Suspected Coeliac Disease Research Articles

Small-bowel mucosal transglutaminase 2-specific IgA deposits in coeliac disease without villous atrophy: A prospective and randomized clinical study

ObjectiveIn coeliac disease, autoantibodies directed against transglutaminase 2 are produced in small-bowel mucosa, and they have been found to be deposited extracellularly. The aim of this study was to investigate whether such mucosal IgA deposits are important in the diagnostic work-up of early-stage coeliac disease without small-bowel mucosal villous atrophy.Material and methodsForty-one adults suspected of coeliac disease owing to increased density of mucosal γδ+ intraepithelial lymphocytes but normal villous morphology were randomized to gluten challenge or a gluten-free diet for 6 months. Clinically and histologically verified gluten dependency was compared with existence of small-bowel mucosal transglutaminase 2-specific extracellular IgA deposits and (coeliac disease-type) HLA DQ2 and DQ8; 34 non-coeliac subjects and 18 patients with classical coeliac disease served as controls.ResultsOf the 41 patients, 5 in the challenge group and 6 in the gluten-free diet group were clinically gluten sensitive; all 11 had HLA DQ2 or DQ8. Ten of these 11 patients showed transglutaminase 2-targeted mucosal IgA deposits, which were dependent on gluten consumption. Minimal IgA deposits were seen in only 3 out of 30 patients with suspected coeliac disease without any clinically detected gluten dependency. The deposits were found in all classical coeliac patients and in none of the non-coeliac control subjects.ConclusionsClinically pertinent coeliac disease exists despite normal small-bowel mucosal villous architecture. Mucosal transglutaminase 2-specific IgA deposits can be utilized in detecting such patients with genetic gluten intolerance.

Optical Coherence Tomography to Identify Villous Morphology in Patients with Suspected Celiac Disease

Introduction: The prevalence of celiac disease (CD) is currently increased compared to our experience in the past. Serological findings are very useful in increasing our screening capacity, but histology remains the gold standard in the diagnosis of CD. OCT is a new imaging technique, similar to B-mode ultrasound (US), but its resolution is far greater (5-10 ìm) near to histology. No data are actually available on the use of OCT in the small intestine and, in particular, in the diagnosis of CD. Aim & Methods: Aim of our study is to test the utility of OCT in patients with serological positivity to antigliadine and antiendomisial antibodies undergone to esofago-gastro-duodenoscopy (EGDS) for histological diagnosis. We enrolled 5 patients with suspected CD and 5 normal subjects who underwent EGDS for dyspepsia. OCT scanning of descending duodenum was performed during diagnostic EGDS and biopsies of the same area of the duodenum were taken. Evaluation of OCT images and histological specimens was blind, the analysis being performed independently by a gastroenterologist and a pathologist. Three patterns of intestinal villous morphology were considered (1 = no atrophy; 2 = mild atrophy; 3 = total atrophy). Results: We obtained the same results about villous pattern into the two group with the two techniques, and similar data about mean villous height in celiac group (0.25 mm in the OCT measures vs 0.28 mm in the histological measures) but with an increased value in the data performed by OCT into the normal subjects group (mean villous height: 0.70 mm vs 0.40 mm). Conclusions: There is a good concordance between histology and OCT to identify villous pattern of CD. However measurements of intestinal villous height show an increased value in OCT, particularly in control patients, possibly due to the villous rhitidosis after histological handling. OCT appears to be a promising technique to identify CD during endoscopy. An unsolved problem remains the impossibility to detect, at present, lymphocitic infiltrate and crypt's hypertrophy, two specific tools in the diagnosis of CD. Our preliminary data must be confirmed by further studies. Introduction: The prevalence of celiac disease (CD) is currently increased compared to our experience in the past. Serological findings are very useful in increasing our screening capacity, but histology remains the gold standard in the diagnosis of CD. OCT is a new imaging technique, similar to B-mode ultrasound (US), but its resolution is far greater (5-10 ìm) near to histology. No data are actually available on the use of OCT in the small intestine and, in particular, in the diagnosis of CD. Aim & Methods: Aim of our study is to test the utility of OCT in patients with serological positivity to antigliadine and antiendomisial antibodies undergone to esofago-gastro-duodenoscopy (EGDS) for histological diagnosis. We enrolled 5 patients with suspected CD and 5 normal subjects who underwent EGDS for dyspepsia. OCT scanning of descending duodenum was performed during diagnostic EGDS and biopsies of the same area of the duodenum were taken. Evaluation of OCT images and histological specimens was blind, the analysis being performed independently by a gastroenterologist and a pathologist. Three patterns of intestinal villous morphology were considered (1 = no atrophy; 2 = mild atrophy; 3 = total atrophy). Results: We obtained the same results about villous pattern into the two group with the two techniques, and similar data about mean villous height in celiac group (0.25 mm in the OCT measures vs 0.28 mm in the histological measures) but with an increased value in the data performed by OCT into the normal subjects group (mean villous height: 0.70 mm vs 0.40 mm). Conclusions: There is a good concordance between histology and OCT to identify villous pattern of CD. However measurements of intestinal villous height show an increased value in OCT, particularly in control patients, possibly due to the villous rhitidosis after histological handling. OCT appears to be a promising technique to identify CD during endoscopy. An unsolved problem remains the impossibility to detect, at present, lymphocitic infiltrate and crypt's hypertrophy, two specific tools in the diagnosis of CD. Our preliminary data must be confirmed by further studies.

Increase in Nitric Oxide Urinary Products During Gluten Challenge in Children with Coeliac Disease

Background: Coeliac disease is a gluten-sensitive enteropathy where pro-inflammatory cytokines and excess nitric oxide (NO) production can contribute to mucosal damage. NO urinary products are elevated in coeliac children on a gluten diet, but it is not known how rapidly this increase develops after gluten exposure. Methods: Oral gluten challenge was performed in 25 children whose families kept a daily record of gluten intake and symptoms. Blood was analysed monthly for antigliadin (AGA) and endomysium antibodies (EMA). Urine was analysed every second week for NO products, i.e. the sum of nitrite and nitrate was measured with a colorimetric method. We performed a third biopsy when clinical symptoms indicated a relapse. Median age at the post-challenge biopsy was 3.8 (2.7-8.8) years. Results: Signs of morphological or serological relapse were seen in all children. Mean daily gluten intake was 0.10 (range 0.02-0.26) g/kg bodyweight. Median NO level was doubled and significantly higher after 4 weeks of challenge but not after 2 weeks. EMA, but not AGA levels, correlated positively with NO. Intraepithelial lymphocyte count was significantly higher in the post-challenge biopsy, but did not correlate with the NO levels. Conclusions: NO products in urine increased during gluten challenge. EMA levels reflected severity of mucosal damage, and NO products reflected the inflammatory response, which was doubled after 4 weeks of challenge. The NO analysis is simple and non-traumatic for the child. It can be performed repeatedly during investigation of children with suspected coeliac disease.

The hunt for coeliac disease in primary care.

Serological screening suggests that most coeliac disease goes undetected. To determine how often coeliac disease is found in patients referred for gastroscopy by general practitioners. Testing of 9971 consecutive patients referred to a single health centre for their first open-access gastroscopy over a 10-year period, without previously-diagnosed coeliac disease or dermatitis herpetiformis. Endoscopy and routine duodenal biopsy were in use throughout the study period. The occurrence of coeliac disease was evaluated in patients with dyspepsia, in those with regurgitation, and in those with symptoms suggestive of coeliac disease. Altogether, 147 (1.47%) patients had coeliac disease: 18/2974 (0.61%) with regurgitation, 41/5347 (0.77%) with dyspepsia, and 88/1650 (5.33%) with suspected coeliac disease. Increasing age reduced the risk very slightly (OR 0.98; 95%CI 0.97-0.99). Risk was significantly increased when there was a suspicion of coeliac disease (OR 9.085; 95%CI 5.371-15.369), while no difference was found between patients with dyspepsia and those with reflux disease (OR 1.33; 95%CI 0.75-2.34). The risk in women was not increased (OR 0.97; 95%CI 0.69-1.38). In this primary-care setting, <1% of patients with upper abdominal symptoms suffered from coeliac disease; population-based serological screening is expected to yield a corresponding prevalence. When physicians had suspected coeliac disease, the condition was nine times more common.

A comparative study of endoscopic duodenal and jejunal biopsies in suspected Celiac Disease

A comparative study of endoscopic duodenal and jejunal biopsies in suspected Celiac Disease

A comparative study of endoscopic duodenal and jejunal biopsies in suspected Celiac Disease

A comparative study of endoscopic duodenal and jejunal biopsies in suspected Celiac Disease

Adult coeliac disease: prevalence and clinical significance.

Although coeliac disease is a common condition, the role of population screening is not clear. The aim of this study was to determine the prevalence and clinical significance of coeliac disease in the adult population of Christchurch, New Zealand. A total of 1064 adults randomly selected from the 1996 Christchurch electoral rolls were enlisted. The subjects were screened for coeliac disease using the anti-endomysial antibody test (EMA), and all those with positive tests were reviewed and underwent a small bowel biopsy. Twelve of the 1064 persons tested (1.1%) were EMA positive and all had small bowel biopsy histology consistent with coeliac disease. Two of the 12 subjects were previously known to be EMA positive although neither had a small bowel biopsy. One additional subject with known and treated coeliac disease was also enrolled but was EMA negative. Thus, the overall prevalence of coeliac disease was 13 of 1064 subjects (1.2%, or 1:82), 10 of whom were newly diagnosed (0.9%, or 1:106) and three were previously known or suspected to have coeliac disease (0.3%, or 1:355). The prevalence in both sexes was similar. Nine of the 12 EMA-positive coeliac disease subjects identified by the use of screening reported symptoms, of which tiredness and lethargy were the most common. The subjects were of normal stature, although females tended to be lean. None of the subjects were anaemic, but four were iron deficient and four folate deficient. Five of the 12 had sustained bone fractures. Bone mineral density was reduced in males but not in females. The prevalence of coeliac disease in the adult population of Christchurch, New Zealand, is 1.2%. Unrecognized coeliac disease which was detected by population screening was three-fold more common than proven or suspected coeliac disease. Population screening may identify subjects who could benefit from treatment.

Identifying immunoglobulin-A--deficient children and adults does not necessarily help the serologic diagnosis of coeliac disease.

Immunoglobulin A deficiency is more common in patients with coeliac disease and also in patients with other gastrointestinal diseases than in normal people. There is a concern, therefore, that routine serum immunoglobulin (Ig) A testing of all cases of suspected coeliac disease may lead to unnecessary biopsy. Four hundred eighty-two routine consecutive samples from cases of suspected coeliac disease or malabsorption (109 children) were tested for IgA anti-endomysium and total IgA. Four hundred twenty-four sera samples also had IgG antigliadin checked for high-titre antibody. Archived adult sera from 31 patients with coeliac disease and 52 disease control subjects were included in the study. Seven routine cases with serum IgA less than 15% of the mean normal for age and four cases with undetectable IgA were identified. Four patients, including three of four with clear deficiency, underwent small bowel biopsy, and all four had normal histologic findings and normal intraepithelial lymphocyte counts. Only one of the seven had high-titre IgG antigliadin antibody but that patient had normal histologic findings. One (3%) of 31 adults with established coeliac disease and 1 (2%) of 52 control subjects were IgA deficient. Of patients with IgA deficiency, only those with both IgA deficiency and high-titre IgG antigliadin antibody should be routinely considered for biopsy.

Is small bowel biopsy necessary in adults with suspected coeliac disease and IgA anti-endomysium antibodies?

Is small bowel biopsy necessary in adults with suspected coeliac disease and IgA anti-endomysium antibodies?

Antigliadin antibody measurement by chemiluminescence ELISA in the diagnosis of coeliac disease.

To develop a chemiluminescence enzyme linked immunosorbent assay (ELISA) for the detection of circulating gliadin antibodies in the diagnosis of coeliac disease. To compare this method for linearity and sensitivity with an established colorimetric method. Three sets of age and sex matched patient groups were studied: normal controls (patients with no clinical signs of intestinal disorders); gastrointestinal controls (patients with a known gastrointestinal disorder other than coeliac disease); and patients in whom suspected coeliac disease had been confirmed by positive jejunal biopsy. IgG antigliadin antibody (IgG-AGA) and IgA antigliadin antibody (IgA-AGA) titres were determined. Comparison of the colorimetric and chemiluminescence methods showed close correlation of measured antibody levels for both control patient groups. In the coeliac patients correlation of antibody levels measured by both methods was not possible because the colorimetric assay is limited by the spectrophotometer's limits of detection. This problem was overcome by the chemiluminescence method which was linear over a greater range and to far higher values. The chemiluminescence ELISA performs as well as the colorimetric assay at low and average antibody levels and has the advantage of also giving a numerical value to higher antibody titres. The method was accurate and reproducible in confirming the diagnosis of coeliac disease in patients with positive jejunal biopsy and was capable of monitoring progress of the disease.

Predictive value for coeliac disease of antibodies to gliadin, endomysium, and jejunum in patients attending for jejunal biopsy.

To investigate the extent to which the detection of antibodies to gliadin, endomysium, and jejunum predicts the eventual diagnosis of coeliac disease according to the revised ESPGAN diagnostic criteria in a group of patients in whom there is a high suspicion of coeliac disease. Clinical assessment and laboratory analysis of patients with suspected coeliac disease. Gastroenterology department of teaching hospital. 96 adults with suspected coeliac disease attending for jejunal biopsy. Diagnosis of coeliac disease with the revised criteria of the European Society of Paediatric Gastroenterology and Nutrition in patients with and without antibodies associated with coeliac disease. 28 patients had a clinical diagnosis of coeliac disease, seven of other gastrointestinal diseases, and 12 of miscellaneous diseases; 49 had no diagnosis. Gliadin IgA detected by ELISA was found in all patients with coeliac disease and none of those without, giving a sensitivity, specificity, positive and negative predictive values, and predictive efficiency of 100% for diagnosing coeliac disease within the group. Endomysial IgA was found in 25 (89%) patients with coeliac disease and jejunal IgA in 21 (75%); neither IgA was found in patients without coeliac disease. Detection of gliadin IgA by ELISA and to a lesser extent the endomysial IgA should allow better selection of patients for jejunal biopsy and thus make diagnosing coeliac disease simpler and more efficient.

Serum IgG and IgA Anti‐gliadin Antibodies as Markers of Mucosal Damage in Children with Suspected Celiac Disease upon Gluten Challenge

Serum anti‐gliadin antibodies (AGAs) of the IgG and IgA isotypes were determined in 17 children (mean age of 5.6 years) by means of an enzyme‐linked immunosorbent assay (ELISA). All children were suspected of celiac disease. They had been on dietary treatment for at least 10 months before they were challenged with gluten. Based on jejunal biopsy findings, 10 of the 17 children had to be considered positive. The sensitivity of the measurement of AGA at 6 weeks after gluten challenge was found to be 90% for IgG, 100% for IgA, and 100% for IgG/IgA combined. The specificity for IgG, IgA, and the IgG/IgA combination was 100, 71, and 100%, respectively. Twelve weeks after gluten challenge, the sensitivity as well as the specificity of AGA determination for IgG, IgA, and IgG/IgA were 100%. It is concluded that testing both IgG AGA and IgA AGA in children suspected of celiac disease is valuable in monitoring the course of the diagnostic provocation protocol and that jejunal biopsies can be abolished. This inexpensive tool can be useful in reducing the number of intestinal biopsies.

Serum IgG and IgA Anti-gliadin Antibodies as Markers of Mucosal Damage in Children with Suspected Celiac Disease upon Gluten Challenge

Serum anti-gliadin antibodies (AGAs) of the IgG and IgA isotypes were determined in 17 children (mean age of 5.6 years) by means of an enzyme-linked immunosorbent assay (ELISA). All children were suspected of celiac disease. They had been on dietary treatment for at least 10 months before they were challenged with gluten. Based on jejunal biopsy findings, 10 of the 17 children had to be considered positive. The sensitivity of the measurement of AGA at 6 weeks after gluten challenge was found to be 90% for IgG, 100% for IgA, and 100% for IgG/IgA combined. The specificity for IgG, IgA, and the IgG/IgA combination was 100, 71, and 100%, respectively. Twelve weeks after gluten challenge, the sensitivity as well as the specificity of AGA determination for IgG, IgA, and IgG/IgA were 100%. It is concluded that testing both IgG AGA and IgA AGA in children suspected of celiac disease is valuable in monitoring the course of the diagnostic provocation protocol and that jejunal biopsies can be abolished. This inexpensive tool can be useful in reducing the number of intestinal biopsies.

Intestinal Permeability Assessed with Different-Sized Polyethylene Glycols in Children Undergoing Small-Intestinal Biopsy for Suspected Celiac Disease

The gastrointestinal permeability was assessed by means of an oral load of a mixture of different-sized polyethylene glycols (PEG 400 and PEG 1000) in 76 children undergoing small-intestinal biopsy because of suspected celiac disease. Children with a mucosal abnormality suggestive of celiac disease had a lower urinary recovery of larger PEG molecules. They also displayed an altered permeability barrier, as evidenced by a lower ratio of recovery between large (1074 Da) and small (370 Da) PEG molecules. Gluten elimination and gluten challenge caused a significant change in PEG recoveries in children undergoing repeated PEG tests. Repeated assessments of intestinal permeability by means of different-sized PEGs after gluten withdrawal and challenge could complement or indicate suitable time for performing small-intestinal biopsy in children with gluten intolerance.

46. PREDICTABILITY OF SMALL BOWEL MUCOSAL DAMAGE BY RETICULIN (ARA) AND GLIADIN ANTIBODIES (AGA)

The sera of 340 children undergoing small bowel biopsy because of suspected coeliac disease were tested for IgA- and IgG-class ARA and AGA. ARA were determined using an immunofluorescence method and AGA were measured by a solid-phase enzyme-linked immunosorbent assay. Altogether 44 children had flat mucosa (SVA), 43 partial villous atrophy (PVA) and 253 normal small bowel mucosa. The sensitivity of IgA-ARA to detect SVA was 93 %, specificity 100 % and positive predictive value 100 %. The corresponding figures for IgA-AGA were 86 %, 78 % and 41 %. IgA-ARA gave no wrong positive tests in contrast to that of IgA-AGA (59 %). The sensitivity increased (98 %) when the tests were combined meaning that the individual tests missed different patients. IgA-ARA was not suitable for screening SVA (sensitivity 41 %, positive predictive value 78 %) whereas IgG-AGA was a sensitive test (86 %) but its positive predictive value was only 25 %. In PVA the sensitivity of combined AGA tests was 88 % in contrast to that of ARA (1 %). We conclude that AGA tell when small bowel mucosal abnormality caused by gluten or other factors should be suspected and IgA-ARA emphasizes the need of small bowel biopsy to detect children with small, flat intestinal mucosa and coeliac disease.

Humoral response to alpha gliadin as serological screening test for coeliac disease.

The diagnostic value of measuring alpha gliadin antibodies in children with suspected coeliac disease has been evaluated prospectively. Jejunal biopsy and alpha gliadin antibody measurements were performed in 77 consecutive children who were being investigated for a suspected malabsorption syndrome. The typical small intestinal histological lesion of coeliac disease was found, and this diagnosis was subsequently confirmed clinically in 20 children. Raised IgG alpha gliadin antibody concentrations were found in 19 (95%). Fifty of 57 patients (88%) with a normal jejunal mucosa had normal alpha gliadin antibody concentrations. These results are similar to those previously reported in a prospective study of adult patients with coeliac disease and indicate that measurement of alpha gliadin antibody is a highly sensitive and specific screening test for childhood coeliac disease.

Plasma enteroglucagon related to malabsorption in coeliac disease.

Plasma enteroglucagon was measured before and during three hours after a standard meal in 21 untreated adult patients with suspected coeliac disease who all had villous atrophy of the small intestinal mucosa and malabsorption, and in nine control subjects. In 11 of these patients the diagnosis of coeliac disease was confirmed and 10 were again investigated on a gluten free diet. The coeliac patients had higher basal (37 +/- 9 pmol/l, mean +/- SE, p less than 0.05) and postprandial (70 +/- 9 pmol/l, p less than 0.005) mean plasma enteroglucagon concentrations than the control subjects (basal 14 +/- 4 pmol/l, postprandial 25 +/- 5 pmol/l). The 10 coeliac patients on gluten free diet for five to 20 months had a basal mean plasma enteroglucagon concentration not significantly lower than before treatment (25 +/- 5 pmol/l) but significantly lower postprandial enteroglucagon concentrations than before treatment (40 +/- 7 pmol/l, p less than 0.025). Postprandial plasma enteroglucagon concentration after 90 minutes in untreated patients correlated positively to the faecal fat excretion (r = 0.58, p less than 0.02). It correlated negatively to the urinary five hour D-xylose excretion after an oral load of 165 mmol D-xylose (r = -0.71, p less than 0.01). Thus, the postprandial plasma enteroglucagon concentrations in untreated coeliac disease were related to the degree of malabsorption and they normalised during treatment with a gluten free diet.

Endoscopic duodenal biopsies in coeliac disease and duodenitis.

Endoscopic duodenal biopsies were taken from 27 patients with suspected coeliac disease and compared with intubation capsule jejunal biopsies. The specimens were reported without knowledge of the patients' names or symptoms. In 24 patients (89%), coeliac disease could either be diagnosed or excluded with 100% accuracy, despite the inability to orientate the biopsies correctly. Six biopsies were considered technically unsatisfactory, but only in three (11%) was it impossible to exclude coeliac disease. Duodenal biopsies were also taken from 118 consecutive patients attending for routine upper gastrointestinal endoscopy, and 1 patient with coeliac disease was discovered. We conclude that endoscopic duodenal biopsies are a reliable and worthwhile screening test for coeliac disease in certain patients attending for routine upper gastrointestinal endoscopy.

Coeliac disease diagnosed by means of duodenoscopy and endoscopic duodenal biopsy.

Nineteen patients with suspected coeliac disease were examined by duodenoscopy and biopsy. In all patients a histopathology consistent with coeliac disease was demonstrated in endoscopic biopsies of the duodenal mucosa. On close-up view villous atrophy was seen in vivo. Fourteen patients were re-examined on a gluten-free diet. In 13 patients a restitution of the duodenal mucosa was shown. Duodenoscopy combined with biopsy seems to be a reliable method for the assessment of the mucosal change in coeliac disease.

Lactose intolerance, detected by the hydrogen breath test, in infants and children with chronic diarrhoea

Twenty-three infants and children aged 2½ months to 13 years with chronic diarrhoea and 6 patients without diarrhoea were investigated for lactose malabsorption with the hydrogen breath test (HBT) adapted for use in young infants and children. A further 8 children with proven or suspected coeliac disease were also investigated. The HBT was compared with the histology of the jejunal mucosa, mucosal lactase estimations, a lactose tolerance test, symptoms during the test, and follow-up after starting a lactose free diet. The 6 patients without diarrhoea showed no evidence of hypolactasia and the hydrogen (H₂)* concentration on the HBT was below 7 parts per million (ppm), a level considered to be clinically nonsignificant. 12 of the 23 patients with diarrhoea had a breath H₂ concentration greater than 24 ppm and this correlated well with their clinical symptoms during or after the test and with the remission of the diarrhoea after lactose withdrawal. Of the remaining 11 patients with diarrhoea whose breath H₂ concentration was lower than 25 ppm, symptoms did not improve when a lactose-free diet was started in 3, while a further 4 improved on a full diet. There was poor correlation between the HBT and the findings on the jejunal mucosal specimens. All but one of the coeliac patients had an HBT less than 20 ppm and none of these required lactose withdrawal for remission of symptoms. The HBT is a noninvasive test particularly suitable for outpatients and it gives a useful prognostic guide to the efficacy of lactose-free diet in the treatment of chronic diarrhoea in children.