ABSTRACT: Serum endomysial antibody (EMA) is a highly specific marker of untreated coeliac disease (CD). The published estimates of sensitivity however vary widely and the explanation for this remains unclear.
To determine the relative prevalence of EMA-negative CD and to identify clinical and histological characteristics which relate to EMA status.
Retrospective analysis of prospectively collected data on incident cases of CD in a single hospital over a 10-year period with determination of EMA status before gluten withdrawal.
From a total of 241 participants, 37 [15% (95% confidence interval: 11, 20%)] were EMA negative, of whom only four were IgA deficient. EMA-positive and EMA-negative patients shared a number of characteristics including female predominance and a high prevalence of HLA DQ2. EMA status was associated with age-test sensitivity and exceeded 98% below the age of 35 years, falling to around 80% in older age groups overall, and lower still in current cigarette smokers. EMA status was not influenced by sex, family history of CD, other autoimmune disease, or by potential clinical or histological markers of disease severity.
A substantial proportion of patients with true CD are EMA negative. This has implications for the pathogenesis of the disease. It also limits the value of EMA as a screening test, particularly in older adults and cigarette smokers.
European Journal of Gastroenterology & Hepatology 11/2007; 19(10):890-5. · 1.76 Impact Factor
ABSTRACT: Previous studies have shown an association between cigarette smoking and coeliac disease, but it has yet to be established whether this relationship is causal. The aim of this study was to assess causality using the Bradford Hill criteria.
A matched case-control study using a questionnaire to establish a detailed smoking history for 138 incident cases of adult coeliac disease and 276 age-matched and sex-matched controls. Subjects were categorized according to their active cigarette exposure prior to diagnosis of the matched case, and odds ratios and tests for linear trends were calculated.
At the time of diagnosis, 10% of cases and 30% of controls were current smokers (odds ratio, 0.21 and 95% confidence interval, 0.11-0.40 for coeliac disease in current smokers versus never smokers). A biological gradient was demonstrated for total, recent and current cigarette exposure. The greatest risk reduction related to current exposure (odds ratio, 0.15, and 95% confidence interval, 0.06-0.37 for coeliac disease in current heavy smokers versus never smokers).
This study strengthens the case for a causal relationship between smoking and coeliac disease by demonstrating a strong, temporally appropriate and dose-dependent effect, thus meeting the Bradford Hill criteria. This suggests that cigarette smoking truly protects against the development of adult coeliac disease.
European Journal of Gastroenterology & Hepatology 10/2003; 15(9):995-1000. · 1.76 Impact Factor
ABSTRACT: To clarify the relationship between childhood environment and the risk of subsequent development of Crohn's disease or ulcerative colitis.
A case-control study, assessing the risk of inflammatory bowel disease in relation to a series of historical and serological markers of childhood circumstance, analysed using the maximum likelihood form of conditional logistic regression.
District general hospital (secondary care institution).
Subjects with Crohn's disease (n = 139) or ulcerative colitis (n = 137) aged between 16 and 45 years, each matched for sex and age with an outpatient control.
Helicobacter seroprevalence was substantially reduced in Crohn's disease (OR 0.18; 95% CI, 0.06-0.52) but not in ulcerative colitis (OR 0.91; 95% CI, 0.38-2.16). In ulcerative colitis, a strong negative association with childhood appendectomy was confirmed (OR 0.05; 95% CI, 0.01-0.51). Crohn's disease was associated with childhood eczema (OR 2.81; 95% CI, 1.23-6.42) and the frequent use of a swimming pool (OR 2.90; 95% CI 1.21-6.91). There was no association between hepatitis A seroprevalence and either disease.
The findings are consistent with the hypothesis that improved childhood living conditions are associated with increased risk of Crohn's disease. The study confirms that the negative association between appendectomy and ulcerative colitis relates primarily to events in childhood. Overall, the findings strongly support the assertion that childhood environment is an important determinant of the risk of inflammatory bowel disease in later life, with quite distinct risk factors for ulcerative colitis and Crohn's disease.
European Journal of Gastroenterology & Hepatology 06/2002; 14(5):529-34. · 1.76 Impact Factor
ABSTRACT: Objective: To determine the relative incidence and characteristics of endomysial antibody (EMA)-negative coeliac disease in adults.
Design: Retrospective analysis of prospectively collected data on adults with newly diagnosed coeliac disease, with determination of EMA status before gluten withdrawal.
Setting: District general hospital (secondary care institution).
Participants: Sixty consecutive incident cases.
Main outcome measures: (i) Proportion of cases who were EMA-negative; (ii) comparison of clinical and laboratory variables at diagnosis for EMA-positive and EMA-negative subjects.
Results: Fifteen subjects (25%, 95% CI 15-38%) were EMA negative, of whom only two were IgA deficient. There was clinical evidence in all 15 patients and histological evidence in 13 patients of a response to gluten withdrawal. No significant differences were found between EMA-positive and EMA-negative subjects with respect to histological features, age, gender, clinical manifestations, concurrent autoimmune disorders, family history of coeliac disease, or haemoglobin and albumin concentrations at diagnosis. However, EMA-negative status at diagnosis was associated strongly with current or recent cigarette smoking (OR 7.0, 95% CI 1.7-31.5, P = 0.003).
Conclusions: A substantial minority of patients with otherwise typical coeliac disease are EMA negative, and most of these are IgA replete. The value of EMA as a screening tool is therefore limited. EMA status in untreated coeliac disease correlates strongly with cigarette smoking history: this may be of pathogenic significance, given the previously demonstrated association between smoking and the risk of coeliac disease.
European Journal of Gastroenterology & Hepatology 05/2001; 13(6):667-671. · 1.76 Impact Factor