1. Non-Celiac Gluten Sensitivity

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1 Canada was well represented at the 2015 International Celiac Disease Symposium (ICDS) held in Prague in June Professional Advisory Board members Dr. Decker Butzner, Dr. Don Duerksen, Dr. Elena Verdu and Dr. Jenni Zelin attended the conference, and Dr. Verdu served on the organizing committee. Dr. Jocelyn Silvester, a former CCA Young Investigator Award winner presented her research about her research. Dr. Justine Dowd was present to discuss her research poster and current and CCA-sponsored research was reported in at least six additional posters. CCA Board Member Mark Johnson and Operations Manager Sue Newell represented the CCA at the conference and met with representatives from more than 20 Patient Support Groups worldwide. This report represents their report to you on what they learned at the conference. If you prefer a shorter presentation, a 30-minute audio interview is available at 1. Non-Celiac Gluten Sensitivity This mysterious and most unpleasant disorder has been a point of major contention as of late, with some media reports suggesting that it may not exist. This is rather misleading there is certainly something going on here, but some have suggested that non-celiac gluten sensitivity (NCGS) may in fact not be accurate in terms of its name. Research continues on the causes and indicators of this condition. At ICDS, the assertion that NCGS is something that might be all in your head never came up we know there is a problem, we just do not yet know exactly what it is. NCGS prevalence was estimated to be 1:438 in , but now it s more like 1:10. This is a major shift. There are opposing views out there on what NCGS is. Some believe it to be a reaction to gluten or something else in wheat, rye and barley. Others are thinking it may be a result of a sensitivity to FODMAPs. At least one scientist presenting at ICDS preferred to refer to NCGS as gluten ataxia. The research on NCGS is still quite young but many trials and tests are taking place. NCGS isdefinitely not a wheat allergy and cannot be compared to such a condition. Wheat allergy is a rapid, allergic response, very distinct from celiac disease and NCGS. Comprehensive research on wheat allergies is difficult to undertake because the condition is extremely rare. 1

2 NCGS is clinically the same as celiac, but without enteropathy or serology. The lack of definitive biomarkers means that NCGS has been very difficult to diagnose. For the moment, NCGS needs to be diagnosed by exclusion. According to Dr. Carlo Catassi of Italy, NCGS patients will have a negative blood serology for celiac disease, negative immune-allergy tests to wheat, and no intestinal damage. A gene test is also helpful for excluding celiac disease. As with celiac, NCGS symptoms can be intestinal and/or non-intestinal. For someone believed to have NCGS, the clinical response to the gluten-free diet needs to be analyzed. The symptoms should be measured and compared with the response when the patient goes gluten-free. If the patient is already eating gluten-free, a gluten challenge should be undertaken to determine whether they are celiac, NCGS, or something else. Patients are considered responsive to the gluten-free diet when at least 30% of the baseline score reduces in terms of symptoms. One interesting study, out of the UK and Iran, found that dyspepsia (indigestion) may be the main presentation of NCGS patients, so that is something to watch out for. 68% of NCGS patients had dyspepsia versus just 12% of celiacs. Weight loss and osteopenia were also often noted in NCGS patients. From a scientific research perspective, testing of patients for NCGS needs to take place with pure gluten not with gluten-containing products like wheat. Results can then be compared with patients taking a placebo. Some trials have found that many patients in studies that think they are NCGS actually do not show a reaction to gluten so that s when we get into considering whether the issue may be wheat, FODMAPs, or other conditions. The research to date is conflicted, and may be impacted by the placebo effect, whereby people expecting to feel symptoms will report feeling symptoms. Dr. Catassi emphasized that NCGS cannot be self-diagnosed. It can also not be diagnosed by simple elimination of foods. It needs a positive diagnosis and for celiac disease to be firmly excluded. Starting with the genetic testing is a good idea, since if celiac can be permanently excluded, that may save a lot of hassle down the road. Studies are looking at whether we might be able to nail down some kind of blood marker for NCGS. For example, one study found IgG antigliadin antibodies in up to 56% of patients claiming to have NCGS, and the antibodies have been shown to disappear quickly when the patient goes glutenfree. Interestingly, in about 40% of celiacs, these antibodies remained positive after a period on the gluten-free diet. But for the NCGS patients, almost all disappeared. Because of the difficulty of getting a firm NCGS diagnosis, the condition is often taken less seriously by one s medical professional(s). As a result, according to a Norwegian study, celiacs are more likely to be professionally coached on diet than those with NCGS. And yet, adherence to the gluten-free diet was found to be only minimally higher in celiac patients vs. the gluten sensitive. At ICDS, there was significant discussion of how to test subjects for NCGS. How much gluten per day? How many times a day? For how long? What delivery medium? (e.g. bars, capsules, 2

3 powder, etc.) Testing with bars, muffins etc. creates the problem that research subject may be able to figure out for certain which is placebo and this knowledge could taint the results of the research. Researchers are also looking at whether there may be conditions associated with NCGS. For example, research out of the UK found a high incidence of self-reported NCGS in patients with postural tachycardia syndrome. Be aware that there is an acknowledged scarcity of well-conducted studies relating to NCGS.Many scientists at ICDS were pushing for more research studies looking at open or blinded wheat/gluten challenges to further analyze NCGS. Stay tuned for additional developments! From the Scientific Forum At the previous ICDS presentation there was a lot of discussion of FODMAPs as a possible cause of NCGS. FODMAPs represent short chain carbohydrates and sugar alcohols that are very difficult for everyone to diagnose. Wheat, barley and rye contain fructans, one of the types of FODMAPS. This year, there was still discussion about fructans as a possible trigger but there was also consideration given to amylase trypsin inhibitors (ATIs), a natural pesticide found in these grains. ATIs may have an influence on the intestinal inflammation found in people with NCGS. This inflammation has been demonstrated in mouse studies. One of the challenges in identifying which trigger is responsible for reactions is that these three compounds are all present in wheat. The other question is the wide variation in presentation of patients with NCGS. There may be a variety of causes leading to similar symptoms. One study did a very careful double blind gluten challenge and found that 25% of their group responded negatively to gluten. A similar doubleblind challenge in patients diagnosed with Irritable Bowel Syndrome had fewer symptoms on a gluten-free diet than on a placebo diet. 2. Prevention of celiac disease? For years, researchers have been looking at ways of possibly preventing celiac disease rather than simply treating diagnosed cases. As you may be aware, breastfeeding has been hailed as having a protective effect, and there were guidelines as to when to introduce gluten into an infant s diet, especially when the risk is high for celiac disease. Unfortunately, breastfeeding as a way to prevent celiac has been disproven. Still, due to the positives, and with breast milk containing bioactive substances, hormones with anti-inflammatory properties, and neuropeptides, breastfeeding is still highly recommended! We do know that breastfed children tend to have fewer infections and higher IQs than those that are not. 3

4 Studies show that gender, amount of gluten, breastfeeding duration, and intestinal infection did not make much difference in terms of celiac risk.whether children are partially or totally breastfed was also inconsequential. Feeding patterns in the first years of life seem to play a minor role in terms of celiac disease. Dr. Joe Murray of the Mayo Clinic cautions, however, that more research is needed to confirm these findings. That said, in terms of celiac risk, the genetic makeup of a child appears to be much more important than the diet. Celiac, as we know, is nothing like a food allergy. However, it may still be possible to prevent the onset of celiac disease, and scientists have looked at a number of factors. According to Dr. Alessio Fasano, what happens in the gut may have tremendous consequences for us, including effects on the brain. Intestinal health is important for everyone. Generally, you are much better off if you were delivered vaginally (as opposed to by caesarean section) and in early life had proper nutrition, no infections, and no antibiotic treatments. Early antibiotic treatment in children increases the risk of allergies in particular because of the effect on microbiota.one study also found that more frequent maternal infections during pregnancy are associated with an increased risk of the child developing celiac.swedish research found no connection between children getting a rotavirus or respiratory infections and likelihood of developing celiac disease. The gluten impact on the brain, outside of celiac disease, is an exciting area of new research.studies are also going on to see whether certain infections may play a role in someone s likelihood of developing celiac disease. Several presenters used the word epidemic in relation to celiac disease, particularly in some areas of the world (e.g. Scandinavia). Worldwide, the prevalence of celiac has increased fivefold since the mid-1970s. Given that our genome has not been changing much, the blame is being put on yet-to-be-confirmed environmental factors. For example, Israeli research is currently looking at whether certain food additives may play a role in the increased celiac prevalence and gut permeability. We know environmental factors are key so, theoretically, it should be possible to prevent celiac disease. Dr. Frits Koning of the Netherlands is working hard on research trying to identify if certain cells may be responsible for the onset of celiac disease. His focus now is on certain t-cell receptors that seem to be present in celiacs. Dr. Koning himself, for example, has the genes for celiac, but does not have the t-cell receptors, and does not have celiac disease yet. With knowledge of what cells may be causing the development of celiac, if we can get rid of them, we can reduce the risk. However, Dr. Koning warned that it took 20 years of research to get where he is now, and we're a good 10 years away from a solution here. 4

5 3. Celiac Disease Diagnosis Celiac disease is chronic small intestinal immune-mediated enteropathy precipitated by exposure to gluten in genetically predisposed people. That s according to Sweden s Dr. Jonas Ludvigsson. Gluten is the most important protein fraction (80%) in wheat, rye and barley, and the average European consumes grams of gluten per day. For celiacs, the toxic fractions are in both gliadins and glutenins. However, the gluten proteins in maize, rice, millet and sorghum are safe for celiac patients. Gluten is Latin for glue and indeed, it holds things together. Looking way back, the first cases of celiac were believed found in ancient Egypt or Greece. Traces have been noted to the second century. It was largely off the medical community s radar until during World War II, when the condition of many children improved due to a switch to tulip flour. After the war, when wheat was reintroduced, the problems returned, and were eventually traced to gluten.celiac disease used to be considered a disease of children and many medical professionals still believe this to the case. However, the reality is that now, for every pediatric case of celiac, there are nine adult cases! There was fretting at ICDS about how people waste money and cause themselves more problems in the long term thanks largely to misinformation on the Internet. For example, these food intolerance test kits that people are buying and using are flawed, argued the president of the Austrian Coeliac Society. Too often they say people are sensitive to all kinds of foods when in fact they are not. Stool testing is not useful and you should save your money. Also, there are NO enzymes or anything else on the market that can make gluten safe for a celiac. The best course remains to continuing eating gluten if feasible and get a proper diagnosis so that you are in the best possible position to manage your health. The delay between the onset of symptoms and a celiac disease diagnosis ranges from eight to twelve years, depending on the study as well as gender (women tend to be diagnosed more quickly, and earlier in their lives). Undiagnosed celiac disease leads to reduced quality of life, and consumes a lot of health care resources. Diagnosis delay for celiac is linked to reduced wellbeing as well as greater use of pharmaceuticals, according to one Finnish study. Compared to other gastrointestinal ailments, celiac patients suffer from a wider range of symptoms, complicating firm diagnosis efforts. We all know the gold standard of celiac disease with a positive blood serology and biopsy demonstrating villous atrophy. However, things continue to evolve. Recent research suggests that, while a ttg+/ema+ serology is highly predictive of having celiac, ttg+/ema- is likely to be associated with other diagnoses. This is one reason why the full panel of blood testing is better than picking just one test. Be careful with a positive ttg serology. A ttg level at least 10 times above that of normal is a good level to confirm celiac, especially in the case of children who may not be going to the biopsy stage. Just being above normal could be caused by any number of conditions and as a measuring rod risks leading to many false positives for celiac disease. You and your doctor should be looking at your results in depth before proceeding. In a child, a positive EMA should also be noted, as well as the presence of symptoms, in order to 5

6 diagnose without a biopsy. Diagnosis via a high blood serology and celiac symptoms is largely accepted for small children, given the difficulties in taking a biopsy. As we know, symptoms of celiac disease can often be symptoms of other, better-known conditions, complicating the path to diagnosis. Further, there are other conditions that can cause a positive blood serology for example, high levels of gluten-related antibodies have been found in those with schizophrenia. Crohn s and a soy sensitivity, among others, may present with villous atrophy.certain drugs can also lead to the intestinal damage present in a celiac. Any number of ailments can cause the iron deficiency anemia that often accompanies celiac disease. We now know that most adult celiac patients are atypical, without the classical gastrointestinal symptoms. Atypical celiac disease can manifest itself in infertility, pre-term birth, arthritis, and malignancy. Diagnosis can occur when donating blood (in some countries), during an unrelated gastroscopy, or by way of at-risk group targeted screenings.one researcher in Prague is finding that up to 90% of diagnosed patients are asymptomatic, meaning screening is critical. There is no relation between the intensity of celiac symptoms and the severity of intestinal damage. While celiac disease used to be associated with images of frail, super-thin people, one Dutch researcher noted that, in his clinical practice, around 40% of newly diagnosed celiacs are actually obese. Several studies found that most celiac patients were a normal weight, but with around 40% being overweight/obese there are actually very few underweight people being diagnosed, relatively speaking. A major study conducted at the Celiac Disease Research Center at the University of Chicago found that the most common extraintestinal symptoms among children were short stature (33%), fatigue (28%), headache (20%) and rash (19%). In adults, the most common symptoms were iron anemia (48%), fatigue (37%) and headache (24%). In mass screening tests, celiac disease was found in 3% of 12-year-olds in Sweden. The southern area of the country has twice as much incidence as the north, leading to questions about environmental and dietary factors. Studies in Finland found that celiac prevalence there has gone up from 1% to 2% in recent years (the incidence of type 1 diabetes paralleled this increase), and incidence in US has gone up from around 0.3% to 1% in last sixty years. For some reason, it s only around 0.5% in Germany. Across the board, celiac is more common in girls than in boys. Who should be tested for celiac disease? Your instant reaction might be everyone, and indeed, in the past Italy has gone the route of testing all children for celiac disease. Dr. Anneli Ivarsson of Sweden suggests that all children should be offered celiac screening at the age of three. Such an approach may catch many more sufferers, but the financial considerations are problematic. To effectively and efficiently increase diagnosis rates, at-risk groups must be targeted. Dr. Maria Luisa Mearin of the Netherlands is also optimistic in terms of the efficacy of mass screening, but she notes that, while the Swedish people were willing to pay for mass screening, perhaps other populations would not be. Indeed, there is an immense price tag 6

7 associated with these mass screenings. Studies are ongoing to determine how widely applied such screenings should be. Research from Dr. Govind Makharia of India found that, while the risk for first-degree relatives to be celiac is 8.1%, there are great variances within that group. Sisters and daughters of a celiac have the highest risk at 1 in 6. For sons or brothers, it is 1 in 10, and for parents, it is 1 in 20.Generally speaking, prevalence of celiac among first-degree relatives was higher in USA than in Europe, Asia or South America. Looking at a child and their risk, does a parent or sibling have celiac disease? Does the child have unexplained short stature, fatigue, tooth enamel defects, broken nails, poor bone health, headaches, constipation or diarrhea? Does he or she have any other autoimmune conditions, especially type 1 diabetes, autoimmune thyroiditis, or Down, Turner, or Williams syndromes? Is the child experiencing joint pain when running, or easy fractures when falling down? If the answer to any of these questions is yes, test them for celiac disease. Even if they seem perfectly healthy, at least get the blood testing done. Many show no overt symptoms, even as they suffer on the inside. Do you have twins? If one monozygotic twin gets celiac, the other twin has over 80% chance of also developing it. The associated prevalence is much lower in non-identical twins around 30%. According to Dr. Sibylle Koletzko of Germany, If we only screened symptomatic children, we would only diagnose 34% of children with celiac disease. Screening of at-risk groups is very important. For example, 12-13% of patients with autoimmune liver disease will also have celiac disease. All should be tested. If children do have the DQ2/DQ8 genes and test negative for celiac, they should still be tested every 5-10 years. What has been called latent or celiac disease means a positive blood test result but no biopsy or a negative biopsy. Ongoing monitoring of these patients is necessary. Celiac disease can activate at any time, and without the knowledge of the sufferer given the frequent lack of overt symptoms. Many patients find that they knew something was wrong, and just didn't know what, but then when the celiac was discovered, they realized how much better they felt on the gluten-free diet. Why do children tend to be diagnosed quicker than adults? Romanian researcher Dr. Alina Popp argues that when adults have various symptoms that could be celiac, they delay medical treatment more than they would for their kids. Adults might try to self-treat, and ignore their symptoms. For their kids, they might go to the doctor over and over, increasing the likelihood of diagnosis. If only adults took their health as seriously as they do for their children! 7

8 From the Scientific Forum Diagnosis issues were also extensively addressed in the scientific forum. Mass screening is not considered to be cost effective for the general population, but in selected groups, it can be very valuable. There is no question that it is worthwhile to screen children and siblings of people diagnosed with celiac disease, and perhaps screening for girls should begin earlier than screening for boys. In general, female first degree relatives significantly are more likely than male first degree relatives to have celiac disease. Siblings are more likely than children to also have CD. Curiously, the likelihood of finding a first degree relative with celiac disease is much greater in the United States (14.9%) than in South America (5.4%) or in Asia and Europe (7%) Interestingly, adults found by screening generally feel that they do not have symptoms, but after a period of time they generally report their health has improved and anxiety levels have decreased. One problem that was note with screening is that primary care physicians are not very good at identifying which patients should be screened for celiac disease. In one poster from the U.K. referrals from primary care physicians were no better than results found from mass screening. This indicates a need for more continuing education for family physicians. 4. Genetics Many speakers at ICDS 2015 emphasized the importance of using gene testing to exclude celiac disease, especially in children. If a child does better on a gluten-free diet but does not have the HLA-DQ2 or HLA-DQ8 genes, they almost certainly do not have and will never have celiac disease. Dr. Cisca Wijmenga of the Netherlands reports that HLA-DQ2 accounts for 25% of the genetic risk factors for celiac disease. If you get this gene from BOTH parents, your risk of developing celiac is much higher. Those in this boat are in fact more than 3 times as likely to become celiac by age 3 as those with only one HLA-DQ2 gene, says Dr. Maria Luisa Mearin of the Netherlands. Still, that means the other 75% of the risk should be connectable to the many, many other genes in our genome. For example, coming from a Caucasian background puts you at higher risk of celiac than other ethnic backgrounds. The paradox as referred to by Dr. Fritz Koning of the Netherlands is that 95% of celiac patients are HLA-DQ2 positive, but 95% of HLA-DQ2 positive individuals are not celiac. If you have HLA-DQ8 but not HLA-DQ2, you actually have a very low risk of becoming celiac. The risk is much higher with HLA-DQ2. 8

9 Genes for celiac disease do overlap with the genes associated with other autoimmune diseases. This may explain linkages between celiac and such disorders as type 1 diabetes, multiple sclerosis and Crohn's disease. Down the road, genetics are expected to provide insight into why the immune cells do not work properly in celiac patients. Genetics can also be used to find other factors that may influence other disease development, and perhaps prevent the onset of disease. From the Scientific Forum Genetics got a lot of attention in the scientific forum as well. Work continues to find additional genes that contribute to the risk of developing celiac disease. At this point there is no more low hanging fruit, even in families severely affected with celiac disease. One researcher reported finding genes that cover approximately 18% of the risk for celiac disease. Another identified genes that are much more common in children with CD than adults with CD, suggesting that childhood onset and adult onset celiac disease may be identifiable, leading to different monitoring strategies. More research is needed in this area. 5. Neurology There is much exciting research going on in this area! Patients with neurological dysfunction do show a higher tendency of having gluten issues. More and more we hear of celiac patients experiencing neurological and psychological issues that seem to be connected to being glutened. A UK study of newly diagnosed celiac patients found 61% had neurological symptoms, most commonly headaches, balance problems and sensory issues. Gluten ataxia involves patients having significant problems with coordination, making life very difficult. Studies show that 18% of all ataxias are gluten-related, and 15% of genetic ataxias are gluten-related. Gluten ataxia is found in patients with celiac disease as well as those with nonceliac gluten sensitivity. Improvement of ataxia was usually seen within a year of the strict gluten-free diet even in those without enteropathy (intestinal damage). Dr. Marios Hadjivassiliou of the UK, who spoke about this issue, finds it very easy to justify putting people with gluten ataxia on the gluten-free diet, as the benefits are significant. In his research, Dr. Hadjivassiliou found neurophysiologic evidence of improvement of neuropathy within a year of the gluten-free diet among his test subjects. Gluten neuropathy was not common at the time of diagnosis of celiac (2%), but much more common in the long term. The onset of gluten ataxia averaged around 56 years of age, and the prevalence was roughly equal between men and women. In terms of why there seemed to be an increase in neuropathy in people long after the celiac diagnosis, he chalks it up to poor adherence to the gluten-free diet. Further, he argues, 9

10 cheating on the diet when you suffer from gluten ataxia may put you at increased risk of vascular dementia. From the Scientific Forum Discussion in the Scientific Forum focussed more generally on extra-intestinal manifestations of celiac disease. Celiac disease is now being described as a multi-system disorder, a major change from the earlier definition that focused only on gastrointestinal manifestations. One question that remains is whether extra-intestinal manifestations of celiac disease respond to a gluten-free diet in the same way as intestinal symptoms. Research from the University of Chicago indicates that approximately 75% of children on a strict gluten-free diet showed symptom resolution, a higher rate than symptom resolution found in adults. 6. Follow-up So you ve been diagnosed with celiac disease. Now what? There are a lot of differing opinions out there, but a definite consensus on the need for followups with and monitoring by medical professionals. Dr. Pavel Kohout of the Czech Republic recommends that celiac patients undergo repeat ttg blood test once a year to ensure compliance with gluten-free diet. Dr. Joe Murray of the Mayo Clinic recommends a follow-up biopsy months after a celiac diagnosis to ensure healing has taken place. If you re undergoing a biopsy for an unrelated reason, it is a good idea for the gastroenterologist to also check on the condition of the villi in the small intestine. Adherence to the gluten-free diet must be ensured. Especially for asymptomatic celiac patients, it can be hard to convince them (and their families) that the gluten-free diet must be strictly followed. Failure to respect the diet can lead to debilitating health complications down the road. Dr. Daniel Adelman of the US has found that up to 60% of adult celiac patients remain symptomatic despite being on the gluten-free diet for years. Adults do tend to have slower intestinal healing than do children, but there may be other issues at play as well. Regular physicals and blood tests for key vitamins and minerals are advisable. People who are diagnosed celiac as children may find that during puberty or later they may suddenly be able to tolerate gluten. However, this is highly misleading and these people still have celiac disease the nature of their symptoms has simply changed. Once a celiac, always a celiac! A celiac child, following diagnosis, may quickly feel better on the gluten-free diet but this does not mean that the gut has already healed. Be vigilant in ensuring kids stick to the diet.proper support for a celiac patient means consultation with a knowledgeable registered dietitian. This 10

11 applies to adults as well as children. Unresponsive children with short stature must be assessed for comorbidities, as there could be something else going on. Middle-aged celiac patients with persistent iron deficiency anemia should have their colon looked at, as there could be additional issues. With celiac patients, UK research found a 10x increase in inflammatory bowel disease mostlymicroscopic colitis. Around 5% of IBS patients also have celiac disease, and all should be screened for it. Celiacs are also more likely than the general population to have cystic fibrosis, according to a Spanish study. Psychiatric symptoms of celiac disease may actually take the longest to resolve even with the gluten-free diet. Around 2-5% of celiac adults tend to have what Dr. Chris Mulder of the Netherlands calls complicated celiac disease. These would generally be slow responders to the gluten-free diet, and tend to be adults over 50 years of age. In his study of 125 non-responsive celiac patients, some had complicating conditions such as colitis, while around 25% had refractory celiac disease, a dangerous condition that is normally able to be diagnosed through the presence of malabsorption and persistent villous atrophy despite 12 months on a strict, glutenfree diet. Further investigation of non-responsive celiac disease is important given the high risk of lymphomatic cancer. Dr. Carlo Catassi suggests that probiotics are a good idea for celiac patients, especially those still experiencing symptoms. Alteration in the microbiota has been found in celiac patients that are still experiencing symptoms on gluten-free diet. As well, celiac patients with anemia were shown to have slower intestinal healing than those without anemia, according to one Finnish study. T-cell lymphoma has a 5-year survival rate in the area of 10%, so we must do what we can to prevent its development. Diagnostics need to be undertaken to ensure non-responsive patients actually had celiac disease and not another condition that may look similar. For example, a presentation of jejunal stenotic lesions, which can be present in celiac patients, looks the same as Crohn's disease. Proper diagnosis and follow-up care can mitigate much of the risk. The consensus is that the risk over time seems to decrease from the point of initial celiac diagnosis. Switching that inflammation off at an early stage seems to have huge positive effects, according to Dr. David Sanders of the UK. Patients who strictly adhere to the gluten-free diet can see their risk of malignancies normalize within 1-5 years. One nice addition is that, for some reason, celiacs seem to be less likely than the general population to develop breast cancer. We also seem less likely to have problems with high cholesterol. Dr. Lori Welstead of the University of Chicago advises that nonresponsive patients should perhaps be assigned a naked gluten-free diet. Her gluten contamination elimination diet cuts out millet, sorghum, buckwheat, canned fruit, processed meat and more. This is intended to minimize the chances of cross-contamination, avoiding potential sources of gluten, and eating a basic diet. In her experience, most nonresponsive patients showed improvements on this diet. Dr. Markku Mäki of Finland suspects that a long-term lack of mucosal healing is likely gluten-induced. 11

12 Couples wanting to conceive also need to be aware of the potential implications of celiac disease. Dr. Zdenka Ulcova-Gallova of the Czech Republic has been studying celiacs and fertility. There continues to be a link between celiac woman and infertility, but celiac men do not seem to be affected to the same degree. Due to malabsorption, celiac disease may have implications early menopause, infertility, miscarriages, amenorrhea, and more, but the risks can be minimized through strict adherence to the gluten-free diet. A Swedish study found an increased risk for malformation among the offspring of mothers or fathers with celiac disease. Untreated celiac women have higher risk of pre-term babies and other development problems of the fetus. The gluten-free diet must always be followed! Thankfully, a massive study out of the UK found that, for most women with celiac, there was no increased risk for fertility problems. For undiagnosed women presenting with unexplained fertility, silent celiac disease should be considered. 7. Skin Issues It was reported at ICDS that the incidence of dermatitis herpetiformis is decreasing, despite increase in celiac disease prevalence. The prevalence of DH also seems to vary greatly across geographic boundaries in Finland, 13% of celiacs have DH, while the numbers are 8% in the US and UK and just 4% in Italy. DH patients do have the increased risk of non-hodgkin s lymphoma that all celiac sufferers have, so adherence to the gluten-free diet is just as important. Dr. Katri Kaukinen, a Finnish gastroenterologist, spoke about a possible non-dh skin manifestations of celiac disease. In patients with alopecia areata, for example, the incidence of celiac disease was found to be markedly higher than in the general population. Vitiligo is another skin condition that could be linked to celiac, as it is also common in patients with thyroid disease and Addison's disease. Other skin ailments listed as potential celiac connections include atopy and urticaria. 8. Food Some would say celiacs are blessed in a way, since we do not need to be treated with daily injections, bottles of pills, and what have you all we have to do is go on a diet. Fortunately, this diet can include delicious food, from healthy salads right up to delectable desserts. However, for many, adhering to the diet remains problematic, even in this new world of gluten free everywhere we turn! For example, a study of celiac patients in India found that just 53% maintained excellent/good adherence to the diet. We know that respect for the diet increases with public awareness, and with membership in a patient organization like the CCA, so the less-developed infrastructure for celiac support in India may be somewhat responsible. Without awareness, the peer pressure 12

13 can be higher and understanding much lower, increasing the temptation for many to cheat. In the Indian study, with repeated counselling, the adherence of these celiac patients increased to 92% after 6 months. So eating strictly gluten free is possible even in Indian cuisine, much of which is gluten-laden! Interestingly, the celiac incidence in India is far higher in bigger wheatconsuming areas of north; the rates are quite low in the south. It was stated at ICDS that, even today, too many gluten-free foods are too low in fibre, b vitamins, and folate, and too high in sugar, fat and calories. Processed gluten-free foods are not healthier than those made with wheat. Texture can be poor, and there is the risk of crosscontamination. Pressure needs to be put on food manufacturers to offer healthier fare. All patients with celiac disease should consult a knowledgeable registered dietitian, who can review the social and emotional history of patients, look for vitamin or mineral deficiencies, and provide expertise to ensure a balanced gluten-free diet. People may become constipated if they adopt the gluten-free diet but only look for things labelled gluten free. Oats have been a point of concern for many years. While in excess of 95% of celiac patients can tolerate pure, uncontaminated oats, many may incorrectly think they cannot because they experience celiac-like symptoms when ingesting oats. This can happen if the re-introduction of oats into the diet takes place too quickly, since they are so high in fibre. It is important to slowly add them to your diet so that your body gets used to the change. Dr. Knut Lundin of Norway says that if he finds celiac patients who continue to experience symptoms, one strategy his group tries is to cut out oats. A very small percentage of celiacs can experience continued gut damage from the ingestion even of pure oats, and studies are ongoing as to why. The avenins in oats, says Dr. Carlo Catassi of Italy, are what has been shown to stimulate a t-cell response in a small minority of celiacs. We are very lucky in Canada to have such companies as Cream Hill Estates and Avena Foods producing safe, pure, uncontaminated oats. In Romania, for example, gluten-free oats are impossible because no pure sources are available. Compliance with the gluten-free diet can be complicated by many factors, from income to age to availability at restaurants and grocery stores. Do we celiac/non-celiac gluten sensitive patients benefit from the gluten-free fad diet? The consensus based on the results greater awareness in restaurants and among food companies would seem to be yes. According to Dr. Lundin, contrary to what you might assume, nonceliacs on the gluten-free diet were found to be generally quite strict in their adherence. The impact of gluten free on the food sector has been immense. Wheat flour consumption in the US has dropped by over a third since the 1950s. Wheat flour consumption in Norway rose from 1965 to 2000, but since then has fallen pretty steadily. Dr. Lundin asks why: Why do 13

14 people volunteer for the gluten-free diet when many of our baked goods are not healthy or not tasty? Not a celiac, he says I would by far prefer regular bread. The estimated composition of the gluten-free market in Europe is 10% celiac, 40% abdominal problems, and 40% lifestyle. In the US, in contrast, it s more like 2% celiac, 8% abdominal problems, 90% lifestyle. The difference is quite intriguing! Are there other uses for the gluten-free diet besides treating celiac disease and non-celiac gluten sensitivity? As we know, many people are following the gluten-free diet for reasons that some would consider highly questionable such as because Miley Cyrus is eating gluten free. Dr. Fasano says that there are more than 50 possible treatments for autism on the market, but the gluten-free and casein-free diets are by far the most popular. While the jury is still out on whether the gluten-free diet is medically or scientifically advisable for autism patients, the prevalence of celiac disease does seem to be higher among this group than in the general population. The gluten-free diet resolves symptoms in many sufferers of Irritable Bowel Syndrome (IBS) (while the lactose-free diet does not) and, according to Dr. Jonas Ludvigsson of Sweden, patients with Crohn's disease can be "pseudo-improved" by adherence to the gluten-free diet. However, these cases should first be tested for celiac disease. 9. Options for the Future Remember, there are NO pharmacological treatments out yet for celiac disease. Do not fall for the enzyme traps as they are not safe. One interesting suggestion that came up at ICDS 2015 was the possibility of testing for gluten peptides in urine. This would mean that a simple pee test could tell you whether you may be getting glutened without your knowledge. The cost for current test models that are out there is in the range of 10 Euros. We hope to see this generally available soon! From the Scientific Forum There are many proposed treatments and potential cures for celiac disease that are under investigation, and there was much excited discussion about the possibilities at ICDS According to Dr. Ludvig Sollid of Norway, Big Pharma has now taken a big interest in celiac disease because the genetics are similar to other autoimmune diseases. Despite what may be floating about the Internet, today s wheat is not GMO. That said, research is underway looking at genetically modified gluten as a potential way to make it safe for those with celiac disease. Other possible options include enzymes to break down gluten, special anti- 14

15 inflammatory agents, tight junction modulators, and more. Several vaccines are in the works that may be useful to preventing or treating celiac disease. Special peptides for transglutaminate treatment could help protect those with celiac. Polymers sequestering gluten, glutenase, transglutaminase inhibitors, and HLA-blocking are some other potential avenues of interest. Dr. Sollid also discussed anti-cytokine therapy, anti-b cell therapy, blocking intestinal homing, and using topical steroids. Anti-B cell therapy has been developed for use in other autoimmune diseases already, including multiple sclerosis. On the topical steroid question, treatments seem to hold promise, but the side effects are quite extreme. An area of research that is not promising to date is making peptides to block the HLA molecule, protecting us from gluten. 10. International case study shows how fortunate we are in Canada We in Canada may complain with good reason that diagnosis takes too long, that there should be government support for diagnosed celiacs, that it would be nice if gluten-free food was cheaper. However, we must also take stock and realize how far we have come together and how, in many ways, we are leading the world. Thanks to the hard work of the Canadian Celiac Association and others, food labelling in Canada is very clear, with no hidden gluten permitted. The gluten-free standard is in line with the science 20 parts per million. We have an advanced and internationally respected Gluten-Free Certification Program to provide that extra level of assurance to those medically required to follow the gluten-free diet. Many especially in developing countries are not so lucky. Dr. Elena Roslavtseva of Russia spoke to ICDS on the matter of Celiac Disease and Gluten Related Disorders in Russia and Former Soviet Republics. While celiac disease is now well-known in most regions of Russia, with a good deal of research going on, the lack of screening of at-risk groups means that rarely is an asymptomatic patient diagnosed with celiac disease. Diagnosis rates across the country are extremely low, and the lack of good data hinders the ability to conduct professional scientific research. The blood serology for celiac disease is only available in certain areas of Russia. Clinical symptoms are often the only diagnosis tool. Testing for celiac disease is done in private labs not covered by the state health insurance, so patients must pay another definite barrier to diagnosis. In the neighbouring country of Belarus, however, things are a bit better. All diagnostic procedures for celiac disease are covered by the state health care, there is an official national registry for celiac patients, and children with an established celiac diagnosis receive financial support from the government similar to a disability pension. In Georgia, in contrast, insurance 15

16 does not cover the biopsy, so patients tend to be put on the gluten-free diet following a positive blood serology. Understanding among family, friends, etc. of troubles of Russian celiac kids is very low, and leads to problems such as social deprivation.in Russia, there is no state requirement for manufacturers to label hidden gluten in their products, and traditional Russian cuisine is rich in gluten ingredients, making compliance with the diet difficult. In Georgia, however, corn bread, buckwheat and chumiza (a type of millet) are very common in the Georgian diet, so eating gluten free is more feasible. In Latvia, the blood, gene and biopsy tests are all readily available. Children and many students with celiac disease receive a monthly aid of 106 euro from the government (approximately $150 CAD). Roslavtseva remains optimistic: diagnosis in Russia and the former Soviet republics is going up, patient societies are growing, and gluten-free food is more available. To view the website of the celiac patient organization in Russia, please visit There is an English section. 11. Codex labelling history Consider how far we have leapt forward on food labelling in recent years. The president of the Austrian Coeliac Society, Hertha Deutsch, told the ICDS that, in 1988, compound ingredients (forming less than 25% of the total product) did not need to be declared in food. Can you imagine? Never mind whether hydrolyzed vegetable protein contains gluten the HVP needed not even be listed on the label! At that time, the protein content in meat products was often boosted with wheat fillers. "Soyfree plant protein" was a frequent filler, and was based on wheat gluten. Wheat gluten did not need to be labelled at all if it was used as a food additive, or for technological reasons. Today, 186 states are members of the international labelling standard Codex Alimentarius (of 194 states accepted by the United Nations). In 1991, Codex accepted an Austrian request to work on improving the labelling in terms of gluten-containing ingredients. Deutsch said that she told the Codex people straight out: It is our human right to know what ingredients are in the food we are eating! At the time, food researchers were looking at adding a gluten-containing compound as a coating on fruit items, as a way to increase protein consumption. After much hard work by celiac patient organizations and others, this project was halted in Gluten used to be put as a coating on cheese as well, and this was stopped in 1998 thanks to hard work by the Netherlands and Austria in particular. 16

17 A 1999 Codex standard meant that cereals containing gluten (wheat, rye, barley, oats, spelt, etc.) shall always be declared. A 2003 Codex standard for cheese stated that- only starch that is gluten free by nature should be used in cheese production. The Codex standard for infant formula (2007) states that all ingredients and food additives should be gluten free. The next step was the gluten-free standard. The 2008 Codex standard on gluten-free foods established that, to be labelled GF, foods must have gluten below 20 mg/kg (20 ppm), and ingredients can't contain gluten. Codex also says that information about key allergens should be put in bold typeface in order to make it stand out on labels. There are exceptions. Products can contain certain gluten ingredients if they meet the standard such as the cleaned wheat starch that has been in European gluten-free products for years. Glucose syrups based on barley, wheat-based maltodextrin, and cereals used for alcohol are allowed as they do not contain gluten. Since oats can be tolerated by nearly all people with celiac disease, pure and uncontaminated oats may be used in gluten-free products, according to Codex. In Canada, we recently celebrated a huge victory on labelling whereby gluten-free products using safe oats can now be labelled as GF, rather than the more vague wheat free or other labels we had seen before. 12. Importance of patient organizations Years ago, patient organizations such as the Canadian Celiac Association were primarily selfhelp groups. Later, they later morphed into information providers, and after that into centres of knowledge. For example, today s CCA is involved in extensive peer support work at the Chapter level, but also serves as a respected advocate for the gluten-free community to government, industry and the medical community. The CCA also funds cutting-edge research, conducts training of food service staff, and works to improve diagnosis rates and quality of life. Dr. Bianca Rootsaert, managing director of the Coeliac Society of the Netherlands, spoke about the importance of patient organizations. The Nederlandse Coeliakie Vereniging (NCV) the Dutch equivalent of the CCA did a survey in 2010 and found that the Coeliac Society was the third-most consulted information source on celiac disease, after specialists and general practitioners. However, by 2014, we had risen to #2, with specialists at the top and dietitians taking third place. The dynamic is changing! In the Netherlands, there is a training program that helps ensure safe, gluten-free meals in restaurants. That s something we re working on at the CCA as well. Coeliac UK (the patient organization) found that key barriers for celiac patients include nutritional adequacy, identifying safe products, food cost, food availability, and strict adherence to the diet. Fortunately for us, the global gluten-free market almost doubled in size between 2009 and

18 Availability of gluten-free food is very high in Europe, Oceania and North America, but much less so in Asia, Africa and South America. For example, there is a significant incidence of celiac disease in North Africa, but finding gluten-free substitute foods can be very difficult. Looking specifically at the UK, it was found that shopping in budget supermarkets or smaller stores meant that gluten-free foods were harder to find. This created an inconsistency where certain socioeconomic groups might be less likely than others to be able to easily comply with the gluten-free diet. Coeliac UK identified eight items as staple gluten-free products and launched an impressive campaign to have ALL food stores carry these foods. That said, the availability of gluten-free foods today is incredible compared to as recently as five years ago. As such, for many celiacs, cost has overtaken availability in terms of posing challenges to adherence with the gluten-free diet. Breads and flours still tend to be 3-4 times more expensive than gluten-containing products, even with the high levels of competition we are seeing. However, it is important to consider that the costs for manufacturers remain far higher than if making gluten-containing items. The need to secure pure supplies and have strict measures in place to avoid cross-contamination will always incur higher costs.some governments in Europe are providing financial support for people with celiac disease, but we know budgets are under significant pressure across the developed world. According to Coeliac UK, consumers absolutely LOVE gluten-free certification, and it serves as the prime way of identifying products. In Canada, we find the gluten-free certification program trademark on hundreds of products across a great variety of stores and supermarkets. We have come a long way, but there remains much to be done for example, getting gluten-free buns at McDonald s restaurants in Canada the way they are in a number of European countries!one step at a time. 18

19 13. What Next Research in all facets of celiac disease continues at an accelerating pace, but it is a complicated disease to find because there are so many different symptom presentations. Celiac disease is a challenging disease to manage and studies show that physicians overestimate the quality of life of their celiac patients compared to the difficulties patients report. One thing that is universally noted is the role of patient support groups in the lifelong treatment of celiac disease. Initially, patient support groups provide very practical advice about what is gluten free and what is not, and where to find products. Over time, they supply advice on lifestyle issues and coping mechanisms for the stresses of lifestyle. Patient support groups are also more effective at dealing with government regulators and food manufacturers when issues of safe food are at stake. Patient support groups around the world are running into the same issue people find information on web sites and blogs and do not have enough background knowledge to determine if the information is valid or nonsense. If they join a support group, they stay for a year or two and then go off on their own. Since celiac disease is a patient-managed disease, celiac specialists highly recommend lifelong membership in a support group. Questions? ICDS_report@celiac.ca. Want to join the Canadian Celiac Association, visit This report was prepared by Mark Johnson and Sue Newell. July 15, Canadian Celiac Association 5025 Orbitor Drive, Building 1, Suite 400 Mississauga, ON L4W 4Y5 Phone: