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    Female Hormones and Autoimmune Disease: The Connection


    Dr. Vikki Petersen D.C, C.C.N
    Image Caption: Dr. Vikki Petersen

    This article originally appeared in the Winter 2011 edition of Celiac.com's Journal of Gluten-Sensitivity.


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    Celiac.com 08/29/2011 - Nearly 75% of the 24 million Americans suffering from autoimmune disease are women, according to the American Autoimmune Related Diseases Association (AARDA).  Women appear to mount larger inflammatory responses than men when their immune systems are triggered, thereby increasing their risk of autoimmunity.  The fact that sex hormones are involved is indicated by the fact that many autoimmune diseases fluctuate with hormonal changes such as those that occur during pregnancy, during the menstrual cycle, or when using oral contraceptives. A history of pregnancy also appears to increase the risk for autoimmune disease.

    The sex hormone that is commonly low in such women is Dehydroepiandrosterone (DHEA). This is a natural steroid and is produced by the adrenal glands, the reproductive organs and the brain.  DHEA is used by the body to make the male and female hormones, testosterone and estrogen respectively, and is known to have anti-inflammatory effects. It has been proposed that a DHEA deficiency is a contributing factor in autoimmune diseases.  Last year a study was done to look at precisely that effect.  The study’s conclusions have been supported by other, similar research and I think you’ll find it quite interesting.

    Dr. Vikki PetersenThe Journal of Clinical Endocrinology & Metabolism Vol. 94, No. 6 2044-2051(2009) published an article entitled “Low Serum Levels of Sex Steroids Are Associated with Disease Characteristics in Primary Sjogren’s Syndrome; Supplementation with Dehydroepiandrosterone Restores the Concentrations”. The authors investigated whether there was a relationship between steroid levels and the disease characteristics of Sjogren’s.

    They based their study on the known data that DHEA not only declines with aging but is reduced in Sjogren’s, an autoimmune disease. The study was populated by 23 post-menopausal women with primary Sjogren’s syndrome and subnormal levels of DHEA. The investigation was a controlled, double blind crossover study, conducted over a 9 month period, where DHEA was assessed by sophisticated laboratory measurements and typical symptoms of Sjogren’s such as dry mouth and eyes and salivary flow rates were similarly assessed.

    Results revealed a strong correlation between low DHEA and Sjogren’s symptoms.  DHEA and its sex hormone metabolites (testosterone and estrogen) were found to increase with DHEA supplementation but not with the placebo. Symptoms such as dry eyes were seen to improve as estrogen levels

    The researchers concluded that the disease manifestations of primary Sjogren’s syndrome were associated with low sex hormone levels and the supplementation of DHEA allowed the body to transform into androgens, testosterone and estrogen, with testosterone production predominating.

    Please allow me to add some personal interpretation. For the most part I agree with the premise and applaud the results. The facts that autoimmune disease occurs more often in women, that women frequently have low DHEA, and that androgens have anti-inflammatory effects that can benefit autoimmune disease are all true.

    But should we simply give such women DHEA and call it a day? I don’t think so.  I propose that we do three things: First, evaluate hormonal levels in women regularly; Second, address WHY their hormonal levels are imbalanced;  And third, when supplementing with hormones such as DHEA, ensure that the delivery system is one that mimics what the body does naturally.

    Remember that autoimmune disease can begin many years before the first symptoms become manifest. Therefore evaluating hormonal levels in our younger women is a good idea.  When I find DHEA levels that are low, my first order of business is to assess why.  Frequently it is due to a phenomenon known as “pregnenelone steal” that occurs when the adrenal glands are under stress.  It is a common occurrence and one of the fantastic abilities of the human body to shift from one pathway to another when under stress.  The “steal” pathway diverts the body away from making sex hormones and instead it makes more “stress” hormones.  So while adding some DHEA into the mix might very well help, does it make sense to find out WHY it’s being diverted away from making sex hormones?  I hope so because it’s the very foundation of the medicine that we practice—functional medicine.

    Once you understand the root cause of the deficiency you can take steps to truly remedy it rather than simply covering it up by taking DHEA.  Not to keep hitting you over the head with this concept, but supplementing with DHEA as your sole treatment misses the underlying cause since the body is designed to make adequate quantities of DHEA.

    A common reason for the diversion or “steal” pathway to become activated is adrenal stress from poor absorption of nutrients, unstable blood sugar and the presence of infections—all problems we see with the gluten intolerant patient! While I’m not implying that every autoimmune patient has a gluten intolerance, it certainly warrants screening all of them because of its high prevalence.
    As we travel down the road to optimal health through avoiding any food the body isn’t tolerating well, improving the integrity of the small intestine and normalizing adrenal function, there are certainly times when hormonal supplementation is beneficial. I don’t recommend the oral route because the first place the hormone travels is to the liver and this can be burdensome to that organ.  When the body makes hormones naturally it delivers them straight to the bloodstream.  In an effort to mimic that delivery system we use a buccal route (placed between cheek and gum in the mouth) that does a good job in bringing the hormone directly to the bloodstream and bypassing the liver and digestive tract.

    Autoimmune diseases comprise the third leading cause of death in our country and research strongly suggests that its rapid increase is due to environmental factors, especially those that weaken the small intestine. I am committed to earlier diagnosis while the disease is still remediable, as well as overall reduction of incidence through addressing digestive health.

    I hope you find this informative.  Please share this information with those who have autoimmune disease themselves as well as in their family.

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    Guest CeliBelli

    Posted

    I applaud you for your approach and analysis. All too often these columns only reiterate a study's abstract. The celiac community needs to assess these studies and scrutinize them to keep pressure in the right directions. The questions you pose are right on target. It is not enough to say, "Aha!" We must keep asking, why, why why?

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    Guest Elaine Hoffmann

    Posted

    This fits with my celiac disease experience. My metabolism changed after my first pregnancy and I probably was gluten intolerant. Many years later when I changed to a different birth control pill, I developed celiac disease overnight. It took seven years to diagnose the condition. I have been gluten free for seven years and feel so much better.

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    Guest Elizabeth

    Posted

    I so agree with all of what you have said. I wish I could find a doctor who thought and work in a similar way as yourself. At least I can bring your article to his attention and hope by slowly continuing to drip feed him in this way, he and his colleagues will see the light. Thank you!

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    Thanks for submitting this article. I have primary Sjogren's and celiac. My opinion is that there are many more people with gluten issues that have been overlooked in the past. I am so glad that the medical profession is becoming more aware of this problem and testing more frequently when an autoimmune disease is involved.

    I educate people whenever I can.

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    Amazing, I just started taking DHEA, I work in clinical research, I am 57 years old and I went undiagnosed with celiac disease for 40 years. I diagnosed myself and went off of gluten 4 years ago and have not been sick since, I also gained 20 pounds--I was basically malnourished--and now I feel great, however my libido needs a kick in the pants, I will let you know, thanks!

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    Guest Dr. Mary

    Posted

    Thank you for posting this. I am on bio identical hormone replacement and was diagnosed with Rheumatoid and Lupus last year after my doctor changed my prescription dramatically and the result was an acute flare. I'm currently having problems and was actually checking into suggestions to be sure they have the other female hormones balanced. I didn't expect to find the DHEA connection. I wish they would do more comprehensive studies. I had to have an ablation 2 years ago for a substantial tachycardia and when I take more than a very low dose of the DHEA, it causes my heart to race. The information had no suggestion as to dosages and that is imperative to success if prescribing or checking on your doctor's choice. Too bad in these studies they don't look at the down side and then make some conclusion based on the whole person. Thank you for the information, again.

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    Dr. Vikki Petersen D.C, C.C.N
    This article originally appeared in the Winter 2011 edition of Celiac.com's Journal of Gluten-Sensitivity.
    Celiac.com 05/16/2011 - Nearly 75% of the 24 million Americans suffering from autoimmune disease are women, according to the American Autoimmune Related Diseases Association (AARDA).  Women appear to mount larger inflammatory responses than men when their immune systems are triggered, thereby increasing their risk of autoimmunity.  The fact that sex hormones are involved is indicated by the fact that many autoimmune diseases fluctuate with hormonal changes such as those that occur during pregnancy, during the menstrual cycle, or when using oral contraceptives. A history of pregnancy also appears to increase the risk for autoimmune disease.
    The sex hormone that is commonly low in such women is Dehydroepiandrosterone (DHEA). This is a natural steroid and is produced by the adrenal glands, the reproductive organs and the brain.  DHEA is used by the body to make the male and female hormones, testosterone and estrogen respectively, and is known to have anti-inflammatory effects. It has been proposed that a DHEA deficiency is a contributing factor in autoimmune diseases.  Last year a study was done to look at precisely that effect.  The study’s conclusions have been supported by other, similar research and I think you’ll find it quite interesting.
    The Journal of Clinical Endocrinology & Metabolism Vol. 94, No. 6 2044-2051(2009) published an article entitled “Low Serum Levels of Sex Steroids Are Associated with Disease Characteristics in Primary Sjogren’s Syndrome; Supplementation with Dehydroepiandrosterone Restores the Concentrations”. The authors investigated whether there was a relationship between steroid levels and the disease characteristics of Sjogren’s.
    They based their study on the known data that DHEA not only declines with aging but is reduced in Sjogren’s, an autoimmune disease. The study was populated by 23 post-menopausal women with primary Sjogren’s syndrome and subnormal levels of DHEA. The investigation was a controlled, double blind crossover study, conducted over a 9 month period, where DHEA was assessed by sophisticated laboratory measurements and typical symptoms of Sjogren’s such as dry mouth and eyes and salivary flow rates were similarly assessed.
    Results revealed a strong correlation between low DHEA and Sjogren’s symptoms.  DHEA and its sex hormone metabolites (testosterone and estrogen) were found to increase with DHEA supplementation but not with the placebo. Symptoms such as dry eyes were seen to improve as estrogen levels
    The researchers concluded that the disease manifestations of primary Sjogren’s syndrome were associated with low sex hormone levels and the supplementation of DHEA allowed the body to transform into androgens, testosterone and estrogen, with testosterone production predominating.
    Please allow me to add some personal interpretation. For the most part I agree with the premise and applaud the results. The facts that autoimmune disease occurs more often in women, that women frequently have low DHEA, and that androgens have anti-inflammatory effects that can benefit autoimmune disease are all true.
    But should we simply give such women DHEA and call it a day? I don’t think so.  I propose that we do three things: First, evaluate hormonal levels in women regularly; Second, address WHY their hormonal levels are imbalanced;  And third, when supplementing with hormones such as DHEA, ensure that the delivery system is one that mimics what the body does naturally.
    Remember that autoimmune disease can begin many years before the first symptoms become manifest. Therefore evaluating hormonal levels in our younger women is a good idea.  When I find DHEA levels that are low, my first order of business is to assess why.  Frequently it is due to a phenomenon known as “pregnenelone steal” that occurs when the adrenal glands are under stress.  It is a common occurrence and one of the fantastic abilities of the human body to shift from one pathway to another when under stress.  The “steal” pathway diverts the body away from making sex hormones and instead it makes more “stress” hormones.  So while adding some DHEA into the mix might very well help, does it make sense to find out WHY it’s being diverted away from making sex hormones?  I hope so because it’s the very foundation of the medicine that we practice—functional medicine.
    Once you understand the root cause of the deficiency you can take steps to truly remedy it rather than simply covering it up by taking DHEA.  Not to keep hitting you over the head with this concept, but supplementing with DHEA as your sole treatment misses the underlying cause since the body is designed to make adequate quantities of DHEA.
    A common reason for the diversion or “steal” pathway to become activated is adrenal stress from poor absorption of nutrients, unstable blood sugar and the presence of infections—all problems we see with the gluten intolerant patient! While I’m not implying that every autoimmune patient has a gluten intolerance, it certainly warrants screening all of them because of its high prevalence.
    As we travel down the road to optimal health through avoiding any food the body isn’t tolerating well, improving the integrity of the small intestine and normalizing adrenal function, there are certainly times when hormonal supplementation is beneficial. I don’t recommend the oral route because the first place the hormone travels is to the liver and this can be burdensome to that organ.  When the body makes hormones naturally it delivers them straight to the bloodstream.  In an effort to mimic that delivery system we use a buccal route (placed between cheek and gum in the mouth) that does a good job in bringing the hormone directly to the bloodstream and bypassing the liver and digestive tract.
    Autoimmune diseases comprise the third leading cause of death in our country and research strongly suggests that its rapid increase is due to environmental factors, especially those that weaken the small intestine. I am committed to earlier diagnosis while the disease is still remediable, as well as overall reduction of incidence through addressing digestive health.
    I hope you find this informative.  Please share this information with those who have autoimmune disease themselves as well as in their family.


  • 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. 
    The team cross-referenced each article with the words ‘Asia,’ ‘Europe,’ ‘Africa,’ ‘South America,’ ‘North America,’ and ‘Australia.’ They defined celiac diagnosis based on European Society of Pediatric Gastroenterology, Hepatology, and Nutrition guidelines. The team used 96 articles of 3,843 articles in their final analysis.
    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.

    Jefferson Adams
    Celiac.com 06/16/2018 - Summer is the time for chips and salsa. This fresh salsa recipe relies on cabbage, yes, cabbage, as a secret ingredient. The cabbage brings a delicious flavor and helps the salsa hold together nicely for scooping with your favorite chips. The result is a fresh, tasty salsa that goes great with guacamole.
    Ingredients:
    3 cups ripe fresh tomatoes, diced 1 cup shredded green cabbage ½ cup diced yellow onion ¼ cup chopped fresh cilantro 1 jalapeno, seeded 1 Serrano pepper, seeded 2 tablespoons lemon juice 2 tablespoons red wine vinegar 2 garlic cloves, minced salt to taste black pepper, to taste Directions:
    Purée all ingredients together in a blender.
    Cover and refrigerate for at least 1 hour. 
    Adjust seasoning with salt and pepper, as desired. 
    Serve is a bowl with tortilla chips and guacamole.

    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.
    So how, you may ask, is all this related to gluten? As a starting point, one report from the medical literature identifies a patient who developed aphasia after admission for severe diarrhea. By the time celiac disease was diagnosed, he had completely lost his faculty of speech. However, his speech and normal bowel function gradually returned after beginning a gluten free diet (8). This finding was so controversial at the time of publication (1988) that the authors chose to remain anonymous. Nonetheless, it is a valuable clue that suggests gluten as a factor in compromised speech production. At about the same time (late 1980’s) reports of connections between untreated celiac disease and seizures/epilepsy were emerging in the medical literature (9).
    With the advent of the Internet a whole new field of anecdotal information was emerging, connecting a variety of neurological symptoms to celiac disease. While many medical practitioners and researchers were casting aspersions on these assertions, a select few chose to explore such claims using scientific research designs and methods. While connections between stuttering and gluten consumption seem to have been overlooked by the medical research community, there is a rich literature on the Internet that cries out for more structured investigation of this connection. Conversely, perhaps a publication bias of the peer review process excludes work that explores this connection.
    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.
    The team divided the TCR-GR patterns into clonal, polyclonal and prominent clonal peaks (PCPs), and correlated these patterns with clinical and pathological features. In all, they detected clonal TCR-GR products in biopsies from 67% of patients with RCDII, 17% of patients with RCDI and 6% of patients with gluten-free diet. They found PCPs in all disease phases, but saw no significant difference in the TCR-GR patterns between the non-RCDII disease categories (p=0.39). 
    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).
    The research team included Y.‐H. Dong; Y. Jin; TN Tsacogianis; M He; PH Hsieh; and JJ Gagne. They are variously affiliated with the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School in Boston, MA, USA; the Faculty of Pharmacy, School of Pharmaceutical Science at National Yang‐Ming University in Taipei, Taiwan; and the Department of Hepato‐Gastroenterology, Chi Mei Medical Center in Tainan, Taiwan.
    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.
    This is the first comprehensive multi‐database study to document a higher rate of enteropathy in olmesartan initiators as compared to initiators of other ARBs, though absolute rates were low for both groups.
    Source:
    Alimentary Pharmacology & Therapeutics