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Celiac.com 03/21/2024 - For people with celiac disease, managing symptoms and maintaining a gluten-free lifestyle are essential for overall health. However, recent research has uncovered another potential cause of enteropathy that presents a diagnostic challenge for both patients and healthcare providers: olmesartan-induced enteropathy. Olmesartan, an angiotensin II receptor antagonist commonly prescribed for hypertension, has been linked to enteropathy in rare cases, and another brand name for it is Benicar. This side effect, while uncommon, can manifest as chronic diarrhea, weight loss, and signs of malabsorption, mirroring the symptoms of celiac disease. A team of researchers set out to study the diagnostic challenges related to non-celiac enteropathy, specifically focusing on olmesartan-induced enteropathy. Here's what they found. The research team included Doukas S G, Doukas P G, and Velpari S. They are variously affiliated with the Department of Medicine, Saint Peter's University Hospital in New Brunswick, NJ, USA; the Department of Forensic Sciences and Laboratory of Toxicology, University of Crete, Medical School in Heraklion, GRC; and the department of Gastroenterology and Hepatology, Rutgers Robert Wood Johnson Medical School/Saint Peter's University Hospital in New Brunswick, USA. Their recent study focused on a 73-year-old woman who presented to the emergency department with watery diarrhea, weight loss, and electrolyte imbalances. Despite extensive testing, including celiac disease panels and imaging studies, the cause of her symptoms remained elusive until duodenal biopsies revealed moderate to severe villi blunting and intraepithelial lymphocytosis—a hallmark of olmesartan-induced enteropathy. History of Taking Olmesartan The patient's history of olmesartan use prompted the discontinuation of the medication, leading to a remarkable improvement in her symptoms and duodenal biopsy results within one month. This case underscores the importance of considering medication history and ruling out other potential causes of enteropathy in patients with symptoms suggestive of malabsorption. Olmesartan-induced enteropathy can mimic celiac disease both clinically and histopathologically, often leading to unnecessary diagnostic investigations and delays in appropriate treatment. Greater awareness of medication-related diarrheal syndromes, such as olmesartan-induced enteropathy, is crucial for prompt diagnosis and management. Healthcare providers should be vigilant in recognizing the potential link between olmesartan use and enteropathy, as simple discontinuation of the medication can lead to significant clinical improvement. For people with celiac disease and other gastrointestinal conditions, understanding the potential causes of enteropathy beyond gluten exposure is essential for effectively managing symptoms, and optimizing health outcomes. By staying informed and working closely with healthcare providers, patients can navigate the complexities of non-celiac enteropathy, and advocate for their well-being. Read more at Cureus 16(2): e54373. doi:10.7759/cureus.54373

Celiac.com 10/24/2022 - The advisability of considering the extra-intestinal manifestations of celiac disease, even in patients without typical intestinal symptoms, is not well studied. A team of researchers recently set out to examine the literature regarding the occurrence of thrombotic events in celiac disease, and to synthesize the data from case reports and case series. The research team included Nikola Pantic, Ivana Pantic, Dorde Jevtic, Vanajakshi Mogulla, Stevan Oluic, Momcilo Durdevic, Terri Nordin, Mladen Jecmenica, Tamara Milovanovic,Tatjana Gavrancic, and Igor Dumic. The team performed a systematic review of medical literature by searching the Pub-Med/MEDLINE database through January 2022, to identify published cases and case series on this topic, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The team included a total of 55 cases in the study. Most patients were previously healthy people, with no comorbidities. In nearly one-third of the cases, a celiac disease diagnosis was made before thrombosis began. In just over one-third of the other patients, thrombosis preceded the celiac diagnosis or was made together with the celiac diagnosis. Most thrombosis (about 1 in 3 cases) was found in hepatic veins, while thrombosis of cerebral blood vessels, deep venous thrombosis of lower extremities, and pulmonary thromboembolism were less common. Nearly 4 out of 5 cases of thrombosis were restricted to one site only. Nearly 70% of thrombosis patients were treated with anticoagulants, and placed on a gluten-free diet. This study reinforces the importance of considering extra-intestinal manifestations of celiac disease, even in patients without typical intestinal symptoms. The original article belongs to the Special Issue Celiac Disease and Non-celiac Gluten Sensitivity, Extraintestinal-Associated Conditions: Efficacy of a Gluten-Free Diet. Read more at MDPI.com The researchers are variously affiliated with the Clinic of Hematology, University Clinical Center of Serbia, Belgrade, Serbia; the Clinic of Gastroenterology and Hepatology, University Clinical Center of Serbia, Belgrade, Serbia; the Elmhurst Hospital Center, Department of Internal Medicine, Elmhurst, NY, USA; the Icahn School of Medicine at Mount Sinai, New York, NY, USA; the Mayo Clinic Alix School of Medicine, Rochester, MN, USA; the Department of Hospital Medicine, Mayo Clinic Health System, Eau Claire, WI, USA; the Department of Internal Medicine, Loyola University Medical Center, Maywood, IL, USA; the Department of Hospital Medicine, Advocate Aurora Health, Green Bay, WI, USA; the Oceana Gastroenterology Associated, Corona, CA, USA; and the Department of Hospital Medicine, Mayo Clinic, Jacksonville, FL, USA.

Celiac.com 04/12/2019 - In this 4-part Series, we’re going to look at the world of gluten sensitivity, what the current science tells us, the frustrations gluten sensitive and celiac patients often experience, and how to use the science in getting healthier. Part 1: Why the Tests are Often Wrong Part 2: Why Don’t I Feel Great on a gluten-free diet: Cross-Reactive foods Part 3: Why Don’t I Feel Great on a gluten-free diet: the Intestinal Milieu Part 4: Why Don’t I Feel Great on a gluten-free diet: Invaders in the House Many of us believe that the toxic peptides of gluten found in wheat, rye and barley may detrimentally affect any tissue in the body and are not restricted to the intestines. As a matter-of-fact, one of the ‘mantras’ of the Gluten Sensitivity Network comes from an 8-year old article: “That gluten sensitivity is regarded as principally a disease of the small bowel is a historical misconception.(1)” There is a key word in this statement which I suspect emphasizes the Author’s message and sets the tone for this article (and this network movement). That key word is ‘principally’. Is Gluten sensitivity ‘principally’ a disease of the small intestine? Point-blank answer-no, it is not. For every Gluten sensitive patient with the symptoms of an enteropathy (classic celiac disease), there are 8 more with no GI symptoms(2, 3). And the importance of recognizing this? Unfortunately, too many doctors will tell their patients that if the intestinal symptoms are not severe, or if there is no advanced intestinal damage (total villous atrophy), then the patient does not need to be vigilant in avoiding gluten exposure at all costs(4). Many patients are advised to follow the World Health Organization or Food and Agricultural Organization Codex Alimentarius gluten-free diet, which allow up to 0.3% of gluten per 100 g of protein in foods, whereas others follow a strict GFD with no detectable gluten. However, trace amounts of gluten may be responsible for persistent symptoms in some patients with celiac disease. Up to 75% of patients with persistent symptoms despite a World Health Organization or Food and Agricultural Organization Codex Alimentarius gluten-free diet will improve when put on a ‘‘no detectable gluten’’ diet(5). We know that for gluten-sensitive patients, eating gluten will cause inflammation in the intestines, and often in other parts of the body(6, 7, 8, 9). The importance of ‘quieting down’ the inflammatory cascade from gluten exposure? Mortality in celiac patients is highest (6-fold higher) in those not adherent to a gluten-free diet. Non-adherence to a gluten-free diet was defined as eating gluten once-per-month(10). Vigilance is paramount. You can’t be a little pregnant. There is no convincing evidence that you can have a little gluten if you have gluten sensitivity. The ‘conundrum of gluten sensitivity’ is when patients know they have a problem with wheat, their doctors run the standard blood profile, and one of two things happens: -IgA anti-transglutaminase or anti-endomysial antibodies come back negative(11), or; -IgA anti-transglutaminase or anti-endomysial antibodies come back negative and anti-gliadin, or anti-deamidated gliadin antibodies come back positive and the doctor tells the patient “it’s okay to eat wheat because the tissue antibodies are negative”. The patient is left in a state of confusion. They don’t WANT to give up wheat. After all, they believe it’s a staple of life. And their doctor says it’s okay to eat it. Yet they know they don’t feel as well when they eat it. So many will rationalize “Oh well, it must be the stress of my life making me feel bad”, and they order their bagel. That’s the conundrum. Where’s the problem? The problem is the test. Gluten sensitivity is a systemic autoimmune disease with diverse manifestations(12). Celiac disease, or gluten-sensitive enteropathy, is only one aspect of a range of possible manifestations of gluten sensitivity. And yet, this enteropathy, ‘one of the most common lifelong disorders in both the U.S. and Europe(13), receives the lion’s share of focus to the point of ignoring other manifestations. Auto-immune disease, the 3rd leading cause of morbidity and mortality in the industrialized world(14), is ten times more common in a gluten sensitive enteropathy than in the general population(15). The correlation is undeniable. The exact mechanisms of how this correlation manifests is being investigated intensively. What we can say, with a good deal of research behind us, is that the toxic peptides of gluten may act as a trigger in the development of the auto-immune mechanism (the immune system attacking our own tissues). Traditionally, doctors do not recognize this connection and wait for the accumulated damage from the immune system attacking our tissue (our thyroid, or our brains, or our skin, or…), they wait until the damage is extensive enough that there are obvious symptoms, and then we receive a diagnosis of an auto-immune disease (celiac disease, Hashimoto’s thyroiditis, type 1 diabetes, systemic lupus, inflammatory bowel disease, inflammatory skin diseases, ….)(16). Thus, the burden on society imposed by gluten sensitivity is difficult to overestimate. Earlier identification might result in earlier treatment, better quality of life and an improved prognosis for these patients(17). The diagnosis of gluten sensitivity has been proposed to include not just intestinal damage (celiac disease), but also gluten-reactive patients without intestinal lesions. From the skin (dermatitis herpetiformis, psoriatic arthritis, alopecia areata, dermatomyositis, cutaneous vasculitis,), to the muscles (inflammatory myopathies), to the brain (gluten ataxia, altered neurotransmitter production, schizophrenia, anxiety, depression, attention deficit disorders,…) to the nerves (peripheral neuralgias, carpal tunnel syndrome, idiopathic neuropathies,…), and beyond. Pathology in response to gluten exposure can occur in multiple systems without evidence of intestinal damage(18-27). Now, what about this conundrum? The tests are negative, yet the person feels better when they do not eat gluten. Many studies have validated the sensitivity and specificity using anti-endomysial and/or anti-transglutaminase antibody testing to identify celiac disease(28, 29). This means that the science says these tests are very, very accurate. Then how is there a conundrum? Here’s the problem: the definition of celiac disease requires total villous atrophy(30). Not partial villous atrophy; not increased inflammation without any visible atrophy. The definition of celiac disease requires total villous atrophy. Thus, when researchers look at populations who have celiac disease confirmed by biopsy, and look to see how accurate the blood tests are, they come up with percentages above 95%, because they’re only including people who have total villous atrophy in their study group-because that’s the definition of celiac disease. If we were to expand the definition of celiac disease to include those with partial villous atrophy, or include those who currently show only the mechanism that wears down the villi (increased intraepithelial lymphocytes), then the sensitivity and specificity of anti-endomysial or anti-transglutaminase goes down, in some studies dramatically down, to as low as 27-32%(31, 32, 33, 34). So do we want to base our health guidance and decisions on blood tests that are limited to identifying celiac disease at its end stage of intestinal deterioration (total villous atrophy)(35, 36)? Or would we want to include testing that has a much bigger picture in mind and identifies gluten sensitivity inside and outside the intestines and at earlier stages? If we recognize the fact that gluten sensitivity may manifest as celiac disease, or it may manifest outside of the intestines(37), one of the ways of expanding our diagnostic range is to focus on whether or not our immune system is saying that gluten is a problem. We may know where the problem is manifesting, or we may not. But if our immune system is saying “We’ve got a problem here”, it is likely worth listening to. As a comparison, if your car is running fine on the highway at 60 miles per hour, do you listen when the immune system of the car (the dashboard gauges) says “we’ve got a problem here”, and the hot light has lit up, or do we say “the car’s running fine-I don’t see or feel any problem”, and keep driving? I think most would agree that is not a very wise move. The same is true for your body. You may ‘feel’ a problem; you may not. We’ll talk more about that in a future article. For now, the point I want to make is that we will benefit from ‘listening’ to what our immune system is saying to us. We just have to be able to hear what it’s trying to say. The problem is accurate communication The current blood test that every laboratory offers in looking for an immune reaction to the gluten fraction of wheat is elevated antibodies to gliadin or deamidated gliadin - every laboratory. And there are many studies that have shown that looking for elevated antibodies to gliadin is not as accurate in identifying celiac disease as looking for elevated antibodies to transglutaminase or endomysial antibodies. Why? Because sometimes the antibodies to gliadin are positive and the biopsy shows there is no celiac disease. And sometimes the gliadin antibodies are negative and the biopsy shows there is celiac disease. Thus, the consensus in the scientific community is that looking for antibodies to wheat (gliadin) is not sensitive enough when looking for celiac disease. You can’t rely on it. Now that doesn’t make much sense, does it? If the gluten peptide is the problem, why can’t we measure the immune reaction to it when other gauges on the dashboard are hot? Two reasons: Researchers tell us it is “inappropriate” to compare gliadin antibodies against transglutaminase or endomysial antibodies because gluten sensitivity can exist without villous atrophy. Thus the gliadin antibodies may be elevated (and often are) without recognizable celiac disease. It’s showing us a bigger problem than just Celiac disease. They’re not ‘false positives’. It’s the immune system saying “we’ve got a problem here” that is not currently manifesting in the intestines-it is likely manifesting somewhere else, such as in the brain or the nervous system(38). Identifying antibodies just against the fraction of gluten called gliadin is not thorough enough in looking for an immune reaction to gluten(39). Amino acids are the building blocks of protein. When we eat protein, any protein, it’s the job of the digestive system to break down that protein into 1, 2, or at most 3 amino acid peptides that are easily absorbed into the blood stream through the ‘cheesecloth’ of the intestines. When someone has gluten sensitivity, the gluten molecules in wheat, barley and rye are not digested into small enough molecules to easily fit through the cheesecloth, be absorbed into the blood stream, and they remain in larger peptides, sometimes very large peptides. These large peptides, called macromolecules, trigger the immune system to say “these are not good for me(40, 41)”. An exposure to a large peptide on a rare occasion would not likely have initially been a problem. But with pancakes for breakfast, a sandwich for lunch, pasta for dinner, toast for breakfast, a sandwich for lunch, croutons on the salad at dinner, day in and day out, eventually you’ve got a hot light on the dashboard that is reaching the critical stage(42). Then ‘boom’ your engine overheats and you begin to notice symptoms-perhaps in the intestines, perhaps in the joints, perhaps in the skin, perhaps in the skull (depression, anxiety, headaches), perhaps fatigue,….. So let’s get back to the large peptides left in the intestines due to an inability to digest the gluten molecule. We know there are many peptides of gluten result from poor digestion(43). One study identified over 60 putative peptides of gluten(44). Yet the current blood tests only test for one - gliadin. Studies have said that gliadin is the primary toxic peptide. But, only about 50% of celiac patients have antibodies to the gliadin peptide of gluten(39). The rest of the celiacs don’t. They have antibodies to other peptides of gluten(45). This is the reason for the conundrum-you test for it, the test only looks for antibodies to gliadin, the test comes back negative, and yet you ‘know’ you feel better off of gluten. It’s the test! In that example, the person does not react to the gliadin peptide-they are likely to be reacting to a different peptide of gluten. Why don’t laboratories test for other peptides of gluten? Good question. I do not know the answer to that. Some of the studies on this go back to the mid 1990’s. Probably a supply and demand issue for commercial laboratories. Well, no longer. There is a new blood test, looking at 12 different peptides of gluten-not just Gliadin. You can go to www.cyrexlabs.com or to my web site www.theDr.com to read more about this test. Looking at antibodies to 12 different peptides of gluten (including gliadin) will certainly increase the detection rate of the immune system saying “we’ve got a problem here with gluten”. We know celiac disease is due to sensitivity to the peptides of gluten found in wheat, barley and rye, many of the peptides in gluten-not just to gliadin. And now, another diagnostic tool has been added to your doctor’s repertoire assisting in accurately identifying gluten sensitivity with or without the serious end-stage of tissue destruction-total villous atrophy. And my personal prayer is that as a result of this expanded test looking for a reaction to gluten, we no longer miss those with earlier stages of celiac disease and gluten sensitivity thus being able to calm down the ‘fire in the belly’, the hot light on the dashboard, before the engine blows up. Before the diagnosis of attention deficit hyperactivity disorder, before the diagnosis of autoimmune thyroid disease, before the diagnosis of type 1 diabetes, before the diagnosis of migraines, before the loss of a pregnancy,…. and doctors will have the tools to truly guide their patients in increasing their health - tuning the engine before it blows up with a diagnosable disease. So our bodies can carry us through life purring instead of rumbling along. References: 1. Hadjavassilios, M., Gluten sensitivity as a Neurological illness, J Neurol Neurosurg Psychiatry 2002;72:560–563 2. van Heel D., West J, Recent Advances in Coeliac Disease, Gut 2006;55:1037–1046 3. Fasano A, Catassi C., Current Approaches to Diagnosis and Treatment of Celiac disease: An Evolving Spectrum Gastroenterology 2001;120:636-651 4. Goddard CJ., Gillett H R., Complications of coeliac disease: are all patients at risk? Postgrad. Med. J. 2006;82;705-712 5. Green PHR, Stavropoulos SN, Panagi SG, et al. Characteristics of adult celiac disease in the USA: results of a national survey. Am J Gasroenterol 2001;96:126–31. 6. Olesen M, Eriksson S, Bohr J, Jarnerot G, Tysk C. Microscopic colitis: a common diarrhoeal disease. An epidemiological study in Orebro, Sweden, 1993-1998. Gut, 2004; 53:346-350. 7. Gillet HR, Freeman HJ. Prevalence of celiac disease in collagenous and lymphocytic colitis. Can J Gastroenterol, 2000; 14: 919-921. 8. Koskela RM, Niemelä SE, Karttunen TJ, Lehtola JK. Clinical characteristics of collagenous and lymphocytic colitis. Scand J Gastroenterol, 2004;39: 837-845. 9. Dickey W, Celiac disease and the Colon, PRACTICAL GASTROENTEROLOGY • SEPTEMBER 2008 10. Corrao G, Corrazza GR, Bagnardi V, et al. Mortality in patients with coeliac disease and their relatives: a cohort study. Lancet 2001;358:356–61. 11. Hill I Salem W, Dirks M, Liptak G, Colletti R , Fasano A, Guandalini S, Hoffenberg E, Horvath K, Murray J, Pivor M, Salem W, Seidman E, Guideline for the Diagnosis and Treatment of Celiac disease in Children: Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, J Pediatr Gastroenterol Nutr, Vol. 40, No. 1, January 2005 12. Hadjavassilios, M, Gluten sensitivity: from Gut to Brain. Lancet Neurol 2010; 9: 318–30 13. Fasano, A, Celiac disease-How to handle a Clinical Chameleon, NEJM 348;25 June 19,2003 14. Arnson Y, Amital H, and Shoenfeld Y, Vitamin D and autoimmunity: new aetiological and therapeutic considerations, J of Immunology, 2005, 175: 4119–4126. 15. Alaedini A, Okamoto H, Briani, C, Wollenberg K, Shill H, Bushara K, Sander H, Green P, Hallett M, Latov N, Immune Cross-Reactivity in Celiac disease: Anti-Gliadin Antibodies Bind to Neuronal Synapsin I, The Journal of Immunology, 2007, 178: 6590–6595. 16. Bland J., Understanding the Origins and Applying Advanced Nutritional Strategies for Autoimmune Disease, Metagenics Seminar Series, 2006 17. Green P, Alaedini A, Sander HW, Brannagan III TH, Latov N, Chin R, Mechanisms underlying celiac disease and its Neurologic Manifestations Cell. Mol. Life Sci. 62 (2005) 791–799 18. Marietta E, Black K, Camilleri M, Krause P, Rogers RS 3rd, David C, Pittelkow MR, Murray JA., A new model for dermatitis herpetiformis that uses HLA-DQ8 transgenic NOD mice, J Clin Invest. 2004 Oct;114(8):1090-7 19. Lindqvist U, Rudsander A, Boström A, Nilsson B, Michaëlsson G., IgA antibodies to gliadin and coeliac disease in psoriatic arthritis, Rheumatology (Oxford). 2002 Jan;41(1):31-7. 20. Humbert P, Pelletier F, Dreno B, Puzenat E, Aubin F, Gluten intolerance and skin diseases, Eur J Dermatol 2006; 16 (1): 4-11 21. Selva-O’Callaghan A, Casellas F, de Torres I, Palou E, Grau-Junyent JM, Vilardell-Tarrés M., CELIAC DISEASE AND ANTIBODIES ASSOCIATED WITH CELIAC DISEASE IN PATIENTS WITH INFLAMMATORY MYOPATHY, Muscle Nerve. 2007 Jan;35(1):49-54. 22. Hadjivassiliou M, Grünewald R, Sharrack B, Sanders D, Lobo A, Williamson C, Woodroofe N, Wood N, Davies-Jones A., Gluten ataxia in perspective: epidemiology, genetic susceptibility and clinical characteristics, Brain. 2003 Mar;126(Pt 3):685-91. 23. Hadjivassiliou M, Aeschlimann D, Grünewald RA, Sanders DS, Sharrack B, Woodroofe N, GAD antibody-associated neurological illness and its relationship to gluten sensitivity, Acta Neurol Scand. 2010 Apr 15 24. Eaton W, Mortensen PB, Agerbo E, Byrne M, Mors O, Ewald H., Coeliac disease and schizophrenia: population based case control study with linkage of Danish national registers, BMJ. 2004 Feb 21;328(7437):438-9 25. Hadjivassiliou M, Grünewald RA, Chattopadhyay AK, Davies­Jones GAB, Gibson A, Jarratt JA, et al. Clinical, radiological, neurophysiological and neuropathological characteristics of gluten ataxia. Lancet 1998;352:1582­5. 26. J Neurol Neurosurg Psychiatry. 2006 Nov;77(11):1262-6., Hadjivassiliou M, Grünewald RA, Kandler RH, Chattopadhyay AK, Jarratt JA, Sanders DS, Sharrack B, Wharton SB, Davies-Jones GA, Neuropathy associated with gluten sensitivity. 27. Gluten sensitivity: from gut to brain., Hadjivassiliou M, Sanders DS, Grünewald RA, Woodroofe N, Boscolo S, Aeschlimann D, Lancet Neurol. 2010 Mar;9(3):318-30 28. Hopper A., et.al., Pre-endoscopy serological testing for coeliac disease:evaluation of a clinical decision tool, BMJ. 2007 Apr 7;334(7596):729 29. Hill ID., What are the sensitivity and specificity of serologic tests for celiac disease? Do sensitivity and specificity vary in different populations? Gastroenterology. 2005 Apr;128(4 Suppl 1):S25-32 30. Memeo L, Jhang J, Hibshoosh H, Green PH, Rotterdam H, Bhagat G., Duodenal intraepithelial lymphocytosis with normal villous architecture: common occurrence in H. pylori gastritis, Mod Pathol. 2005 Aug;18(8):1134-44 31. Abrams JA, Diamond B, Rotterdam H, Green PH. Seronegative celiac disease: increased prevalence with lesser degrees of villous atrophy, Dig Dis Sci. 2004 Apr;49(4):546-50 32. Tursi A., Seronegative Coeliac Disease: a Clinical Challenge. BMJ 26 April, 2005 33. Rostami, K., Unforgiving Master of Non-Specificity and Disguise, BMJ 27, April 2005 34. Lebwold, Green P., Screening for Celiac disease. N Engl J Med Oct.23 2003,1673-4 35. Freeman HJ., Pearls and pitfalls in the diagnosis of adult celiac disease. Can J Gastroenterol 2008;22(3):273-280. 36. Bonamico M., Serologic and Genetic Markers of Celiac disease: A Sequential Study in the Screening of First Degree Relatives, Journal of Pediatric Gastroenterology and Nutrition 42:150–154 37. Fasano A., Catassi C., Current Approaches to Diagnosis and Treatment of Celiac disease: An Evolving Spectrum, GASTROENTEROLOGY 2001;120:636–651 38. Hadjavassiliou M., Grunewald R., The Neurology of Gluten sensitivity:Science vs. Conviction Practical Neurology, 2004, 4, 124–126 39. Camarca, A., et.al., Intestinal T Cell Responses to Gluten Peptides Are Largely Heterogeneous: Implications for a Peptide-Based Therapy in Celiac disease, J. Immunol. 2009;182;4158-4166 40. Meresse B., , Ripoche J., Heyman M., Cerf-Bensussan N., Celiac disease: from oral tolerance to intestinal inflammation, autoimmunity and lymphomagenesis, Nature Vol 2 No 1, JANUARY 2009 41. Bethune M.,Parallels Between Pathogens and Gluten Peptides in Celiac Sprue, Plos Pathogens Feb 2008 Vol 4: 2;e34 42. Ehrhardt G., et.al. Discriminating gene expression profiles of memory B cell subpopulations JEM VOL. 205, August 4, 2008 43. Martucci S., Corazza G., Spreading and Focusing of Gluten Epitopes in Celiac disease GASTROENTEROLOGY Vol. 122, No. 7, 2002 44. Pastore L., et.al., Orally Based Diagnosis of Celiac disease: Current Perspectives, J Dent Res 87(12):1100-1107, 2008 45. Vader W., et.al., The Gluten Response in Children With Celiac disease Is Directed Toward Multiple Gliadin and Glutenin Peptides, GASTROENTEROLOGY 2002;122:1729–1737

Celiac.com 01/23/2018 - Benicar (olmesartan medoxomil) is a hypertension drug used for high blood pressure, and which is known to cause numerous side-effects in patients, including dangerous celiac sprue-like enteropathy, and is the subject of numerous lawsuits, and a $300 million settlement. Now the respected consumer advocacy group Public Citizen is calling for the FDA to ban the sale Benicar, due to the potential for side effects to which Public Citizen refers as "life-threatening." According to Public Citizen, originally founded by consumer advocate Ralph Nader, olmesartans risks outweigh any benefits. In a November 15 press release following their 20-page petition to the FDA, the organization warned that "Keeping the medication on the market would continue to put hypertension patients' lives at risk for the sake of corporate profits." While the FDA has formally acknowledged receiving the petition, there is no indication that any action is forthcoming any time soon. The agency can sometimes take years to act. Numerous drug experts note the availability of comparable hypertension drugs that are equally effective in lowering blood pressure without such dire side effects as the sprue-like enteropathy that "leads to severe and chronic diarrhea, vomiting, abdominal pain and weight loss…that often lands a patient in the hospital," noted the petition. Sometimes this sprue-like enteropathy is misdiagnosed as a celiac disorder, when in reality it is due to olmesarten use. Benicar, together with Azor, Benicar HCT, and Tribenzor, are unique in their association with sprue-like enteropathy. It is why so many plaintiffs reference Benicar defective products in their allegations, and why Public Citizen wants them off the market. Source: lawyersandsettlements.com

Celiac.com 04/20/2010 - A team of researchers recently set out to determine whether new serology assays can detect gluten sensitivity among enteropathy patients seronegative for anti–tissue transglutaminase. Emilia Sugai, Hui Jer Hwang, Horacio Vázquez, Edgardo Smecuol, Sonia Niveloni, Roberto Mazure, Eduardo Mauriño, Pascale Aeschlimann, Walter Binder, Daniel Aeschlimann and Julio C. Bai comprised the research team. They are variously affiliated with the Small Bowel Section of the Department of Medicine at C. Bonorino Udaondo Gastroenterology Hospital in Buenos Aires, Argentina, the Matrix Biology and Tissue Repair Research Unit at the Cardiff University School of Dentistry in Cardiff, UK, and with INOVA Diagnostics, Inc., of San Diego, California. Some patients with celiac disease may not show a normal positive reaction to the test most commonly used for IgA anti–tissue transglutaminase (anti-tTG) antibodies. The research team set out to determine the usefulness of newer assays incorporating synthetic deamidated gliadin-related peptides (DGPs), or other TG isoenzymes as antigen, for detecting gluten sensitivity in IgA anti-tTG–seronegative patients. The team tested blood samples drawn at diagnosis from 12 anti-tTG–seronegative patients with a celiac-like enteropathy, from 26 patients with skin biopsy–proven dermatitis herpetiformis (DH) and, lastly, from 26 patients with IgA anti-tTG–positive celiac disease. All patients showed typical levels of total IgA. On each patient, the team conducted intestinal biopsy and serum testing for detection of IgA and IgG isotypes of both anti-DGP and anti-tTG in a single assay (tTG/DGP Screen; INOVA Diagnostics). They also tested each patient for simultaneous detection of both IgA and IgG anti-DGP antibody isotypes (DGP Dual; INOVA Diagnostics). Lastly, they tested each patient for the detection of antibodies to transglutaminase 3 (TG3) or transglutaminase 6 (TG6). All patients who showed positive anti-tTG results also tested positive in anti-DGP assays. The tTG/DGP Screen caught six of the 19 anti-tTG seronegatives (31.6%), while anti-DGP Dual produced caught five of these cases (26.3%). Whereas both assays detected 2 anti-tTG–negative DH patients with partial villous atrophy, they were positive in only 2 of the 5 cases with no histologically discernible mucosal damage. Testing for antibodies to TG3 and TG6 caught seven of the 19 anti-tTG–negative patients (36.8%), five of whom also tested positive for anti-DGP. From these results, the team concludes that using tTG/DGP Screen, or anti-DGP Dual, to detect anti-DGP improves diagnostic sensitivity of gluten sensitive patients with non–IgA- deficiency, or anti-tTG–seronegativity, and celiac-like enteropathy. The same enhancement is also achieved by detecting antibodies to other TG isoenzymes. Source: Clinical Chemistry 56: 661-665, 2010.

Celiac.com 07/09/2010 - The enteropathy associated with common variable immunodeficiency (CVID) is the most common symptomatic primary antibody deficient syndrome, with an estimated prevalence of one in one-hundred thousand to one in fifty thousand. However, the relationship between CVID and Enteropathy is still unclear. CVID is characterized by decreased levels of of two or more serum immunoglobulin (Ig) isotypes and the presentation of reoccurring infections specifically in the respiratory tract. Gastrointestinal symptoms are widespread with CVID patients as exhibited in as many as 50% of patients presenting with chronic diarrhea. A team of doctors evaluated the medical files of 50 CVID patients who exhibited gastrointestinal symptoms to determine the “clinical and hitopathological features of the enteropathy associated with CVID”. Fifteen patients were excluded from the study because they did not meet the recognized criteria for CVID. Data was collected from all patients and included, gender, age, symptoms, body mass index (BMI), as well as parasitological stool testing. Blood samples were taken from each test patient including hemogram, serum protein electrophoresis and measurements of serum folic acid, vitamin B12, iron, and calcium. The doctors found the mean age for initial CVID diagnosis to be 36.8 years. Four of the patients were discovered to have a family history of immunodeficiency. 40% of the patients that were tested were determined to have immunodeficiency as revealed by their digestive symptoms. Chronic diarrhea was observed as the most common gastrointestinal symptom with a rate of 92% of the patients studied. Gluten-free diet was initiated by 12 patients with villous atrophy, but clinical improvements and partial villous healing only occurred in two patients. Interestingly, the two patients presenting with celiac antibodies, did not show an improvement of symptoms. All patients showed positive improvements from steroid therapy. Furthermore, as a result of this study, the observing doctors concluded, that of the CVID patients exhibiting gastrointestinal symptoms, histological lesions were found in around 80% of the biopsies taken from the colon, stomach, or small bowel. The enteropathy corresponding with CVID was found to have has many features that differentiate it from other etiopathological conditions including celiac disease. While replacement Ig therapy was demonstrated to be inadequate for improving gastrointestinal symptoms, steroids, specifically budesonide,were proven successful in reducing inflammation and restoring mucosal architecture. Source: The American Journal of Gastroenterology , (15June2010) | doi:10.1038/ajg.2010.214