Exclusion Of Coeliac Disease Research Articles

PTH-183 The Diagnostic Utility of Endoscopic Duodenal Biopsies for Gastrointestinal Investigation

IntroductionDuodenal biopsies are usually taken at upper gastrointestinal endoscopy to exclude coeliac disease (CD). To date, few studies have investigated overall duodenal pathologies in this group. Serological testing for anti-tissue...

PWE-175 Duodenal eosinophilia and early satiety in functional dyspepsia (FD): confirmation of a positive biomarker association for FD in an Australian Cohort

IntroductionFunctional dyspepsia (FD), defined by unexplained pain or discomfort centred in the upper abdomen, affects 15% of the population. Diagnosis and treatment of FD based on the symptom-based Rome III...

PTU-137 Does a prompt from the histology report to perform serology to exclude coeliac disease mean this is done?

IntroductionLymphocytic duodenosis (LD) is a histological diagnosis comprising normal duodenal architecture, but an intraepithelial lymphocyte (IELs) count >25/100 enterocytes. A diagnosis of coeliac disease (CD) can be made in up...

975 Duodenal Eosinophilia and Early Satiety in Functional Dyspepsia (FD): Confirmation of a Positive Biomarker Association for FD in an Australian Cohort

Introduction Functional dyspepsia (FD), defined by unexplained pain or discomfort centred in the upper abdomen, affects 15% of the population. Diagnosis and treatment of FD based on the symptom-based Rome III criteria remains challenging. Recently, subtle eosinophilic inflammation in the duodenum has been implicated in the pathophysiology of FD in adults based on a Swedish case-control study. 1 Specifically, increased eosinophils in early satiety and postprandial distress have been replicated in the UK, 2 in paediatric dyspepsia in the USA 3 and in post-infectious FD in Japan, 4 but the association remains controversial. The aim of this study was to characterise upper gastrointestinal tract pathology in an Australian cohort and correlate this with available clinical data in FD cases and controls. Methods Patients prospectively referred for an upper gastrointestinal endoscopy (n=55; mean age, 49.6 years; 61.8% female) were entered to the study (with informed consent), stratified to FD cases (n=33) and controls (n=22) by Rome II criteria and completed a validated Bowel Symptom Questionnaire. Two blinded independent observers assessed the eosinophil count in five high power fields, in the duodenal bulb (D1) and second part (D2). H pylori status was assessed by gastric histology. Associations with clinical symptoms were assessed by Mann–Whitney U test. Results Cases and controls were demographically similar. There was a significant increase in eosinophils in D1 vs D2 for both cases (p=0.0003) and controls (p=0.008). Abdominal pain was associated with eosinophilia in both D1 (p=0.03) and D2 (p=0.007). Duodenal eosinophilia was significantly increased in subjects experiencing early satiety, (p=0.015). This association remained after exclusion of coeliac disease (n=2) and H pylori (n=9, 16%) (p=0.04) in D2 but not in D1. Subjects who “felt food staying in their stomach” similarly had increased D2 eosinophilia (p=0.002); this remained significant on exclusion of coeliac disease and H pylori (p=0.004). Smoking was also associated with eosinophilia in D2 (p=0.008). Conclusion Data supporting subtle duodenal eosinophilia in subsets of FD has become credible. The potential role of duodenal eosinophils as biomarkers has implications for diagnosis and therapeutic trials. Competing interests None declared.

123 Helicobacter pylori-Associated Hypochlorhydria in Children Relates to the Development of Iron Deficiency

Introduction Acute H pylori infection is associated with transient hypochlorhydria of variable duration. Hypochlorhydria in H pylori-associated atrophy has a role in iron deficiency (ID) through changes in the physiology of iron absorption. The role of hypochlorhydria in H pylori-associated ID in childhood has not been investigated. The aims were to evaluate the association between H pylori-associated hypochlorhydria and ID in children. Methods A total of 123 children were prospectively enrolled in the study. Any child with peptic ulceration, or who received antacids, PPIs, H2 antagonists, and antibiotics in the previous 4 weeks was excluded. Blood was taken for complete blood count and iron profile. Gastric biopsies were taken for H. pylori determination by histology and rapid urease test. H pylori status was defined as +ve if either test was positive. Gastric juice was obtained at the beginning of the endoscopy avoiding water insufflation. Duodenal biopsies were taken for exclusion of coeliac disease (CD). Stool samples were collected for parasitology/microbiology. Of the 123 children, 2 with CD, 8 with non-specific duodenal inflammation (DI), 5 with lost blood analysis and 9 with parasitic infections (2 with DI) were excluded. Results Of the remaining 101 children 31 were H pylori +ve and 10 were hypochlorhydric (pH>4). There were no differences in demographic characteristics with regard to infection status, or gastric pH. In H pylori +ve children with pH >4 (n=6) serum iron (median (IQR): 60.2 (45–66) μg/dl) and transferrin saturation levels percentage (16.6 (15–19)) were significantly lower (p 4 (n=4) both iron (119 (101–137)), and transferrin saturation (36.4 (31–41)), were not significantly different from children with pH≤4 (n=66) (iron 98.7 (80–122); transferrin saturation 32.2 (25–40)). Conclusion Low serum iron and transferrin in childhood H pylori infection is associated with hypochlorhydria. In uninfected children, hypochlorhydria was not associated with altered serum iron parameters, indicating a combination of H pylori infection and/or inflammation and hypochlorhydria has a role in the aetiology of iron deficiency. Even though H pylori-associated hypochlorhydria may reflect a transient period during acute gastritis, it alters iron homeostasis with clinical impact in developing countries with a high H pylori prevalence. Funded by EU CONTENT Project (INCO-CT-2006-032136) and CONICYT/BM (RUE #29).

Revival of Gliadin Antibodies in the Diagnostic Work-up of Celiac Disease

Revival of Gliadin Antibodies in the Diagnostic Work-up of Celiac Disease

Meta‐analysis: deamidated gliadin peptide antibody and tissue transglutaminase antibody compared as screening tests for coeliac disease

Following the appreciation of the importance of gliadin deamidation in the immunopathogenesis of coeliac disease, diagnostic tests based on antibodies to deamidated gliadin peptides have been developed and shown to have high sensitivity and specificity. To compare the performance of the deamidated gliadin peptides antibody test with the current standard, the tissue transglutaminase antibody test, through a meta-analysis of published studies. Databases from 1998 to 2008 were searched for relevant studies. These were assessed for methodological quality and standard statistical tests were applied to compare particularly the sensitivity and specificity of the two tests for the diagnosis of coeliac disease. Most studies had methodological flaws, especially ascertainment bias. The pooled sensitivities for the deamidated gliadin peptides antibody and tissue transglutaminase antibody tests were 87.8% (95% CI, 85.6-89.9) and 93.0% (95% CI, 91.2-94.5) respectively and the pooled specificities were 94.1% (95% CI, 92.5-95.5) and 96.5% (95% CI, 95.2-97.5) respectively. Although both tests perform well, the tissue transglutaminase antibody test outperforms the deamidated gliadin peptides antibody test and remains the preferred serological test for the diagnosis and/or exclusion of coeliac disease.

Gamma/delta T cells and the diagnosis of coeliac disease

Gamma/delta T cells are increased in the gut epithelium of patients with coeliac disease compared with normal controls. The aim of this study was to determine whether the increase in gamma delta intraepithelial lymphocytes (IEL) is specific for coeliac disease, in which case it could be of diagnostic importance. Biopsies were obtained from children with no intestinal disease, coeliac disease, cow-milk-sensitive enteropathy/post-enteritis syndrome (CMSE PES) and miscellaneous other enteropathies (n = 67). Intraepithelial CD3+ and gamma delta T cells were identified in frozen sections using peroxidase immunohistochemistry. In normal biopsies there were 0-7 gamma delta IEL/100 cells in the epithelium. In untreated coeliac patients this increased to 9-22 gamma delta IEL/100 cells in the epithelium (P = 0.000004). Of 27 patients with morphologic intestinal damage which was not due to coeliac disease, four with CMSE/PES had gamma delta IEL/100 cells in the epithelium in the same range as the patients with coeliac disease. Of these, two had high densities of CD3+ IEL in the epithelium and were indistinguishable from patients with untreated coeliac disease. The other two could be excluded as possible coeliacs because their CD3+ IEL/100 epithelial cells were in the normal range. Thus an increase in gamma delta IEL is not specific for coeliac disease. However, enumeration of both of gamma delta IEL and CD3+ IEL densities will be useful in the exclusion of coeliac disease as a diagnosis in some children.

Value of routine duodenal biopsy in diagnosing coeliac disease in patients with iron deficiency anaemia

Background: Iron deficiency anaemia (IDA) is a recognised feature of coeliac disease in adults and can be its only presentation. Objective: To determine the yield of routine distal duodenal biopsies...

Histology of the terminal ileum in coeliac disease

Background: 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. Methods: 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). Results: 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 ≥25 had a sensitivity for duodenal villous atrophy (VA) of 60% and specificity of 100%. Conclusions: 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.

Alpha/beta intraepithelial lymphocytes, serum gliadin antibodies and allergy test positivity in children

Aim: To determine whether the amount of αβ‐positive intraepithelial lymphocytes (IELs) is connected to allergy test positivity in children with gastrointestinal symptoms and whether elevated serum gliadin antibodies have any role in the diagnosis. Methods: Twenty‐seven children suffering from gastrointestinal‐symptoms in whom intestinal biopsies had previously been obtained via endoscopy or with capsule biopsy to exclude coeliac disease were included into the study. The other inclusion criteria were increased amounts of CD3 and αβ‐positive IELs with normal amounts of γδ‐positive IELs in duodenal or jejunal biopsy specimens. At the control visit, the children underwent a physical examination and parents filled in a questionnaire concerning gastrointestinal‐and atopic symptoms. Skin prick‐ and patch tests were done and serum gliadin, endomysium, transglutaminase antibodies and specific IgEs were measured. Results: Only nine children (33%) had at least one positive result in the allergy tests, the rest remaining test negative. In children with digestive symptoms, IgG‐class gliadin antibody titres were higher than those of the non‐symptomatic children. A significant correlation was found between IgG‐class gliadin antibodies and total amount of αβ‐positive IELs (p= 0.017). Conclusion: No positive skin test or specific IgE positivity for cereals in children with high intestinal T‐cell densities was observed. The correlation between IgG‐class gliadin antibodies and the total amount of αβ‐TCR positive‐cells is likely to be a reflection of local immune response of the gut.

Alpha/beta intraepithelial lymphocytes, serum gliadin antibodies and allergy test positivity in children.

To determine whether the amount of alphabeta-positive intraepithelial lymphocytes (IELs) is connected to allergy test positivity in children with gastrointestinal symptoms and whether elevated serum gliadin antibodies have any role in the diagnosis. Twenty-seven children suffering from gastrointestinal-symptoms in whom intestinal biopsies had previously been obtained via endoscopy or with capsule biopsy to exclude coeliac disease were included into the study. The other inclusion criteria were increased amounts of CD3 and alphabeta-positive IELs with normal amounts of gammadelta-positive IELs in duodenal or jejunal biopsy specimens. At the control visit, the children underwent a physical examination and parents filled in a questionnaire concerning gastrointestinal- and atopic symptoms. Skin prick- and patch tests were done and serum gliadin, endomysium, transglutaminase antibodies and specific IgEs were measured. Only nine children (33%) had at least one positive result in the allergy tests, the rest remaining test negative. In children with digestive symptoms, IgG-class gliadin antibody titres were higher than those of the non-symptomatic children. A significant correlation was found between IgG-class gliadin antibodies and total amount of alphabeta-positive IELs (p = 0.017). No positive skin test or specific IgE positivity for cereals in children with high intestinal T-cell densities was observed. The correlation between IgG-class gliadin antibodies and the total amount of alphabeta-TCR positive-cells is likely to be a reflection of local immune response of the gut.

HLA-DQ typing in the diagnosis of celiac disease

OBJECTIVE: More than 95% of celiac patients share the major histocompatibility complex II class human leukocyte antigen (HLA) DQ2 or DQ8 haplotype; patients negative for both types are unlikely to suffer from celiac disease. Our aim was to investigate whether HLA-DQ2 and -DQ8 typing is helpful when diagnosis is uncertain because of the absence of unequivocal small bowel villous atrophy. METHODS: HLA-DQ2 and -DQ8 typing was carried out in 59 patients evincing nondiagnostic small bowel mucosal lesion or positive celiac serology, and in 17 patients maintaining a gluten-free diet without biopsy-proven celiac disease. HLA findings were compared to small bowel mucosal morphology; intraepithelial lymphocytes; and serum endomysial (EmA), reticulin, tissue transglutaminase (anti-tTG) and gliadin antibodies. RESULTS: Of the 59 patients evincing only minor small bowel mucosal changes or positive celiac disease serology, 22 (37%) were negative for DQ2 and DQ8. All EmA-positive patients had celiac-type HLA, but antireticulin antibody, anti-tTg, and antigliadin antibody were also present in HLA-DQ2– and -DQ8–negative individuals. Eleven of 17 patients (65%) observing a gluten-free diet before small bowel biopsy did not share celiac-type HLA. None of the 17 had apparent villous atrophy. Serum EmA and anti-tTG were negative in all. HLA-DQ typing is less expensive than follow-up biopsy in the exclusion of celiac disease. CONCLUSIONS: HLA-DQ2 and -DQ8 determination is useful in exclusion, probably lifelong, of celiac disease in individuals with an equivocal small bowel histological finding. The low specificity of this test must, however, be borne in mind.

Cost-effective strategy for the serological investigation of coeliac disease

Increased numbers of requests for serological investigation of coeliac disease, and a local trend to request both anti-gliadin antibodies (AGA) and anti-endomysium antibodies (AEA) simultaneously, resulted in cost pressures that prompted a review of our practice. Serology results from all patients (771 children, 511 adults) investigated for coeliac disease over a 3-year period were compared with small intestine histology where available. IgG AGA and IgA AGA were measured by enzyme-linked immunosorbent assay (in-house), IgA AEA by immunofluorescence (send-away contract). Overall diagnostic performance was as follows: AGA sensitivity 84%, specificity 88%, positive predictive value (PPV) 24%, negative predictive value (NPV) 99%; AEA sensitivity 88%, specificity 97%, PPV 65%, NPV 99%. Results showed AGA, with its high NPV, to be a suitable first-line test to exclude coeliac disease. The high specificity of AEA makes it a suitable confirmatory test when AGA is positive. Introduction of this step-wise approach to coeliac disease investigation resulted in cost savings of at least £5000 per year without detriment to the clinical service.

Cost-effective strategy for the serological investigation of coeliac disease.

Increased numbers of requests for serological investigation of coeliac disease, and a local trend to request both anti-gliadin antibodies (AGA) and anti-endomysium antibodies (AEA) simultaneously, resulted in cost pressures that prompted a review of our practice. Serology results from all patients (771 children, 511 adults) investigated for coeliac disease over a 3-year period were compared with small intestine histology where available. IgG AGA and IgA AGA were measured by enzyme-linked immunosorbent assay (in-house), IgA AEA by immunofluorescence (send-away contract). Overall diagnostic performance was as follows: AGA sensitivity 84%, specificity 88%, positive predictive value (PPV) 24%, negative predictive value (NPV) 99%; AEA sensitivity 88%, specificity 97%, PPV 65%, NPV 99%. Results showed AGA, with its high NPV, to be a suitable first-line test to exclude coeliac disease. The high specificity of AEA makes it a suitable confirmatory test when AGA is positive. Introduction of this step-wise approach to coeliac disease investigation resulted in cost savings of at least Pound Sterling 5000 per year without detriment to the clinical service.

Similarities in intestinal humoral immunity in dermatitis herpetiformis without enteropathy and in coeliac disease

Intestinal humoral immunity was examined in eight patients with dermatitis herpetiformis and normal jejunal histology (as determined by quantitative morphometry) on a gluten-containing diet. Jejunal aspirate was taken at the time of jejunal biopsy, and levels of total immunoglobulins (IgA, IgM, IgG) and specific antibody to gliadin and two other dietary proteins, betalactoglobulin and ovalbumin, were measured. The pattern of secretory immune responses in the dermatitis herpetiformis patients was similar to that in twenty-six patients with untreated coeliac disease—ie, higher than normal concentrations of IgA, IgM, and IgG and high levels of specific antibodies (IgA and IgM) to the three dietary proteins. Serum levels of IgA antigliadin were similar in the dermatitis herpetiformis and control (twenty-eight patients who underwent jejunal biopsy to exclude coeliac disease) groups, and serum levels of IgG antigliadin were intermediate between those of the control and coeliac disease groups. These findings suggest that investigation of gut humoral immunity may provide a diagnostic index of latent coeliac disease. The definition of coeliac disease as a permanent gluten-sensitive enteropathy may have to be revised if the proposed two-stage model is confirmed.

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.

The two-film barium meal in the exclusion of coeliac disease

Prospective experience over five years is described in assessing the two-film barium meal as a test for the exclusion of untreated celiac disease in children in order to try to make jejunal biopsy unnecessary. 287 meals were examined in children between 3 months and 10 years of age with a variety of gastro-intestinal symptoms and signs that might be attributed to celiac disease. From the two-film barium meal the calibre and transverse mucosal folds of the upper small bowel were measured. In 48 children with untreated coeliace disease there were only three (6%) with negative two-film barium meals. In 45 children with malabsorption from causes other than coeliac disease, there were four (9%) with negative two-film barium meals. It is concluded that the two-film barium meal is a reasonably reliable test for the exclusion of untreated coeliac disease in children. It is simple, cheap, safe and economical of radiological time, and it compares favourably in accuracy with other screening tests, other than jejunal biopsy.