Potential coeliac disease in Type 1 diabetes mellitus: does a positive antibody lead to increased complications?

BACKGROUND AND AIMS: Coeliac disease (CD) is more common in people with Type 1 diabetes and is associated with poorer glycaemic control, lipid profiles, nephropathy and retinopathy. Potential CD (positive serology but normal duodenal biopsy) is associated with neuropathy but patients with coexisting Type 1 diabetes were excluded. The aim was to determine whether potential CD is associated with increased microvascular complications in patients with Type 1 diabetes. METHODS AND RESULTS: Four groups were recruited; 1) patients with Type 1 diabetes and potential CD, 2) patients with Type 1 diabetes and newly identified CD, 3) patients with Type 1 diabetes alone and 4) patients with CD alone. Glycaemic control, quality of life, lipid profile and microvascular complication rates were examined. As many as 76 individuals were included in the study: 22 in group 1, 14 in group 2, 24 in group 3 and 16 in group 4. There were no differences in age, gender, BMI and diabetes duration between the groups. Patients in group 1 had significantly lower total cholesterol compared to group 3 (p = 0.003) but higher than group 2 (p = 0.027). There were no significant differences in HbA1c, HDL cholesterol, cholesterol:HDL ratio, creatinine, quality of life scores or prevalence of neuropathy between individuals in group 1 and the other groups. CONCLUSIONS: This is the first study to assess the effects of potential CD in patients with Type 1 diabetes. It appears that an enteropathy is required as well as antibody positivity in order to increase the risk of diabetes related complications. This pilot data requires further longitudinal validation.

Quality not quantity for transglutaminase antibody 2: the performance of an endomysial and tissue transglutaminase test in screening coeliac disease remains stable over time.

National Institute of Clinical Excellence (NICE) and European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidance for the diagnosis of coeliac disease has been published. However, there is some controversy regarding the advice on the use of stratifying levels of immunoglobulin (IgA) tissue transglutaminase antibody (TG2) test positivity in the absence of test standardization and the vagueness of the indication to test equivocal samples. Using repeat service audit, we demonstrate that a combination of TG2 followed by IgA endomysial antibodies (EMA) is the best strategy for all degrees of mucosal abnormality using our test combination. Reliance upon immunoassay titre is not as effective, and cannot be applied consistently across populations in the absence of assay standardization. Guidelines advocating the use of tests should involve experts in laboratory diagnostics and external quality assurance to ensure that errors of generalization do not occur and that test performance is achievable in routine diagnostic use.

Serological testing for coeliac disease in Type 1 diabetes mellitus: is immunoglobulin A level measurement necessary?

AIMS: Immunoglobulin A (IgA) measurement is advocated when case finding for coeliac disease in patients with Type 1 diabetes mellitus. Currently, there is a paucity of contemporary studies assessing IgA deficiency in Type 1 diabetes. This study evaluates the prevalence of IgA deficiency in individuals with Type 1 diabetes, compared with patients with coeliac disease and control subjects. In addition, we evaluate whether routine IgA measurement is justifiable when case finding for coeliac disease in patients with Type 1 diabetes. METHODS: All patients were assessed using IgA endomysial antibodies, IgA anti-tissue transglutaminase antibodies and total IgA levels. Altogether, 2434 individuals were tested: 1000 patients with Type 1 diabetes, 234 patients with coeliac disease and 1200 population control subjects. Definitive IgA deficiency was defined as total IgA levels < 0.07 g/l. RESULTS: The prevalence of IgA deficiency was significantly more common in patients with Type 1 diabetes (0.9%, n = 9/1000; P = 0.036) and coeliac disease (1.29%, n = 3/234; P = 0.041) when compared with population control subjects (prevalence of 0.17%, 2/1200). No statistical difference between Type 1 diabetes and coeliac disease for IgA deficiency was identified (P = 0.87). Of patients in the group with Type 1 diabetes, 3.3% (33/1000) had coeliac disease, and of those only one patient had IgA deficiency leading to an antibody-negative presentation. Both IgA-deficient individuals within the population control subjects had normal duodenal biopsies and no relevant symptoms. CONCLUSIONS: IgA deficiency is more common in Type 1 diabetes compared with population control subjects. Despite this, very few individuals with Type 1 diabetes and IgA deficiency appear to have villous atrophy on biopsy. These outcomes question the practice of routine IgA measurement when case finding for coeliac disease in patients with Type 1 diabetes.

Autoimmune pancreatitis: an important diagnostic consideration in obstructive jaundice due to a pancreatic mass lesion.

Autoimmune or immunoglobulin G subtype (IgG4) pancreatitis is a newly recognised clinical entity and is an important differential diagnosis for patients presenting with obstructive jaundice. Knowledge of autoimmune pancreatitis (AIP) continues to evolve both for pathogenesis and management; however diagnosis is often not straightforward or even considered, therefore a high index of suspicion remains an important tool for the treating physician. The six cases presented illustrate both the difficulties in diagnosis as well as management of this condition.

Patchy villous atrophy in adult patients with suspected gluten-sensitive enteropathy: is a multiple duodenal biopsy strategy appropriate?

BACKGROUND AND STUDY AIMS: The current internationally accepted gold standard for diagnosing celiac disease is a small-bowel biopsy demonstrating villous atrophy. However, it has been suggested that the diagnosis might not be considered as confirmed if the villous atrophy is patchy. Our aim was to assess whether there is an optimal duodenal biopsy strategy for detecting villous atrophy in adult patients with suspected gluten-sensitive enteropathy. PATIENTS AND METHODS: Patients who had positive endomysial or tissue transglutaminase antibodies were prospectively recruited. Nine biopsies were taken from the duodenum: one from the duodenal bulb, four from the proximal duodenum, and four from the distal duodenum. Each biopsy was graded according to the Marsh criteria. All possible biopsy regimes were evaluated for their ability to detect the presence and severity of villous atrophy. RESULTS: A total of 56 patients were recruited (23 men [41 %], 33 women [59 %]; mean age 47, range 16 - 85): 53/56 patients had villous atrophy present in at least one biopsy; 10/53 patients had biopsy specimens that showed "patchy" villous atrophy. In all 53 patients with villous atrophy this was detected by taking a minimum of three biopsies (sensitivity 100 %, 95 % confidence interval [CI] 93.2 % - 100 %). However, this strategy always incorporated a duodenal bulb biopsy. The most severe degree of villous atrophy in all 56 patients was only detected by using a five-biopsy regime (sensitivity 100 %, 95 % CI 93.6 % - 100 %). CONCLUSIONS: In this study we observed that villous atrophy in adult patients with suspected gluten-sensitive enteropathy (antibody-positive) is patchy. For this reason we would suggest a minimum of three biopsies, incorporating a duodenal bulb biopsy, to ensure that villous atrophy is detected. However, a five-biopsy regime is required for recognition of the most severe lesion.

Is formal training necessary for capsule endoscopy? The largest gastroenterology trainee study with controls.

BACKGROUND: Little is known about the infrastructure to train gastroenterologists in capsule endoscopy. The level of capsule endoscopy exposure among trainees in the United Kingdom or Europe has also not been quantified. AIMS AND METHODS: To assess the ability of 10 gastroenterology trainees with endoscopy experience to interpret 10 capsule endoscopy videos against five medical students, with an expert in capsule endoscopy as the gold standard. Parameters assessed included gastric emptying time, small bowel transit and the diagnosis made. A questionnaire survey assessed the level of capsule endoscopy exposure among United Kingdom trainees. RESULTS: Trainees were better at determining the gastric emptying time (p=0.013) and more likely to record true positives compared to the students (p=0.037). They were also less likely to record false positives (p=0.005) and more likely to reach the correct diagnosis (p=0.001, OR 3.6, CI 1.8-7.4). Our survey found that, 65% of trainees had prior exposure to capsule endoscopy but only 13% had done capsule endoscopy reporting. Sixty seven percent felt capsule endoscopy should be incorporated into their training. CONCLUSION: This study has shown that prior endoscopic experience enables trainees to interpret capsule endoscopy more accurately than medical students. However, there is a demand for focussed training which would enable trainees to reliably interpret pathology on capsule endoscopy.

Is exocrine pancreatic insufficiency in adult coeliac disease a cause of persisting symptoms?

BACKGROUND: Patients with coeliac disease may have diarrhoea despite being on a gluten-free diet. AIM: To assess whether exocrine pancreatic insufficiency causes persisting symptoms compared with controls, we determined whether pancreatic enzyme supplementation provided symptomatic benefit in coeliac patients with chronic diarrhoea. METHODS: Patients (n = 259) were subdivided into four groups: (a) new coeliac disease (n = 57), (b) coeliac disease patients on a gluten-free diet without gastrointestinal symptoms (n = 86), (c) coeliac disease patients on a gluten-free diet with chronic diarrhoea (n = 66) and (d) patients with chronic diarrhoea without coeliac disease (n = 50). Stool frequency and weight, before and after treatment with pancreatic enzyme supplementation were recorded. RESULTS: The prevalence of a low faecal elastase-1 within the groups was: group (A) six of 57 (11%), group (B) five of 86 (6%), group (C) 20 of 66 (30%) and group (D) two of 50 (4%). Low faecal elastase-1 was more frequent in coeliac disease patients with chronic diarrhoea vs. other subgroups of coeliac disease (P < or = 0.0001) and controls (P < or = 0.0003). In 18 of 20 stool frequency reduced following pancreatic enzyme supplementation from four per day to one (P < or = 0.001). No weight increase (P = 0.3) was observed. CONCLUSIONS: Low faecal elastase is common in patients with coeliac disease and chronic diarrhoea, suggesting exocrine pancreatic insufficiency. In this group of patients, pancreatic enzyme supplementation may provide symptomatic benefit.

Capsule endoscopy: an alternative to duodenal biopsy for the recognition of villous atrophy in coeliac disease?

BACKGROUND: Villous atrophy present on a duodenal biopsy remains the 'gold standard' diagnostic test for coeliac disease. However, endoscopic biopsy may cause morbidity and discomfort. Our aim was to evaluate wireless capsule endoscopy as an alternative test for the recognition of villous atrophy. METHOD: Twenty-one patients with a positive endomysial antibody referred for endoscopy and duodenal biopsy were also offered a wireless capsule endoscopy to evaluate their small bowel. Concurrently, other patients (n=23) referred for a wireless capsule endoscopy acted as controls. Wireless capsule endoscopy reports were assessed for the presence of villous atrophy by one blinded investigator. RESULTS: Twenty endomysial antibody positive patients subsequently had villous atrophy on duodenal biopsy. The controls all had normal duodenal biopsies (with a negative endomysial antibody) and no evidence of villous atrophy noted on their wireless capsule endoscopy. Of the 20 endomysial antibody positive patients with confirmed villous atrophy on biopsy, 17 had villous atrophy also detected by wireless capsule endoscopy. The sensitivity, specificity, positive and negative predictive values for wireless capsule endoscopy recognising villous atrophy were 85%, 100%, 100%, 88.9%, respectively. CONCLUSION: Wireless capsule endoscopy may be an option to recognise villous atrophy in patients with a positive endomysial antibody who are unwilling, or unable to have a gastroscopy. However, a negative test should be followed by a biopsy if coeliac disease is to be excluded.

The occurrence of terminal ileal histological abnormalities in patients with coeliac disease.

INTRODUCTION: Coeliac disease causes histological changes throughout the small bowel, but is often a proximal lesion. We wanted to assess whether terminal ileal histological abnormalities occurred more commonly in patients with coeliac disease and if specific assessment of intraepithelial lymphocytes increases the recognition of undiagnosed coeliac disease. METHODS: Terminal ileal biopsies were prospectively examined over a 3-year period (April 2001-May 2004). Patients were included if they were found to have a synchronous duodenal biopsy that gave a new diagnosis of coeliac disease (n=20). Terminal ileal biopsies taken at colonoscopy during the same period were also examined from four groups of patients: coeliac disease established on a gluten-free diet but with persisting symptoms (n=25), inflammatory bowel disease (n=47), chronic diarrhoea (n=44) and polyp surveillance (n=47). All biopsies were graded according to the Marsh criteria and an intraepithelial lymphocytes count per 100 enterocytes was obtained. RESULTS: There was only one patient from all five groups who had villous atrophy of the terminal ileal. This patient had a new diagnosis of coeliac disease. The mean intraepithelial lymphocytes count in the coeliac disease group was 23.7 intraepithelial lymphocytes/100 enterocytes. This was significantly higher than the control groups: coeliac disease on a gluten-free diet=17.5 (p<0.012), inflammatory bowel disease=12.3 (p<0.0001), diarrhoea=12.6 (p<0.0001) and polyp=13.7 (p<0.0002). Validating terminal ileal villous intraepithelial lymphocytes counts as a test for coeliac disease using an intraepithelial lymphocytes/100 enterocytes of >25 gives a sensitivity of 45% and a specificity of 97.8%. CONCLUSION: Routinely quantifying terminal ileal intraepithelial lymphocytes may be of limited clinical value. However, subjective recognition of raised intraepithelial lymphocytes on a terminal ileal biopsy should alert the clinician to the possibility of coeliac disease.

A prospective study into the aetiology of lymphocytic duodenosis.

BACKGROUND: Lymphocytic duodenosis is defined by normal villous architecture and intraepithelial lymphocytes (IELs) >25 per 100 enterocytes. Such patients should not be diagnosed with coeliac disease, solely by histology, as previous retrospective studies have suggested other associations with lymphocytic duodenosis. AIM: To study prospectively the aetiology of lymphocytic duodenosis. METHODS: One hundred patients with lymphocytic duodenosis were investigated rigorously for coeliac disease and other known associations for lymphocytic duodenosis by initial investigations of coeliac serology, and exclusion of infection. Of 34 with no explanation for lymphocytic duodenosis, 29 underwent repeat duodenal biopsies following a gluten challenge. RESULTS: Coeliac disease was present in 16% of patients with lymphocytic duodenosis. In the absence of a positive coeliac diagnosis, lymphocytic duodenosis was most commonly associated with drugs (21%), infection (19%), immune dysregulation (4%), inflammatory bowel disease (2%), microscopic colitis (2%), sarcoidosis (1%) and IgA deficiency (1%). Of 34 with no known associations, 18 had symptoms of irritable bowel syndrome (IBS), and in 29 patients investigated with repeat duodenal biopsies, the IEL count returned to normal in 22. CONCLUSIONS: In 66% of cases of lymphocytic duodenosis, a known association can be found by further investigations; importantly, 16% will have coeliac disease. In those with no apparent cause, there may be an association with IBS and the IEL count becomes normal on repeat biopsy in 76%.