Measurement of gluten using a monoclonal antibody to a coeliac toxic peptide of A-gliadin

BACKGROUND: Future European Community regulations will require a sensitive and specific assay for measurement of coeliac toxic gluten proteins in foods marketed as gluten-free. To avoid spurious cross reactions with non-toxic proteins, specific antibodies and target antigens are required. A synthetic 19 amino acid peptide of A gliadin has been shown to cause deterioration in the morphology of small intestinal biopsy specimens of coeliac patients in remission. AIMS: To develop an assay for detection of gluten in foods, based on measurement of a known toxic peptide. METHODS: A monoclonal antibody raised against the toxic A gliadin peptide, with a polyclonal anti-unfractionated gliadin capture antibody, was used to develop a double sandwich enzyme linked immunosorbent assay (ELISA) for the measurement of gluten in foods. RESULTS: Standard curves for gliadin and for rye, barley, and oat prolamins were produced. The sensitivity of the assay was 4 ng/ml of gliadin, 500 ng/ml for rye prolamins, and 1000 ng/ml for oat and barley prolamins. The assay could detect gluten in cooked foods, although at reduced sensitivity. Prolamins from coeliac non-toxic rice, maize, millet, and sorghum did not cross react in the assay. A variety of commercially available gluten-free foods were analysed; small quantities of gluten were detected in some products. CONCLUSION: The assay may form the basis of a sensitive method for measurement of gluten in foods for consumption by patients with coeliac disease.     

Prevalence of autoimmune diseases in islet transplant candidates with severe hypoglycaemia and glycaemic lability: previously undiagnosed coeliac and autoimmune thyroid disease is identified by screening.

AIMS: Autoimmune diseases such as Addison's or coeliac disease can contribute to hypoglycaemia or malabsorption and are more common in Type 1 diabetes (T1DM). This brief report describes the prevalence of known and newly detected autoimmune disease in clinical islet transplant candidates with longstanding T1DM and severe hypoglycaemia and/or glycaemic lability who are routinely screened for coexisting autoimmune disease. METHODS: One hundred and twenty-four C-peptide negative T1DM subjects [77 (62%) female, mean age 44 +/- 9 years, diabetes duration 28 +/- 11 years, body mass index 24.9 +/- 3.5 kg/m(2)] with indications for clinical islet transplantation at the University of Alberta were screened for autoimmune disease by history and measurement of anti-transglutaminase antibodies (positive > 10 U/ml), 09.00 h cortisol (followed by adrenocorticotrophic hormone-stimulation if < 495 nmol/l) and thyroid-stimulating hormone to determine the prevalence of coeliac disease, Addison's disease and autoimmune thyroid disease, respectively. RESULTS: Forty per cent of subjects had one or more coexisting autoimmune disease. The prevalence of autoimmune disease was 35%, coeliac disease 8% and Addison's disease 1.6%. In 11 individuals (9%), one or more autoimmune disease were newly detected (seven coeliac disease and five thyroid disease). Seven of 10 cases of coeliac disease were newly detected. A gluten-free diet in individuals with newly diagnosed coeliac disease reduced gastrointestinal symptoms, but indications for clinical islet cell transplantation persisted. CONCLUSIONS: Coexisting autoimmune disease is common in candidates for clinical islet cell transplantation. Screening in this group identified a substantial number of previously unrecognized cases. Clinicians should consider the presence of autoimmune disease even in the absence of classical symptoms.     

Are lower gastrointestinal investigations necessary in patients with coeliac disease?

BACKGROUND: Colonoscopy may be indicated in patients with coeliac disease who present with iron deficiency anaemia or in coeliac disease patients who have persisting diarrhoea despite being on a gluten-free diet. However, there are limited data to support this approach. METHODS: We prospectively recruited patients who were found to have coeliac disease, having been referred with newly diagnosed iron deficiency anaemia. We also recruited a second group of patients with known coeliac disease. These patients had persisting diarrhoea despite being on a gluten-free diet for 6 months. All patients had colonoscopy and were matched with controls (without coeliac disease) who had similar indications for colonoscopy. RESULTS: Ninety-eight consecutive new patients with coeliac disease and concurrent iron deficiency anaemia had colonoscopy performed. Twelve (12.2%) had pathology, three of which were carcinomas. This diagnostic yield was not significantly different from the findings in the control group 62/362 (17.1%) P=0.24. In coeliac disease patients with persisting diarrhoea (n=37), the diagnostic yield at colonoscopy was 1/37 (2.7%). This was significantly lower than our findings in the control group with chronic diarrhoea 55/390 (14%) P=0.05. CONCLUSION: Colonoscopy should be considered in patients with coeliac disease (over the age of 45 years) who present with iron deficiency anaemia. Whilst, for coeliac disease patients with persisting diarrhoea (on a gluten-free diet) in the absence of sinister symptoms, a flexible sigmoidoscopy may be the initial investigation in order to exclude microscopic colitis. However, further larger prospective studies are required to evaluate this approach.     

Wheat starch-containing gluten-free flour products in the treatment of coeliac disease and dermatitis herpetiformis. A long-term follow-up 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 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.     

Low circulating insulin-like growth factor I in coeliac disease and its relation to bone mineral density.

BACKGROUND: Patients with coeliac disease have low bone mineral density (BMD), but the underlying mechanisms are unclear. Our aim was to study circulating insulin-like growth factor I (IGF-I) and its possible relationship to BMD in adults with untreated coeliac disease and after 1 year on a gluten-free diet. METHODS: In 29 consecutive adult coeliac patients fasting IGF-I and BMD (n = 28) were examined before and 1 year after starting a gluten-free diet. Intact parathyroid hormone (PTH) was measured (n = 20) before the gluten-free diet was started. RESULTS: Untreated coeliac patients had lower IGF-I values than controls matched for age and sex, and their BMD was low. A relationship was observed between BMD and IGF-I but not independent of age and body mass index. During the 1st year on a gluten-free diet BMD increased (P < 0.001), as did the circulating IGF-I levels in 21 of the 29 patients (P = 0.078). In the subgroup of 14 patients with normal initial PTH the increase in IGF-I correlated positively with the increase in BMD (femoral trochanter, r = 0.62, P < 0.05, and lumbar spine, r = 0.70, P < 0.02). CONCLUSIONS: BMD and circulating IGF-I levels are low in adults with untreated coeliac disease. In patients with normal initial PTH level there is an association between the change in BMD and circulating IGF-I, although this parallel increase may not be causally connected.     

Coeliac disease: Oral ulcer prevalence, assessment of risk and association with gluten-free diet in children

AIMS: Oral mucosal lesions may be markers of chronic gastrointestinal disorders, such as those causing malabsorption. Our objectives were to assess the prevalence of recurrent oral aphthous-like ulcers in coeliac disease patients living in the Mediterranean area, and to evaluate the impact of a gluten-free diet. METHODS: A test group of 269 patients (age range 3-17 years) with coeliac disease confirmed both serologically and histologically was compared with a control group of 575 otherwise clinically healthy subjects for the presence, or a positive history of aphthous-like ulcers. Coeliac disease patients with aphthous-like ulcers were re-evaluated 1-year after starting a gluten-free diet. RESULTS: Aphthous-like ulcers were found significantly more frequently in coeliac disease, in 22.7% (61/269) of patients with coeliac disease versus 7.1% (41/575) of controls (p=<0.0001; chi-square=41.687; odds ratio=4.3123; 95% confidence interval=2.7664:6.722). Most coeliac disease patients with aphthous-like ulcers and adhering strictly to gluten-free diet (71.7%; 33/46) reported significant improvement on gluten-free diet, with no or reduced episodes of aphthous-like ulcers (p=0.0003; chi-square=13.101; odds ratio=24.67; 95% confidence interval=2.63:231.441). CONCLUSIONS: The epidemiological association found between coeliac disease and aphthous-like ulcers suggests that recurrent aphthous-like ulcers should be considered a risk indicator for coeliac disease, and that gluten-free diet leads to ulcer amelioration.     

Gastrointestinal Symptoms Rating Scale in Coeliac Disease Patients on Wheat Starch-based Gluten-free Diets

Background: A wheat starch-based gluten-free diet is widely adopted in the treatment of coeliac disease, even though the products contain trace amounts of gluten. The aim here was to establish whether such a diet sustains abdominal symptoms. Methods: The Gastrointestinal Symptom Rating Scale (GSRS) was applied to 58 coeliac disease patients on gluten-free diets and 110 non-coeliac controls. An estimate was made of daily dietary fibre and wheat starch-derived gluten. Psychological well-being was evaluated by a structured interview. Twenty-three coeliac patients consented to small-bowel biopsy. Results: The mean GSRS score in coeliac disease patients did not differ from that in control subjects. Poorer psychological well-being was associated with abdominal symptoms in coeliac patients, whereas the daily amount of wheat starch had no effect on GSRS score. Overall dietary compliance was good, and villous atrophy was found in only 2 out of 23 patients. The average fibre consumption, 13 g per day, was lower than recommended. Conclusions: Wheat starch-based gluten-free products are well-tolerated in coeliac disease patients, provided that their diets are otherwise strict.     

Frontal cortical perfusion abnormalities related to gluten intake and associated autoimmune disease in adult coeliac disease: Tc-ECD brain SPECT study

OBJECTIVE: Since brain perfusion abnormalities have been described by single-photon emission computed tomography in some autoimmune diseases, the aim of the present study was to evaluate the incidence of perfusion abnormalities by brain single-photon emission computed tomography in a group of coeliac disease patients, and to investigate whether gluten intake and associated autoimmune diseases may be considered risk factors in causing cerebral impairment. METHODS: Thirty-four adult coeliac patients (16 on a gluten-free diet and 18 on a gluten-containing diet, 18 (53%) with autoimmune diseases) underwent 99mTc-ethyl cysteinate dimer brain single-photon emission computed tomography and qualitative evaluation of brain perfusion was performed together with a semiquantitative estimation using the asymmetry index. Ten subjects on our database, matched for sex, age and ethnic group, who were proved normal by histology ofjejunal mucosa (four males and six females; median age 39 years, range 27-55 years), were included as control group. RESULTS: Twenty-four out of 34 patients (71%) showed brain single-photon emission computed tomography abnormalities confirmed by abnormal regional asymmetry index (>5%; range 5.8-18.5%). Topographic comparison of the brain areas showed that the more significant abnormalities were localised in frontal regions, and were significantly different from controls only in coeliac disease patients on unrestricted diet. The prevalence of single-photon emission computed tomography abnormalities was similar in coeliac disease patients with (74%) and without (69%) associated autoimmune disease. CONCLUSIONS: Abnormalities of brain perfusion seem common in coeliac disease. This phenomenon is similar to that previously described in other autoimmune diseases, but does not appear to be related to associated autoimmunity and, at least in the frontal region, may be improved by a gluten-free diet.     

Gastrointestinal symptoms rating scale in coeliac disease patients on wheat starch-based gluten-free diets

BACKGROUND: A wheat starch-based gluten-free diet is widely adopted in the treatment of coeliac disease, even though the products contain trace amounts of gluten. The aim here was to establish whether such a diet sustains abdominal symptoms. METHODS: The Gastrointestinal Symptom Rating Scale (GSRS) was applied to 58 coeliac disease patients on gluten-free diets and 110 non-coeliac controls. An estimate was made of daily dietary fibre and wheat starch-derived gluten. Psychological well-being was evaluated by a structured interview. Twenty-three coeliac patients consented to small-bowel biopsy. RESULTS: The mean GSRS score in coeliac disease patients did not differ from that in control subjects. Poorer psychological well-being was associated with abdominal symptoms in coeliac patients, whereas the daily amount of wheat starch had no effect on GSRS score. Overall dietary compliance was good, and villous atrophy was found in only 2 out of 23 patients. The average fibre consumption, 13 g per day, was lower than recommended. CONCLUSIONS: Wheat starch-based gluten-free products are well-tolerated in coeliac disease patients, provided that their diets are otherwise strict.     

Type 1 diabetes mellitus, coeliac disease, and lymphoma: a report of four cases.

INTRODUCTION: Patients with Type 1 diabetes mellitus have a high prevalence of coeliac disease, symptoms of which are often mild, atypical, or absent. Untreated coeliac disease is associated with an increased risk of malignancy, particularly of lymphoma. We describe four patients with Type 1 diabetes mellitus and coeliac disease who developed lymphoma. CASE REPORTS: Two patients were male and two female. In three patients, coeliac disease and lymphoma were diagnosed simultaneously. Enteropathy-associated T cell lymphoma occurred in two patients, Hodgkin's disease in one, and B cell lymphoma in one. Response to treatment was in general poor, and three patients died soon after the diagnosis of lymphoma was made. CONCLUSION: As the relative risk of lymphoma is reduced by a gluten-free diet, a high index of suspicion for coeliac disease should exist in all Type 1 diabetic patients with unexplained constitutional or gastrointestinal symptoms.     

Paediatric aspects of coeliac disease: old challenges and new ones…

The concept of coeliac disease has expanded from a gastrointestinal disease with malabsorption to a systemic immunological disease with a genetic basis. Epidemiological studies indicate that environmental factors, like the infant feeding pattern, affect the clinical presentation while population-screening studies indicate that the prevalence, at least in Caucasian populations, is similar. Secondary complications, like malignancies, osteopenia - osteoporosis, gynaecological and obstetrical problems and autoimmune diseases, are common. The risk is reduced or prevented by treatment with a gluten-free diet. The basis for such a secondary prevention is: 1. early case-finding by a) knowledge about different presentations of the disease and factors affecting that, b) generous serological testing in patients with vague symptoms, c) screening of risk groups, and, 2. support for children and adolescents with coeliac disease to comply with the gluten-free diet.     

Is coeliac disease a potentially treatable cause of liver failure?

Hypertransaminasaemia is a common abnormality found in up to 40% of untreated coeliac patients, which resolves with the institution of a gluten-free diet. A much rarer occurrence is the association of chronic liver disease with coeliac disease. Primary biliary cirrhosis, primary sclerosing cholangitis, and chronic autoimmune hepatitis have all been recognized in coeliac patients. More recently, the occurrence of coeliac disease in patients with chronic liver disease is found to be 10 times greater than that in the general population. Of particular note are the 13 patients reported to date with liver failure and coeliac disease. Among those patients commenced on a gluten-free diet an improvement in liver function was observed. The relationship between coeliac disease, a gluten-free diet, and the course of chronic liver disease needs to be clarified.     

Should we screen reflux oesophagitis patients for coeliac disease?

OBJECTIVES: Oesophagitis and gastro-oesophageal reflux have been implicated recently in the manifestations of coeliac disease. The aim was to investigate this association in a primary-care setting. METHODS: First, the prevalence of coeliac disease was calculated in 1198 adults with oesophagitis, in 2541 adults with reflux symptoms and in 200 adults suffering from dysphagia; 5459 patients with a history consistent with dyspepsia and 709 patients with a suspicion of coeliac disease served as controls. Second, the prevalence of oesophagitis was estimated in 382 untreated and 232 treated coeliac patients; controls here comprised 5404 patients with dyspeptic symptoms and 2525 patients with reflux symptoms. Third, oesophagitis and oesophageal reflux symptoms were investigated before and after a gluten-free diet was followed in 67 adults with coeliac disease. The diagnosis of coeliac disease was based on small-bowel histology; histological exclusion of the disease was unambiguous in all controls. Oesophagitis was identified by endoscopic inspection. RESULTS: Altogether, 0.9% of patients with oesophagitis and 0.6% of those with oesophageal reflux symptoms had coeliac disease. The corresponding percentages were 1.0% in patients with dyspepsia and 12% with suspicion of coeliac disease. The prevalence of oesophagitis was 5.2% in untreated coeliac disease, 5.6% in treated coeliac disease, 7.0% in patients with dyspepsia, and 27% in symptomatic reflux disease. In coeliac patients, the reflux symptoms were mild but nevertheless were alleviated on a gluten-free diet. CONCLUSIONS: This study does not support the conception that patients with reflux oesophagitis should be screened vigorously for coeliac disease. The association between these two conditions is, at most, weak, but a gluten-free diet may still bring symptomatic relief for reflux symptoms in coeliac disease.     

Analysis and clinical effects of gluten in coeliac disease.

The prolamin working group coordinates research on laboratory gluten analysis in food and on clinical evaluation of patient sensitivity to prolamins. As an observer organization to the Codex Alimentarius Commission, the group summarizes current data on analysis and effects of gluten in coeliac disease. All types of gliadin, the ethanol-soluble fraction of gluten, contain the coeliac-active factor. However, coeliac toxicity and immunogenicity (humoral and cellular) of various prolamins are not identical in coeliac patients. There are no conclusive data on the threshold of gluten sensitivity of coeliac patients. Information as to the long-term risk to coeliac patients exposed to small doses of gliadin is lacking. Therefore, every effort should be made to keep the diet of coeliac patients as gluten-free as possible. The prolamin group is currently evaluating a new enzyme-linked immunosorbent assay (ELISA) protocol for gluten analysis that could serve as a basis for further Codex regulations. The group recommends adherence to a single Codex limit for gluten-free foods. The current limit of 200 ppm gluten is questionable and requires reconsideration based on new information that will be available soon.     

Fasting plasma nitric oxide products in coeliac disease

OBJECTIVES: In coeliac disease, inducible nitric oxide synthase activity in the duodenal mucosa is greatly increased, resulting in increased production of nitric oxide. We investigated whether this resulted in increased plasma concentrations of its stable end products (nitrate/nitrite: NOx). METHODS: Fasting plasma NOx was determined in 66 patients attending for upper gastrointestinal endoscopy. Of these, 21 had coeliac disease (nine were on a gluten-free diet). The remainder had a variety of other gastrointestinal disorders. NOx was determined using the Griess reaction. Distal duodenal biopsies for coeliac patients were graded according to the Marsh score. RESULTS: Patients with untreated coeliac disease had a higher fasting NOx concentration (mean 117.5 microM) than either those with coeliac disease taking a gluten-free diet (mean 71.2 microM) or those with other diseases (mean 33.5 microM; one-way analysis of variance, P < 0.001). Coeliac patients with higher fasting NOx concentrations had more marked histological changes (P < 0.05). CONCLUSION: Fasting plasma NOx is significantly elevated in untreated coeliac disease and correlates with histological grade. The potential clinical utility of serial NOx measurements to monitor improvement on a gluten-free diet requires further study.     

13C-xylose and 14C-xylose breath tests for the diagnosis of coeliac disease

OBJECTIVES: Xylose absorption testing has traditionally involved measurement of serum xylose and/or measurement of excreted xylose in urine. However, by enriching xylose with a 13C- or 14C-isotope, absorption of an oral xylose load will be reflected in the time-dependent pattern of 13CO2 or 14CO2 exhaled in breath. Our objectives were to evaluate the diagnostic properties of 13C-xylose and 14C-xylose breath tests in coeliac disease, and to develop a diagnostic breath test index. MATERIAL AND METHODS: We reviewed data from 41 coeliac patients who underwent the 14C-xylose breath test before and after commencement of a gluten-free diet, and 60 coeliac patients who underwent the 13C-xylose breath test, 37 of whom repeated the test after starting a gluten-free diet. Coeliac patients were compared with healthy control subjects. RESULTS: Coeliac patients exhaled significantly less 13CO2 or 14CO2 than healthy controls during the first hour of the test and more isotope-labelled CO2 than control subjects after 3 h. Diagnostic accuracy was optimal with test duration of 210 min combining gas measurements at 30 min and 210 min in a simple fraction. This gas fraction index (30 min/210 min) distinguished between coeliac patients and healthy control subjects with 84-95% sensitivity and 87-94% specificity. After commencement of a gluten-free diet, the gas fraction index increased in most coeliac patients, but remained lower than that in healthy control subjects. CONCLUSIONS: 13C-xylose- and 14C-xylose breath tests discriminate between coeliac patients and healthy control subjects with high sensitivity and specificity. The stable isotope 13C-xylose breath test has comparable diagnostic accuracy to the radioactive isotope 14C-xylose breath test and should be the preferred alternative to traditional xylose absorption tests.     

IgA anti-actin antibodies ELISA in coeliac disease: A multicentre study

BACKGROUND: Previous studies have demonstrated that serum anti-actin antibodies are a reliable marker of intestinal damage severity in coeliac disease. AIMS: To validate in a multicentre study the clinical usefulness of serum IgA anti-actin antibody ELISA and its possible use in monitoring intestinal mucosa lesions during gluten-free diet. PATIENTS AND METHODS: Four centres recruited 205 newly diagnosed coeliac disease patients with villous atrophy, 80 healthy controls and 81 "disease" controls. Twelve coeliac disease patients on gluten-free diet but with persistent symptoms underwent serum IgA anti-actin antibody assay and intestinal histology evaluation. IgA anti-actin antibody ELISA was performed with a commercial kit. All coeliac disease patients underwent intestinal histology study. RESULTS: IgA anti-actin antibodies showed a sensitivity of 80% and a specificity of 85% in the diagnosis of coeliac disease patients with villous atrophy. The area under the receiving operator curve for anti-actin antibodies was 0.873 [95% C.I. 0.805-0.899]. Serum anti-actin antibodies values were significantly higher in coeliac disease patients than in healthy or "disease" controls (P<0.0001). Serum anti-actin antibodies were positive in 41 of the 60 coeliac disease patients with mild intestinal histology lesions (69%) and in 123 of the 145 with severe lesions (85.3%) (P<0.05). There was a significant inverse correlation between anti-actin antibody values and the villi/crypts ratio (r=-0.423; P<0.0001). In the 12 coeliac disease patients on gluten-free diet who underwent re-evaluation as they were persistently symptomatic, intestinal histology showed three cases with persistent villous atrophy: all of these were positive for serum anti-actin antibodies ELISA, whereas both serum anti-tTG and EmAs were negative. The other nine patients showed normal intestinal villi and were negative for serum anti-actin antibodies. CONCLUSIONS: Anti-actin antibodies are a reliable marker of severe intestinal mucosa damage in coeliac disease patients and a simple ELISA technique offers an accurate method for their determination. These antibodies seem to be a very reliable marker of persistent intestinal damage in coeliac disease patients.     

Persistent Mucosal Abnormalities in Coeliac Disease Are Not Related to the Ingestion of Trace Amounts of Gluten

Background: It is expected that in patients with coeliac disease the small-bowel mucosal mucosa will return to normal if they adhere to a gluten-free diet (GFD). However, in many this is not the case. This study aims to determine whether this persistent villous atrophy (VA) could be due to continued ingestion of the trace amounts of gluten in `gluten-free' foods, as defined by the WHO/FAO Codex Alimentarius. Methods: Duodenal biopsy specimens from 89 adults with long-standing coeliac disease were examined, and the findings correlated with their form of gluten-free diet. Results: In 51 subjects the duodenal specimen was normal, whereas in 38 there was villous atrophy (partial, 28; subtotal, 8; total, 2). There was no relationship between the presence or absence of VA and ingestion of either a GFD as defined by the Codex Alimentarius (Codex-GFD; 39 patients) or a GFD that contained no detectable gluten (NDG diet; 50 patients). Intraepithelial lymphocyte counts were higher, and lactase levels lower, in subjects with an abnormal biopsy specimen than in those in whom it was normal. However, within each of these biopsy groups there was no difference in these variables between patients on a Codex-GFD and those on an NDG-GFD. IgA antigliadin antibody was detected in 4 of 29 patients on a Codex-GFD and in 3 of 13 on a NDG-GFD (NS). Conclusion: The persistent mucosal abnormalities seen in patients with coeliac disease on a GFD are not due to the ingestion of trace amounts of gluten. The consequences of these abnormalities have yet to be determined.     

Persistent mucosal abnormalities in coeliac disease are not related to the ingestion of trace amounts of gluten.

BACKGROUND: It is expected that in patients with coeliac disease the small-bowel mucosal mucosa will return to normal if they adhere to a gluten-free diet (GFD). However, in many this is not the case. This study aims to determine whether this persistent villous atrophy (VA) could be due to continued ingestion of the trace amounts of gluten in 'gluten-free' foods, as defined by the WHO/FAO Codex Alimentarius. METHODS: Duodenal biopsy specimens from 89 adults with long-standing coeliac disease were examined, and the findings correlated with their form of gluten-free diet. RESULTS: In 51 subjects the duodenal specimen was normal, whereas in 38 there was villous atrophy (partial, 28; subtotal, 8; total, 2). There was no relationship between the presence or absence of VA and ingestion of either a GFD as defined by the Codex Alimentarius (Codex-GFD; 39 patients) or a GFD that contained no detectable gluten (NDG diet: 50 patients). Intraepithelial lymphocyte counts were higher, and lactase levels lower, in subjects with an abnormal biopsy specimen than in those in whom it was normal. However, within each of these biopsy groups there was no difference in these variables between patients on a Codex-GFD and those on an NDG-GFD. IgA antigliadin antibody was detected in 4 of 29 patients on a Codex-GFD and in 3 of 13 on a NDG-GFD (NS). CONCLUSION: The persistent mucosal abnormalities seen in patients with coeliac disease on a GFD are not due to the ingestion of trace amounts of gluten. The consequences of these abnormalities have yet to be determined.     

Case-finding in coeliac disease should be intensified

Large-scale screening studies on CD have been published and suggest a prevalence of CD in USA, Europe, Middle-East and Australia of about 1:100. The costs of finding coeliacs hasn't been discussed in these studies. Coeliac disease can be classified to be an important health problem. It might be relevant to have a low threshold for biopsies when screening for coeliac disease. Screening asymptomatics may be harmful for individuals. A lifelong gluten-free diet is not easy to maintain and quality of life may deteriorate. In countries familiar with coeliac disease, the classic pattern of severe malabsorption and cachexia, as described in textbooks, has become rare. CD is not borne in minds of doctors diagnosing dyspepsia and/or irritable bowel disease, or associated auto-immune diseases. The consequence is a delay in diagnosis, with secondary problems as long term auto-immune stimulation, osteoporosis and secondary malignancies. Enteropathy associated T-cell lymphomas are well known, but considering coeliac disease in T-cell lymphomas presenting outside the GE-tract is uncommon. Nation-wide screening programmes have not started, which are common for phenylketonury and other metabolic defects. It is debatable whether coeliacs found by screening adhere to a gluten-free diet similar to symptomatic coeliacs. Whether a gluten-free diet is of benefit to this subgroup is controversial.