Complications of coeliac disease: are all patients at risk?

Coeliac disease is a common condition that is increasingly being recognised as a result of the development of sensitive and specific serology. The diagnosis of coeliac disease and its subsequent treatment with a gluten-free diet have implications for the patient, not just for symptom control but also for the possible effect on quality of life and risk of complications. Whether the mode of presentation of coeliac disease has an effect on survival or risk of complication is yet unclear. This article reviews the available evidence regarding these issues.

High prevalence of celiac disease in patients with type 1 diabetes detected by antibodies to endomysium and tissue transglutaminase.

OBJECTIVE: To establish the prevalence of celiac disease (CD) in children with type 1 diabetes in British Columbia. PATIENTS AND METHODS: Two hundred thirty-three children with type 1 diabetes were prospectively screened for CD using blind testing with the current 'gold standard', immunoglobulin A endomysium antibody (EmA), and the novel immunoglobulin A tissue transglutaminase (tTG) antibody. Those children with positive results were offered small bowel biopsy; a gluten-free diet was recommended if CD was confirmed. RESULTS: Nineteen children were positive for EmA and had an elevated tTG level. One patient from this group was already known to have CD, and the other 18 patients consented to biopsy. One biopsy was normal, three biopsies demonstrated elevated intraepithelial lymphocyte counts with normal morphology and 14 biopsies had morphological changes consistent with CD. Growth parameters were normal in all patients, and nine of 19 children who were positive for EmA were asymptomatic. Seven patients had mild elevation of tTG levels alone. Two children from this latter group had normal biopsies, and five declined biopsy. CONCLUSIONS: At least 14 new cases of CD were detected in addition to four known cases, yielding an overall biopsy-confirmed prevalence of CD of 7.7% (18 of 233). The present study confirms that CD is as prevalent in the pediatric type 1 diabetic population in British Columbia as it is in Europe. Serological screening of these children is important because many children have no symptoms or signs suggestive of CD. This study suggests that tTG serology may also be useful in monitoring response and compliance with a gluten-free diet.

Increased prevalence of celiac disease in girls with Turner syndrome detected using antibodies to endomysium and tissue transglutaminase.

OBJECTIVE: To establish the prevalence of celiac disease (CD) in girls with Turner syndrome (TS) in British Columbia. METHODS: Forty-five girls with TS were prospectively screened for CD using blinded testing with the current 'gold standard' - immunoglobulin A (IgA) endomysium antibody (EmA) and the novel IgA tissue transglutaminase antibody (tTG). Those with positive results were offered small bowel biopsies, and a gluten-free diet was recommended if CD was confirmed. RESULTS: One asymptomatic prepubertal East Indian girl was positive for EmA, had an elevated tTG concentration of 560 U/mL and histological evidence of CD. Seven girls were negative for EmA but had elevated tTG concentrations (175 to 250 U/mL); five were white, one was Asian and one was East Indian. Small bowel biopsies were performed on three girls, and the histologies were normal. The remaining four patients declined biopsy. CONCLUSIONS: One girl with TS was identified with CD from 45 screened, giving an overall biopsy-confirmed prevalence of 2.2%. This study confirms previous observations placing girls with TS at higher risk for CD and suggests a similar high prevalence in British Columbia.

Prevalence of celiac disease in collagenous and lymphocytic colitis.

Both collagenous and lymphocytic colitis have been described in patients with celiac disease, suggesting an association between the conditions. Over the past few years, the availability, sensitivity and specificity of serological markers for celiac disease have improved - the most recent advancement being the description of tissue transglutaminase as the major antigen for endomysium antibody. A quantitative ELISA was used to measure titres of immunoglobulin A (IgA) antibody to tissue transglutaminase (tTG) along with an immunofluorescent technique for IgA endomysium antibody (EmA) in 15 patients with lymphocytic colitis and eight with collagenous colitis to determine whether celiac disease latency could be detected. One patient with lymphocytic colitis demonstrated both elevated titres of tTG antibody and positive EmA, and small bowel biopsy confirmed celiac disease. One patient with collagenous colitis had a slightly elevated titre of tTG antibody with a negative EmA, and results of a small bowel biopsy were normal. Three other patients with lymphocytic colitis were already treated for previously diagnosed celiac disease. The prevalence of celiac disease occurring in lymphocytic colitis was found to be 27%, but no cases of celiac disease in association with collagenous colitis were found.

Comparison of IgA endomysium antibody and IgA tissue transglutaminase antibody in celiac disease.

The antigen for immunoglobulin (Ig) A endomysium antibody (EmA), a sensitive and specific serological marker for celiac disease, has recently been described as tissue transglutaminase (tTG). The aim of this study was to compare the assays used to measure IgA EmA and IgA tTG antibody in patients with celiac disease and disease control subjects. Sera from 21 patients with untreated celiac disease, 48 patients with treated celiac disease and 128 disease control subjects were tested both for IgA EmA with the use of indirect immunofluorescence against human umbilical cord and for IgA tTG antibody with the use of ELISA. Titres of IgA tTG antibody were significantly higher in both the untreated and treated celiac groups than in the disease control group. Titres in the treated group were, however, significantly lower than in the untreated group. A reference range was calculated to include 99.8% of the disease control group in whom small bowel biopsy showed no evidence of celiac disease. One patient from the disease control group with raised IgA tTG antibody titres and positive IgA EmA was found to have celiac disease on small bowel biopsy. The sensitivity, specificity, and positive and negative predictive values of the IgA EmA assay were all 100%. The sensitivity of the IgA tTG antibody assay was 95%, specificity 100%, positive predictive value 100% and negative predictive value 97.7%. An ELISA used to measure IgA tTG antibody is an excellent tool to screen for celiac disease and may prove useful for monitoring response to treatment.

Prevalence of IgA antibodies to endomysium and tissue transglutaminase in primary biliary cirrhosis.

The association between celiac disease and primary biliary cirrhosis has been described in several case reports and small screening studies, with varying prevalence rates. Stored sera from 378 patients with primary biliary cirrhosis were tested for immunoglobulin (Ig) A endomysium and tissue transglutaminase antibodies. Ten patients were positive for both antibodies (2.6%); five of these patients had had small bowel biopsies confirming celiac disease. A further 44 patients (11.6%) had raised titres of IgA tissue transglutaminase antibody but were negative for IgA endomysium antibody. The increased prevalence of celiac-related antibodies in patients with primary biliary cirrhosis suggests that the two conditions are associated, although the reason for the association remains unclear. Patients with primary biliary cirrhosis should be considered to be at high risk for celiac disease. Although liver biochemistry does not improve when these patients are fed a gluten-free diet, the complications of untreated celiac disease warrant the identification and treatment of the condition in this population.

Serological testing in screening for adult celiac disease.

Assays for celiac-related antibodies are becoming widely available, and the present review aims to clarify the use of these investigations in the diagnosis of, management of and screening for adult celiac disease. The sensitivities and specificities of various antibody tests are discussed, along with their clinical use as an adjunct to small bowel biopsy, and as a first-line investigation for patients with atypical symptoms of celiac disease or patients at high risk of developing sprue.

New polyethylene glycol electrolyte solution for the treatment of constipation and faecal impaction.

Results from a controlled clinical trial indicate that low doses of polyethylene glycol solutions are more effective and have fewer side-effects than lactulose. Large doses of polyethylene glycol are effective in the treatment of faecal impaction. Resolution of faecal impaction was obtained in all patients, and in 25/30 patients with three administrations in a three-day period.

Autoantibodies to tissue transglutaminase as predictors of celiac disease.

BACKGROUND & AIMS: Immunoglobulin A (IgA) autoantibodies to endomysium (EMA) are highly specific and sensitive markers for celiac disease. Recently, we identified tissue transglutaminase (tTG) as the major if not sole endomysial autoantigen. METHODS: An enzyme-linked immunosorbent assay (ELISA) was established to measure IgA anti-tTG titers in serum samples from 106 celiac patients with partial or subtotal villous atrophy, 43 celiac patients on a gluten-free diet, and 114 diseased and healthy controls. Results were correlated with clinical and histological data and with EMA titers. RESULTS: In patients with biopsy-proven celiac disease consuming a normal, gluten-containing diet, 98.1% of the serum samples had elevated IgA titers against tTG, whereas 94.7% of the control sera were negative. IgA anti-tTG correlated positively with semiquantitative IgA EMA titers (r = 0.862; P < 0.0001). CONCLUSIONS: An ELISA based on tTG allows diagnosis of celiac disease with a high sensitivity and specificity. IgA anti-tTG and IgA EMA show an excellent correlation, further confirming the enzyme as the celiac disease autoantigen. Because the assay is quantitative, not subjected to interobserver variation, and easy to perform, it will be a useful tool for population screening of a hitherto underdiagnosed disease.

Highly effective new oral therapy for faecal impaction.

We reasoned that relief of faecal impaction could be achieved if a bolus of polyethylene glycol/electrolyte solution was delivered to the caecum over a few hours. Thus, 16 patients with faecal impaction (duration of constipation 5-23 days) were treated in an open study with up to three daily treatments of one litre of polyethylene glycol/electrolyte solution daily, taken orally over 4-6 hours. Complete resolution of impaction, strictly defined, was obtained in 13 patients, and significant improvement in the other three. Only one patient was faecally incontinent and the only side-effect was an increase in borborygmi. Polyethylene glycol/electrolyte solution, given as a treatment dose of one litre daily for up to three days, is a highly effective and acceptable oral therapy for faecal impaction.

Heterogeneity of celiac disease: clinical, pathological, immunological, and genetic.

In this paper we consider recent new data on the pathological features of gluten sensitivity and on the disease-associated antigens, in the context of a multistage hypothesis that we have been developing for the last five years. This incorporates concepts of oral tolerance induction, mucosal T-cell and antibody-mediated injury, and genetic contributions. Until now, there has been complete agreement that the diagnosis of celiac disease must be based on small bowel histology. There are patients with low-grade gluten-sensitive enteropathy, in whom the only morphological abnormality is a high count of intraepithelial lymphocytes (IEL). Some, but not all, also have positive serum IgA anti-endomysium antibody (AEA). With good techniques, in a properly accredited laboratory, in a patient suspected on clinical grounds to have celiac disease, a positive serum IgA AEA test (perhaps, alternatively, high-titer anti-transglutaminase by ELISA), is virtually diagnostic of the condition. Our hypothesis of a stepwise pathogenesis of severe gluten-sensitive enteropathy is re-examined in the light of these new data. It is evident that there are at least five different levels at which genetic influences may operate.