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    Should HLA Come First in Celiac Disease Screening for Arthritis Patients?


    Jefferson Adams
    Image Caption: Photo: CC--Keoni Cabral

    Celiac.com 03/16/2017 - When screening arthritis patients for celiac disease, should HLA be done before serology? During the past decades, an accumulating evidence shows a dramatic rise in the frequency of autoimmune diseases, including rheumatoid arthritis and gastrointestinal conditions, such as celiac disease.


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    HLA genes have been shown to be strongly associated with numerous autoimmune diseases, including rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA) and celiac disease. A team of researchers recently set out to assess the performance of celiac disease associated serology in face of a rheumatologic patient, when gluten enteropaty is suspected.

    The research team included Hakim Rahmoune, Nada Boutrid, Mounira Amrane, and Belkacem Bioud. They are variously affiliated with the Pediatrics Department and the Biochemistry Department of Setif University Hospital at Setif-1 University in Algeria.

    The main question they sought to answer was: Should HLA be done prior to the serology? Could unnecessary serial serological celiac disease screening in such rheumatology patient be avoided by performing an HLA typing, as a long-life marker of genetically celiac disease-susceptible patients?

    Serogenetic screening without the requirement for follow-up small bowel biopsies provides a flexible, cost-effective methodology that could be widely applied to obtain accurate estimates of the prevalence of celiac disease in large group studies.

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    Guest Audrey VanWyk

    Posted

    I lived 67 years with so many issues including severe arthritis, gut, migraine, neurophy, depression, acne, leg pain and other issues. I went to specialists at university teaching hospitals and after everything was eliminated, I asked if it could be gluten related. No, you didn't test for celiac. Three sisters and we all have issues and my younger sister determined it was gluten and I went gluten-free. I did DNA research. Yes HLA DQA1. No doctor asks for that info perhaps because they don't know. Rhumatoligist for scleroderma acknowledged confirmation of gluten intolerance. My 21 year old grandson confirmed autoimmune diseases. Why isn't DNA used as a tool? Years of illness untreated means years of lost quality of life.

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  • About Me

    Jefferson Adams is a freelance writer living in San Francisco. He has covered Health News for Examiner.com, and provided health and medical content for Sharecare.com. His work has appeared in Antioch Review, Blue Mesa Review, CALIBAN, Hayden's Ferry Review, Huffington Post, the Mississippi Review, and Slate, among others.

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  • Related Articles

    Scott Adams
    Arthritis may be an allergic response to materials in the food supply. Diet revision may be helpful in reducing the activity of inflammatory arthritis and in some instances may halt the progression of the disease. There are many patterns of arthritis. A group of related joint and connective disorders have been called rheumatic diseases. All these diseases are immune-mediated, and all are expressions of inflammation in connective tissues. Inflammation damages joints and surrounding tissues resulting in loss of function and deformities. Variations in the patterns of these diseases reflect the many possibilities for immune damage to disturb and distort structure and function. Severity ranges from mildly painful, chronic activity to drastic, disabling disease. Rheumatoid arthritis, often severe and disabling, is the dominant rheumatic disease that can attack all joints in the body.
    Rheumatoid arthritis is often considered to be an autoimmune disease. Our idea is that no disease is just internally generated and must involve outside contributions. Arthritis is often associated with inflammatory bowel disease. The mechanisms of food allergy link abnormal Gastrointestinal Tract (GIT) function with immune attacks on connective tissue. In all arthritic patients, normal GIT function should be rigorously sought by adaptive dietary adjustments.
    Simple allergic arthritis is a definite entity that is often not recognized as a food allergy. Typically, a dramatic, acute, and painful swelling develops in one or more joints asymmetrically. Eating a food, either an unusual food eaten for the first time or sometimes a regular food eaten in excess usually brings on the joint inflammation. This presentation is similar to and often confused with gout. Any food can cause allergic arthritis. Staple foods such as milk, eggs, and wheat (rye, oats, barley), coffee, beef, pork, and food additives are the most common food triggers. Carinini and Brostroff reviewed the concepts of and evidence for food-induced arthritis. They stated:


    Despite an increasing interest in food allergy and the conviction of innumerable patients with joint disease that certain foods exacerbate their symptoms, relatively little scientific attention has been paid to this relationship. Abnormalities of the gastrointestinal tract are commonly found in rheumatic disease...Support for an intestinal origin of antigens comes from studies of patients whose joint symptoms have improved on the avoidance of certain foods antigens, and become worse on consuming them. These have included patients with both intermittent symptoms, palindromic rheumatism and more chronic disease.
    In another study, 33 of 45 patients with rheumatoid arthritis improved significantly on a hypoallergenic diet. The authors concluded: Increasing numbers of scientific studies suggest that dietary manipulation may help at least some rheumatoid patients and perhaps the greatest need now is for more careful and well-designed research so that preconceptions may be put aside and role of diet, as a specific or even a nonspecific adjunctive therapy, may be determined.
    Unfortunately, dairy products, wheat and its close relatives, oats, barley, and rye, have proved to be a major problem in the diets of our patients. There are many possible reasons for cereal grains to become pathogenic. Hypersensitivity mechanisms triggered by grain proteins, collectively called Gluten, are the likely cause of the illnesses related to intake of cereal grains. Gluten is a mixture of individual proteins classified in two groups, the Prolamines and the Glutelins. The prolamine fraction of gluten concerns us the most when grain intolerance is suspected. The prolamine, Gliadin, seems to be a problem in celiac disease; gliadin antibodies are commonly found in the immune complexes associated with this disease. Recently marketed grains, spelt and kamut, are wheat variants (despite claims to the contrary) and are likely to cause problems similar to other wheat varieties.
    A wheat gluten mechanism has been studied in rheumatoid arthritis patients. The clinical observation is that wheat ingestion is followed within hours by increased joint swelling and pain. Little and his colleagues studied the mechanism, as it developed sequentially following gluten ingestion. Dr. Parke and colleagues concurred with this explanation of the gut-arthritis link in their report of three patients with celiac disease and rheumatoid arthritis. The mechanism involves several stages:
    GIT must be permeable to antigenic proteins or peptide fragments, derived from digested gluten. The food antigens appear in the blood stream and are bound by a specific antibody (probably of IgA or IgG, not IgE class), forming an antigen-antibody complex, a circulating immune complex (CIC). The antigen-antibody complex then activates the rest of the immune response, beginning with the release of mediators - serotonin is released from the blood platelets. Serotonin release causes symptoms as it circulates in the blood stream and enhances the deposition of CICs in joint tissues. Once in the joint, the immune complexes activate complement, which in turn damages cells and activates inflammation. More inflammation results in more pain, swelling, stiffness, and loss of mobility.
    Arthritis is usually treated with salicylates or related anti-inflammatory drugs generally referred to as NSAIDs. These drugs alleviate the terrible pain of active arthritis but do not favorably affect the outcome of the disease. All anti-arthritic medication can produce asthma or chronic rhinitis and a variety of allergic skin rashes. Gastrointestinal surface irritation, bleeding, and ulceration are routine problems of anti-arthritic medication.
    The first attack of joint swelling and pain should be treated as an urgent problem to be solved. Inflammation may damage joints. Often NSAIDs and physiotherapy are the only treatments prescribed and inflammation is given every opportunity to ravage tissues. We have seen countless patients, just treated with NSAIDs, who progressed rapidly to a severe disabling disease, often with poor pain control. In unlucky patients, severe deformities of joints accumulate in the first few months of a severe attack. There is a trend to recommend more aggressive treatments, using drugs that impair the immune response. The best drug is prednisone, but it is seldom used because it has long-term side effects which scare both physicians and patients. Prednisone is often a magic drug that relieves terrible pain and suffering often in the first 48 hours of therapy. Beyond prednisone, there is a grab bag of immune suppressant drugs to treat arthritis-chloroquine, penicillamine, gold and methotrexate have emerged as the favored drug therapies. All these drugs have impressive side effects and great potential for toxicity.
    Our preference is to try to stop the inflammatory activity as soon as possible with diet revision. All inflammation is likened to a fire. You get out the fire-extinguishers and go to work. No matter what pattern the immune attack assumes, our standard defense can be tried first. The Core Program method of diet revision is used. Food is replaced with an elemental nutrient formula, ENFood, for a clearing period of 10 to 20 days. Prednisone and/or NSAIDs are drug options during the clearing period and then the dosage is reduced after pain and swelling have subsided. Improvement is followed by slow food reintroduction (see Core Program). Each returning food is carefully screened for arthritis- triggering effects. You hope that food allergy caused the problem and that food control can be successful controlling the disease in the long- term. Nothing is lost by taking this approach and complete control of the disease can sometimes be obtained. If strict food control proves to be inadequate, then other drug treatments can be instituted.
    End Notes/Sources:
    Carinini C, Brostroff J. Gut and joint disease. Annals of Allergy 1985;55:624-625. Darlington et al. Lancet Feb 1 1986;236-238. Keiffer M et al. Wheat gliadin fractions and other cereal antigens reactive with antibodies in the sera of of celiac patients. Clin Exp Immunol 1982;50:651-60. Little C, Stewart AG, Fennesy MR. Platelet serotonin release in rheumatoid arthritis: a study in food intolerant patients. Lancet 1983;297-9. Parke AI et al. Celiac disease and rheumatoid arthritis. Annals of Rheum Dis 1984;43:378-380. Voorneveld CR, Rubin LA Disease-modifying antirheumatic drugs: early use is better. Medicine North Amer. Oct 1991 3177-3184.

    Jefferson Adams
    Celiac.com 06/08/2007 - In the first study, doctors Ibrahim S. Alghafeer, and Leonard H. Sigal conducted a routine gastroenterology follow-up of 200 adult celiac patients. Arthritis was present in 52 of 200 patients, or 26%. The arthritis was peripheral in 19 patients, Axial in 15 patients, and an overlap of the two in 18 patients. The doctors found that joint disease was much less common in those patients who were following a gluten-free diet (1).
    A related study by Usai, et al found that 63% of patients with celiac disease show axial joint inflammation (2).
    In that study, doctors conducted bone scintigraphy using 99m Tc methylene diphosphonate. 14 of these patients (65%) signs compatible with sacroiliitis. 11 of the 14 suffered from low back pain. In five of the 11 patients with low back pain, scintigraphy was negative. Sacroiliac radiographs were conducted on 4 of those 5 patients, and all of them were shown to have bilateral sacroiliitis. One patient had rheumatoid arthritis, but all patients in the studied showed negative HLA-B27 results.
    Rheumatoid Symptoms Less Common in Celiacs on Gluten-free Diet
    In patients with gluten enteropathy, symptoms of arthritis and other rheumatic complaints are common, and the associated clinical abnormalities routinely show improvement on a gluten-free diet. (3,4,5)
    In 9 of 74 patients with spondyloarthropathies, results show increased level of antigliadin antibodies, with 1 patient showing elevated antiendomysium antibodies and biopsy proven celiac disease (6). These results show that antiendomysial antibody testing is recommended as a screening tool in patients with suspected gluten enteropathy. Another study found that 3.3% of sprue patients had Sjogrens syndrome (7).
    55 celiac patients who were tested for serial bone density showed osteoporosis in 50% of men and 47% of women. These findings confirm that celiac disease was an independent risk factor for osteoporosis (8).
    Bulletin on the Rheumatic Diseases, Volume 51, Number 2.
    Usai P. Adult celiac disease is frequently associated with sacroiliitis. Dig Dis Sci 1995;40:1906-8 Lubrano E, Ciacci C, Ames PR, et al. The arthritis of celiac disease: prevalence and pattern in 200 adult patients. Br J Rheumatol 1996;35:1314-8. Usai P. Adult celiac disease is frequently associated with sacroiliitis. Dig Dis Sci 1995;40:1906-8. Bagnato gluten-free, Quattrocchi E, Gulli S, et al. Unusual polyarthritis as a unique clinical manifestation of celiac disease. Rheumatol Int 2000;20:29-30. Borg AA, Dawes PT, Swan CH, Hothersall TE. Persistent monoarthritis and occult celiac disease. Postgrad Med J 1994;70:51-3. Collin P, Korpela M, Hallstrom O, et al. Rheumatic complaints as a presenting symptom in patients with celiac disease. Scan J Rheumatol 1992;21:20-3. Kallilorm R, Uibo O, Uibo R. Clin Rheumatol 2000;19:118-22. health writer who lives in San Francisco and is a frequent author of articles for Celiac.com.

    Jefferson Adams
    Celiac.com 04/08/2013 - Numerous studies have shown a connection between celiac disease and various types of arthritis.
    A team of researchers recently set out to investigate the occurrence of lower limb enthesopathy in celiac disease patients without clinical signs of articular involvement. Entheses are the places where collagen fibers of a tendon, ligament or muscle are mineralized and connected into bone tissue. Entheseal abnormalities are abnormalities of these areas, and are often associated with arthritis.
    The team wanted to use ultrasound to investigate the presence of entheseal abnormalities in patients with celiac disease without clinical signs of articular involvement, and then compare the results with healthy control subjects.
    The research team included M. Atteno, L. Costa, R. Tortora, A. Cozzolino , A. Del Puente, F. Caso, P. Sfriso, R. Scarpa, and C. Ciacci. They are affiliated with the Rheumatology Research Unit in the Department of Clinical and Experimental Medicine of the Gastroenterology Research Unit in the Department of Clinical and Experimental Medicine at University Federico II of Naples, Naples, the Gastroenterology Unit at Santo Ottone Hospital in Ariano Irpino, Avellino, the Rheumatology Research Unit of the Department of Clinical and Experimental Medicine at the University of Padova in Padova, and the Department of Medicine and Surgery, Gastroenterology, at the University of Salerno in Salerno, Italy.
    For their study, the team looked at sixty patients with asymptomatic celiac disease who attended the gastroenterology outpatient clinic of the University Federico II of Naples. They then compared the celiac patients with sixty healthy control subjects matched for age and sex. Both groups of patients received clinical and ultrasound examination.
    The results showed that 24 of the sixty celiac disease patients (40%) showed at least one entheseal abnormality, compared with just six of the sixty (10%) healthy control subjects (P < 0.01).
    Interestingly, the celiac disease patients more commonly showed abnormalities of the patella (distal and proximal), while nearly all abnormalities in the healthy controls were found in the Achilles tendon.
    The results of this study demonstrate the ability of ultrasound to detect signs of subclinical entheseal abnormalities, and reveal higher rates of subclinical entheseal abnormalities in people with asymptomatic celiac disease.
    Source:
    Rheumatology (Oxford). 2013 Jan 7.

    Jefferson Adams
    Celiac.com 07/09/2015 - Children presenting for rheumatology evaluation have undiagnosed celiac disease at double the rates of the general population, says the latest study.
    However, current clinical guidelines do not consider patients with rheumatic conditions to be at high risk for celiac disease despite numerous reported associations between the two in adults and children.
    A team of researchers set out to assess the prevalence of celiac disease among kids receiving a rheumatology evaluation. The research team included Yekaterina Sherman, BA, Rose Karanicolas, MD, Brittany DiMarco, BA, Nancy Pan, MD, Alexa B. Adams, MD, Laura V. Barinstein, MD, L. Nandini Moorthy, MD, and Thomas J. A. Lehman, MD. They are variously affiliated with the Division of Pediatric Rheumatology, Hospital for Special Surgery, New York, New York; the Division of Rheumatology, Mount Sinai Medical Center, New York, New York; and the Division of Pediatric Rheumatology, Robert Wood Johnson Medical School in New Brunswick, New Jersey.
    The team conducted celiac disease screenings on a total of 2,125 patients presenting for initial evaluation by the Division of Pediatric Rheumatology at the Hospital for Special Surgery between June 2006 and December 201, as a part of the standard initial serologic evaluation. The team then reviewed the charts at the end of this period. From this information, the team diagnosed celiac disease in a total of 36 patients (30 girls, 6 boys, mean age 9.4 ± 4.3 years, range 2–16 years), after serologic testing and evaluation by pediatric gastroenterology.
    Eight additional patients with known celiac disease diagnoses presented during this time period. The total prevalence of celiac disease over this 6.5-year period was 2.0%. The most commonly reported complaints among patients diagnosed with celiac disease were myalgias, arthralgias, and skin rash.
    Less frequently, patients reported gastrointestinal complaints including abdominal pain, nausea, and diarrhea.
    All patients reported improvement or complete resolution of their musculoskeletal symptoms after beginning a gluten-free diet.
    In this study, the team found 36 new cases of celiac disease among children presenting for rheumatology evaluation, for an overall prevalence rate of 2.0%.
    The majority of patients who ultimately received a diagnosis of celiac disease presented with extra-intestinal manifestations.
    These results underscore the importance of celiac disease screening in children receiving a rheumatology evaluation.
    Source:
    http://pediatrics.aappublications.org/content/early/2015/06/09/peds.2014-2379.abstract

  • Recent Articles

    Christina Kantzavelos
    Celiac.com 07/20/2018 - During my Vipassana retreat, I wasn’t left with much to eat during breakfast, at least in terms of gluten free options. Even with gluten free bread, the toasters weren’t separated to prevent cross contamination. All of my other options were full of sugar (cereals, fruits), which I try to avoid, especially for breakfast. I had to come up with something that did not have sugar, was tasty, salty, and gave me some form of protein. After about four days of mixing and matching, I was finally able to come up with the strangest concoction, that may not look the prettiest, but sure tastes delicious. Actually, if you squint your eyes just enough, it tastes like buttery popcorn. I now can’t stop eating it as a snack at home, and would like to share it with others who are looking for a yummy nutritious snack. 
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    Jefferson Adams
    Celiac.com 07/19/2018 - Maintaining a gluten-free diet can be an on-going challenge, especially when you factor in all the hidden or obscure gluten that can trip you up. In many cases, foods that are naturally gluten-free end up contain added gluten. Sometimes this can slip by us, and that when the suffering begins. To avoid suffering needlessly, be sure to keep a sharp eye on labels, and beware of added or hidden gluten, even in food labeled gluten-free.  Use Celiac.com's SAFE Gluten-Free Food List and UNSAFE Gluten-free Food List as a guide.
    Also, beware of these common mistakes that can ruin your gluten-free diet. Watch out for:
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    Jefferson Adams
    Celiac.com 07/18/2018 - Despite many studies on immune development in children, there still isn’t much good data on how a mother’s diet during pregnancy and infancy influences a child’s immune development.  A team of researchers recently set out to assess whether changes in maternal or infant diet might influence the risk of allergies or autoimmune disease.
    The team included Vanessa Garcia-Larsen, Despo Ierodiakonou, Katharine Jarrold, Sergio Cunha,  Jennifer Chivinge, Zoe Robinson, Natalie Geoghegan, Alisha Ruparelia, Pooja Devani, Marialena Trivella, Jo Leonardi-Bee, and Robert J. Boyle.
    They are variously associated with the Department of Undiagnosed Celiac Disease More Common in Women and Girls International Health, Johns Hopkins School of Public Health, Baltimore, Maryland, United States of America; the Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College London, London, United Kingdom; the Section of Paediatrics, Department of Medicine, Imperial College London, London, United Kingdom; the Centre for Statistics in Medicine, University of Oxford, Oxford, United Kingdom; the Division of Epidemiology and Public Health, University of Nottingham, Nottingham, United Kingdom; the Centre of Evidence Based Dermatology, University of Nottingham, Nottingham, United Kingdom; and Stanford University in the USA.
    Team members searched MEDLINE, Excerpta Medica dataBASE (EMBASE), Web of Science, Central Register of Controlled Trials (CENTRAL), and Literatura Latino Americana em Ciências da Saúde (LILACS) for observational studies conducted between January 1946 and July 2013, and interventional studies conducted through December 2017, that evaluated the relationship between diet during pregnancy, lactation, or the first year of life, and future risk of allergic or autoimmune disease. 
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    They found a high bias risk in nearly half of the more than 250 milk feeding studies and in about one-quarter of studies of other dietary exposures. Evidence from 19 intervention trials suggests that oral supplementation with probiotics during late pregnancy and lactation may reduce risk of eczema. 44 cases per 1,000; 95% CI 20–64), and 6 trials, suggest that fish oil supplementation during pregnancy and lactation may reduce risk of allergic sensitization to egg. GRADE certainty of these findings was moderate. 
    The team found less evidence, and low GRADE certainty, for claims that breastfeeding reduces eczema risk during infancy, that longer exclusive breastfeeding is associated with reduced type 1 diabetes mellitus, and that probiotics reduce risk of infants developing allergies to cow’s milk. 
    They found no evidence that dietary exposure to other factors, including prebiotic supplements, maternal allergenic food avoidance, and vitamin, mineral, fruit, and vegetable intake, influence risk of allergic or autoimmune disease. 
    Overall, the team’s findings support a connection between the mother’s diet and risk of immune-mediated diseases in the child. Maternal probiotic and fish oil supplementation may reduce risk of eczema and allergic sensitization to food, respectively.
    Stay tuned for more on diet during pregnancy and its role in celiac disease.
    Source:
    PLoS Med. 2018 Feb; 15(2): e1002507. doi:  10.1371/journal.pmed.1002507

    Jefferson Adams
    Celiac.com 07/17/2018 - What can fat soluble vitamin levels in newly diagnosed children tell us about celiac disease? A team of researchers recently assessed fat soluble vitamin levels in children diagnosed with newly celiac disease to determine whether vitamin levels needed to be assessed routinely in these patients during diagnosis.
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    The team evaluated 27 female, 25 male celiac patients, and an evenly divided group of 50 healthy control subjects. Patients averaged 9 years, and weighed 16.2 kg. The most common symptom in celiac patients was growth retardation, which was seen in 61.5%, with  abdominal pain next at 51.9%, and diarrhea, seen in 11.5%. Histological examination showed nearly half of the patients at grade Marsh 3B. 
    Vitamin A and vitamin D levels for celiac patients were significantly lower than the control group. Vitamin A and vitamin D deficiencies were significantly more common compared to healthy subjects. Nearly all of the celiac patients showed vitamin D insufficiency, while nearly 62% showed vitamin D deficiency. Nearly 33% of celiac patients showed vitamin A deficiency. 
    The team saw no deficiencies in vitamin E or vitamin K1 among celiac patients. In the healthy control group, vitamin D deficiency was seen in 2 (4%) patients, vitamin D insufficiency was determined in 9 (18%) patients. The team found normal levels of all other vitamins in the healthy group.
    Children with newly diagnosed celiac disease showed significantly reduced levels of vitamin D and A. The team recommends screening of vitamin A and D levels during diagnosis of these patients.
    Source:
    BMC Pediatrics

    Jefferson Adams
    Celiac.com 07/16/2018 - Did weak public oversight leave Arizonans ripe for Theranos’ faulty blood tests scam? Scandal-plagued blood-testing company Theranos deceived Arizona officials and patients by selling unproven, unreliable products that produced faulty medical results, according to a new book by Wall Street Journal reporter, whose in-depth, comprehensive investigation of the company uncovered deceit, abuse, and potential fraud.
    Moreover, Arizona government officials facilitated the deception by providing weak regulatory oversight that essentially left patients as guinea pigs, said the book’s author, investigative reporter John Carreyrou. 
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    According to Carreyrou, Theranos’ lies and deceit made Arizonans into guinea pigs in what amounted to a "big, unauthorized medical experiment.” Even though founder Elizabeth Holmes and Theranos duped numerous people, including seemingly savvy investors, Carreyrou points out that there were public facts available to elected officials back then, like a complete lack of clinical data on the company's testing and no approvals from the Food and Drug Administration for any of its tests.
    SEC recently charged the now disgraced Holmes with what it called a 'years-long fraud.’ The company’s value has plummeted, and it is now nearly worthless, and facing dozens, and possibly hundreds of lawsuits from angry investors. Meantime, Theranos will pay Arizona consumers $4.65 million under a consumer-fraud settlement Arizona Attorney General Mark Brnovich negotiated with the embattled blood-testing company.
    Both investors and Arizona officials, “could have picked up on those things or asked more questions or kicked the tires more," Carreyrou said. Unlike other states, such as New York, Arizona lacks robust laboratory oversight that would likely have prevented Theranos from operating in those places, he added.
    Stay tuned for more new on how the Theranos fraud story plays out.
    Read more at azcentral.com.