am allergic to other things due to leaky gut. I am healthier than most. Wonder if the 25% earlier death is for celiacs that comply. Thanks for your article. I sensed I was wise but people often ask about biopsy. I am now 62.

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    I was diagnosed on blood tests alone at age 51, 6 years ago. All of my markers were off the charts high. I had been having unusual blood work for years - high platelets, elevated liver enzymes, thyroid issues, etc. The blood work was so definitive, even after 2 weeks of no gluten, that by the time I saw the gastroenterologist a month later, he did not want to reintroduce gluten and made the diagnosis on blood work - I had the full celiac panel, all markers were high.

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    Guest Lindsey

    Posted

    I was just diagnosed with celiac with the blood test - my numbers were extremely high and the doctor gave me the option to do the biopsy. He said with as high as my numbers were it wasn't really necessary if I didn't want it. I have chosen not to get the biopsy done. rnrn

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    Guest Pam Newbury

    Posted

    I am surprised to hear two people in the comments say they were "diagnosed" using a genetic test. Genetic tests for celiac disease can, in some cases, exclude a diagnosis of celiac disease, but they cannot diagnose it. One third of the population have the genetic markers for celiac disease. Only a small percentage of those will develop celiac disease. Genetic testing must be followed up by other tests. I am concerned that people are being told that testing positive for the genetic markers for celiac disease is a "diagnosis". While I think that, in some cases, a strongly positive result on celiac disease blood tests can eliminate the need for biopsy to confirm, I think that when celiac disease is suspected and tests are negative or unclear, a biopsy should always be performed. I also think there is value in knowing how badly damaged the gut is and in seeing how much healing has been done in a follow-up biopsy at a later date.

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  • About Me

    Jefferson Adams is a freelance writer living in San Francisco. He has covered Health News for Examiner.com, and provided health and medical content for Sharecare.com. His work has appeared in Antioch Review, Blue Mesa Review, CALIBAN, Hayden's Ferry Review, Huffington Post, the Mississippi Review, and Slate, among others.

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  • Related Articles

    Jefferson Adams
    Celiac.com 01/09/2017 - Some researchers have criticized the usefulness of the 7 level Marsh-Oberhuber classification of mucosal damage in patients with celiac disease.
    Even though assessing duodenal biopsies with dissecting microscopy is a somewhat crude method, it can provide useful information in cases of obvious villous atrophy.
    For the past 15 years, one research team has analyzed duodenal biopsies with dissecting microscopy before sending them to the pathology department for histology. Their feeling is that, if dissecting microscopy and traditional histology were comparable, the grading of the histological lesion would be unnecessary, or even pointless, for proper diagnosis of most enteropathies.
    That research team recently set out to settle that question. The team included F Biagi, C Vattiato, M Burrone, A Schiepatti, S Agazzi, G Maiorano, O Luinetti, C Alvisi, C Klersy, and GR Corazza. They are variously affiliated with the First Department of Internal Medicine, the Biometry and Statistics, the Department of Pathology at University of Pavia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; and with the Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy.
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    Their results, using κ statistics, showed a substantial agreement of the two methods (κ statistics 0.78). Sensitivity of dissecting microscopy for detection of severe villous atrophy was 85.1% (95% CI 81.2% to 88.5%) and specificity was 95% (95% CI 93.8% to 96%).
    Although dissecting microscopy is no substitute for traditional histology, these results suggest that most celiac disease-related and other flat enteropathies can be sufficiently diagnosed without grading villous atrophy.
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    J Clin Pathol. 2016 Dec;69(12):1051-1054. doi: 10.1136/jclinpath-2016-203711. Epub 2016 May 4.

    Jefferson Adams
    Celiac.com 12/12/2016 - Studies suggest that celiac disease affects about 0.5% to 1% of the North American population. There is no good screening data based on small intestinal biopsy performed during routine endoscopic evaluation.
    Researcher Hugh James Freeman, MD CM FRCPC FACP, of the Gastroenterology unit in the Department of Medicine at the University of British Columbia in Vancouver, British Columbia, recently set out to review the detection of adult celiac disease using duodenal screening biopsies over a 30-year period.
    Dr. Freeman reviewed data from patients referred between January 1982 and December 2011 for evaluation of gastrointestinal symptoms, requiring elective investigative upper endoscopic evaluation, and who underwent duodenal biopsies to determine whether changes of adult celiac disease were present. He found a total of 9,665 patients, including 4,008 male and 5,657 female, who underwent elective endoscopy and duodenal biopsy.
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    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.
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    AllergicLiving.com

    Jefferson Adams
    Celiac.com 06/05/2017 - Doctors diagnose celiac disease by confirming various clinical, genetic, serologic, and duodenal morphology features. Based on retrospective data, recent pediatric guidelines propose eliminating biopsy for patients with IgA-TTG levels more than 10-times the upper limit of normal (ULN), along with a few other criteria.
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    The research team included Johannes Wolf, David Petroff, Thomas Richter, Marcus KH. Auth, Holm H. Uhlig, Martin W. Laass, Peter Lauenstein, Andreas Krahl, Norman Händel, Jan de Laffolie, Almuthe C. Hauer, Thomas Kehler, Gunter Flemming, Frank Schmidt, Astor Rodriques, Dirk Hasenclever, and Thomas Mothes.
    Their team conducted a prospective study of 898 children undergoing duodenal biopsy analysis to confirm or rule out celiac disease at 13 centers in Europe. They then compared results from antibody tests with results from biopsies, follow-up data, and diagnoses made by the pediatric gastroenterologists. In all cases, diagnosis was made for celiac disease, no celiac disease, or no final diagnosis.
    Blinded researchers measured levels of IgA-TTG, IgG-DGL, and endomysium antibodies, while tissue sections were analyzed by local and blinded reference pathologists. The team validated two procedures for diagnosis: total-IgA and IgA-TTG, as well as IgG-DGL with IgA-TTG. Patients whose antibody concentrations for all tests were below 1-fold the ULN were assigned to the no celiac disease category.
    Those whose antibody concentrations for at least one test were above 10-fold the ULN were assigned to the celiac disease category. All other cases were considered to require biopsy analysis.
    The team calculated the ULN values using the cut-off levels suggested by the test kit manufacturers. They conducted HLA-typing for 449 participants. To extrapolate the PPV and NPV to populations with lower rates of celiac disease, they used models that accounted for how specificity values change with prevalence.
    In all, the team found 592 patients with celiac disease, 345 who did not have celiac disease, and 24 with no final diagnosis.
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    Gastroenterology. DOI: http://dx.doi.org/10.1053/j.gastro.2017.04.023  
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    Those scientists recently gathered some of the first evidence to show that cheap, over-the-counter antacids can prompt the spleen to promote an anti-inflammatory environment that could be helpful in combating inflammatory disease.
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    The research team included P Singh, A Arora, TA Strand, DA Leffler, C Catassi, PH Green, CP Kelly, V Ahuja, and GK Makharia. They are variously affiliated with the Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Lady Hardinge Medical College, New Delhi, India; Innlandet Hospital Trust, Lillehammer, Norway; Centre for International Health, University of Bergen, Bergen, Norway; Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Gastroenterology Research and Development, Takeda Pharmaceuticals Inc, Cambridge, MA; Department of Pediatrics, Università Politecnica delle Marche, Ancona, Italy; Department of Medicine, Columbia University Medical Center, New York, New York; USA Celiac Disease Center, Columbia University Medical Center, New York, New York; and the Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.
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    This systematic review and meta-analysis showed celiac disease to be reported worldwide. Blood test data shows celiac disease rate of 1.4%, while biopsy data shows 0.7%. The prevalence of celiac disease varies with sex, age, and location. 
    This review demonstrates a need for more comprehensive population-based studies of celiac disease in numerous countries.  The 1.4% rate indicates that there are 91.2 million people worldwide with celiac disease, and 3.9 million are in the U.S.A.
    Source:
    Clin Gastroenterol Hepatol. 2018 Jun;16(6):823-836.e2. doi: 10.1016/j.cgh.2017.06.037.