[Show abstract][Hide abstract] ABSTRACT: Patients with celiac disease (CD) are at increased risk of osteoporosis and compromised B-vitamin status. Emerging evidence supports a beneficial role of folate and the metabolically related B-vitamins in bone health in generally healthy adults, but no previous study has investigated this in CD patients. The aim of the current study was to examine the relationship of folate, vitamins B12, B6 and B2 (riboflavin), and the related metabolite homocysteine, with bone mineral density (BMD) in CD patients.
Of the 400 treated adult CD patients invited to participate, 110 responded and met the eligibility criteria for study participation. BMD was measured using dual energy X-ray absorptiometry scanning at the lumbar spine (L1-L4), femoral neck, and total hip sites. Biomarker status of the relevant B-vitamins and homocysteine, and dietary B-vitamin intakes, were measured.
The significant predictors of low BMD were increasing age (B = 0.080, p < 0.001) and decreasing weight (B = 0.072, p = 0.004), whereas no significant relationship with serum 25-hydroxyvitamin D (B = 0.093, p = 0.928) was observed. Following adjustment for these predictors, serum vitamin B12 (but no other B-vitamin biomarker) was found to be a significant determinant of BMD at the femoral neck (β = 0.416, p = 0.011) and total hip (β = 0.327, p = 0.049) in men only. No significant relationships were found between any of the B-vitamin biomarkers investigated and BMD (at any measured site) in women.
These findings add to current evidence suggesting a potential role of vitamin B12 in BMD, particularly in men, and show such a relationship for the first time in CD patients.
[Show abstract][Hide abstract] ABSTRACT: Osteoporosis, a metabolic skeletal disease characterised by decreased bone mass and increased fracture risk, is a growing public health problem. Among the various risk factors for osteoporosis, calcium and vitamin D have well-established protective roles, but it is likely that other nutritional factors are also implicated. This review will explore the emerging evidence supporting a role for certain B-vitamins, homocysteine and the 677C→T polymorphism in the gene encoding the folate-metabolising enzyme methylenetetrahydrofolate reductase, in bone health and disease. The evidence, however, is not entirely consistent and as yet no clear mechanism has been defined to explain the potential link between B-vitamins and bone health. Coeliac disease, a common condition of malabsorption, induced by gluten ingestion in genetically susceptible individuals, is associated with an increased risk both of osteoporosis and inadequate B-vitamin status. Given the growing body of evidence linking low bone mineral density and/or increased fracture risk with low B-vitamin status and elevated homocysteine, optimal B-vitamin status may play an important protective role against osteoporosis in coeliac disease; to date, no trial has addressed this possible link.
Proceedings of The Nutrition Society 02/2014; 73(02):1-10. DOI:10.1017/S0029665114000044 · 5.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Coeliac disease (CD), traditionally perceived as a rare childhood condition presenting with malabsorption, is instead an autoimmune multisystem disorder usually presenting in adulthood, affecting > or = 1% of the population and linked to the genetic expression of human leucocyte antigens (HLA) DQ2 and DQ8. Presentation occurs most often in the 40-60 years age-group, but potentially at any age. Symptoms attributable to the gut or to malabsorption may be mild, non-specific or absent; under one-third of patients have diarrhoea and almost half are overweight. Histological diagnosis no longer requires small intestine villous atrophy. The Marsh classification recognizes increased intraepithelial lymphocytes and crypt hyperplasia with intact villi as part of the gluten enteropathy spectrum, while some individuals have more subtle abnormalities identified only on electron microscopy. Serological testing for CD autoantibodies (to endomysium and tissue transglutaminase) has revolutionized diagnosis, shifting the process towards primary care. However, a substantial number of patients with CD are seronegative, particularly those without villous atrophy. The autoantibody to endomysium may be produced before histological change. The immune response to transglutaminase is crucial to the disease process. An exciting new development is the link between antibodies to organ-specific transglutaminases and clinical presentation; transglutaminases 2 (gut), 3 (skin) and 6 (nervous system). Negative testing for CD does not preclude its development later and HLA testing may allow 'once and for all' exclusion. In conclusion, an increasing proportion of patients with CD do not meet the 'classic' picture of malabsorption, positive serological testing and villous atrophy. Insisting on all these criteria for diagnosis will result in under diagnosis.
Proceedings of The Nutrition Society 07/2009; 68(3):234-41. DOI:10.1017/S0029665109001414 · 5.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Serum autoantibodies to transglutaminase and endomysium are found in the majority of patients with celiac disease, an autoimmune multisystem disorder affecting approximately 1% of Western and Middle-Eastern populations. Detection of these antibodies plays a crucial role in the diagnosis of celiac disease. The aim of this review is to summarize recent publications in this field, with particular focus on the applications and limitations of celiac autoantibody testing in routine clinical practice.
[Show abstract][Hide abstract] ABSTRACT: (Table is included in full-text article). Studies suggest that oats can be tolerated in the gluten-free diet by a majority of patients with coeliac disease. Concerns remain, however, about the possibility of contamination of commercially available oat products by wheat, barley and rye. The R5 ELISA allows the identification and quantification of wheat, barley and rye prolamins, and has demonstrated significant contamination in a range of products. If patients with coeliac disease are to take oats, it is important that those consumed are free of contamination. This assay should allow the identification of safe oat products.
European Journal of Gastroenterology & Hepatology 07/2008; 20(6):494-5. DOI:10.1097/MEG.0b013e3282f465c1 · 2.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hyperhomocysteinaemia is considered to be a risk factor for cardiovascular disease (particularly stroke) and has been implicated in recurrent miscarriage and osteoporotic fracture, recognized manifestations of coeliac disease (CD). The objective of this study was to compare plasma homocysteine levels and biomarker status of metabolically related B vitamins (folate, vitamin B(12), B(6) and riboflavin) in treated and untreated CD patients and healthy controls.
CD patients attending a clinic for either initial or follow-up biopsy (at least 12 months after commencing a gluten-free diet) were categorized into three groups: 1) newly diagnosed (untreated; n=35); 2) persistent villous atrophy (VA) at follow-up (n=24) or 3) recovered VA at follow-up (n=41). Blood samples were analysed for plasma homocysteine, serum and red cell folate and serum vitamin B(12) levels, and for plasma pyridoxal 5-phosphate (PLP, vitamin B(6)) and riboflavin (vitamin B(2)) status.
Homocysteine concentrations were significantly higher (p=0.05) and red cell and serum folate significantly lower (p<0.001) in untreated patients compared with controls, while all three reached normal levels in recovered VA patients. Although untreated and persistent VA patients tended to have lower B(12) levels, these did not reach significance. There was no evidence of compromised B(6) or riboflavin status, even in untreated CD patients. Homocysteine concentrations were inversely associated with both serum (r=-0.421; p<0.001) and red cell (r=-0.459; p<0.001) folate and with serum vitamin B(12) (r=-0.353; p=0.001).
Gluten exclusion in CD improves folate status and normalizes homocysteine concentrations. Reducing the risk of homocysteine-related disease may be another reason for aggressive diagnosis and treatment of CD.
[Show abstract][Hide abstract] ABSTRACT: A 65-year-old white female who presented with flatulence and weight loss was investigated by celiac antibody testing, esophagogastroduodenoscopy, duodenal biopsy and colonoscopy. There were no positive findings, except for diverticulosis. Almost 5 years later repeat investigations performed in response to the patient's anemia confirmed the development of celiac disease. After 18 months of symptom improvement as a result of gluten exclusion the patient developed diarrhea, and colonoscopy revealed ulcerative colitis.
Physical examination; analysis of full blood count; measurement of serum ferritin, vitamin B(12), folate and C-reactive protein levels; thyroid and autoantibody profiling (including analysis of endomysial and tissue transglutaminase antibodies); CT scanning of the chest, abdomen and pelvis; and performance of esophagogastroduodenoscopy, push enteroscopy, colonoscopy and wireless capsule endoscopy.
Celiac disease and ulcerative colitis.
Gluten-free diet, mesalazine and prednisolone.
[Show abstract][Hide abstract] ABSTRACT: Celiac disease is common and can present with nonspecific upper gastrointestinal symptoms. Patients may therefore undergo esophagogastroduodenoscopy as their initial investigation. Markers of villous atrophy, which can be seen in the duodenum during endoscopy, are well described. They have limited sensitivity for patients with mild enteropathy and duodenal biopsies should be performed if there is strong suspicion of celiac disease irrespective of endoscopic appearance. Endoscopic markers do, however, allow the selection of patients with nonspecific symptoms for duodenal biopsy, and these markers should, therefore, be looked for routinely during esophagogastroduodenoscopy.
[Show abstract][Hide abstract] ABSTRACT: It is well established that a minority of celiac patients present with "classic" symptoms due to malabsorption. However, few studies have focussed on the distribution of body mass index (BMI) in celiac populations and its relationship to clinical characteristics, or on its response to treatment.
We reviewed BMI measurements and other clinical and pathological characteristics from a database of 371 celiac patients diagnosed over a 10-yr period and seen by a single gastroenterologist. To assess response to gluten exclusion, we compared BMI at diagnosis and after 2 yr treatment in patients with serological support for dietary compliance.
Mean BMI was 24.6 kg/m2 (range 16.3-43.5). Seventeen patients (5%) were underweight (BMI < 18.5), 211 (57%) were normal, and 143 (39%) were overweight (BMI > or = 25), including 48 (13% of all patients) in the obese range (BMI > or = 30.0). There was a significant association between low BMI and female gender, history of diarrhea, reduced hemoglobin concentration, reduced bone mineral density (BMD), osteoporosis, and higher grades (subtotal/total) of villous atrophy. Of patients compliant with a gluten-free diet, 81% had gained weight after 2 yr, including 82% of initially overweight patients.
Few celiac patients are underweight at diagnosis and a large minority is overweight; these are less likely to present with classical features of diarrhea and reduced hemoglobin. Failed or delayed diagnosis of celiac disease may reflect lack of awareness of this large subgroup. The increase in weight of already overweight patients after dietary gluten exclusion is a potential cause of morbidity, and the gluten-free diet as conventionally prescribed needs to be modified accordingly.
The American Journal of Gastroenterology 11/2006; 101(10):2356-9. DOI:10.1111/j.1572-0241.2006.00750.x · 10.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Serological testing, using IgA class endomysial and tissue transglutaminase antibodies has high sensitivity and specificity for coeliac disease and allows case finding by clinicians other than gastroenterologists. We reviewed new coeliac patients seen over a 9-year period to determine how the availability of serology, particularly to primary care physicians, has changed rates and sources of diagnosis.
Files of patients attending a specialist coeliac clinic who were diagnosed from 1996 through 2004 were reviewed. Patients with villous atrophy consistent with gluten sensitive enteropathy (Marsh III) on duodenal biopsy were selected. Data analysed included clinical characteristics, endomysial and tissue transglutaminase antibodies status and source of request for serology.
Over the study period 347 new coeliac patients, comprising adults and children aged 10 years and over, were identified, of whom 163 (47%) were identified by serological testing in primary care, 152 (44%) at the hospital gastroenterology department and 32 (9%) by other physicians in secondary care. Over three consecutive 3-year periods, the percentage of patients identified in primary care rose from 28% through 47% to 60%, with a rise in total numbers diagnosed from 93 through 118 to 136. There was no change in patient clinical characteristics over the study period. Though tissue transglutaminase antibodies were less sensitive than endomysial antibodies, combined testing obtained a sensitivity of over 90%. Patients identified in primary care were significantly younger and more likely to present with diarrhoea as a primary symptom.
Currently over half of our coeliac patients are identified by serological testing in primary care, which has resulted in an overall rise in diagnosis rates. Primary care practitioners have an important role in the diagnosis of coeliac disease, particularly of patients who present with non-gastrointestinal symptoms. The contribution of specialists other than gastroenterologists in secondary care is disappointing and may improve with directed education.
[Show abstract][Hide abstract] ABSTRACT: The reported incidence of adenocarcinoma in patients with Barrett's oesophagus in surveillance programmes varies widely. Great Britain has one of the highest incidence rates of this cancer in the world, but there are no data from Ireland reporting its incidence in patients with Barrett's oesophagus undergoing surveillance. We carried out a study of all such patients at a large District General Hospital in Northern Ireland.
A retrospective review of all patients with Barrett's oesophagus from January 1986 to March 2004 at Altnagelvin Area Hospital, Derry, Northern Ireland was performed. Barrett's oesophagus was defined as specialized intestinal metaplasia present in the tubular oesophagus.
A total of 277 patients had Barrett's oesophagus. Twenty-one patients had adenocarcinoma and two patients had high-grade dysplasia at initial endoscopy and were excluded. Of the remaining 254 patients, 178 were entered into the surveillance programme (127 men, 51 women). The average follow-up period was 3.4 years, resulting in 613 patient-years of follow-up. Three patients developed adenocarcinoma, an incidence of 1/204 patient-years of follow-up. Two of the three patients had early-stage (T1 or T2) cancers detected and are alive and well. A total of 429 surveillance endoscopies were performed, and a marked year-on-year increase in the workload generated as a result of the surveillance programme was observed.
The incidence of adenocarcinoma in patients in Northern Ireland was similar to the incidence reported by other large institutions. Clinical benefit is suggested but is not certain from these data, because of biases that affect surveillance programmes. Large multicentre studies are required to determine whether surveillance is beneficial.
European Journal of Gastroenterology & Hepatology 11/2005; 17(10):1029-35. · 2.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Screening studies indicate a prevalence of coeliac disease (CD) of up to 1% in populations of European ancestry, yet the majority of cases remain undiagnosed. Serological markers for CD now available have high sensitivity and specificity, offering the option of mass population screening. The principles of disease screening as set out by Wilson and Jugner can be applied to CD to predict whether this is appropriate. CD is an important health problem for the individual and the community because of high prevalence, associated specific and non-specific morbidity, and long-term complications of which the most important are gut malignancy and osteoporosis. However, recent studies indicate that the prevalence of malignancy and the health impact of osteoporosis are much less than previously supposed, so the prophylactic benefits of early diagnosis through screening may be low. While CD has an accepted and effective treatment, dietary gluten exclusion, this is difficult for the individual and asymptomatic cases may be poorly motivated to comply. Diagnosis of CD is by histological confirmation on duodenal biopsy. We now recognise milder degrees of gluten sensitive enteropathy without villous atrophy (Marsh I, II lesions) and the benefits to the individual by identifying these early lesions through screening is unknown: whether to treat such individuals needs to be agreed before programmes commence. Screening with serum antibodies is relatively non-invasive but may have to be repeated during each individual's lifetime. HLA typing beforehand to identify the 30% of the population with DQ2 or DQ8, who are at potential risk of CD, will allow one-off exclusion of a large percentage of the population but like all genetic testing has ethical implications. The economic costs of screening and treatment versus morbidity prevented have not been calculated.
Baillière' s Best Practice and Research in Clinical Gastroenterology 07/2005; 19(3):441-52. DOI:10.1016/j.bpg.2005.02.004 · 3.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the use and value of fluoroscopic imaging in difficult colonoscopy.
Few endoscopy centers have easy access to fluoroscopy to facilitate difficult colonoscopy. Its benefits are therefore unclear. Although interest in colonoscope imaging has recently been stimulated by magnetic imaging techniques, these are expensive and unlikely to be widely available for some time.
During routine colonoscopy lists, a mobile fluoroscopy unit was used when colonoscopy could not be completed in the absence of stricturing despite changes in patient position and application of external pressure. This retrospective review assesses the percentage of procedures completed with and without fluoroscopy.
A series of 1551 procedures in adult patients without colon resection and with satisfactory bowel preparation was analyzed. The cecal intubation rate was 95.1% (1475/1551), rising to 96.5% (1475/1528) when impassable strictures were excluded. Fluoroscopy was used in 61 (4%) of the 1528 procedures without stricture, but allowed completion in only 13% (8/61). In the absence of stricture, fluoroscopy improved completion rate by only 0.5% (from 96.0% to 96.5%).
Fluoroscopy is seldom required and even then contributes little to success. Magnetic imaging, which provides continuous 3-dimensional images, may be more likely to speed and facilitate completion.
[Show abstract][Hide abstract] ABSTRACT: The histological lesion of gluten sensitivity primarily affects the proximal small bowel. The purpose of this study was to assess whether there were features of gluten-sensitive enteropathy in biopsies taken from the terminal ileum during colonoscopy/ileoscopy. Specific and sensitive abnormalities might facilitate diagnosis of coeliac disease in patients undergoing colonoscopy as their initial procedure or help select those who should proceed to upper gastrointestinal endoscopy and duodenal biopsy.
Terminal ileal biopsies, taken from 30 patients with duodenal villous atrophy consistent with coeliac disease and from 60 control patients with no evidence of coeliac or inflammatory bowel disease, were reviewed blindly and compared. Biopsies were assessed for the presence or absence of villous atrophy and crypt hyperplasia, and counts were made of intraepithelial lymphocytes (IELs).
One patient only, in the coeliac group, had partial villous atrophy with crypt hyperplasia in the terminal ileum. IEL counts were significantly higher (P< 0.005) in the coeliac group than among controls (mean per 100 enterocytes 26 versus 10). An ileal IEL count > or =25 had a sensitivity for duodenal villous atrophy (VA) of 60% and specificity of 100%.
Coeliac disease may affect the entire small bowel. Increased IEL density in the terminal ileum is associated with duodenal VA and should prompt a search for coeliac disease by serology and duodenal biopsy. Conversely, a normal IEL count does not allow the exclusion of coeliac disease with confidence.
[Show abstract][Hide abstract] ABSTRACT: There are various, well-documented, duodenal endoscopic markers caused by the villous atrophy of celiac disease. Another abnormality seen in association with villous atrophy, erosions in the second part of the duodenum, is described. To our knowledge, this finding has not been heretofore described in patients with celiac disease.
Five patients with celiac disease and erosions were encountered over a period of 2 years.
The erosions were multiple, superficial, and present in the second part of the duodenum but not the duodenal bulb. All 5 patients had findings typical of celiac disease (iron deficiency, osteopenia/osteoporosis), and 4 had at least one other endoscopic marker: scalloped duodenal folds (3), fold loss (2), or mosaic pattern mucosa (2). These patients represented 7% of new cases of celiac disease during the same time period. This pattern of erosion was not observed in over 1200 other patients undergoing upper endoscopy during the study period.
In a European population, the finding of erosions confined to the second part of the duodenum is specific for villous atrophy, although sensitivity is low. Erosions in the second part of the duodenum should be added to the list of endoscopic markers of celiac disease.
[Show abstract][Hide abstract] ABSTRACT: Coeliac disease and colorectal neoplasia are both common, present most often in patients over 40 and cause similar symptoms. Greater awareness and early use of serological tests have improved the diagnosis of coeliac disease, but raise the concern that co-existing colorectal neoplasia may be missed. This study assessed the prevalence of colorectal neoplasia among patients with coeliac disease diagnosed after the age of 40 who presented with altered bowel habit or iron deficiency.
All patients meeting the above criteria underwent colonoscopy unless this or barium enema had been performed shortly before.
Of 69 patients with coeliac disease undergoing colonoscopy, 7 (10%) had colon neoplasia: 5 had tubulovillous polyps, and 2 had carcinoma. The prevalence figures for coeliac patients undergoing colonoscopy with iron deficiency and altered bowel habit alone were 11% (5 of 47) and 10% (2 of 22), respectively None of a further 13 who had undergone previous colon investigation (all by barium enema) had neoplasia, although these were probably a selected population. The seven patients with colorectal neoplasia had not reported rectal bleeding. The prevalence of colorectal neoplasia was not significantly higher than in two series of non-coeliac patients undergoing colonoscopy for investigation of iron deficiency (12%) or altered bowel habit (8%).
There is a high prevalence of colorectal neoplasia among older patients with coeliac disease who present with iron deficiency or altered bowel habit, though this is no higher than for non-coeliac patients with these presentations. The possibility of dual pathology should be considered and excluded by colon investigation.