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Celiac.com 12/03/2018 - Biomarkers in blood samples are not effective indicators for diagnosis or monitoring of celiac disease. A team of researchers recently set out to assess biomarkers of celiac disease derived from neoepitopes of deamidated gliadin peptides (DGP) and tTG fragments, and to assess their usefulness in identifying patients with celiac disease with mucosal healing. The research team included RS Choung, SK Rostamkolaei, JM Ju, EV Marietta, CT Van Dyke, JJ Rajasekaran, V Jayaraman, T Wang, K Bei, KE Rajasekaran, K Krishna, HK Krishnamurthy, and JA Murray. They are variously affiliated with the Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA; Vibrant Sciences LLC, San Carlos, CA, USA; and with the Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA. The team began by analyzing serum samples from 90 patients with biopsy-proven celiac disease, along with 79 healthy control subjects for immune reactivity against the tTG-DGP complex. They used a fluorescent peptide microarray platform to estimate the antibody binding intensity of each synthesized tTG-DGP epitope. They validated results in 82 patients with newly diagnosed celiac disease, and in 217 control subjects. They assessed the ability of the peptide panel to spot patients with mucosal healing based on histologic results and using serum samples from 85 patients with treated and healed celiac disease; 81 patients with treated but unhealed celiac disease who showed villous atrophy despite adhering to a gluten-free diet; 82 patients with untreated celiac disease; 27 disease control subjects who showed villous atrophy without celiac disease; and 217 healthy control subjects. To assess their data, they relied on principal component analysis followed by machine learning and support vector machine modeling. In all, the team found 172 immunogenic epitopes of the tTG-DGP complex. Compared with control subjects, celiac patients showed substantially higher immune reactivity against these epitopes. In the test group, neoepitopes derived from the tTG-DGP complex identified people with celiac disease with a remarkable 99% sensitivity and 100% specificity. Blood samples from untreated celiac patients showed the greatest average antibody-binding intensity against the tTG-DGP complex. Blood from patients with treated but unhealed CeD mucosa (15.1 ± 7.5) showed significantly higher average antibody-binding intensity than blood from patients with treated and healed CeD mucosa (5.5±3.4) (P<.001). The test spotted celiac patients with healing mucosa with 84% sensitivity and 95% specificity. The research team discovered immunogenic epitopes of the tTG-DGP complex, and found that a test that measures immune response to epitopes accurately identified both celiac patients and patients with mucosal healing. From this study, the team concludes that the biomarker method for celiac testing could be useful in both the detection and monitoring of celiac disease. Read more at: Gastroenterology.

Scand J Gastroenterol 1999 Feb;34(2):163-9 Kaukinen K, Collin P, Holm K, Rantala I, Vuolteenaho N, Reunala T, Maki M Dept. of Medicine, Tampere University Hospital, Finland. BACKGROUND: We investigated whether wheat starch-based gluten-free products are safe in the treatment of gluten intolerance. METHODS: The study involved 41 children and adults with coeliac disease and 11 adults with dermatitis herpetiformis adhering to a gluten-free diet for 8 years on average. Thirty-five newly diagnosed coeliac patients at diagnosis and 6 to 24 months after the start of a gluten-free diet and 27 non-coeliac patients with dyspepsia were investigated for comparison. Daily dietary gluten and wheat starch intake were calculated. Small bowel mucosal villous architecture, CD3+, alphabeta+, and gammadelta+ intraepithelial lymphocytes, mucosal HLA-DR expression, and serum endomysial, reticulin, and gliadin antibodies were investigated. RESULTS: Forty of 52 long-term-treated patients adhered to a strict wheat starch-based diet and 6 to a strict naturally gluten-free diet; 6 patients had dietary lapses. In the 46 patients on a strict diet the villous architecture, enterocyte height, and density of alphabeta+ intraepithelial lymphocytes were similar to those in non-coeliac subjects and better than in short-term-treated coeliac patients. The density of gammadelta(+)cells was higher, but they seemed to decrease over time with the gluten-free diet. Wheat starch-based gluten-free flour products did not cause aberrant up-regulation of mucosal HLA-DR. The mucosal integrity was not dependent on the daily intake of wheat starch in all patients on a strict diet, whereas two of the six patients with dietary lapses had villous atrophy and positive serology. CONCLUSION: Wheat starch-based gluten-free flour products were not harmful in the treatment of coeliac disease and dermatitis herpetiformis.

Celiac.com 02/13/2014 - A team of researchers recently set out to assess the validity and effectiveness of near-patient celiac immunological testing in dietician-led celiac disease follow-up clinics, and to compare the results against standard laboratory immunological techniques. The research team included D.A. George, L.L. Hui, D. Rattehalli, T. Lovatt, I. Perry, M. Green, K. Robinson, J.R.F. Walters, and M.J. Brookes. They are variously affiliated with the Department of Gastroenterology at New Cross Hospital in Wolverhampton, and the Department of Gastroenterology at Imperial College London, in London, UK. Each of the two phases of the study assessed the near-patient test and standard laboratory immunological techniques. In Phase 1, the team analyzed stored serum samples, while in Phase 2 they analyzed whole blood from patients attending the dietician-led celiac disease clinics. Between March 2010 and February 2011, the team recruited 50 patients from New Cross Hospital, Wolverhampton, and 30 from Imperial College London. All patients had a diagnosis of celiac disease for greater than 12 months, and attended dietician-led celiac disease clinics. During the study, the team took whole blood samples for routine analysis, along with regular capillary finger-prick blood samples. The team wanted to determine if the whole blood and serum near-patient test results correlated with outcomes of standard laboratory evaluation. The first phase of the study showed that the near-patient serum test had a sensitivity of 93.5% (95% CI 0.79% to 0.98%), and a specificity of 94.9% (0.83% to 0.99%), when compared with the standard laboratory ELISA. The second phase showed that whole blood measurements had a sensitivity of 77.8% (0.45% to 0.93%), and specificity of 100% (0.94% to 1%). The team concludes that the study results suggest a possible role for near-patient testing in celiac disease, but they suggest additional studies to corroborate and refine such a role. Disclosure: The team noted the receipt of a £2250 (approximately $3,750.00) bursary award from Dr. Falk Pharma and Core. Source: Frontline Gastroenterol. 2014;5(1):20-25.

Celiac.com 07/08/2016 - If their symptoms don't get worse, many patients diagnosed with celiac disease as children do not pursue follow-up care as adults, according to data presented at Digestive Disease Week 2016. There's been some really good stuff coming out of Digestive Disease Week 2016 in San Diego. One example is a talk given by Norelle Reilly, MD, from the division of pediatric gastroenterology and the Celiac Disease Center at Columbia University Medical Center in New York City. According to data presented by Dr. Reilly many patients diagnosed with celiac disease as children do not pursue follow-up gastroenterology care as adults, unless symptoms worsen. Reilly and colleagues sent a 33-question survey to nearly 8,000 recipients via the medical center's proprietary distribution list and received 98 qualified responses. According to Reilly, 37% of respondents said they were not seeking ongoing care for celiac disease. These respondents reported an average of 2 to 5 years, and sometimes as many as 10 years, between doctor visits for their celiac disease. Compare that with an average of six months between doctor visits for people who were getting regular care. Large numbers of patients diagnosed with celiac disease in childhood do not seek follow-up care as adults, especially those diagnosed earlier in childhood, who may have fewer ongoing symptoms, Reilly said. She ended her talk by asking "providers caring for children and adolescents with celiac disease [to] educate early as to the importance of ongoing care, emphasize the importance of follow-up and the reasons for follow-up, particularly with patients who lack symptoms and may not seek care otherwise and to provide a referral, and formally transition the patient to adult care to improve compliance." Reference: Reilly N, et al. Abstract #35. Presented at: Digestive Disease Week; May 21-24, 2016; San Diego. Read more at Helio.com.

Celiac.com 01/05/2015 - Doctors recommend medical follow-up of celiac disease patients for gluten-free diet (GFD) adherence monitoring and complication detection. But, what happens to celiac kids who don’t get good medical follow-up? A team of researchers recently tried to figure out how the LTFU kids fared health-wise compared to kids who did receive follow-up, and what barriers the LTFU kids might face in successfully following a gluten-free diet. The research team included L. Barnea, Y. Mozer-Glassberg, I. Hojsak, C. Hartman, and R. Shamir. They are variously affiliated with the Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel, Petach Tikva and the Sackler Faculty of Medicine at Tel-Aviv University in Tel Aviv, Israel. They had previously shown that 35% of children with celiac disease were lost to follow-up (LTFU), that is, they did not receive follow-up care for their celiac disease. The study team used a telephone questionnaire to assess 50 LTFU patients regarding frequency of follow-up, serology testing, and adherence to GFD measured by validated Biagi score. They had fifty two regular follow-up patients serve as a control group. The results showed that the LTFU patients had poor adherence to GFD, with an average Biagi score of 2.0 ± 1.4, compared to control scores of 3.0 ± 1.0 (p < 0.001). Only 22% of LTFU performed periodic celiac serology testing compared to 82% of the control group (p < 0.001). Fifty percent of the LTFU kids had higher prevalence of positive celiac serology tests, compared to 25% of controls, (p = 0.01). Just 24% of LTFU kids were National Celiac Association members, compared with 44% of control kids (p = 0.05). Regression analysis showed positive relationships between LTFU and poor adherence to GFD (R2 = 0.26737, p = 0.001), older age at diagnosis (R2 = 0.30046, p = 0.03), and non-membership in a celiac association (R2 = 0.18591, p = 0.0001). So, when the dust settled, the study showed that children LTFU were more likely to not follow a strictly gluten-free diet, and to have positive blood tests for anti-gluten antibodies. Accordingly, the team recommends that risk factors for LFTU be identified and addressed in order to improve patient care. Source: Digestion. 2014 Dec 19;90(4):248-253

Celiac.com 09/07/2012 - Many people with celiac disease will tell you that getting a proper diagnosis is just part of the battle. Maintaining a strict gluten-free diet, and getting adequate medical follow-up care can be nearly as challenging as getting a proper diagnosis. A group of researchers, led by Joseph A. Murray, MD, AGAF, of Mayo Clinic, confirms that assessment in a new study. The study appears in Clinical Gastroenterology and Hepatology, and shows that follow-up care for patients with celiac disease is often poor and inconsistent. For their study, researchers collected data on 122 patients diagnosed with celiac disease between 1996 and 2006 in Olmsted County, MN. The patients were 70 percent women, and averaged 42 years of age. The researchers then calculated the rates at which patients were given follow-up exams from six months to five years after celiac disease diagnosis. Of the 113 patients the study followed for more than four years, only 35 percent received follow-up analyses that met AGA guidelines. The other patients did not receive medical follow-up that met "even the most lax interpretation of current guidelines,” said Dr. Murray. The researchers used the Kaplan-Meier method to estimate event rates at 1 and 5 years. They classified patients according to categories of follow-up procedures recommended by the American Gastroenterological Association (AGA). The study shows that even with widespread circulation of follow-up recommendations, plenty of patients are not getting proper follow-up for celiac disease. According to Dr. Murray, gastroenterologists with the expertise in celiac disease need to encourage active follow-up of celiac patients and improve their overall quality of medical care. Basically, says Dr. Murray, celiac disease "should not be different from other chronic conditions for which medical follow up is a given such as liver disease, inflammatory bowel disease or even gastroesophageal reflux disease." Anecdotally, many patients with celiac disease feel that they must manage celiac disease on their own,” Murray adds, pointing out that it is important for doctors and patients to understand the need for proper medical follow-up of celiac disease. The authors note that, since gastroenterologists are leading the way in the detection of celiac disease, and since it is a chronic condition, with possible long-term complications, improved communication between gastroenterologists and patients can help to ensure that patients get important follow-up care, and thus improve outcomes in celiac disease. What are your thoughts? Do you feel that you've gotten adequate follow-up care for your celiac disease? Share your comments below. Source: Clinical Gastroenterology and Hepatology

Celiac.com 05/21/2012 - A trio of researchers recently compared duodenal and jejunal small intestinal biopsies for diagnosis and follow-up of celiac disease. The researchers included J.W. Meijer, P.J. Wahab, and C.J. Mulder from the Department of Pathology, Rijnstate Hospital Arnhem, The Netherlands. Current pediatric guidelines advise doctors to take intestinal mucosal specimens from the jejunum using a suction capsule. This method can be stressful for patients, time-consuming, expensive and requires the use of imaging technology. Taking mucosal biopsies from the distal duodenum using forceps is less stressful for patients, easier, cheaper and can be done using an endoscope. For those reasons, the researchers wanted to compare the histological results of biopsies taken from the duodenal mucosa by forceps and from the jejunal mucosa using suction capsule. To do so, they evaluated 171 paired biopsies taken from 109 patients from 1 to 75 years of age. Biopsies were made from the distal duodenal mucosa using jumbo forceps and from the jejunal mucosa using Crosby suction capsule. For histological interpretation they applied modified Marsh classification, including partial-, subtotal and total villous atrophy as Marsh IIIA, B, and C. A total of fourteen (8%) of the suction capsule biopsies were too low quality to be properly scored, while all duodenal biopsies taken with forceps produced adequate material for histological scoring. Of the remaining biopsies, a total of 145 of 157 (92%) showed no difference in histological scores. The remaining 12 biopsies showed some discrepancy in scoring, four of those showed more severe lesions in the duodenum, while eight showed more severe lesions in the jejunum. The differences were clinically significant, and included the presence and absence of villous atrophy in nine of the 157 paired biopsies (6%). The results showed that mucosal specimens taken from the distal duodenal and jejunal mucosa are strongly correlated, with clinically significant discrepancies were present in only 6% of paired biopsies. Based on these results, the researchers suggest that diagnosis and follow-up of celiac disease can be done using mucosal specimens taken from the duodenum using forceps, rather than the traditional biopsy of the jejeunum using Crosby suction capsule. Source: Virchows Arch. 2003 Feb;442(2):124-8. Epub 2002 Dec 20.

Celiac.com 07/28/2010 - Most people with celiac disease keep themselves healthy by following a gluten free diet. More and more, doctors are recognizing the importance of confirming gut recovery through follow-up evaluation. Still, among clinicians, there is currently no standard for follow-up confirmation of gut healing in celiac disease treatment. Many guidelines recommend an initial follow-up biopsy at 4-6 months after the patient begins a gluten-free diet. However, the use of biopsy to confirm gut healing is still controversial, as it can yield enormously variable results. A group of researchers recently set out to establish the amount of time it takes for full gut recovery in patients with celiac disease. The research team was made up of J.M. Hutchinson, N.P. West, G.G. Robins and P.D. Howdle. They are variously affiliated with the Sections of Medicine, Surgery and Anesthesia, the Section of Pathology & Tumour Biology at the Leeds Institute of Molecular Medicine in Leeds, and with the Department of Gastroenterology of the York Foundation Hospitals Trust, York, UK. The team enrolled patients who attended a specialty celiac disease clinic prior to March 2009, and recorded various clinicopathological information into a database. The team reviewed histopathology reports for all duodenal biopsies, and scored each biopsy for histopathology based on a modified Marsh grade. The team indexed and performed at least one biopsy on two hundred and eighty-four patients. The team found marked gut improvement in two-hundred and twenty-seven patients (80%), and a complete return to normal histology in 100 patients (35%). Average recovery time was 1.9 years, with a range of 1.0–4.8 years. Patients with less serious celiac disease at the start showed a better overall response (r = 0.281, P < 0.0001), while older patients recovered more quickly (r = –0.200, P = 0.001). Patients who best followed a gluten-free diet showed the best biopsy scores (r = –0.134, P = 0.040) and the greatest degree of histological recovery (r = 0.161, P = 0.014). Current guidelines for treatment of celiac disease recommend timing repeat biopsy 4-6 months after commencing a gluten free diet. These results shows histological recovery generally takes longer than traditionally thought, and that doctors looking to conduct such follow-ups might do well to factor in the patient’s age at diagnosis, the initial disease score, as well as the level of compliance with a gluten free diet. Source: QJM 2010 103(7):511-517

Celiac.com 07/26/2010 - There is very little information currently available regarding the effects of follow up strategies for those celiac patients that follow a gluten-free diet. Therefore, it was the aim of of researchers in Italy to determine the t-transglutaminase antibodies (t-TG) in celiac disease patients while they were enrolled in a community based follow-up program over a 5-year period. Most patients that are diagnosed with celiac disease are told they need to adhere to a gluten-free diet for the remainder of their lives, and then they are usually left to figure it out on their own. However, it is recommended that celiac patients have regularly scheduled follow-ups after diagnosis for early detection of celiac related complications, and to reinforce the importance of adhering strictly to a gluten-free diet. In the year 2000, a community based “celiac disease-Watch” follow-up program was designed by the Local Health Authority of the Brescia Province in Northern Italy. The hope for the celiac disease-Watch program was to increase awareness of celiac disease and to standardize diagnostic criteria for celiac disease among health care professionals. Beginning in January 2003, all celiac patients that reside in the Province of Brescia have been enrolled in an ongoing celiac disease-Watch follow-up program. To encourage celiac patients to enroll in the follow-up program, the Italian government gives patients a bonus to subsidize their gluten-free diets, and all patients are required to contact the Local Health Authority every year to renew their bonuses. Furthermore, the celiac disease-Watch program requires all patients to have their serum tested once a year for detection of t-TG antibodies. Testing for the antibodies begins 12-16 months after a celiac diagnosis. The testing is free of charge to the patients and they can choose any laboratory they like. Results from the t-TG testing is reported to the Local Health Authority, and it is a requirement to continue to receive subsidization, although patients continue to receive subsidization regardless of their t-TG results. Those that test positive for t-TG antibodies during their annual follow up, are referred back to the clinic where they were initially diagnosed. At the clinic they receive a clinical evaluation, and dietary counseling. While those that have a clean bill of health are scheduled for follow up appointments every 3 years. Through this study, researchers found that as a result of the celiac disease-watch program, celiac patients with negative t-TG antibodies advanced from 83% to 93%. Respectively, using mathematical modelling to t-TG conversion rates observed in the study, the projected population of t-TG negative patients increased in population from 90% to 95% over the 5 year period. From this study, researchers were able to determine with confidence that without a follow-up strategy in place, patients with celiac disease will be inconsistent with adhering to a gluten-free diet. It is therefore strongly emphasized that regular serological and clinical follow-ups are a sustainable strategy to promote dedicated compliance to a gluten-free diet. Source: Digestive and Liver Disease doi:10.1016/j.dld.2010.05.009

Dr. Peter Green is a gastroenterologist and the director of the GI Endoscopy Unit at Columbia-Presbyterian Medical Center in New York City. He has a large celiac patient base. On September 29th, Dr. Green spoke to the Westchester Celiac Sprue Support Group and presented an excellent review of the medical care an adult Celiac patient should receive. What follows is a summary of Dr. Greens presentation, compiled by Sue Goldstein, a past president of the Westchester group. Initial Assessment Dr. Green sees a lot of patients who, either through their own frustration or because of physician advice, have started a gluten-free (gluten-free) diet without obtaining a biopsy-proven diagnosis of celiac disease (celiac disease). However, the need for a biopsy to establish a diagnosis of celiac disease must be emphasized. celiac disease is a lifelong illness with serious potential implications. In addition, sensitivity to gluten doesnt go away, and a radical lifestyle change is involved. You also need to be certain of the diagnosis because celiac patients families should be screened. The initial biopsy is also needed to serve as a baseline because one doesnt know what the future may involve. Basic blood work is also included in the initial assessment. Such things as anemia and liver function need to be looked for. But its very important to go further than that, and knowledge of the physiology of the small intestine should lead a physician to measure those nutrients that could be malabsorbed. celiac disease involves the small intestine, where iron, folic acid, calcium, fat soluble vitamins (K, A, D, and E) and zinc are absorbed. These nutrients should be measured in the initial assessment and also during the course of the illness. Physicians will see patients who present with malabsorption of just one of these nutrients. If they are aware of the consequences of all these nutrient deficiencies, it will help them consider celiac disease as a possible diagnosis. The patient should also have the celiac antibodies blood testing, but the diagnosis is still established on the biopsy pathology. In Dr. Greens experience, about 30% of celiacs have negative antibodies at diagnosis, so positive antibodies are not required to make the diagnosis. Antibodies testing often helps establish the need for a biopsy, but they also have great value in establishing a baseline so that an assessment can be made on how the patient is doing later on. All the antibodies should normalize, in time, when gluten is eliminated from the diet. What about the patient who seeks a diagnosis, but has already eliminated gluten from the diet? It is very difficult for many patients to go back on a gluten-containing diet to secure a biopsy-proven diagnosis. This can often take three to six months or longer. Columbia-Presbyterian has been talking about setting up alternative means of securing a diagnosis, such as a rectal challenge. The physician can take a biopsy of rectal tissue, and then instill gliadin extract into the rectum and do a repeat biopsy a certain number of hours afterward to demonstrate an inflammatory response similar to that in the small bowel. However, interpreting the results of the gluten challenge would require a pathologist who is very experienced, and sophisticated immunology on the cells of the rectal biopsy may be needed. Follow-up Care Soon after diagnosis and adhering to a gluten-free diet, patients will often report an increased feeling of well-being. How well they feel--and how quickly--will also depend on what the manifestations of their disease were. For example, if the patient was iron-deficient, it will take time for the iron stores to be restored. An assessment of vitamin and mineral levels should be part of the follow-up care. Specific deficiencies need to be addressed, treated, and monitored. Patients have been seen who have been ingesting too much of the fat-soluble vitamins, with resulting problems such as liver disease (from vitamin A toxicity), and hypercalcemia (from vitamin D toxicity) which can cause confusion, constipation, and kidney problems. Certain vitamins and minerals may need to be administered, but the patient should be under a physicians guidance as to how much should be taken. After a diagnosis of celiac disease, a bone mineral density test should be performed to assess the condition of the bones. Reports have shown that between 50-100% of people at initial diagnosis of celiac disease will have osteopenia or osteoporosis. Ostopenia is thinner bones, usually less than 2 standard deviations from normal. Osteoporosis involves an even greater deviation from normal.. In Dr. Greens experience, nearly 100% of the celiac patients at diagnosis will have osteoporosis. Surveys of celiac patients have shown an increased incidence of fractures prior to diagnosis and after diagnosis. If the bone mineral density is low, the patient should be referred to a bone mineral expert for assessment and specific individual treatment. For example, calcium and vitamin D needs will be addressed and monitored, and exercise and hormone replacement (in post-menopausal women) will be considered. At diagnosis, patients should get a Pneumovax, because it is very common for celiacs to have poor splenic function, which puts them at risk of developing certain bacterial infections such as pneumoccal pneumonia and meningitis. Since there is a genetic predisposition to celiac disease, another important issue in the follow-up is screening family members for celiac disease. Children and other first-degree relatives should have their antibodies status measured. About 10-15% of first-degree relatives have positive antibodies, and the bulk of the people with positive antibodies will have the disease, even though 50% of those people will be asymptomatic, even with a flat biopsy. What annual follow-up care should the celiac patient be getting? The most important thing is a good physical examination. Blood work, x-rays, CAT scans, mammograms and PSA tests, while valuable, do not replace a physical examination. The physical exam should include a breast exam for women, prostate exam for men, and a rectal exam for everyone. Blood work should include measurements of folic acid, calcium, and iron, and antibodies testing. Bone mineral density testing should be repeated annually for those with abnormal results, and every several years for those with normal results. Finally, patients with celiac disease should have at least one follow-up biopsy to confirm response--normalization of the biopsy sample. Patients who are non-responders, or whose clinical situation is somewhat confusing, may need more repeated biopsies at intervals. Non-responders What about the non-responders or people who relapse? The first thing is to check the diet with antibodies testing. People may be ingesting gluten, such as in medications, and not be aware of it. They may be getting gluten from licking stamps or envelopes. They may have misinformation from food labels or manufacturers. However, the antibodies can normalize and the biopsy still look quite flat, so once again, the antibodies have only a limited value--but they are still important to measure. It is also important to check the original biopsy to make sure of the diagnosis. Not all pathologists are experienced enough to properly diagnose celiac disease. Pathology departments, by law, have to keep the biopsies for a lengthy period of time--some keep them for 50 years. So it is important for the physician to review the biopsy sample with a pathologist who understands the spectrum of celiac disease. The pathologist needs to know, for example, how to identify latent celiac disease and different subtle aspects of the biopsy, such as increased intraepithelial lymphocytes. A problem that comes up in non-responders is other food sensitivities. Its very rare for people with celiac disease to also have sensitivities to other foods that result in the abnormal biopsy. There are, however, reports of ingestion of soy protein or egg or some kind of meats that cause the biopsy not to normalize. There are other conditions that can co-exist with celiac disease and confuse physicians. For example, pancreatic insufficiency can cause diarrhea and steatorrhea (malabsorption of fat), and bacterial overgrowth can affect absorption of nutrients. Patients may have colonic pathology. Having one disease doesnt mean you cant have another disease, and other conditions need to be investigated in the celiac disease patient who is not doing well. When there is no improvement in the biopsies, patients remain at the risk of developing or maintaining bone disease and vitamin deficiencies, and they are at a higher risk for malignancy. Patients who are refractory may need other therapies such as corticosteroids or immunosuppressent drugs such as cyclosporin. One doesnt engage in these therapies lightly (for example, steroids will thin the bones); being closely evaluated while on these drugs is important. Prognosis for the Celiac Patient The studies that have indicated increased mortality in celiac disease are from other countries where people have different smoking and dietary habits. It is hard to extrapolate these studies to our patient population. Dr. Green believes existing studies indicate that the mortality rate among adult celiacs is about two to three times that of the general population, and the increased mortality is found mainly in the first five years after diagnosis. After that, the mortality rate approaches that of the normal population. That tends to suggest that it is the continued ingestion of gluten that is responsible for the increased mortality. This is especially so in regard to malignancies, where the risk of diagnosis of malignancy such as lymphoma is usually highest in the first year after diagnosis, and then decreases in incidence downward until it equals that of the normal population after about five years. There is certainly the suggestion that adhering to a gluten-free diet reduces the risk of developing a malignancy. A Final Word--Looking For Celiac Disease Traditionally, the incidence of celiac disease in this country, based upon epidemiological work, suggests that celiac disease occurs in about 1 in 4,600 people. Certainly its much more common than that. Serology testing of blood donors by Dr. Fasano suggests the same prevalence as in European countries, about 1 in 300 people. Dr. Green, who does a lot of endoscopies, has found an incidence of celiac disease in about 1 in 280 patients who were having endoscopies for reasons other than suspicion of celiac disease. It is important, therefore, for the gastroenterologist to have a higher suspicion for the possibility of celiac disease, and for physicians to screen for celiac disease, particularly among their patients who have associated diseases such as Insulin Dependent Diabetes, Sjogrens, and Autoimmune Thyroid Disease.

GUT 2002;50:332-5 Celiac.com 03/19/2002 - According to a long term study conducted by Dr Matti Uusitupa and colleagues from the University of Kuopio, Kuopio, Finland, long-term ingestion of a moderate amount of oats in an otherwise gluten-free diet is safe for adult patients with celiac disease. In a previous study Dr. Uusitupa found no harmful effects from oats after patients ate them for 12 months, which was reflected by the patents symptoms, nutritional status, duodenal villous architecture, and mucosal mononuclear cell infiltrate, as seen in celiac patients who are in remission. The earlier study also showed that ingestion of oats did not delay recovery of mucosal damage in newly diagnosed celiacs. Dr. Uusitupas first study compared the effects of a gluten-free diet and a gluten-free diet that included oats with a randomized trial involving 92 adult celiac patients: 45 in the oats group whose intake averaged approximately 34 grams per day, and 47 patients in the control group. Patients in the oats group were allowed to eat oats freely in conjunction with an otherwise gluten free diet. After five years 35 patients in the original oats group, 23 of whom were still eating oats at least twice a week, and 28 in the control group that was on a conventional gluten free diet were examined. The results confirmed that eating oats did not cause ANY duodenal mucosal damage to the adult celiac patients in the study. Further, the patients were also examined using histological, histomorphometric, and immunological methods, and AGA, ARA, and EMA serological test results of those in the oat group showed no negative effects that could be linked to eating oats. According to Dr. Uusitupa, the high antibody levels that appeared in some of the patients that were in both groups are most likely explained by poor compliance to a gluten free diet, and the reason why celiac patients can tolerate oats must be based on structural differences between the proteins of oats, wheat, barley, and rye. The toxic portion of the harmful gluten protein lies in the ethanol soluble fraction called gliadins, whose toxicity remains after digestion. With oats, however, it is possible that the absence of specific amino acid sequences that are found in wheat gliadin but are not found in oat avenin allow oats to be tolerated by celiacs. Last, the researchers note that taking oats off of the list of forbidden cereals might improve patient compliance to the gluten-free diet by giving them more food choices.

Aliment Pharmacol Ther. 2005;22(4):317-324. Celiac.com 09/14/2005 - In an effort to determine whether general screening for celiac disease should be conducted in high-risk groups, Finnish researchers conducted a 14 year follow-up study which focused on dietary compliance, quality of life, and bone mineral density in 53 consecutive screen-detected celiac disease patients who were diagnosed and treated around 14 years ago. The researchers assessed dietary compliance via an interview, a 4-day food record, and a blood antibody screening. Quality of life was measured via the Psychological General Well-Being and SF-36 questionnaires, while gastrointestinal symptoms were evaluated using the Gastrointestinal Symptom Rating Scale, and bone mineral density was measured using dual-energy x-ray absorptiometry. The researchers compared the results of these evaluations with those of 44 symptom-detected and treated celiac disease patients, 110 non-celiac disease subjects, and the general population. The researchers found that 96% of screen-detected and 93% of symptom-detected celiac disease patients adhered to a strict or fairly strict gluten-free diet. In the screen-detected group quality of life and gastrointestinal symptoms were similar to that of the symptom-detected patients and non-celiac disease controls, and their bone mineral densities were similar to that of the general population. The researchers conclude that dietary compliance in long-term screen-detected patients was good, and quality of life and bone mineral densities were comparable to that of the non-celiac disease subjects and the general population. Based on these results active screening for celiac disease in risk groups is beneficial and in no way harmful.

Digestion 2002;66(3):178-85 PMID: 12481164 Ciacci C, Cirillo M, Cavallaro R, Mazzacca G. Department of Internal Medicine, Gastrointestinal Unit, Federico II University of Naples, Naples, Italy. Celiac.com 01/12/2003 - Background and Aims: Celiac disease is the most common severe food intolerance in the Western world and is due to gluten ingestion in genetically susceptible children and adults. Intestinal biopsy is the golden standard for evaluation of mucosal damage associated with celiac disease. Gluten-free diet is the key treatment for celiac disease. Data on the long-term control of celiac disease are few and limited to small series of patients. The study reports data on the control of celiac disease and on its correlates in a large cohort of celiac adults during long-term treatment with gluten-free diet. Methods: The study cohort comprises 91 men and 299 women having undergone treatment with a gluten-free diet for at least 2 years and with complete records for visits at the time of diagnosis of celiac disease (baseline). Data collection included gender, age, education, weight, bowel habit, blood hemoglobin, plasma albumin and cholesterol, serum antiendomysium antibodies (EMA), dietary compliance to gluten-free diet (coded as good, low, or very low), and intestinal damage at biopsy (coded as absent, mild, or severe). Results: The duration of follow-up was 6.9 +/- 7.5 years (mean +/- SD, range 2-22 years). At follow-up visit, intestinal damage was absent in 170 patients (43.6%), mild in 127 (32.6%), and severe in 93 (23.8%). At follow-up, intestinal damage was significantly associated with dietary compliance, EMA, and plasma albumin (follow-up value and change value from baseline to follow-up). Baseline education significantly predicted dietary compliance and intestinal damage at follow-up. Conclusions: Celiac disease is often poorly controlled in the majority of patients on long-term treatment with a gluten-free diet as demonstrated by intestinal biopsy. Lack of adherence to strict gluten-free diet is the main reason of poorly controlled disease in adults. Laboratory and clinical information have a high positive predictive value and low negative predictive value for intestinal damage on long-term treatment. Dietary compliance as assessed by interview is the best marker of celiac disease control due to low cost, noninvasivity, and strong correlation with intestinal damage. Copyright 2002 S. Karger AG, Basel

Wahab PJ, Meijer JW, Mulder CJ. Department of Gastroenterology and Hepatology, Rijnstate Hospital Arnhem, The Netherlands. Am J Clin Pathol 118(3):459-463, 2002 Celiac.com 10/28/2002 - The following study strongly supports follow-up care and testing for people with celiac disease. As the study found, over 10% of people with diagnosed celiac disease have still not fully recovered even after five years of treatment. To assess histologic recovery in response to gluten withdrawal in celiac disease, 158 patients seen in our hospital during a 15-year period underwent follow-up small intestine biopsies (SIBs) within 2 years after starting a gluten-free diet; further SIBs were done if villous atrophy was present. A modified Marsh classification was used (IIIA, partial villous atrophy; IIIB, subtotal villous atrophy; IIIC, total villous atrophy). Of patients with Marsh IIIA, IIIB, or IIIC lesions, histologic remission was seen in 65.0% within 2 years, 85.3% within 5 years, and 89.9% in long-term follow-up. Eleven patients (7.0%) with persisting (partial) villous atrophy had symptoms and signs of malabsorption and were considered to have refractory celiac disease; 5 of them developed an enteropathy-associated T-cell lymphoma. Children recovered up to 95% within 2 years and 100% in the long-term. Histologic recovery in celiac disease after starting a gluten-free diet takes time and is incomplete or absent in a substantial subgroup of patients (10.1% villous atrophy after 5 years). Systematic follow-up of patients with celiac disease and the malabsorption syndrome and secondary complications is needed.

Scand J Gastroenterol 1999 Feb;34(2):163-9 PMID: 10192194, UI: 99206412 Authors: Kaukinen K, Collin P, Holm K, Rantala I, Vuolteenaho N, Reunala T, Maki M Dept. of Medicine, Tampere University Hospital, Finland. (Celiac.com 05/14/2000) SPECIAL NOTE: European Codex Alimentarius quality wheat starch was used in this study. BACKGROUND: We investigated whether wheat starch-based gluten-free products are safe in the treatment of gluten intolerance. METHODS: The study involved 41 children and adults with coeliac disease and 11 adults with dermatitis herpetiformis adhering to a gluten-free diet for 8 years on average. Thirty-five newly diagnosed coeliac patients at diagnosis and 6 to 24 months after the start of a gluten-free diet and 27 non-coeliac patients with dyspepsia were investigated for comparison. Daily dietary gluten and wheat starch intake were calculated. Small bowel mucosal villous architecture, CD3+, alphabeta+, and gammadelta+ intraepithelial lymphocytes, mucosal HLA-DR expression, and serum endomysial, reticulin, and gliadin antibodies were investigated. RESULTS: Forty of 52 long-term-treated patients adhered to a strict wheat starch-based diet and 6 to a strict naturally gluten-free diet; 6 patients had dietary lapses. In the 46 patients on a strict diet the villous architecture, enterocyte height, and density of alphabeta+ intraepithelial lymphocytes were similar to those in non-coeliac subjects and better than in short-term-treated coeliac patients. The density of gammadelta(+)cells was higher, but they seemed to decrease over time with the gluten-free diet. Wheat starch-based gluten-free flour products did not cause aberrant up-regulation of mucosal HLA-DR. The mucosal integrity was not dependent on the daily intake of wheat starch in all patients on a strict diet, whereas two of the six patients with dietary lapses had villous atrophy and positive serology. CONCLUSION: Wheat starch-based gluten-free flour products were not harmful in the treatment of coeliac disease and dermatitis herpetiformis.

Scand J Gastroenterol 1999 Feb;34(2):163-9 PMID: 10192194, UI: 99206412 Authors: Kaukinen K, Collin P, Holm K, Rantala I, Vuolteenaho N, Reunala T, Maki M Dept. of Medicine, Tampere University Hospital, Finland. (Celiac.com 05/14/2000) SPECIAL NOTE: European Codex Alimentarius quality wheat starch was used in this study. BACKGROUND: We investigated whether wheat starch-based gluten-free products are safe in the treatment of gluten intolerance. METHODS: The study involved 41 children and adults with coeliac disease and 11 adults with dermatitis herpetiformis adhering to a gluten-free diet for 8 years on average. Thirty-five newly diagnosed coeliac patients at diagnosis and 6 to 24 months after the start of a gluten-free diet and 27 non-coeliac patients with dyspepsia were investigated for comparison. Daily dietary gluten and wheat starch intake were calculated. Small bowel mucosal villous architecture, celiac disease3+, alphabeta+, and gammadelta+ intraepithelial lymphocytes, mucosal HLA-DR expression, and serum endomysial, reticulin, and gliadin antibodies were investigated. RESULTS: Forty of 52 long-term-treated patients adhered to a strict wheat starch-based diet and 6 to a strict naturally gluten-free diet; 6 patients had dietary lapses. In the 46 patients on a strict diet the villous architecture, enterocyte height, and density of alphabeta+ intraepithelial lymphocytes were similar to those in non-coeliac subjects and better than in short-term-treated coeliac patients. The density of gammadelta(+)cells was higher, but they seemed to decrease over time with the gluten-free diet. Wheat starch-based gluten-free flour products did not cause aberrant upregulation of mucosal HLA-DR. The mucosal integrity was not dependent on the daily intake of wheat starch in all patients on a strict diet, whereas two of the six patients with dietary lapses had villous atrophy and positive serology. CONCLUSION: Wheat starch-based gluten-free flour products were not harmful in the treatment of coeliac disease and dermatitis herpetiformis.

The following was written by Donald D. Kasarda who is a research chemist in the Crop Improvement and Utilization Research Unit of the United States Department of Agriculture. If you have any questions or comments regarding the piece, please address them to Don at: kasarda@pw.usda.gov The work from Prof. Auricchios laboratory (Troncone et al.) in Naples is certainly of interest and I shall look forward to seeing the details, but I will just point out for the sake of balance that studies with patients who ingest, or have instilled into their intestines, the substance to be tested represent the gold standard and in vitro testing (that is, in glass, or in the test-tube), while valuable, does not carry as much weight. The results from the Finnish group and from Dr. Feigherys group (not yet published), Dublin, Ireland, are very impressive. The results based on in vitro testing would have to be truly exceptional to undermine the excellent work that has been done on the safety of oats. So, we shall have to wait and see, but I doubt there is reason to be overly concerned just yet.

In volume 334, number 13 of the New England Journal of Medicine was published a follow-up article concerning additional research which seems to contradict their October 19, 1995 (Vol. 333, No. 16) article which stated that pure oats are safe for celiacs. David Branski, M.D., Margot Shine, M.D., and Shaare Zedek Medical Center, Jerusalem 91031, Israel report their belief that allowing oats in the diet is premature. They sited the short duration of the study and the increased risk of cancer related through small intake of gluten (Holmes et al). It does appear that the initial study is being continued for an additional five years.

Colin, et al, published a follow-up study to the Catassi (Ceeliac Disease in the Year 2000: Exploring the Iceberg - University of Ancona, Italy) in the Scandinavian Journal of Gastroenterology - 28(7):595-8, 1993, which demonstrated that approximately one third of the patients from the Catassi Study who had raised antibodies but no villous atrophy, did have villous atrophy when tested two years later. These results raise the amount of diagnosed celiacs from the Catassi, et al study to over 1 in 200.