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lcarter

Member Since 20 Apr 2008
Offline Last Active Oct 21 2012 05:00 AM
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Topics I've Started

Gi Biopsies

14 October 2012 - 05:10 AM

I know we need to be eating gluten for quite a few weeks before being blood tested, but not necessary for gene tests. But, what about GI biopsies? I have been gluten free for 6+ yrs and my GI went ahead and did GI biopsies which were all negative. There's no doubt that wheat gives me GI problems.

Bp Drug Linked To Gluten Sensitivity

23 June 2012 - 04:00 AM

BP Drug Linked to Gluten Sensitivity
By Chris Kaiser, Cardiology Editor, MedPage Today
Published: June 22, 2012
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Action Points
Explain that a case series from the Mayo Clinic describes an association between a severe enteropathy, similar to celiac disease, and olmesartan, a common angiotensin-receptor blocker effective for the treatment of hypertension.
Note that 22 patients described improved clinically and histologically with discontinuation of the drug, while a gluten-free diet had had no impact on their chronic diarrhea.

Symptoms mimicking gluten sensitivity (celiac disease) may occur in some patients treated with olmesartan (Benicar), a commonly prescribed angiotensin receptor blocker (ARB).In a span of 3 years, 22 patients presented to the Mayo Clinic in Rochester, Minn., with symptoms suggestive of celiac disease, but antibody blood tests did not support that diagnosis, reported Joseph A. Murray, MD, and colleagues in a study published online in the Mayo Clinic Proceedings. The common denominator was olmesartan, and when the patients stopped taking the drug, their symptoms improved, Murray said during a press briefing. "It's probably a rare association, but an important one," he said.
But hypertension specialists had mixed reactions to Murray's findings. "I use this agent all the time with excellent results with respect to blood pressure lowering," said Henry Black, MD, a professor of internal medicine at NYU Langone Medical Center in New York City, in an email to MedPage Today and ABC News. "I find it very difficult to believe this especially because it is a very small sample of individuals who may well have many factors that would also be possible explanations for the findings."
All but one patient was over 50 years old. "It may be that the intestines of older people are more vulnerable to this syndrome, but more research needs to be conducted to narrow down specific risk factors," Black said. "This report would suggest a drug allergy of sorts and findings that would not relate to the mechanism of action of this drug in that no such reports have even arisen with the several other drugs in this class," wrote Domenic Sica, MD, chair of clinical pharmacology and hypertension at Virginia Commonwealth University in Richmond, in an email to MedPage Today and ABC News. "Olmesartan has been on the market for several years and these results are surprising this far out into its life cycle," Sica said. "Nonetheless, the findings send a powerful message suggesting the need for a critical look at what the FDA and other drug regulatory agencies around the world have in hand that might suggest prior similar occurrences with olmesartan or, for that matter, any of the drugs in this class." "There is no question that the report from the Mayo Clinic documenting that olmesartan has severe gastrointestinal adverse effects is of concern," Franz Messerli, MD, director of the hypertension program at St. Luke's-Roosevelt Hospital in New York City, said to MedPage Today and ABC News. "Olmesartan sales have exceeded $500 million a year in the U.S. alone and the drug, as with all ARBs, stands out because of its paucity of side effects," Messerli said.
Murray reported the phenomenon to the FDA in late 2009 after he had "reasonable evidence of an association." The FDA subsequently conducted a retrospective analysis of patients on olmesartan with a hospital discharge diagnosis of celiac disease. The agency found no statistically significant association with ARBs as group or individually, he said.
The initial two patients with the syndrome had stopped their medication because of low blood pressure due to chronic diarrhea. When they started again, their symptoms returned, according to the patients' own accounts. However, Murray and colleagues emphasized that their findings do not prove causality. One avenue to prove causality would be to rechallenge the patients with olmesartan once their symptoms improved, but researchers didn't want to do that because of the "life-threatening nature of the syndrome." One patient, for example, had lost 125 lbs, Murray said, and many patients were given steroids to help suppress the inflammation in their intestines.
A total of 18 patients had follow-up biopsies that showed the intestinal damage had improved, Murray said. Interestingly, all patients had severe intestinal damage, unlike in celiac disease where the damage would vary from mild to severe. Although the mechanism of intestinal damage is unknown, he and colleagues speculated it might be related to inhibition of transforming growth factor-beta (TGF-beta), an intestinal cytokine that helps maintain homeostasis. Prior studies have suggested that ARBs, the class of drug to which olmesartan belongs, have an inhibitory effect on TGF-beta, he said. "The gut has to learn to tolerate a lot of different bacteria and TGF-beta is an important chemical messenger for that tolerance," Murray told MedPage Today. Twelve patients had bacterial overgrowth in the small intestine that was not resolved with antibiotics. 20 patients went on a gluten-free diet with no apparent clinical success. But once patients stopped taking olmesartan, their health improved, some quicker than others.
After initially encountering several patients with the syndrome, Murry retrospectively examined his records back to 2004 and found similar cases. These patients are currently being followed, but some of them with ongoing severe symptoms were taken off olmesartan, after which they improved, Murray told MedPage Today. "We also examined several thousand cases of celiac disease and it didn't look like this drug was any more common among them than in the general population," he said. "My impression is that this drug is not associated with real celiac disease. It's associated with something that mimics celiac disease."
In the current analysis, all 22 patients (13 women) experienced diarrhea and weight loss at the time of presentation, while nausea, vomiting, abdominal pain, bloating, and fatigue were also present in most patients. The diarrhea was chronic, having been present for a median of 19.2 months. 14 of the 22 patients were hospitalized because of the severity of their symptoms. "We thought these cases were celiac diseases initially because their biopsies showed features very like celiac disease, such as villous atrophy and mucosal inflammation. What made them different was they didn't have the antibodies in their blood that are typical for celiac disease," Murray said. All but one patient in the series were Caucasian, he said. Geographically, the patients came from 16 different states. Serotyping identified 68% with human leukocyte antigen DQ2, a risk factor for celiac disease. "It might suggest an immune basis for this syndrome," Murray told MedPage Today.
Interestingly, olmesartan was a very effective blood pressure medication for these patients and it was a "challenge to take them off and find a replacement medication," Murray said. Some patients required multiple antihypertensive medications to replace olmesartan. Others had lost so much weight their blood pressure normalized. One interesting feature, according to Murray, is the relatively long lag time -- several months to years -- between drug initiation and the onset of diarrhea, which "is not typical for drug-induced diarrhea."
This study was supported by National Institutes of Health, American College of Gastroenterology Junior Faculty Development Award, The Swedish Society of Medicine, the Swedish Research Council Medicine, the Swedish Celiac Society, and the Fulbright Commission.
Murray did not report any conflicts of interest.

Negative Biopsies?

29 November 2011 - 04:51 AM

Here's a significant research paper of interest to all of those who have had a negative biopsy. Another reason not to fully trust negative biopsies is (1)labs miss read them 20% of the time, according to the attached research report, (2)the doctor may not take enough samples -8 are recommended,(3) or there are not enough taken in the right places, as damage can be spotty.

Variability in small bowel histopathology reporting between different pathology practice settings: impact on the diagnosis of coeliac disease.

Source: J Clin Pathol. 2011 Nov 12. Celiac Disease Center at Columbia University Medical Center, Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, New York, New York, USA.

ABSTRACT
Background and Aims - Coeliac disease (celiac disease) diagnosis requires the detection of characteristic histological alterations of small bowel mucosa, which are prone to interobserver variability. This study evaluated the agreement in biopsy interpretation between different pathology practice types.
Methods - Biopsies from community hospitals (n=46), university hospitals (n=18) and commercial laboratories (n=38) were blindly assessed by a pathologist at our institution for differences in histopathology reporting and agreement in diagnosis of celiac disease and degree of villous atrophy (VA) by κ analysis.
Results - Agreement for primary diagnosis was very good between this institution and university hospitals (κ=0.888), but moderate compared with community hospitals (κ=0.465) or commercial laboratories (κ=0.419). Diagnosis differed in 26 (25%) cases, leading to a 20% increase in celiac disease diagnosis after review. Among those diagnosed with celiac disease by both institutions (n=49), agreement in degree of villous atrophy (VA) was fair (κ=0.292), with moderate agreement between the authors and commercial laboratories (κ=0.500) and fair with university hospitals (κ=0.290) or community hospitals (κ=0.211). The degree of VA was upgraded in 27% and downgraded in 2%. Within different Marsh score categories, agreement was poor (κ<0.0316) for scores 1 and 2, both missed at other centres, and fair or moderate for scores 3a and 3b. Information regarding degree of VA and intraepithelial lymphocytosis was lacking in 26% and 86% of reports and non-quantifiable descriptors, eg, 'blunting' or 'marked atrophy' were prevalent.
Conclusions - celiac disease-related histological changes are underdiagnosed in community-based hospitals and commercial pathology laboratories. Because incorrect biopsy interpretation can cause underdiagnosis of celiac disease, greater celiac disease awareness and uniformity in small bowel biopsy reporting is required among pathologists.

New! Biopsy For The Folks On gluten-free Diet

16 October 2011 - 03:54 AM

WOW! This is great news! Hopefully it will be available real soon to those of us who are asked to do a gluten challenge so that biopsies can be done:

Patients who do not get a confirmed celiac diagnosis from standard tests could obtain one from an in vitro gliadin challenge, in which biopsied duodenal mucosa are tested using the toxic part of wheat gluten called gliadin, according to a study in the American Journal of Gastroenterology. University of Salerno researchers said the challenge method is helpful for patients who are on a gluten-free diet prior to the biopsy because they do not have to revert to eating gluten foods to achieve the diagnosis.

In Vitro Gliadin Challenge: Diagnostic Accuracy and Utility for the Difficult Diagnosis of Celiac Disease
The American Journal of Gastroenterology , (27 September 2011) | doi:10.1038/ajg.2011.311
Raffaella Tortora, Ilaria Russo, Giovanni D De Palma, Alessandro Luciani, Antonio Rispo, Fabiana Zingone, Paola Iovino, Pietro Capone and Carolina Ciacci

Abstract
OBJECTIVES: Diagnosis of celiac disease is difficult when treatment with gluten-free diet (GFD) is started before diagnosis and/or when the results of tests are inconsistent. The objective of this study was to evaluate the in vitro gliadin challenge.
METHODS: The study cohort included patients without celiac disease (negative controls, n=57), patients with celiac disease (positive controls, n=166 untreated and n=55 on GFD), and patients with difficult diagnosis (n=59). All patients underwent endoscopy for collection of duodenal samples, which served for the diagnosis of celiac disease and for the in vitro evaluation of the gliadin-induced mucosal expression of seven inflammatory markers: PY99, ICAM-1 (intercellular cell adhesion molecule), HLA-DR, CD3, CD25, CD69, and transglutaminase 2 IgA. Diagnostic work-up for celiac disease included the search of specific serum antibodies. Patients of the difficult diagnosis group were asked to stop GFD for repeated search of these antibodies under untreated conditions. The area under the receptor-operated curve (ROC) was used for statistical analyses on accuracy.
RESULTS: HLA-DR had the highest accuracy for celiac disease diagnosis in analyses on negative controls and positive controls also excluding patients on GFD (area under ROC=0.99). Accuracy of test did not increase combining data of HLA-DR with data of other markers. Findings were similar in the 39 patients of the difficult diagnosis group undergoing the search celiac disease-specific antibodies under untreated conditions.
CONCLUSIONS: The in vitro response of mucosal HLA-DR to gliadin is an accurate tool for the diagnosis of celiac disease also in patients with difficult diagnosis.