Bp Drug Linked To Gluten Sensitivity
Posted 23 June 2012 - 04:00 AM
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
• 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.
Posted 23 June 2012 - 04:58 AM
"I will try again tommorrow" (Mary Anne Radmacher)
celiac 49 years - Misdiagnosed for 45
Blood tested and repeatedly negative
Diagnosed by Allergist with elimination diet and diagnosis confirmed by GI in 2002
Misdiagnoses for 15 years were IBS-D, ataxia, migraines, anxiety, depression, fibromyalgia, parathesias, arthritis, livedo reticularis, hairloss, premature menopause, osteoporosis, kidney damage, diverticulosis, prediabetes and ulcers, dermatitis herpeformis
All bold resoved or went into remission with proper diagnosis of Celiac November 2002
Some residual nerve damage remains as of 2006- this has continued to resolve after eliminating soy in 2007
Mother died of celiac related cancer at 56
Twin brother died as a result of autoimmune liver destruction at age 15
Children 2 with Ulcers, GERD, Depression, , 1 with DH, 1 with severe growth stunting (male adult 5 feet)both finally diagnosed Celiac through blood testing and 1 with endo 6 months after Mom
Positive to Soy and Casien also Aug 2007
Gluten Sensitivity Gene Test Aug 2007
HLA-DQB1 Molecular analysis, Allele 1 0303
HLA-DQB1 Molecular analysis, Allele 2 0303
Serologic equivalent: HLA-DQ 3,3 (Subtype 9,9)
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