Endomysial Antibody Test Research Articles

Orally Based Diagnosis of Celiac Disease: Current Perspectives

Celiac disease (CD) is a lifelong immune-mediated disorder caused by the ingestion of wheat gluten in genetically susceptible persons. Most cases of CD are atypical and remain undiagnosed, which exposes the individuals to the risk of life-threatening complications. Serologic endomysial and tissue transglutaminase antibody tests are used to screen at-risk individuals, although a firm diagnosis requires demonstration of characteristic histopathologic findings in the small-intestinal mucosa. A gluten challenge, with a repeat biopsy to demonstrate recurrence of histopathologic changes in the intestinal mucosa after the re-introduction of gluten, is considered for those persons in whom diagnosis remains in doubt. In this paper, we review studies that evaluated: (1) the possibility of using oral mucosa for the initial diagnosis of CD or for local gluten challenge; and (2) the possibility of using salivary CD-associated antibodies as screening tests. Our review shows that orally based diagnosis of CD is attractive and promising, although additional evaluations with standardized collection and analysis methods are needed. There is some evidence of a dissociation between systemic and oral mucosal immune responses in CD. The hypothesis that gluten could stimulate naive lymphocytes directly in the oral cavity would have important implications for the understanding, diagnosis, and management of CD.

Is there any requirement for celiac disease screening routinely in postmenapausal women with osteoporosis?

Screening studies indicate a prevalence of celiac disease (CD) of up to 1% in populations of European ancestry, yet the majority of cases remain undiagnosed. One of the common complication of CD is intestinal osteopathy or osteoporosis [bone mineral density (BMD) based diagnosis]. Available data regarding the prevalence of CD in the patients with osteoporosis are limited and controversial. The objective of this study was to perform serological testing to screen for CD among postmenopausal women with osteoporosis. We studied 192 postmenopausal women with low BMD with a mean age of 62.75 +/- 8.58 years. Among the patients, a total of 137 had osteoporosis and 55 had osteopenia. Venous blood samples were obtained for serological screening of CD and evaluation of bone metabolism. The serological screening protocol consisted of determining serum level of IgA antigliadin antibodies (AGA), IgG-AGA, IgA endomysial antibody (EMA), IgG-EMA. Subjects who were positive for both IgA-AGA and IgA-EMA were classified as having CD. Bone metabolism was evaluated by serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone, 25 (OH) vitamin D, osteocalcin, serum C-telopeptide cross-linked collagen type I levels. Of the 192 patients evaluated, only one (0.5%) was found to have positive for both IgA-AGA and IgA EMA tests and accepted as having CD. Prevelance of CD in postmenopausal women with low BMD (0.5%) did not differ from prevelance of CD in normal healthy population (0.3-1%). BMD values at proximal femur level were significantly lower in IgA-AGA (+) patients when compared to IgA-AGA (-) patients. However, the mean levels of bone metabolism markers were found similiar in both IgA-AGA (+) and (-) patients. In conclusion, the results of our study suggest that there is no need for routine screening of CD in postmenopausal women with osteoporosis.

Comparison of a Novel Whole Blood Transglutaminase‐based ELISA With a Whole Blood Rapid Antibody Test and Established Conventional Serological Celiac Disease Assays

Serum immunoglobulin A-class tissue transglutaminase (tTG-ab) and endomysial antibody (EMA) tests play a key role in the diagnostic evaluation of celiac disease. Recently, a novel whole blood rapid test based on self-tissue transglutaminase (tTG) was developed for celiac disease case finding. Based on the same principle, a whole blood self-tTG enzyme-linked immunosorbent assay (ELISA), especially applicable to large-scale screening of celiac disease, has been produced. We assessed the value of this new test in celiac disease antibody detection. The new test uses endogenous tTG found in red blood cells of whole blood in IgA-class tTG-ab measurement by detecting tTG-tTG-ab complexes formed after hemolysis of the whole blood sample. Stored whole blood samples from 150 untreated celiac disease patients and 107 control individuals without celiac disease were evaluated, and the test results were compared with those of the whole blood rapid test, 2 conventional serum-based tTG-ab ELISA tests, and 2 EMA tests. A total of 15 whole blood samples were found to be clotted or dried after storage and were excluded from further evaluation. The whole blood ELISA test had a specificity (98%) comparable to that of the conventional serological tests, the sensitivity (91%) being slightly lower. The test was concordant with the whole blood rapid test in 92% of cases, with 2 serological ELISA tests in 91% and 94% of cases and with EMA tests in 94% and 93% of cases. Whole blood self-tTG-based testing is accurate in celiac antibody detection, also when an ELISA method is applied. The testing requires no serum separation or external tTG.

A “Case” of Granuloma

Purpose: Case Presentation: A 22 year old Vietnamese immigrant in Canada for 16 years presented with a 5 month history of abdominal pain, weight loss and diarrhea. History was negative for medical problems, medication and drug use, smoking, alcohol, gastrointestinal bleeding, constitutional symptoms, infectious contacts, recent travel and extraintestinal manifestations of inflammatory bowel disease (IBD). Family history was negative for tuberculosis, IBD and colon cancer. Physical exam showed a pale, cachectic, afebrile, hypotensive (88/54) man with no postural drop. There was mild left lower quadrant tenderness and no lymphadenopathy. Lab investigations revealed hemoglobin 117 g/L, white blood cell count 20.6 × 109/L, neutrophil count 16.9 × 10∧9/L, mean corpuscular volume 79.1 fL and serum albumin 29 g/L. Remaining blood tests including electrolytes, creatinine, liver enzymes, amylase and TSH were within normal limits. Serum endomysial antibody and stool testing were negative. Colonoscopy showed a fistulous opening at the base of the cecum, marked mucosal nodularity with multiple pseudopolyps, deep ulcers and areas of denudation in the cecum, ascending and mid-transverse colon. Corticosteroid therapy was deferred due to possibility of tuberculosis. Intestinal biopsies showed moderate acid-fast bacillus with necrotizing granulomas. Nucleic acid amplification test was positive for Mycobacterium tuberculosis complex. The patient's gastrointestinal symptoms improved with antituberculous treatment and he made a full recovery. Discussion: Our case illustrates three important principles in the diagnosis and treatment of gastrointestinal tuberculosis (GI TB). First, tuberculosis infection should be considered in patients with clinical, endoscopic, radiological and histopathological features of Crohn's disease, especially where there is a predominance of ileal and cecal involvement. Immigration from a country with known endemic tuberculosis is an important risk factor, even if immigration is a remote event. Nonspecific symptoms of GI TB include fever, night sweats, weight loss, abdominal pain and diarrhea. Diagnosis of GI TB is based on detection of acid-fast bacilli in tissue or stool. Second, it is important to exclude the possibility of tuberculosis before the commencement of corticosteroid therapy, often used in the treatment of IBD, since corticosteroid therapy will increase morbidity of the patient with GI TB. Third, treatment of GI TB is primarily medical and although complications such as fistula formation, perforation and hemorrhage may require surgery, it is possible to treat gastrointestinal fistulae due to tuberculosis successfully with medical therapy alone.

Predictors of Family Risk for Celiac Disease: A Population-Based Study

There is an elevated prevalence of celiac disease (CD) in family members (FMs) of CD patients, but most prior studies have been done on selected populations. Our aim was to determine the clinical, serologic, and genetic predictors of CD in FMs of a population-based cohort of index cases. Index cases from southeast Minnesota provided contact information for their first-degree relatives. FMs were examined for endomysial antibodies (EMAs), tissue transglutaminase antibodies (tTGAs), and HLA-DQ genotyping. Two questionnaires were applied, Bowel Disease Questionnaire and Short Form Health Survey. Intestinal biopsies were offered if there were any positive autoantibody or seronegative FMs with gastrointestinal symptoms and HLA-DQ at risk for CD. We recruited 111 index cases that had 579 FMs, of whom 344 (59%) were investigated. The average screening rate among families was 65%. A positive tTGA test was found in 47 (14%), 33 with a positive EMA test. CD was diagnosed in 39 (21 males), with an estimated prevalence of 11% (lambda(R) = 16.1). All affected FMs carried the at-risk genotypes. Twenty-one (54%) had "silent" disease, most with severe intestinal villous atrophy. Carrying HLA-DQ2 (odds ratio, 16.1; 95% confidence interval, 2.1-123) and being a sibling (odds ratio, 2.5; 95% confidence interval, 1.1-5.8) are high-risk factors for CD. CD is more common in first-degree relatives than previously reported in the United States, with siblings having the greatest risk. There is male preponderance of new cases, and many had silent disease despite severe histologic injury. A more proactive case-finding strategy in FMs might improve the diagnostic rate of CD in North America.

Prevalence of iron deficiency anemia in chronic diarrhoea and celiac disease - a western UP experience.

To study the prevalence of iron deficiency anaemia in chronic diarrhoea and celiac disease. Cases included 45 children between 1-12 years with chronic diarrhoea, who underwent investigations like haemogram with GBP, RBC indices, serum iron and TIBC. After a course of antibiotic therapy for 6 weeks with iron and folic acid with no improvement noted within 2 weeks, they were subjected to duodenal biopsy. If biopsy showed features of celiac disease, then anti-endomysial antibody test was performed to substantiate the diagnosis. 30 cases (66.7%) were males and 15 (33.3%) females. 8 cases (17.8%) had watery diarrhoea, 20 (44.4%) semiformed and 17 (37.8%) had watery and semiformed diarrhoea. Bloody diarrhoea was present in 5 (11.1%) and abdominal distension in 21 cases (46.7%). Pallor seen in all the cases. The mean age of the cases was 55 ± 1.5 months and mean duration of diarrhoea was 18 ± 1.4 months. Mean haemoglobin observed was 8.1 ± 1.6 gm%. MCV, MCH and MCHC were 79.1 ± 8.6 fl, 26.9 ± 3 pg and 29.6 ± 2.3 g/dl respectively. Mean serum iron was 32.1 ± 1.2 g/ dl and TIBC was 432 ± 3.2 g/ dl. On peripheral smear, 28 cases (82.4%) showed microcytic hypochromic anaemia. 26 cases showed evidence of celiac disease on duodenal biopsy. Anti endomysial antibody (AEA) test was positive in 15 of the 19 celiac cases on which performed. Mean duration of diarrhoea (23.5 months) was significantly more in celiacs as compared to non-celiacs (11.6 months). Better awareness of the clinical profile and early detection of celiac disease would help detection and management of iron deficiency anaemia associated with celiac disease.

What Is the Role of Serologic Testing in Celiac Disease? A Prospective, Biopsy-Confirmed Study With Economic Analysis

The optimal serologic tests for the detection of celiac disease and follow-up assessment remains controversial. Our aim was to evaluate all current immunologic assays for diagnosing celiac disease using the gold standard of duodenal biopsy. We also assessed whether tissue transglutaminase (tTG) antibody is a quantitative marker for histologic severity. Consecutive adult patients referred for gastroscopy without a previous known diagnosis of celiac disease were recruited (group 1). Concurrently, patients with a known diagnosis of celiac disease on a gluten-free diet for more than 1 year undergoing repeat duodenal biopsy were identified (group 2). All patients had duodenal biopsies and serologic analysis performed for immunoglobulin(Ig) A and antibodies to human immunoglobulin (Ig)A-tTG, IgA-gliadin, IgG-gliadin, and IgA-endomysial antibody. Two thousand patients were recruited in the first group. Seventy-seven (3.9%) patients were diagnosed with new celiac disease. The sensitivity, specificity, positive predictive value, and negative predictive value for IgA tTG were 90.9%, 90.9%, 28.6%, and 99.6%. When adopting a 2-step approach using tTG first and then EMA the sensitivity, specificity, positive predictive value, and negative predictive value was 85.7%, 98.6%, 71.7%, and 99.7%, respectively. The use of nondeamidated IgA/IgG gliadin antibodies conferred no additional diagnostic benefit when considering the detection of adult celiac disease. In the second group 48 patients with celiac disease on a gluten-free diet were identified. Sixteen of 48 of these patients had persisting villous atrophy, but 7 of 16 (44%) had a normal tTG level. IgA tTG alone is a sensitive marker for celiac disease. A normal tTG level does not predict recovery of villous atrophy in patients with celiac disease on a gluten-free diet.

Performance of a new rapid whole blood coeliac test in adult patients with low prevalence of endomysial antibodies

Background In coeliac disease endomysial and transglutaminase autoantibodies are directed against the human autoantigen, transglutaminase. The conventional coeliac antibody tests are performed from serum samples in centralized laboratories. Aims To evaluate a rapid and easy immunoglobulin A-class whole blood point-of-care test and its commercial application, the Biocard test, in coeliac autoantibody detection. Methods In the whole blood point-of-care test transglutaminase is liberated from the red blood cells by haemolysis. Transglutaminase antibodies, if present, complex with the liberated antigen, and are visualized. Altogether 51 biopsy-proven untreated coeliac adult patients, 48 of the same patients after treatment, and 36 controls were tested. The point-of-care test results were compared with serum endomysial and transglutaminase antibody and Biocard test results and histology. Results The whole blood point-of-care test was as sensitive (82%) as the serum endomysium test (80%) in detecting untreated coeliac disease while the serum transglutaminase antibody test was superior (88%). The tests had 100% specificity. A positive point-of-care test result seroconverted or the test reaction weakened in 90% of the treated coeliac patients. Biocard test-positive were 22 of the 24 tested untreated coeliac patients. Biocard test-negative were 15 of 19 controls. Conclusions The whole blood rapid tests are as reliable as the conventional serological tests in detecting untreated coeliac disease and in coeliac disease diet monitoring.

Celiac Disease: Are Endomysial Antibody Test Results Being Used Appropriately?

The aim of this study was to retrospectively examine how positive IgA-endomysial antibody (EMA) test results for celiac disease were being interpreted and acted on by physicians in the Calgary Health Region. We reviewed consecutive EMA test results, with or without a serum IgA, obtained during a 17-month period. Seropositive tests were cross-referenced to the surgical database to determine the number of patients who underwent intestinal biopsy and the results of the biopsy. We sent questionnaires to the ordering physicians of positive tests with no record of intestinal biopsy. Among 11,716 EMA tests in 9533 patients, 349 results were positive in 313 patients (3%). Intestinal biopsies were performed in 218 (70%) of the seropositive patients; 194 of them were diagnostic of celiac disease. Celiac disease was also found in 10 EMA-negative patients. Of the 109 positive tests performed in 95 patients with no subsequent biopsy, 28 had appropriate indications to not perform a biopsy; the most common reason being that the test had been ordered to follow up on a previous biopsy-proven diagnosis of celiac disease (n = 21). For 33 other positive test results without a subsequent biopsy, management appeared to be inappropriate, most commonly (n = 21) because of a recommendation to follow a gluten-free diet despite lack of a tissue diagnosis of celiac disease. For the remaining 48 positive EMA results, administrative issues prevented evaluation (n = 19), the patients refused further evaluation (n = 11), or physician surveys were not returned (n = 18). Celiac disease affected 2% of patients, with a similar prevalence in male and female patients. Most positive EMA tests (77%) were appropriately managed by physicians. Beginning a gluten-free diet without biopsy or failing to follow up on a positive EMA test remain common errors of management.

Endomysial Antibody Testing Improves Sensitivity in Screening for Celiac Disease in Young Children; a Five Year Single Center Experience

Endomysial Antibody Testing Improves Sensitivity in Screening for Celiac Disease in Young Children; a Five Year Single Center Experience

Polymorphisms of the TNF-? gene and risk of celiac disease in T1DM children

Type 1 diabetes mellitus (T1DM) and celiac disease (CD) frequently occur together. Previous reports suggested that the (-308)A variant of the tumor necrosis factor-alpha (TNF-alpha) gene is associated either with T1DM or with CD. The aim of our study was to determine whether (-308)A and (-238)A allelic variants of the TNF-alpha gene might have any impact on the risk of CD in T1DM children. Three hundred and one T1DM children were enrolled to the study. The presence of CD was screened with IgA endomysial antibodies (EMA) test. Jejunal biopsy was performed to confirm CD. TNF-alpha-308 and -238 genetic variants were tested using the method of restriction fragment length polymorphism. The prevalence of CD in the enrolled diabetic children was 6.3% (19 out of 301 children). The frequency of the (-308)A TNF-alpha variant was similar in the CD and the non-CD groups, exceeding the Hungarian healthy reference value. The number of (-238)A allele carriers was higher in the CD (4/19) than in the non-CD group (17/277) (p < 0.05). Our study is limited by the small number of CD patients. On the basis of our findings, carriers of TNF (-308)A allele do not seem to have an increased risk for CD in T1DM. The association between TNF-alpha(-238)A allele carrier state and CD requires further investigation.

Review: tissue transglutaminase test is almost as accurate as endomysial antibody test for diagnosis of coeliac disease

Review: tissue transglutaminase test is almost as accurate as endomysial antibody test for diagnosis of coeliac disease

Resurrection of gliadin antibodies in coeliac disease. Deamidated gliadin peptide antibody test provides additional diagnostic benefit

Objective. Circulating antibodies against naïve, whole gliadin have been replaced by more accurate endomysial and tissue transglutaminase antibody tests in the diagnosis of coeliac disease. The purpose of this study was to compare these serological tests with a new test recognizing antibodies against deamidated and defined gliadin peptides. Material and methods. The study population comprised selected coeliac disease patients in a tertiary clinic: newly detected patients before and after a gluten-free diet, patients with persistent small-bowel mucosal villous atrophy despite a strict gluten-free diet and non-coeliac controls reporting abdominal symptoms after ingestion of cereals. Comparisons were made between serum IgA-class gliadin peptide, endomysial, tissue transglutaminase and conventional gliadin antibodies. Results. The deamidated gliadin peptide antibody test showed a sensitivity of 91% and a specificity of 98% in coeliac disease. The tissue transglutaminase antibody test performed equally well. The specificity of endomysial antibody was just as high, but its sensitivity was lower, 80%. The conventional gliadin antibody test showed poor sensitivity and specificity. Combination of the deamidated gliadin peptide and tissue transglutaminase tests offered the best sensitivity without loss of specificity in the diagnosis of coeliac disease. All antibody levels declined in line with mucosal recovery. The deamidated gliadin peptide antibody test showed six of the nine cases with small-bowel mucosal damage persisting on a gluten-free diet, whereas tissue transglutaminase detected only two cases and endomysial antibody none. Conclusions. The new gliadin peptide antibody test proved highly accurate in the diagnostic work-up and follow-up of coeliac disease and can be endorsed in combination with the tissue transglutaminase test.

Malignancy and mortality in a population-based cohort of patients with coeliac disease or ‘gluten sensitivity’

To determine the risk of malignancy and mortality in patients with a positive endomysial or anti-gliadin antibody test in Northern Ireland. A population-based retrospective cohort study design was used. Laboratory test results used in the diagnosis of coeliac disease were obtained from the Regional Immunology Laboratory, cancer statistics from the Northern Ireland Cancer Registry and mortality statistics from the General Registrar Office, Northern Ireland. Age standardized incidence ratios of malignant neoplasms and standardized mortality ratios of all-cause and cause-specific mortality were calculated. A total of 13 338 people had an endomysial antibody and/or an anti-gliadin antibody test in Northern Ireland between 1993 and 1996. There were 490 patients who tested positive for endomysial antibodies and they were assumed to have coeliac disease. There were 1133 patients who tested positive for anti-gliadin antibodies and they were defined as gluten sensitive. Malignant neoplasms were not significantly associated with coeliac disease; however, all-cause mortality was significantly increased following diagnosis. The standardized incidence and mortality ratios for non-Hodgkin's lymphoma were increased in coeliac disease patients but did not reach statistical significance. Lung and breast cancer incidence were significantly lower and all-cause mortality, mortality from malignant neoplasms, non-Hodgkin's lymphoma and digestive system disorders were significantly higher in gluten sensitive patients compared to the Northern Ireland population. Patients with coeliac disease or gluten sensitivity had higher mortality rates than the Northern Ireland population. This association persists more than one year after diagnosis in patients testing positive for anti-gliadin antibodies. Breast cancer is significantly reduced in the cohort of patients with gluten sensitivity.

Adult population screening for coeliac disease: comparison of tissue-transglutaminase antibody and anti-endomysial antibody tests

Serological screening tests for coeliac disease have significantly advanced the diagnosis of this condition. The very high specificity (almost 100%) of anti-endomysial antibody detection has been repeatedly confirmed, whereas a lower specificity (90-95%) is found with anti-tissue transglutaminase antibody assays. In the study by Malekzadeh and colleagues, a group of study participants were identified with raised anti-tissue transglutaminase antibodies, but the endomysial antibody test was negative in 86%. Although many of these participants were found to have raised intra-epithelial lymphocytes in their small intestinal mucosa, there is currently insufficient evidence to confidently diagnose gluten-sensitive disease in these patients. Hence, their report that a minimum prevalence of 1:104 of gluten sensitivity is found in the general population of Iran is likely to be an over-estimate and requires confirmation.

Systematic review: the use of serology to exclude or diagnose coeliac disease (a comparison of the endomysial and tissue transglutaminase antibody tests)

With the appreciation of the high prevalence of coeliac disease there is increasing use of serology in screening asymptomatic people and testing those with suggestive features. To compare the sensitivities and specificities of the endomysial antibody and the tissue transglutaminase antibody tests. Using electronic databases a search was made for relevant papers using the terms tissue transglutaminase and endomysial antibody. Both the endomysial antibody and tissue transglutaminase antibody have very high sensitivities (93% for both) and specificities (>99% and >98% respectively) for the diagnosis of typical coeliac disease with villous atrophy. Human recombinant tissue transglutaminase performs much better than guinea pig tissue transglutaminase. Review of studies comparing endomysial antibody with human recombinant tissue transglutaminase antibody shows that endomysial antibody more often has a higher specificity and human recombinant tissue transglutaminase antibody more often has a higher sensitivity. The human recombinant tissue transglutaminase antibody is the preferred test for screening asymptomatic people and for excluding coeliac disease in symptomatic individuals with a low pretest probability (i.e. <25%) for coeliac disease. Furthermore, it has a number of practical and financial advantages. If the pretest probability is >25%, biopsy is preferred as the post-test probability of coeliac disease with a negative test is still >2%.

Diagnostic accuracy of coeliac serological tests: a prospective study

The best way to test serologically for coeliac disease (CD) remains controversial, with endomysial (EMA), transglutaminase (TTG), and gliadin antibodies (AGA) being assessed in various combinations with no apparent standardization. The objective of this study was to evaluate whether TTG-IgA+/-TTG-IgG could be used as a replacement for endomysial antibodies as a reliable screen for CD in patients presenting to a major Australian tertiary referral hospital for assessment of symptoms consistent with CD. Individuals referred for gastroscopic assessment of possible CD were prospectively evaluated by duodenal biopsy assessment. The following diagnostic methods were compared: dual-isotype transglutaminase (TTG-dual), combined-isotype transglutaminase (TTG-IgA+G), TTG-IgA, combined-isotype gliadin antibodies (AGA-IgA+G), AGA-IgA, and endomysial antibody assays. Clinical performance characteristics (sensitivity, specificity, area under the curve for receiver-operating characteristic analysis; AUROC) were assessed for all kits. The correlation between transglutaminase kits was generally good, with the best transglutaminase kit demonstrating high correlation (r=0.86) with endomysial antibodies. A comparison of different types of endomysial antibody assays displayed variable diagnostic performance (sensitivity 61.90-68.42%; specificity 80.00-98.57%; AUROC 0.71-0.83). Sensitivity (90.48-92.31%), specificity (80.77-82.89%) and AUROC values (0.92-0.94) for dual-isotype transglutaminase kits displayed narrow ranges. AGA assays were less sensitive (AGA-IgA: 42.31-46.15%; AGA-IgG: 61.54%) and less specific (AGA-IgA: 85.09-87.73%; AGA-IgG: 82.46-84.09%). Dual-isotype transglutaminase testing was diagnostically equivalent to transglutaminase-IgA (AUROC 0.92 versus 0.91, P=0.33). Our study suggests that transglutaminase screening (using the IgA+/-IgG isotype) is a sensitive and specific alternative to endomysial antibody testing in the serological assessment of CD. On the basis of our findings, AGA antibody testing no longer appears to be an essential part of the diagnostic strategy for adult CD.

The Role of Autoimmunity at Diagnosis of Type 1 Diabetes in the Development of Thyroid and Celiac Disease and Microvascular Complications

The purpose of this study was to explore whether the presence of thyroid and endomysial autoantibodies at diagnosis of type 1 diabetes in children predicts development of thyroid and celiac disease, respectively, and whether diabetes-associated autoantibodies at diagnosis predict development of microvascular complications up to 13 years later. Autoantibodies were measured at diagnosis of type 1 diabetes in 173 children aged 0-15 years and included thyroperoxidase antibody (TPOA), endomysial antibody (EMA), islet cell autoantibody, GAD antibody (GADA), and insulin autoantibody. Thyroid disease was defined as thyroid stimulating hormone level > or = 5 microU/ml. Celiac disease was confirmed by small-bowel biopsy. Assessment of microvascular complications included stereoscopic fundal photography, pupillometry, thermal threshold, and albumin excretion rate (AER). The incidence rates for thyroid and celiac disease were 0.9 and 0.7 per 100 patient-years, respectively. Within 13 years, 6 of 13 children with positive TPOA tests at diagnosis developed thyroid disease compared with 5 of 139 children with negative TPOA tests (P < 0.001). All four patients with positive EMA titers at diagnosis had biopsy-proven celiac disease. Five of 11 patients who developed thyroid disease and 4 of 8 who developed celiac disease had negative TPOA and EMA tests at diagnosis, respectively. Retinopathy was detected in 39% and elevated AER in 36%. The presence of diabetes-associated autoantibodies at diagnosis did not predict microvascular complications though GADA titer levels predicted pupillary abnormality. Elevated TPOA and EMA levels at diagnosis of type 1 diabetes predict the development of thyroid and celiac disease, respectively. In children with negative antibody titers at diagnosis, screening at 2-year intervals is recommended.

Physician awareness of celiac disease: a need for further education.

Celiac disease is a common disorder (up to 0.7%); however, it is uncommonly diagnosed in the United States. We sought to determine physician awareness of celiac disease. Surveys completed by 2,440 (47%) of 5,191 patients in a support group were analyzed for frequency of diagnosis by physician specialties. Questionnaires were then sent to primary care physicians (PCPs) (n=132) in a southern California county to assess knowledge of celiac disease. In patient surveys, only 11% were diagnosed by PCPs (internists and family physicians) versus 65% by gastroenterologists. Physician surveys (70% response) showed that only 35% of PCPs had ever diagnosed celiac disease. Almost all physicians (95%) knew of wheat intolerance, but few (32%) knew that onset of symptoms in adulthood is common. Physicians were well aware (90%) of diarrhea as a symptom, but fewer knew of common symptoms of irritable bowel syndrome (71%), chronic abdominal pain (67%), fatigue (54%), depression and irritability (24%) or of associations with diabetes (13%), anemia (45%) or osteoporosis (45%), or of diagnosis by endomysial antibody tests (44%). Lack of physician awareness of adult onset of symptoms, associated disorders, and use of serology testing may contribute to the underdiagnosis of celiac disease.

Intestinal Permeability in Long-Term Follow-up of Patients with Celiac Disease on a Gluten-Free Diet

Intestinal permeability is frequently abnormal in patients with celiac disease. The long-term effect of a gluten-free diet on intestinal permeability and the correlation of intestinal permeability with a gluten-free diet are not known. The objectives of this study were to determine the responses of intestinal permeability and antibody testing to gluten free diet and the degree of correlation of these measurements with gluten ingestion. In this prospective study, patients with celiac disease were divided into three groups based on length of time on a gluten-free diet: Group A, < 1 month; Group B, 1 month-1 year; Group C, > 1 year. Patients in Groups B and C were tested at baseline and at 4-12 weeks later for the following: lactulose/mannitol intestinal permeability, endomysial antibody, and 3-day food record. Permeability tests were also performed in Group A and control subjects. Intestinal permeability was elevated in newly diagnosed celiac disease and in individuals on a gluten-free diet for less than 1 year. Intestinal permeability was normal in 80% at visit 1 and 87% at visit 2 in individuals with celiac disease on a gluten-free diet for more than a year. Trace gluten ingestion was associated with increased intestinal permeability on visit 2 (P = 0.0480). The sensitivity of detecting gluten ingestion as measured by a 3-day food record was higher for permeability testing (29 and 36%) compared with endomysial antibody testing (18 and 18%) for visits 1 and 2, respectively. Intestinal permeability normalizes in the majority of individuals with celiac disease on a gluten-free diet. Gluten ingestion as measured by a 3-day food record correlates with intestinal permeability measurements. The role of permeability testing in the follow-up of patients with celiac disease warrants further investigation.