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Jefferson Adams posted an article in Celiac Disease & Gluten Intolerance ResearchCeliac.com 06/27/2018 - Data shows that since celiac blood screening came into use, people with celiac disease are living longer, and dying of things not-related to celiac disease. With screening tests for celiac disease becoming more common, researchers suspected that milder cases of celiac disease coming to diagnosis might bring a reduced risk of mortality for celiac patients. However, there was no consensus for that opinion, so researchers Geoffrey K T Holmes and Andrew Muirhead of the Royal Derby Hospital, and the Department of Public Health for the Derby City Council, Derby, UK., recently set out to re-examine the issue in a larger number of patients for a further 8 years. For their study, the researchers prospectively followed celiac disease patients from Southern Derbyshire, UK, from 1978 to 2014, and included those diagnosed by biopsy and serology. For each patient, the researchers determined cause of death, and calculated standardized mortality ratios for all deaths, cardiovascular disease, malignancy, accidents and suicides, respiratory and digestive disease. To avoid ascertainment bias, they focused analysis on the post-diagnosis period that included follow-up time beginning 2 years from the date of celiac disease diagnosis. They stratified patients by date of diagnosis to reflect increasing use of serological methods. Total all-cause mortality increase was 57%, while overall mortality declined during the celiac blood test era. Mortality from cardiovascular disease, specifically, decreased significantly over time, which means that fewer people with celiac disease were dying from heart attacks. Death from respiratory disease significantly increased in the post-diagnosis period, which indicates that people are living long enough to have lung problems. The standardized mortality ratio for non-Hodgkin’s lymphoma was 6.32, for pneumonia 2.58, for oesophageal cancer 2.80 and for liver disease 3.10. Overall, celiac blood tests have lowered the risk of mortality in celiac disease. The number of celiac patients dying after diagnosis decreased by three times over the past three decades. Basically, people with celiac disease are living longer, and dying of things unrelated to celiac disease, which is good news. The researchers see this data as an opportunity to improve celiac disease survival rates further by promoting pneumonia vaccination programs, and more swift, aggressive treatments for celiac patients with liver disease. Source: BMJ Open Gastroenterology
Jefferson Adams posted an article in Celiac Disease Diagnosis, Testing & TreatmentCeliac.com 01/09/2017 - Some researchers have criticized the usefulness of the 7 level Marsh-Oberhuber classification of mucosal damage in patients with celiac disease. Even though assessing duodenal biopsies with dissecting microscopy is a somewhat crude method, it can provide useful information in cases of obvious villous atrophy. For the past 15 years, one research team has analyzed duodenal biopsies with dissecting microscopy before sending them to the pathology department for histology. Their feeling is that, if dissecting microscopy and traditional histology were comparable, the grading of the histological lesion would be unnecessary, or even pointless, for proper diagnosis of most enteropathies. That research team recently set out to settle that question. The team included F Biagi, C Vattiato, M Burrone, A Schiepatti, S Agazzi, G Maiorano, O Luinetti, C Alvisi, C Klersy, and GR Corazza. They are variously affiliated with the First Department of Internal Medicine, the Biometry and Statistics, the Department of Pathology at University of Pavia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; and with the Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy. They conducted a retrospective analysis of the clinical notes of all 2,075 patients undergoing duodenal biopsy between September 1999 and June 2015. They collected and statistically compared the results of duodenal mucosal evaluation with both dissecting microscopy and traditional histology. Their results, using κ statistics, showed a substantial agreement of the two methods (κ statistics 0.78). Sensitivity of dissecting microscopy for detection of severe villous atrophy was 85.1% (95% CI 81.2% to 88.5%) and specificity was 95% (95% CI 93.8% to 96%). Although dissecting microscopy is no substitute for traditional histology, these results suggest that most celiac disease-related and other flat enteropathies can be sufficiently diagnosed without grading villous atrophy. Source: J Clin Pathol. 2016 Dec;69(12):1051-1054. doi: 10.1136/jclinpath-2016-203711. Epub 2016 May 4.
This article originally appeared in the Summer 2002 edition of Celiac.coms Scott-Free newsletter. On June 2, 2002, hundreds of researchers traveled from all over the world to Paris, France, in order to hear the latest scientific reports on celiac disease research and to present results from their own investigations. Over the course of three days, scientists presented dozens of reports, and displayed over a hundred posters covering all aspects of celiac disease, from laboratory research on the microbiologic aspects of the disease, to quality of life issues in patients who are on the gluten-free diet. There were so many exciting reports presented at the conference, and the following describes the research findings from these new reports concerning the screening and clinical presentation of celiac disease, osteoporosis and osteopathy and neurological conditions. SCREENING ISSUES IN CELIAC DISEASE In order to understand how best to screen populations for celiac disease, it is important to know how celiac disease affects a portion of the population, and how it compares to similar populations in other countries. Mayo Clinic Retrospective Study Dr. Joseph Murray from the Mayo Clinic conducted a retrospective study on the population of people living in Olmsted County, Minnesota. This county has kept medical records on all of its residents for over 100 years. Dr. Murray looked at the medical records to determine which residents were diagnosed with celiac disease from 1950 to 2001. He found 82 cases of celiac disease, with 58 in females and 24 in males. The average age of diagnosis was 45. Pediatric diagnoses of celiac disease during this time period were extremely rare. Dr. Murray found that while the diagnosis rate of dermatitis herpetiformis (DH) remained constant over the 51 year period, the diagnosis rate of celiac disease increased from 0.8 to 9.4 per 100,000 people. He also noted that over time, adults with celiac disease were less likely to present diarrhea and weight loss as symptoms. Encouragingly, he determined that the average life expectancy for a diagnosed celiac in this community was no less than that of the normal population, despite the fact that celiac disease was often diagnosed later in life. What does this mean? The celiac disease diagnosis rate in this county is much lower than the actual incidence rates that have been reported in other studies; however, that rate has greatly increased over the past 51 years. It is also noteworthy that so few children were diagnosed with celiac disease. The analysis highlights interesting and useful information about the presentation of celiac disease in adults, and about the potential life expectancy for people with celiac disease who are diagnosed later in life. United States and Europe Compared Dr. Carlo Catassi of Ancona, Italy is currently a visiting researcher at the University of Maryland Celiac Research Center. He presented an analysis of the similarities and differences between the clinical presentations of celiac disease in the United States and Europe. Dr. Catassi established that the prevalence of celiac disease in the U.S. and Europe are the same and range between 0.5 to 1.0 percent of the general population. The prevalence in at-risk populations is much higher, ranging between 5 and 10 percent, and the prevalence in people with Type 1 Diabetes is approximately 5 percent in both the U.S. and Europe. He found that the typical (symptomatic) cases of celiac disease were less common in the U.S., and that the latent (asymptomatic) cases were much more common. Dr. Catassi stated that these differences could be due to genetic factors (for example, there are more Asians in the United States than in Europe), but are more likely due to environmental factors. He noted that infants born in the U.S. are often breastfed longer than their European counterparts. There is also a lower gluten intake in the first months of life for infants in the U.S. The timing of the introduction of cereals could help explain why many American children have somewhat milder symptoms and a more unusual presentation of the disease. What does this mean? Dr. Catassis analysis underscores the need to better educate physicians in the U.S. so that they learn to see typically atypical signs of celiac disease in children and adults. He also reinforced the importance of breastfeeding as a protective factor for children with a genetic predisposition to celiac disease, which could also improve the outlook for European children in the future. United States Prevalence Research Dr. Alessio Fasano presented a poster which outlined his recent findings that are a follow-up to his now famous 1996 blood screening study. The original study found that 1 in 250 Americans had celiac disease. It was performed using anti-gliadin antibodies (AGA), and when a blood sample tested AGA positive it was confirmed using anti-endomysial (EMA) antibody testing. Now that human tissue transglutaminase (tTG) testing is available, Dr. Fasano and his colleagues wanted to see if the results of their original study would be different using the tTG test. He and his colleagues tested the negative samples in the original study, and found 10 more positives using the tTG test. Two of these samples were confirmed positive when checked using the AGA antibody test. Dr. Fasano concluded that the original (1996) prevalence estimate of 1 in 250 understated the true prevalence rate, which could actually be greater than 1 in 200 Americans. Dr. Michelle Pietzak, a pediatric gastroenterologist at the University of California at Los Angeles, also presented a poster which described the prevalence of celiac disease in Southern California. In a study of 1,094 participants, Dr. Pietzak found that 8% of Hispanics tested positive for celiac disease. The most common symptoms presented by subjects in her study included abdominal pain, diarrhea, constipation, joint pain and chronic fatigue. What does this mean? It is important to understand that the foundation of all U.S. prevalence research on celiac disease began with the blood donor study performed by Dr. Fasano in 1996. His newly revised findings, which have been supported by at least one other major study, show that the prevalence of celiac disease in the U.S. population is much higher than originally believed, and that it could be greater than 1 in 200 people. Additionally, the California study is one of the first to establish a celiac disease prevalence figure for the Hispanic population in the U.S., and if the 8 percent figure is supported by further research it would indicate that celiac disease significantly affects Hispanic Americans. OSTEOPOROSIS AND OSTEOPATHY Dr. Julio Bai of Argentina presented important information on a condition that affects many people with celiac disease, and one that is often overlooked by physicians—osteoporosis or osteopathy (its milder form). Both children and adults with celiac disease can have low bone mineral density, and its method of treatment can have important consequences. Dr. Bai treats adults with bone loss, and has studied the nature of fractures and bone health in adults with celiac disease. In a case-control study of 78 celiac disease patients, Dr. Bai found that symptomatic patients were more likely to experience bone fractures than the normal population. Interestingly, he also found that patients with latent (asymptomatic) celiac disease had lower fracture rates than those with symptoms, and that the rate was equal to that of the normal population. None of the patients, however, experienced a fracture of the more serious type—in the hip, spine or shoulder, and the fractures tended to occur in their arms, legs, hands and feet. The doctor also discussed preliminary evidence which showed that most women with osteopathy and celiac disease who go on a gluten free diet will experience an improvement in bone density, while many men do not. There was, however, no difference found between the fracture rates of men and women. Dr. Bai also found that nutritional and metabolic deficiencies in patients with celiac disease and osteopathy might also contribute to fractures by weakening the muscles that surround essential bones. He added that immunological factors could also enhance or inhibit bone rebuilding, and that there is a bone-specific tissue transglutaminase (tTG) that plays a role in this process. What does this mean? It was certainly good news to hear that most people with low bone density due to celiac disease can reverse the damaging process, and if celiac-related fractures do occur they tend to be of the less serious type. Additionally, it was interesting to learn just how important a role muscle health plays in preventing celiac-related fractures. Osteopathy in Children Dr. Mora, an Italian researcher, presented data on osteopathy in children with celiac disease. His results indicate that a gluten-free diet can improve bone mass, and the effect is maintained even after 10 years. He also added that a gluten-free diet improved the overall bone metabolism of the children, and that the diet alone could cure their osteopathy. Osteopenia and Osteoporosis: Conditions Related to Celiac Disease In a chart prepared by Dr. David Sanders of the United Kingdom, data on 674 patients, 243 with osteoporosis and 431 with osteopenia, were presented. He found 10 cases of celiac disease among a mostly female population that had an average age of 53. In all ten cases, patients either had a history of iron-deficient anemia or gastrointestinal symptoms. He concluded that all patients with osteopenia or osteoporosis and a history of anemia or gastrointestinal symptoms should be screened for celiac disease. What does this mean? Dr. Sanders has identified a subset of people with osteoporosis and osteopenia that should be screened for celiac disease—those who have been anemic or have gastrointestinal symptoms. This helps physicians know when to refer patients for celiac disease screening. NEUROLOGICAL SYMPTOMS Dr. Marios Hadjivassiliou of the United Kingdom presented data on neurological symptoms and gluten sensitivity. In an eight-year study, Dr. Hadjivassiliou screened people who had neurological symptoms of unknown origin using the anti-gliadin antibody (AGA) test. He found that 57 percent of these patients had antibodies present in their blood, compared to 12 percent of healthy controls or 5 percent of patients with a neurological condition of known origin. From this group, he studied 158 patients with gluten sensitivity and neurological conditions of unknown origin (only 33 percent of these patients had any gastrointestinal symptoms). The most common neurological conditions in this group were ataxia, peripheral neuropathies, myopathy, and encephalopathy (very severe headache). Less common were stiff person syndrome, myelopathy and neuromyotonia. He noted that ataxia is not a result of vitamin deficiencies, but is instead an immune-mediated condition. Patients with ataxia have unique antibodies that are not found in patients with celiac disease. Dr. Hadjivassiliou felt that up to 30 percent of idiopathic neuropathies could be gluten-related, and that there is preliminary evidence which indicates that a gluten-free diet is helpful in cases of neuropathy and ataxia. What does this mean? It is interesting to note that Dr. Hadjivassiliou has studied gluten sensitivity and not celiac disease. The test used in this study is not specific enough to identify people who were likely to have celiac disease. However, his finding that the gluten-free diet may be helpful in people with certain types of neuropathy and ataxia opens the door for further research on these conditions in people with celiac disease.
Jefferson Adams posted an article in Celiac Disease Diagnosis, Testing & TreatmentCeliac.com 09/25/2008 - Mucosal inflammation of the small intestine, coupled with damage to intestinal villi, is a classic indication of celiac disease. Recently, doctors have begun to embrace the idea that some patients with positive celiac blood tests may have mucosal lesions that are too small to appear on routine histopathological analysis. In the first study of its kind, a team of researchers based in Ireland set out to analyze enterocyte morphology and cytoskeletal structures using a high content analysis technology. The research team was made up of doctors Bashir M. Mohamed, Conleth Feighery, Yvonne Williams, Anthony Davies, Dermot Kelleher, Yuri Volkov, Jacinta Kelly and Mohamed Abuzakouk. The team examined duodenal biopsies from 14 untreated and 10 treated celiac patients and from 20 non-celiac control subjects. They also investigated tissue sections from six study group subjects before and after the development of gluten-sensitive enteropathy. The research team used an anti-Î±-tubulin antibody to conduct immunohistochemical studies on paraffin-embedded tissue sections. They found important differences in enterocyte morphology and intracellular cytoskeletal structures in the patients with proven celiac disease and those in the study group. Moreover, the team observed that these changes existed in the study group prior to any indication of enteropathy, as determined by standard microscopy. This is the first time researchers have used high content analysis to show specific details of enterocyte morphology. Such an approach permits doctors to quantitatively analyze enterocyte intracellular structure from standard biopsy samples and allows for detection of minute changes that develop before the classic histological lesion. This process could become important for improving the diagnosis of celiac disease. If doctors can spot celiac-related intestinal lesions before they develop, they can begin to prevent celiac disease before it develops and thereby save lives. Central European Journal of Biology Volume 3, Number 3 / September, 2008