Silent Celiac Disease Research Articles

The many faces of celiac disease: Clinical presentation of celiac disease in the adult population

The major modes of presentation of patients with celiac disease are the classic diarrhea-predominant form and silent celiac disease. Those with silent celiac disease lack diarrhea, although they may present with manifestations of celiac disease that include an irritable bowel syndrome, anemia, osteoporosis, neurologic diseases, or malignancy. A significant proportion of patients are diagnosed through screening at-risk groups including relatives of patients and insulin-dependant diabetics. Nondiarrheal presentations now are seen more commonly than those with diarrhea. Patients with celiac disease have a greater burden of disease than the general population because of autoimmune diseases and malignancies. There is a need for screening studies of patients with conditions associated with celiac disease to determine whether the large numbers of people with undiagnosed celiac disease currently are seeking health care.

Consequences of testing for celiac disease

Population screening studies have identified that up to two thirds of celiac disease (CD) cases are asymptomatic. The aim of this study was to conduct a systematic review of the expected consequences of testing for CD in the following populations: (1) patients with symptoms suggestive of CD, (2) asymptomatic at-risk populations, and (3) general population. Standard systematic review methodology was used. A comprehensive literature search was conducted in MEDLINE (1996-2003), EMBASE (1974-2003), CAB (1972 forward), PsychINFO (1840-2003), AGRICOLA (1970-2003), and Sociological Abstracts (1963 forward); searches were conducted in December 2003. Pooled summary estimates were not calculated. The majority of the included studies were before-after studies, case control, or retrospective cohorts. The quality of evidence for the before-after studies is weaker. The overall strength of the evidence for this issue was fair to good. This area of research is relatively new, and further high-quality studies are required. The consequences of testing for celiac disease in symptomatic individuals appears to have a positive impact on patient-relevant outcomes. The data are less clear for those with silent CD or those with lower grade histologic lesions in small bowel biopsy. The literature suggests that compliance is less than ideal in these individuals, especially if diagnosed when adults. Long-term outcomes have not been extensively studied in those with silent CD.

Follow-up of patients with celiac disease: Achieving compliance with treatment

Celiac disease is the only autoimmune condition for which we know the environmental trigger: gluten. Complete removal of gluten from the diet in a patient with celiac disease should result in symptomatic, serologic, and histologic remission. However, compliance with the gluten-free diet, especially in the United States, is extremely challenging. Compliance can be measured both noninvasively, by dietary history and measurement of serum antibodies, and invasively, by using endoscopic and histologic criteria. The advantages and disadvantages of these various modalities are discussed. The highest rates of compliance are reported in patients who are diagnosed as young children, whereas adolescents and those diagnosed via mass serologic screening have the most transgressions. Barriers to compliance include the poor palatability of gluten-free foods, confusing food-labeling practices, and common comorbid psychologic burdens such as anxiety and depression. Because celiac disease is a multisystemic disorder, physicians need to be aware of the potential autoimmune, nutritional, and malignant complications. An algorithm for the follow-up and management of the newly diagnosed celiac disease patient is presented, which includes regular follow-up; measurement of serum antibodies; eliciting a detailed dietary history; and examination for signs and symptoms of nutritional deficiencies, malignancy, and other autoimmune diseases. Ideally, a team approach to the follow-up of the newly diagnosed patient should include regular supervision by an interested physician, medical nutritional counseling by a registered dietician, and access to local and national support groups knowledgeable about this condition.

Clinical presentation of celiac disease in the pediatric population

Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of gluten-containing grains (including wheat, rye, and barley) in genetically susceptible individuals. CD is associated with HLA molecules DQ2 (90%-95%) and DQ8 (5%-10%), and in the continued presence of gluten the disease is self-perpetuating. CD is one of the most common lifelong disorders worldwide and is characterized by a variety of clinical presentations. These include the typical malabsorption syndrome (classic symptoms) and a spectrum of symptoms potentially affecting any organ or body system (nonclassic symptoms). Because CD often is atypical or even clinically silent, many cases go undiagnosed and are exposed to the risk of long-term complications. There is growing interest in the social aspects of CD because the burden of illness related to this condition is doubtless higher than previously thought.

Immunoglobulin Isotype Profile of Tissue Transglutaminase Autoantibodies is Correlated with the Clinical Presentation of Coeliac Disease

Coeliac disease (CD) is characterized by the appearance of autoantibodies against tissue transglutaminase (tTG-Ab). Immunoglobulin A (IgA) tTG-Ab have been described as excellent diagnostic markers, but the Ig subclass distribution and the importance of isotype tTG-Ab have not yet been established. In this study, using newly developed isotype- and subclass-specific radioligand assays, we examined anti-tTG IgA1, IgA2, IgG1, IgG4 and IgE antibodies in 30 symptomatic, untreated patients with CD and 22 subjects suspected to suffer from silent CD (sCD). Among 30 patients with CD, 27 (90.0%) were positive for IgA1 tTG-Ab, whereas only 12 (40.0%) had autoantibodies of the IgA2 subclass (P <0.001). IgG1, IgG4 and IgE tTG-Ab were detected in 17 (56.6%), 0 and 3 (10.0%) individuals, respectively. IgA1 was also the predominant anti-tTG subclass in patients with sCD (n=20, 90.1%), followed by IgA2 antibodies (n=7, 31.8%), IgG1 antibodies (n=4, 18.2%), IgG4 antibodies (n=1, 4.5%) and IgE antibodies (n=1, 4.5%). The comparison between both groups revealed a significantly higher prevalence of IgG1 antibodies in patients with symptomatic CD (P <0.01). In 10 of 11 subjects undergoing an intestinal biopsy, the diagnosis of an sCD was confirmed. In this subgroup, there was a positive association between the presence of IgA2 and IgG1 tTG-Ab and severe (Marsh 2-3) mucosal abnormalities. In conclusion, patients with symptomatic and sCD predominantly have IgA1 tTG-Ab. IgG1 tTG-Ab are associated with symptomatic disease and, when present in patients with sCD, are correlated with a severe mucosal destruction. These data suggest that tTG-Ab subclasses could reflect inflammatory events associated with epithelial destruction.

Undiagnosed silent coeliac disease: A risk for underachievement?

Objective. Silent coeliac disease is reported in 1% of Caucasian populations, but there is a lack of knowledge of its natural course and the risk of complications. The need for population screening is debated. We sought for complications of untreated coeliac disease in a well-defined cohort of Finnish adults. Material and methods. Subjects (n=2427, ages 24–39 years) attending the 21-year follow-up visit of the study “Cardiovascular Risk in Young Finns” completed an extensive questionnaire on their health, diet, social situation and family life, and were given a medical examination. Measurement of serum IgA-transglutaminase and IgA-endomysium antibodies identified 21 subjects with silent coeliac disease. Results. The subjects with silent coeliac disease did not differ from the rest of the cohort in age, gender, stature, weight, medical diagnoses (autoimmune, malignant), health concerns, use of alternative medications, physical activity, or in the cause of death their parents. They had lower serum HDL-cholesterol (1.12 versus 1.29 mmol/L; p=0.015), as described for active coeliac disease. Fewer (5.3% versus 22.8%; p=0.047) had a university or college degree or worked in managerial or professional positions (28% versus 45%; p=0.112). Conclusions. The underachievement in education and working life observed in subjects with silent coeliac disease is a new and intriguing finding and may be related to the increased prevalence of depressive and disruptive behavioural disorders described in teenagers with untreated coeliac disease. Our findings add a new ingredient to the ongoing discussion regarding the need for population screening for silent coeliac disease.

Silent Celiac Disease in Chronic Hepatitis C

To assess the impact of interferon treatment on celiac disease onset in hepatitis C patients and to clarify its clinical relevance and outcome. Hepatitis C is associated with autoimmunity, which can be exacerbated by interferon treatment. Cases of celiac disease activation during interferon treatment have been reported. Retrospective evaluation of 534 hepatitis C patients with or without symptoms compatible with celiac disease onset during interferon treatment and 225 controls. Anti-transglutaminase antibodies were assayed. HLA-DQA1 and -B1 loci were typed. Upper gastrointestinal endoscopy was applied to confirm the diagnosis in antibody-positive patients. Anti-transglutaminase antibodies were detected before treatment in 1.3% of hepatitis C patients and in 0.4% of controls (not significant). Eighty-six percent of patients with anti-transglutaminase antibodies showed activation of celiac disease while on interferon. Symptoms ranged from mild to severe, and interferon had to be discontinued in 2 of 7 (29%) patients. Symptoms disappeared in 6 of 7 patients after interferon withdrawal. Onset of symptoms compatible with celiac disease during interferon therapy was significantly associated with the presence of anti-transglutaminase antibodies (OR 53). In hepatitis C patients, the activation of silent celiac disease during interferon treatment is almost universal and should be suspected, but it uncommonly requires interferon treatment discontinuation. Symptoms subside after interferon withdrawal.

Neurologic Complications of Celiac Disease

Source: Zelnik N, Pacht A, Obeid R, et al. Range of neurologic disorders in patients with celiac disease. Pediatrics. 2004;113:1672–1676.Investigators at the Carmel Medical Center in Haifa, Israel, sought to study the neurologic complications of celiac disease (CD) among a cohort of patients evaluated between 1977 and 2001. Patients with celiac disease [n=111] and controls [n=211] matched for age and gender were questioned regarding neurologic disorders, had their charts reviewed, and received neurologic evaluations, including brain imaging or electroencephalography, if indicated. Prior to 1988, diagnosis of CD was based on 3 consecutive intestinal biopsies. After 1988, the diagnostic approach was simplified and was based on immunoglobulin A antiendomysial antibodies and 1 intestinal biopsy. The mean age of patients and controls was 20.1 ± 9 years, and the male to female ratio was 2:3. The CD was classical infantile (diagnosed at 1.8 years) in 58 (52.3%) patients and later in onset (diagnosed at 14.8 years) in 53 (47.7%) patients. Neurologic disorders were found in 57/111 (51.4%) of patients with CD, whereas only 42/211 (19.9%) control subjects had abnormal neurologic findings. Patients with late-onset CD had more neurologic complications than the classical CD group (54.7% versus 48.3%), but the difference was not significant. Neurologic abnormalities and their frequency compared to controls included: hypotonia, 21.6% versus 3.8% (P<.01); developmental delay, 15.5% versus 3.3% (P<.01); seizures, 7.2% versus 0.8% (P<.09); learning disabilities and ADHD, 20.7% versus 10.5% (P<.01); headache, 27.9% versus 8.1% (P<.01); ataxia, 5.4% versus 0% (P<.01); and tics, 0.9% versus 2.4% (P=.67). Seizure disorders were more frequent with CD but not significantly, and tic disorders showed no increased prevalence. The gluten-free diet only benefited those CD patients with infantile hypotonia and migraine headache.The range of neurologic disorders associated with CD is wider than previously reported and includes chronic migraine headache, developmental delay, hypotonia in infants, learning disabilities, ADHD,1,2 and seizures. Apart from cases of epilepsy with occipital calcifications, recurrent seizures were not significantly correlated with CD.In occipital lobe seizures related to CD, the CD may be clinically asymptomatic.3 The incidence of silent CD in children with idiopathic localization epilepsies and the indications for routine CD screening were established in a study of 72 patients (mean age, 12.6 years) observed over a 5-year period.4 Two (8%) of 25 patients with childhood partial epilepsy with occipital paroxysms (CPEO) had positive IgA-antiendomysium antibodies, and jejunal biopsies showed villous atrophy and crypt hyperplasia, confirming the diagnosis of CD. Brain CT showed occipital calcifications in one. Seizures were controlled by treatment with a gluten-free diet, and no brain calcifications developed in the patient with a normal CT after a 3-year follow-up on a gluten-free diet.Forty-seven patients with childhood partial epilepsy with centrotemporal spikes (CPEC) had negative antibody tests for CD.4 CD screening is recommended in children with CPEO but not in those with CPEC and extraoccipital spikes. Early diagnosis and dietary intervention may reverse the tendency to seizures and brain calcifications. The gluten-free diet was also successful in the relief of migraine headaches. Wheat cereal is a known migraine trigger in some children5 and positive reactors should be screened for CD.The underlying pathophysiology linking gluten to neurologic disorders is not well characterized in this study, which refers only to its non-specific immunologic and inflammatory effects. Nonetheless, the association between gluten and brain disorders appears to be very strong, and some patients’ neurologic symptoms remit when gluten is removed from their diet. Thus, to separate the wheat of celiac disease-associated neurologic disorders from the chaff of the truly idiopathic, we must consider celiac disease as a possible etiology for a variety of neurologic presentations.

Prospective Population Screening for Celiac Disease: High Prevalence in the First 3 Years of Life

ABSTRACTBackground:Celiac disease (CD) is an autoimmune enteropathy that develops in genetically susceptible individuals exposed to gliadin. Early diagnosis of CD may reduce the risk of complications, and several studies have related the duration of gluten exposure to the risk of other autoimmune diseases. It has been proposed that silent CD be diagnosed as soon as possible to avoid potential complications.Objectives:The purpose of this study was to determine the prevalence of CD among children less than 3 years and to provide treatment to those patients diagnosed with CD.Patients and Methods:Parents of 1100 healthy children born between October 1998 and December 1999 were asked at the time of delivery to enroll their children in a program for the early diagnosis of CD. The parents of 830 children agreed to participate. Patients in the study were examined and anti–tissue transglutaminase antibody was first measured at about 1.5 years of age. A second antibody titer was obtained at about 2.5 years of age. Patients with detectable autoantibodies underwent intestinal biopsy for confirmation of CD.Results:Of the 830 children initially enrolled, 613 and 484 returned for the first and second visits, respectively. None had anti–tissue transglutaminase antibodies at the first visit, but 9 had anti–tissue transglutaminase immunoglobulins at the second visit. In 7 of these 9, intestinal biopsy confirmed the diagnosis of CD which suggests a minimum prevalence of CD of 1 per 118 healthy newborns.Conclusions:The authors observed a very high prevalence of CD, comparable to that observed in other European populations, which might even be higher if all of the children initially examined had returned for their second visit. If general screening for CD were accepted, the authors would recommend age 2–3 years as the best time for measuring tissue transglutaminase antibodies.

Prospective population screening for celiac disease: high prevalence in the first 3 years of life.

Celiac disease (CD) is an autoimmune enteropathy that develops in genetically susceptible individuals exposed to gliadin. Early diagnosis of CD may reduce the risk of complications, and several studies have related the duration of gluten exposure to the risk of other autoimmune diseases. It has been proposed that silent CD be diagnosed as soon as possible to avoid potential complications. The purpose of this study was to determine the prevalence of CD among children less than 3 years and to provide treatment to those patients diagnosed with CD. Parents of 1100 healthy children born between October 1998 and December 1999 were asked at the time of delivery to enroll their children in a program for the early diagnosis of CD. The parents of 830 children agreed to participate. Patients in the study were examined and anti-tissue transglutaminase antibody was first measured at about 1.5 years of age. A second antibody titer was obtained at about 2.5 years of age. Patients with detectable autoantibodies underwent intestinal biopsy for confirmation of CD. Of the 830 children initially enrolled, 613 and 484 returned for the first and second visits, respectively. None had anti-tissue transglutaminase antibodies at the first visit, but 9 had anti-tissue transglutaminase immunoglobulins at the second visit. In 7 of these 9, intestinal biopsy confirmed the diagnosis of CD which suggests a minimum prevalence of CD of 1 per 118 healthy newborns. The authors observed a very high prevalence of CD, comparable to that observed in other European populations, which might even be higher if all of the children initially examined had returned for their second visit. If general screening for CD were accepted, the authors would recommend age 2-3 years as the best time for measuring tissue transglutaminase antibodies.

351 Unexpected granulocytic myocarditis detected with endomyocardial biopsy manifesting as severe heart failure with conduction disease in a young patient with silent celiac disease

351 Unexpected granulocytic myocarditis detected with endomyocardial biopsy manifesting as severe heart failure with conduction disease in a young patient with silent celiac disease

Autoantibody testing in children with newly diagnosed type 1 diabetes mellitus.

To determine the role of autoantibody tests for autoimmune diseases in children with newly diagnosed type 1 diabetes mellitus. MEDLINE, EMBASE and the Cochrane Library. Citation lists of included studies were scanned and relevant professional and patient websites reviewed. Laboratories and manufacturers were contacted to identify ongoing or unpublished research. Following scoping searches on thyroid and coeliac autoantibodies, a systematic review of autoantibody tests for diagnosis of coeliac disease was carried out. Studies were included where cohorts of untreated patients with unknown disease status were included, all patients had undergone the reference test (biopsy) and antibody tests, and sensitivity and specificity were reported or calculable. Selected studies were then evaluated against a quality checklist. Summary statistics of diagnostic accuracy, i.e. sensitivity, specificity, positive and negative likelihood ratios and diagnostic odds ratios, were calculated for all studies. A decision analytic model was developed to evaluate the cost utility of screening for coeliac disease at diagnosis of diabetes. All antibody tests for diagnosis of coeliac disease showed reasonably good diagnostic test accuracy. Studies reported variable measures of test accuracy, which may be due to aspects of study quality, differences in the tests and their execution in the laboratories, different populations and reference standards. The decision analytic model indicated screening for coeliac disease at diagnosis of diabetes was cost-effective. Sensitivity analyses exploring variations in the cost and disutility of gluten-free diet, the utilities attached to treated and untreated coeliac disease and the decrease in life expectancy associated with treated and untreated coeliac disease did substantially affect the cost-effectiveness of the screening strategies considered. In terms of test accuracy in testing for coeliac disease, immunoglobulin A (IgA) anti-endomysium is the most accurate test. If an enzyme-linked immunoassay test was required, which may be more suitable for screening purposes as it can be semi-automated, testing for IgA tissue transglutaminase is likely to be most accurate. The decision analytic model shows that the most accurate tests combined with confirmatory biopsy are the most cost-effective, whilst combinations of tests add little or no further value. There is limited information regarding test accuracy in screening populations with diabetes, and there is some uncertainty over whether the test characteristics would remain the same. Further research is required regarding the role of screening in silent coeliac disease and regarding long-term outcomes and complications of untreated coeliac disease.

P0390 VARIABILITY OF HISTOLOGIC LESIONS IN RELATION TO BIOPSY SITE IN CELIAC DISEASE

Introduction: Histologic lesions of celiac disease (CD) range from increased intraepithelial lymphocytes (IEL) to crypt hyperplasia (CH) to villous atrophy (VA). It is believed that the optimal biopsy site for detection of VA is the distal duodenum or proximal jejunum and lesions may have a patchy distribution which could lead to misdiagnosis. We wanted to verify these concepts and establish whether biopsies should always be taken from these areas in order to make a diagnosis of CD. Methods: One-hundred and 12 consecutive children with positive anti-endomysium (EMA) or anti-tissue transglutaminase (tTGA) antibodies who had been referred for suspected CD were enrolled in a prospective fashion. All patients underwent upper GI endoscopy where 4–5 biopsies were taken sequentially with standard biopsy forceps from: Treitz and/or distal duodenum (T-D3), intermediate duodenum (D2), proximal duodenum (D1) and duodenal bulb (B). Biopsies were oriented, fixed in formalin, stained with H&E and subjected to immunohistochemistry with anti-CD3 antibodies for IEL count. Histologic lesions were classified according to Marsh criteria modified by Oberhuber. Results: One-hundred and 10 of 112 patients, all HLA DQ2 or DQ8 positive, had a final diagnosis of CD (59 classic, 28 atypical, 23 silent). Of these 110, 102 (92.7%) had VA with lesion type 3: a) mild, b) moderate or c) severe in at least one site and 94/110 (85.4%) had VA in all sites though with variable degree. VA of identical degree was present in all biopsy sites in 55/110 (50%) patients. Severe VA (type 3c) was present in at least one site in 85/110 (75%), in all sites in 50/110 (45.4%) and was distributed as follows: B 50/110 (45.4%), D1 48/110 (43.6%), D2 70/110 (63.6%), D3/T 83/110 (75.4%), with a significant increase in aborad direction (chi2>26.22 with a=0.01 and g.l.=12). Eight/110 (7.2%) CD patients had exclusively type 1 or 2 lesions (increased IEL ± CH), 9/110 (8.1%) had lesion variability = 1 degree (e.g. type 1 and 2, type 2 and 3a) but no patient had lesion variability >1 degree and none had normal biopsies. There was no statistically significant correlation between type or distribution of histologic lesions and clinical presentation of CD, though interestingly all patients with silent CD had type 3c lesions throughout the duodenum. Conclusion: Mucosal atrophy is present in 85% of CD patients and TVA is significantly more frequent in more distal areas (D3/T). However, in half of the patients VA has the same degree throughout the duodenum including B, and no duodenal areas are histologically normal. Therefore, in genetically susceptible children with positive serology, a diagnosis of CD can reliably be made aven if biopsies are not taken from the distal duodenum or jejunum.

P0411 USING RADIOLIGAND BINDING ASSAYS TO MEASURE TISSUE TRANSGLUTAMINASE ANTIBODIES IN YOUNG CHILDREN

Introduction: Celiac disease (CD) is a chronic small bowel disease affecting 1% of children in Sweden (1). The clinical presentation may range from severe gastrointestinal symptoms to asymptomatic variants defined as silent CD. In this prospective screening two methods were used for identifying young children with potential CD: Immunoglobulin (Ig) A antibodies against endomysium (EMA) together with total-IgA and the combination of IgA and IgG antibodies against tissue transglutaminase (tTG). The aim was to determine if IgA-tTG and IgG-tTG analysed with radioligand binding assays (RBA) can be used as an alternative method to conventional EMA and total-IgA in screening of children for silent CD. Methods: Blood samples were obtained from 652 normal children (320 girls, 332 boys) aged 2.9 (2.5–4.2) years without previously known CD. Sera were analysed for EMA by indirect immunofluorescence and for total IgA with a nephelometric assay. The RBA method measured IgA-tTG and IgG-tTG. A second blood sample was obtained from antibody positive children. Children with persistently high antibody levels were offered intestinal biopsy. Results: In total, 3.2% (95% CI=1.9–4.6%) (21/652) children were positive for at least one antibody at baseline: 2.5% (95% CI=1.3–3.7%) (16/652) for IgA-tTG, 1.7% (95% CI=0.7–2.7%) (11/652) for IgG-tTG and 2.9% (95% CI=1.6–4.2%) (19/652) for EMA, respectively. Ten children were positive for all three antibodies, 5 for both IgA-tTG and EMA, 4 for EMA only, 1 for IgA-tTG and 1 child with IgA deficiency for IgG-tTG. A second blood sample were taken after 1.2 (0.2–1.9) years from all but one child with antibodies at baseline. Seven of 20 children remained positive for all three antibodies, 3 for IgA-tTG only, 1 for both IgA-tTG and EMA, 1 for IgA-tTG and IgG-tTG and 1 child refused further participation. Three biopsies showed villous atrophy, 2 increased intraepithelial lymphocytes and 2 normal findings. Biopsy was not performed in 4 children with low or declining tTG antibody levels at follow-up and in 1 child who declined. CD was evident in 0.5% (95% CI=0.0–1.0%) (3/652). Conclusion: A high number of young children were found to be positive for both tTG antibodies, as well as EMA, in this prospective screening for CD. The majority showed declining levels in antibodies over time and children with transient seropositivity were detected. RBA could be used as an alternative method for quantitative measurement of IgA-tTG and IgG-tTG when change in antibody levels is studied in children.

Searching for coeliac disease in patients with non-alcoholic fatty liver disease

Background. A non-negligible percentage of patients with non-alcoholic fatty liver disease, a leading cause of hepatic progressive disorder related to insulin resistance, have no metabolic risk factors, and abnormal intestinal permeability has been suggested to be involved in the pathogenesis of the liver damage. Coeliac disease, a curable disorder characterised by inflammatory mucosal damage, may show hepatic histological features similar to steatohepatitis. Conflicting data have been reported on the prevalence of coeliac disease in non-alcoholic steatohepatitis. Aim. To search for coeliac disease in a series of patients with non-alcoholic fatty liver disease by screening with anti-tissue transglutaminase and anti-endomysium antibodies. Patients and methods. Fifty-nine consecutive patients with hypertransaminasemia and non-alcoholic fatty liver disease, 38 (64%) with steatohepatitis. Anti-endomysium antibodies were assayed by indirect immunofluorescence, IgA anti-tissue transglutaminase by ELISA. Patients who tested positive underwent HLA DQ typing and endoscopy. Results. Tissue transglutaminase antibodies were positive in six (10%) patients and anti-endomysium in two (3.4%); only two (3.4%), positive for both anti-endomysium positive and anti-transglutaminase, resulted to have coeliac disease based on histological findings. After 6 months of gluten-free diet, liver enzymes normalised. Conclusions. The prevalence of silent coeliac disease is 3.4% in patients with non-alcoholic fatty liver. The inclusion of anti-endomysium antibodies test in studying patients with non-alcoholic fatty liver and persistent biochemical abnormalities has to be taken into account, since positivity for tissue transglutaminase antibodies, in the absence of confirmatory anti-endomysium antibodies, is not sufficient to perform diagnostic endoscopy.

The iceberg cometh: Establishing the prevalence of celiac disease in the United States and Finland

The iceberg cometh: Establishing the prevalence of celiac disease in the United States and Finland

Screening for asymptomatic celiac disease among patients referred for bone densitometry measurement

Celiac disease (CD) is a relatively common gastrointestinal disorder that can be asymptomatic. An increased prevalence of subclinical CD has been reported in many populations. Even among asymptomatic patients a reduction in bone mineral density (BMD) has been observed. The aim of this study was to evaluate the prevalence of silent CD in a cohort of consecutive individuals referred for bone densitometry measurement. Serum samples were taken from 454 women attending for bone densitometry (mean age: 56 ± 11 years). Of the individuals evaluated, 89 had normal BMD and 365 had low BMD ( T score < −1.0). Subjects were screened for the presence of serum IgA anti-endomysial antibodies (EMA) and IgA tissue transglutaminase (tTG) antibodies by indirect immunofluorescence and enzyme-linked immunosorbent assay (ELISA), respectively. BMD was measured by dual X-ray absorptiometry (DEXA) at the lumbar spine and femoral neck. Eight EMA tTG-positive individuals were identified in this population (1.8% or 1:57). Serologically positive women had a lower mean Z score at both the lumbar spine and femoral neck than EMA tTG-negative women. But this did not approach significance. There was no significant difference in the incidence of CD between the normal- and low-BMD groups in this dataset ( P = 0.365). In conclusion, our study indicates that the prevalence of CD in our dataset is high. However, the frequency of asymptomatic CD among low-BMD individuals is similar to that among normal-BMD individuals in our population. These observations do not support the hypothesis that serological testing for CD may be a good accompaniment to DEXA scanning.

The liver in celiac disease.

The liver in celiac disease.

Prevalence of Celiac Disease and Follow‐up of EMA in Children and Adolescents With Type 1 Diabetes Mellitus

ABSTRACTBackground:The prevalence of celiac disease (CD) in children with diabetes mellitus type 1 (DM) is significantly higher than in the nondiabetic population. Most patients with DM and associated CD do not experience typical gastrointestinal symptoms of CD. There is no agreement on the necessity of screening and management of silent CD for patients with DM or on the time scale for screening. Only few data on follow‐up evaluation of children with DM and CD‐related antibodies are available.Methods:One hundred fifty‐seven patients with DM (mean age, 14.8 years; range, 4‐21 years; male, 83) were screened with endomysial antibodies (EMA) between 1993 and 2001. A follow‐up period of at least 3 years, with at least 2 EMA measurements, was possible. Group 1 comprised 37 patients whose first measurement was at the onset of DM. Group 2 comprised 120 patients whose first measurement was during the course of the disease. In patients with positive EMA, small bowel biopsy was performed. Thyroid peroxidase (TPO), thyroglobulin (TgA), glutamate decarboxylase (GAD), antiinsulin (IAA), and islet cell antibodies (IA2) were measured in all patients.Results:EMA was positive in 16 patients, in 5 at onset of DM and in 11 during the course of DM (mean duration, 33.6 months; range, 11‐105 months). Biopsy results showed normal mucosa in seven patients, increased intraepithelial lymphocyte counts in one, and flat mucosa in eight. There was no significant difference between EMA‐positive and EMA‐negative patients regarding height, weight, HbA1c level, frequency of hypoglycemia or hyperglycemia, TPO, TgA, GAD, IAA, or IA2.Conclusion:This study emphasizes the high prevalence of CD in patients with DM. Although several patients already had positive EMA titers at the onset of DM, seroconversion may also occur during the course of the disease. Screening for CD with EMA or tissue transglutaminase should be included in the initial investigation of DM, but should also be repeated over time to detect late seroconversion. JPGN 37:67‐71, 2003.

Prevalence of celiac disease and follow-up of EMA in children and adolescents with type 1 diabetes mellitus.

The prevalence of celiac disease (CD) in children with diabetes mellitus type 1 (DM) is significantly higher than in the nondiabetic population. Most patients with DM and associated CD do not experience typical gastrointestinal symptoms of CD. There is no agreement on the necessity of screening and management of silent CD for patients with DM or on the time scale for screening. Only few data on follow-up evaluation of children with DM and CD-related antibodies are available. One hundred fifty-seven patients with DM (mean age, 14.8 years; range, 4-21 years; male, 83) were screened with endomysial antibodies (EMA) between 1993 and 2001. A follow-up period of at least 3 years, with at least 2 EMA measurements, was possible. Group 1 comprised 37 patients whose first measurement was at the onset of DM. Group 2 comprised 120 patients whose first measurement was during the course of the disease. In patients with positive EMA, small bowel biopsy was performed. Thyroid peroxidase (TPO), thyroglobulin (TgA), glutamate decarboxylase (GAD), antiinsulin (IAA), and islet cell antibodies (IA2) were measured in all patients. EMA was positive in 16 patients, in 5 at onset of DM and in 11 during the course of DM (mean duration, 33.6 months; range, 11-105 months). Biopsy results showed normal mucosa in seven patients, increased intraepithelial lymphocyte counts in one, and flat mucosa in eight. There was no significant difference between EMA-positive and EMA-negative patients regarding height, weight, HbA1c level, frequency of hypoglycemia or hyperglycemia, TPO, TgA, GAD, IAA, or IA2. This study emphasizes the high prevalence of CD in patients with DM. Although several patients already had positive EMA titers at the onset of DM, seroconversion may also occur during the course of the disease. Screening for CD with EMA or tissue transglutaminase should be included in the initial investigation of DM, but should also be repeated over time to detect late seroconversion.