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    Can Celiac Disease be Diagnosed without Intestinal Biopsy?


    Jefferson Adams
    Image Caption: Image: Public Domain--Wikicommons

    Celiac.com 05/28/2013 - Is an intestinal biopsy always necessary to diagnose celiac disease, or can diagnosis be made without biopsy? To answer that question, a team of researchers recently set out to compare celiac disease–specific antibody tests to determine if they could replace jejunal biopsy in patients with a high pretest probability of celiac disease.


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    Image: Public Domain--WikicommonsThe research team included Annemarie Bürgin-Wolff, Buser Mauro, and Hadziselimovic Faruk. They are variously affiliated with the Institute for Celiac Disease in Liestal, Switzerland, and Statistik Dr. M. Buser, Riehen, Switzerland.

    Their retrospective study included blood test data from 149 patients with celiac disease, along with 119 controls. All patients underwent intestinal biopsy, and all samples were analyzed for IgA and IgG antibodies against native gliadin (ngli) and deamidated gliadin peptides (dpgli), as well as for IgA antibodies against tissue transglutaminase and endomysium.

    They found that tests for dpgli were superior to ngli for IgG antibody determination: 68% vs. 92% specificity and 79% vs. 85% sensitivity for ngli and dpgli, respectively. Predictive values were also higher for dpgli than for ngli; positive (76% vs. 93%) and negative (72% vs. 83%).

    Regarding IgA gliadin antibody determination, sensitivity improved from 61% to 78% with dpgli, while specificity and positive predictive value remained at 97% (P less than 0.00001).

    A combination of four tests (IgA anti-dpgli, IgG anti-dpgli, IgA anti- tissue transglutaminase, and IgA anti-endomysium) yielded positive and negative predictive values of 99% and 100%, respectively and a likelihood ratio positive of 86 with a likelihood ratio negative of 0.00.

    Omitting the endomysium antibody determination still yielded positive and negative predictive values of 99% and 98%, respectively and a likelihood ratio positive of 87 with a likelihood ratio negative of 0.01.

    Conclusion: Antibody tests for dpgli yielded superior results compared with ngli. A combination of three or four antibody tests including IgA anti-tissue transglutaminase and/or IgA anti- endomysium enabled reliable diagnosis or exclusion of celiac disease without intestinal biopsy in 78 percent of patients.

    This two-step method of performing jejunal biopsy only in patients with discordant antibody results (22%) would catch all patients except those with no celiac-specific antibodies; who would then be caught through biopsy.

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    Guest Matt Lewis

    Posted

    My wife was diagnosed with celiac disease after stomach biopsy and blood tests were all negative.

     

    She was diagnosed with celiac disease from a capsule endoscopy. Stomach and duodenal biopsies are the tip of the 9 feet of jejunum and often miss celiac disease...

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    Guest tony

    Posted

    I had one GI doctor, swear I had it through blood tests and the fact that I have dermatitis herpetiformis since I was 12 years old. The other GI doctor did a biopsy during a colonoscopy. He swears I don't have it. Pasta is the item that gets me sick. But only for the last 5 years, when I was young I ate ziti, ravs and all pasta with no problems.

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    Guest Rob Carroll

    Posted

    I never had a positive blood test, but the endoscopy (which my 3rd GI ordered for an unrelated reason) found it right away. I don't know if these were the same series of blood tests they were using 10 years ago, but I know a lot of people who had false negatives.

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    Guest Andrea

    Posted

    I had one GI doctor, swear I had it through blood tests and the fact that I have dermatitis herpetiformis since I was 12 years old. The other GI doctor did a biopsy during a colonoscopy. He swears I don't have it. Pasta is the item that gets me sick. But only for the last 5 years, when I was young I ate ziti, ravs and all pasta with no problems.

    Tony,

     

    Doctors at the New York Presbyterian Celiac Center who are world renowned for their research, studies and treatment of celiac disease say that dermatitis herpetiformis is a condition that confirms the presence of celiac disease in patients who are not otherwise confirmed. If you have the anti-bodies as well, then you have a diagnosis of celiac disease.

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    Guest Jenny

    Posted

    My wife was diagnosed with celiac disease after stomach biopsy and blood tests were all negative.

     

    She was diagnosed with celiac disease from a capsule endoscopy. Stomach and duodenal biopsies are the tip of the 9 feet of jejunum and often miss celiac disease...

    Yes I know at least 50 celiacs diagnosed by capsule when standard biopsy and/or blood test was negative.

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    Guest Rosalyn

    Posted

    I could not understand one word in this article; therefore I learned nothing that would be helpful. The article was too technical and not written for the average gluten-free person trying to learn more about the disease.

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    Guest Jules

    Posted

    Do patients undergoing the tests have to be eating gluten to test positive?

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    Guest laura craigo

    Posted

    I have had four positive blood tests months and months apart, but I tested negative on biopsy.

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    Guest Duane Benton

    Posted

    I had one positive and one negative blood test, but definitely have celiac disease from gluten-free diet results.

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    I could not understand one word in this article; therefore I learned nothing that would be helpful. The article was too technical and not written for the average gluten-free person trying to learn more about the disease.

    I so agree with you! I was hoping that I'm not getting a little senile.

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    Guest Adamaris

    Posted

    Do patients undergoing the tests have to be eating gluten to test positive?

    I also would like to know if I have to eat before taking the blood test, IGA-TTG, I'm so confused because when I eat food containing gluten I get sick.

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    I was diagnosed two weeks ago through a blood test. My doctor explained that I needed a biopsy to have an "official" diagnosis, but he usually didn't order such an invasive procedure unless it was a severe case or unless the patient requested it (I certainly didn't want to deal with that, so I just took his word for it). In two weeks of a gluten-free diet, I'm sleeping better, I don't have abdominal discomfort, my nausea and vomiting is gone, I've lost a significant amount of weight, my thyroid problems have stabilized (for the moment; more bloodwork in a month to confirm) and I just FEEL better. The other day, my mother-in-law made a dessert which she assured me was gluten free. It wasn't (who doesn't know that flour is made from wheat???), and I had horrendous stomach pain for two hours after eating it. I don't need a biopsy to confirm what I already know. I know everyone is different, but in my case, the blood test was more than enough.

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    I was diagnosed two weeks ago through a blood test. My doctor explained that I needed a biopsy to have an "official" diagnosis, but he usually didn't order such an invasive procedure unless it was a severe case or unless the patient requested it (I certainly didn't want to deal with that, so I just took his word for it). In two weeks of a gluten-free diet, I'm sleeping better, I don't have abdominal discomfort, my nausea and vomiting is gone, I've lost a significant amount of weight, my thyroid problems have stabilized (for the moment; more bloodwork in a month to confirm) and I just FEEL better. The other day, my mother-in-law made a dessert which she assured me was gluten free. It wasn't (who doesn't know that flour is made from wheat???), and I had horrendous stomach pain for two hours after eating it. I don't need a biopsy to confirm what I already know. I know everyone is different, but in my case, the blood test was more than enough.

    I have heard that there are tax deductions for people DIAGNOSED with celiac. I am sure a biopsy is not worth the while to get them, however, i would make it very clear to your doctor, how you feel after a gluten-free diet and express that it should be noted in your chart. I believe the actual problem lies between diagnosing celiac or gluten intolerance, which is probably the reason for a biopsy.

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    I have heard that there are tax deductions for people DIAGNOSED with celiac. I am sure a biopsy is not worth the while to get them, however, i would make it very clear to your doctor, how you feel after a gluten-free diet and express that it should be noted in your chart. I believe the actual problem lies between diagnosing celiac or gluten intolerance, which is probably the reason for a biopsy.

    Can you expand on what these tax deductions are? How does that work, can you deduct gluten free food as medical expenses or pay them from a health account?

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    I could not understand one word in this article; therefore I learned nothing that would be helpful. The article was too technical and not written for the average gluten-free person trying to learn more about the disease.

    I agree. I think it would be helpful if the article was in English and not medical-alphabet soup.

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    I recently had a negative blood test for celiac and when I had an EGD they took only one biopsy in the small intestine, which came back negative. I am now attempting a gluten free diet and feeling better to a degree. The problems I was having included 20 pound weight loss in 2 months, being extremely shaky, exhausted, dizzy, moody after eating and unable to think clearly. My mom wants me to request a CT scan and not wait on the gluten few diet. I was wondering if anyone had any input on my symptoms from their own experiences?

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    Guest Dylan Cornelius

    Posted

    My wife was diagnosed with celiac disease after stomach biopsy and blood tests were all negative.

     

    She was diagnosed with celiac disease from a capsule endoscopy. Stomach and duodenal biopsies are the tip of the 9 feet of jejunum and often miss celiac disease...

    Hi Matt,

    Where do you find the data that stomach and duodenal biopsies often miss celiac disease? Appreciate your help!

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    Guest Dylan Cornelius

    Posted

    Do patients undergoing the tests have to be eating gluten to test positive?

    When my gastroenterologist ordered my test, he told me since I hadn't been eating gluten recently, it would likely be a negative result. I ate bread every day for 30 days prior to my test as he directed, though he also said this probably wouldn't be sufficient exposure to yield a positive test result. I grew increasingly more tired and had greater digestive distress as those 30 days passed. My sleep increased from 8 hours nightly to 14 by the end. The test result was negative. Your mileage may vary.

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  • Related Articles

    Gryphon Myers
    Celiac.com 02/18/2013 - Currently, there are two main diagnostic tools available to would-be celiacs: biopsy and serological (antibody) tests. For the past few decades, biopsy has been the only relatively reliable (and diagnostically accepted) path to diagnosis. The problem is, biopsies are expensive and highly invasive – antibody tests would be a cheap and painless alternative, but they haven't proven themselves to be accurate enough for conclusive diagnosis. However, a recent analysis shows that antibody tests have improved a great deal in recent years and when used to test for multiple antibodies concurrently, they can be almost as effective as biopsies for diagnosing celiac disease.
    The study's facilitators began their restrospective analysis by collecting serum samples from 268 patients at hospitals throughout Switzerland, Germany and Austria. All included patients suffered from celiac-like symptoms and underwent both biopsy and antibody testing within 2 months of serum collection. All included patients were on gluten-containing diets at the time of testing. 149 of the patients were ultimately diagnosed with celiac disease; the other 119 showed normal intestinal mucosa and were considered celiac-free. These patients were the control group.
    Usually, potential celiac patients are tested for IgA anti- tTG or EMA. If the test is positive, then diagnosis is then confirmed with biopsy. However, there is still a chance that the test will throw a false positive, meaning many people are put through unnecessary biopsies. The goal of the present study was to develop a method for reducing the number of these unnecessary biopsies.
    It was found that when two antibody tests are used, the reliability of the tests increased substantially, weeding out a great many false positives, as well as picking up some false negatives. When three tests were used, the numbers became even more accurate – when used concurrently and all three show a positive result, the IgA anti-dpgli, igG anti-dpgli and IgA anti-tTG achieved an 87% positive likelihood and .01% negative likelihood (compared to a positive likelihood of only 7% and negative likelihood of 0.04% with just the IgA anti-tTG). Using these three tests together, only one test subject came through as a false positive, and only two came through as false negatives (compared to 16 false positives and 5 false negatives with the IgA anti-tTG only). 60 came through with discordant results (meaning at least one of the tests came back negative – in these cases, biopsy is necessary).
    When considering that biopsy really only has a real-world diagnostic accuracy rate of about 90%, the three test combination utilized in this study achieves strong enough numbers that biopsies are starting to look unnecessary. Biopsy still might be the surest way of detecting celiac disease, but this study shows that it is not necessary in all cases, and patients seeking celiac diagnosis have a few more tests they can ask their doctors for.
    Source:
    http://www.biomedcentral.com/1471-230X/13/19

  • Recent Articles

    Jefferson Adams
    Celiac.com 06/18/2018 - Celiac disease has been mainly associated with Caucasian populations in Northern Europe, and their descendants in other countries, but new scientific evidence is beginning to challenge that view. Still, the exact global prevalence of celiac disease remains unknown.  To get better data on that issue, a team of researchers recently conducted a comprehensive review and meta-analysis to get a reasonably accurate estimate the global prevalence of celiac disease. 
    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.
    For their review, the team searched Medline, PubMed, and EMBASE for the keywords ‘celiac disease,’ ‘celiac,’ ‘tissue transglutaminase antibody,’ ‘anti-endomysium antibody,’ ‘endomysial antibody,’ and ‘prevalence’ for studies published from January 1991 through March 2016. 
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    Overall global prevalence of celiac disease was 1.4% in 275,818 individuals, based on positive blood tests for anti-tissue transglutaminase and/or anti-endomysial antibodies. The pooled global prevalence of biopsy-confirmed celiac disease was 0.7% in 138,792 individuals. That means that numerous people with celiac disease potentially remain undiagnosed.
    Rates of celiac disease were 0.4% in South America, 0.5% in Africa and North America, 0.6% in Asia, and 0.8% in Europe and Oceania; the prevalence was 0.6% in female vs 0.4% males. Celiac disease was significantly more common in children than adults.
    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.

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    Cover and refrigerate for at least 1 hour. 
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    Dr. Ron Hoggan, Ed.D.
    Celiac.com 06/15/2018 - There seems to be widespread agreement in the published medical research reports that stuttering is driven by abnormalities in the brain. Sometimes these are the result of brain injuries resulting from a stroke. Other types of brain injuries can also result in stuttering. Patients with Parkinson’s disease who were treated with stimulation of the subthalamic nucleus, an area of the brain that regulates some motor functions, experienced a return or worsening of stuttering that improved when the stimulation was turned off (1). Similarly, stroke has also been reported in association with acquired stuttering (2). While there are some reports of psychological mechanisms underlying stuttering, a majority of reports seem to favor altered brain morphology and/or function as the root of stuttering (3). Reports of structural differences between the brain hemispheres that are absent in those who do not stutter are also common (4). About 5% of children stutter, beginning sometime around age 3, during the phase of speech acquisition. However, about 75% of these cases resolve without intervention, before reaching their teens (5). Some cases of aphasia, a loss of speech production or understanding, have been reported in association with damage or changes to one or more of the language centers of the brain (6). Stuttering may sometimes arise from changes or damage to these same language centers (7). Thus, many stutterers have abnormalities in the same regions of the brain similar to those seen in aphasia.
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    Whatever the reason that stuttering has not been reported in the medical literature in association with gluten ingestion, a number of personal disclosures and comments suggesting a connection between gluten and stuttering can be found on the Internet. Abid Hussain, in an article about food allergy and stuttering said: “The most common food allergy prevalent in stutterers is that of gluten which has been found to aggravate the stutter” (10). Similarly, Craig Forsythe posted an article that includes five cases of self-reporting individuals who believe that their stuttering is or was connected to gluten, one of whom also experiences stuttering from foods containing yeast (11). The same site contains one report of a stutterer who has had no relief despite following a gluten free diet for 20 years (11). Another stutterer, Jay88, reports the complete disappearance of her/his stammer on a gluten free diet (12). Doubtless there are many more such anecdotes to be found on the Internet* but we have to question them, exercising more skepticism than we might when reading similar claims in a peer reviewed scientific or medical journal.
    There are many reports in such journals connecting brain and neurological ailments with gluten, so it is not much of a stretch, on that basis alone, to suspect that stuttering may be a symptom of the gluten syndrome. Rodney Ford has even characterized celiac disease as an ailment that may begin through gluten-induced neurological damage (13) and Marios Hadjivassiliou and his group of neurologists and neurological investigators have devoted considerable time and effort to research that reveals gluten as an important factor in a majority of neurological diseases of unknown origin (14) which, as I have pointed out previously, includes most neurological ailments.
    My own experience with stuttering is limited. I stuttered as a child when I became nervous, upset, or self-conscious. Although I have been gluten free for many years, I haven’t noticed any impact on my inclination to stutter when upset. I don’t know if they are related, but I have also had challenges with speaking when distressed and I have noticed a substantial improvement in this area since removing gluten from my diet. Nonetheless, I have long wondered if there is a connection between gluten consumption and stuttering. Having done the research for this article, I would now encourage stutterers to try a gluten free diet for six months to see if it will reduce or eliminate their stutter. Meanwhile, I hope that some investigator out there will research this matter, publish her findings, and start the ball rolling toward getting some definitive answers to this question.
    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.

    Jefferson Adams
    Celiac.com 06/14/2018 - Refractory celiac disease type II (RCDII) is a rare complication of celiac disease that has high death rates. To diagnose RCDII, doctors identify a clonal population of phenotypically aberrant intraepithelial lymphocytes (IELs). 
    However, researchers really don’t have much data regarding the frequency and significance of clonal T cell receptor (TCR) gene rearrangements (TCR-GRs) in small bowel (SB) biopsies of patients without RCDII. Such data could provide useful comparison information for patients with RCDII, among other things.
    To that end, a research team recently set out to try to get some information about the frequency and importance of clonal T cell receptor (TCR) gene rearrangements (TCR-GRs) in small bowel (SB) biopsies of patients without RCDII. The research team included Shafinaz Hussein, Tatyana Gindin, Stephen M Lagana, Carolina Arguelles-Grande, Suneeta Krishnareddy, Bachir Alobeid, Suzanne K Lewis, Mahesh M Mansukhani, Peter H R Green, and Govind Bhagat.
    They are variously affiliated with the Department of Pathology and Cell Biology, and the Department of Medicine at the Celiac Disease Center, New York Presbyterian Hospital/Columbia University Medical Center, New York, USA. Their team analyzed results of TCR-GR analyses performed on SB biopsies at our institution over a 3-year period, which were obtained from eight active celiac disease, 172 celiac disease on gluten-free diet, 33 RCDI, and three RCDII patients and 14 patients without celiac disease. 
    Clonal TCR-GRs are not infrequent in cases lacking features of RCDII, while PCPs are frequent in all disease phases. TCR-GR results should be assessed in conjunction with immunophenotypic, histological and clinical findings for appropriate diagnosis and classification of RCD.
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    They also noted a higher frequency of surface CD3(−) IELs in cases with clonal TCR-GR, but the PCP pattern showed no associations with any clinical or pathological feature. 
    Repeat biopsy showed that the clonal or PCP pattern persisted for up to 2 years with no evidence of RCDII. The study indicates that better understanding of clonal T cell receptor gene rearrangements may help researchers improve refractory celiac diagnosis. 
    Source:
    Journal of Clinical Pathologyhttp://dx.doi.org/10.1136/jclinpath-2018-205023

    Jefferson Adams
    Celiac.com 06/13/2018 - There have been numerous reports that olmesartan, aka Benicar, seems to trigger sprue‐like enteropathy in many patients, but so far, studies have produced mixed results, and there really hasn’t been a rigorous study of the issue. A team of researchers recently set out to assess whether olmesartan is associated with a higher rate of enteropathy compared with other angiotensin II receptor blockers (ARBs).
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    To get solid data on the issue, the team conducted a cohort study among ARB initiators in 5 US claims databases covering numerous health insurers. They used Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for enteropathy‐related outcomes, including celiac disease, malabsorption, concomitant diagnoses of diarrhea and weight loss, and non‐infectious enteropathy. In all, they found nearly two million eligible patients. 
    They then assessed those patients and compared the results for olmesartan initiators to initiators of other ARBs after propensity score (PS) matching. They found unadjusted incidence rates of 0.82, 1.41, 1.66 and 29.20 per 1,000 person‐years for celiac disease, malabsorption, concomitant diagnoses of diarrhea and weight loss, and non‐infectious enteropathy respectively. 
    After PS matching comparing olmesartan to other ARBs, hazard ratios were 1.21 (95% CI, 1.05‐1.40), 1.00 (95% CI, 0.88‐1.13), 1.22 (95% CI, 1.10‐1.36) and 1.04 (95% CI, 1.01‐1.07) for each outcome. Patients aged 65 years and older showed greater hazard ratios for celiac disease, as did patients receiving treatment for more than 1 year, and patients receiving higher cumulative olmesartan doses.
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    Source:
    Alimentary Pharmacology & Therapeutics