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BACKGROUND. Studies demonstrate an increased prevalence of celiac disease in persons with Down syndrome, leading some organizations and authors to recommend universal screening of children with Down syndrome. However, many children with Down syndrome are asymptomatic, and the long-term implications of screening are unknown. The complication of celiac disease that leads to mortality in the general population is non-Hodgkin's lymphomas. OBJECTIVES. The purpose of this research in asymptomatic children with Down syndrome was to (1) calculate the number needed to screen to prevent a single case of lymphoma and (2) present a cost-effectiveness study of screening. METHODS. We constructed a decision tree using probabilities derived from the published literature for Down syndrome or from the general population where Down syndrome-specific data were not available. Celiac disease was determined by serologic screening and confirmation with intestinal biopsy. Sensitivity analysis was used to alter probability estimates affecting the cost of preventing lymphoma. RESULTS. Using our baseline values, the no-screen strategy is dominant; that is, screening not only costs more but also results in fewer quality-adjusted life-years. A screening strategy costs more than $500 000 per life-year gained. Screening all asymptomatic children with Down syndrome for celiac disease costs almost $5 million to prevent a single case of lymphoma. CONCLUSION. These analyses do not support the cost-effectiveness of screening, and more data are needed before recommendations to screen asymptomatic children with Down syndrome for celiac disease can be made. Key Words Down syndrome, celiac disease, cost-effectiveness Abbreviations CD--celiac disease DS--Down syndrome SIR--standardized incidence ratio SMR--standardized mortality ratio Ig--immunoglobin GFD--gluten-free diet EMA--endomysial antibody tTG--tissue transglutaminase antibody CHD--congenital heart disease CI--confidence interval QALY--quality-adjusted life-year, CELIAC DISEASE (CD) is an immune-mediated enteropathy caused by a permanent sensitivity to gluten in genetically susceptible individuals. (1) Many studies have demonstrated the increased prevalence of CD in Down [...]

Objectives. The use of screening tests for celiac disease has increased the number of patients referred for evaluation. We proposed that the subgroup of patients with very high tissue transglutaminase antibody (TTG) titers is positive for celiac disease and a small-bowel biopsy is not necessary to make the diagnosis. A gluten-free diet should be attempted and, if the patient's symptoms do not improve, then a biopsy should be performed to confirm the diagnosis. Methods. A chart review of data for 103 patients who underwent both TTG testing and a small-bowel biopsy was performed. We examined the impact of using TTG values of >100 U and Results. Fifty-eight of 103 patients demonstrated positive biopsy results. Forty-nine of 103 patients had TTG levels of >100 U, with 48 of 49 exhibiting positive biopsy results. Only 7 of 16 patients with TTG values of 20 to 100 U exhibited positive biopsy results. Three patients with TTG levels of 100 U and Conclusions. When the cutoff values were changed to >100 and, ABBREVIATIONS. TTG, tissue transglutaminase antibody; EGD, esophagogastroduodenoscopy; IDDM, insulin-dependent diabetes mellitus. Celiac disease is the most common cause of malabsorption in western nations, with an estimated prevalence of 1 case [...]

Objective. At-risk groups commonly undergo screening for autoantibodies associated with celiac disease (CD). However, the clinical significance of a positive test remains uncertain. The objective of this study was to evaluate growth and clinical features of children who test positive for an autoantibody associated with CD. Methods. A case-control study of Denver area healthy infants and young children with and without CD autoantibodies was conducted. A cohort of HLA-characterized children were followed prospectively since birth for the development of immunoglobulin A antitissue transglutaminase autoantibodies (TG). Clinical evaluation, questionnaire, blood draw, and small bowel biopsy were performed. Growth and nutrition and frequency of positive responses were measured. Results. Compared with 100 age- and gender-matched TG-negative controls, 18 TG-positive children, 5.5 [+ or -] 0.5 years of age, had a greater number of symptoms and lower z scores for weight-for-height and for body mass index. Responses that were independently associated with TG-positive status were irritability/lethargy, abdominal distention/gas, and difficulty with weight gain. Conclusions. Screening-identified TG-positive children demonstrate mild alterations in growth and nutrition and report more symptoms than control subjects. Additional study is needed on the benefit and risk of identifying CD in at-risk groups. Pediatrics 2004;113: 1254-1259; celiac disease, IgA, transglutaminase, children, body mass index, autoimmunity, screening. ABBREVIATIONS. CD, celiac disease; EMA, endomysial antibodies; TG, transglutaminase antibodies; IgA, immunoglobulin A; BMI, body mass index; OR, odds ratio; CI, confidence interval., Evidence of celiac disease (CD) may be present in 1 in every 100 to 250 children, (1,2) adolescents, (3) and adults (4,5) in Europe and the United States. (6) Individuals [...]

Children with Down syndrome (DS) may have high rates of undiagnosed celiac disease. Celiac disease (CD) is a gastrointestinal condition that causes symptoms when patients eat gluten, a component of many grains. Researchers in Sweden evaluated 43 children with Down syndrome for antibodies to gluten. Seven children had antiendomysium antibodies, and all had villous intestinal atrophy when biopsied. Others had antibodies to gliadin. The rate of CD in these patients was about 50 times that seen in the general population. Antibody testing may be useful for CD screening in DS patients., Objective. This study was undertaken to investigate the prevalence of celiac disease in children and adolescents with Down syndrome. Material and Methods. Forty-three children and adolescents with Down syndrome were screened for IgA-antigliadin antibodies (AGA) and IgA-antiendomysium antibodies (EMA). Patients found to be either AGA- or EMA-positive were investigated further with intestinal biopsy. Results. None of the 43 patients had known celiac disease at entry into the study; 37% (16/43) were found to have AGA levels above normal, and 16% (7/43) to be EMA-positive. Of the 15 patients who underwent biopsy, 8 manifested villous atrophy. Villous atrophy was present in all 7 of the EMA-positive patients, whereas the villi were normal in 7 of the 13 AGA-positive patients who underwent biopsy. Conclusions. EMA is a good immunologic marker for use in screening for celiac disease, and screening is justified in patients with Down syndrome. Pediatrics 1998; 101:272-275; Down syndrome, celiac disease, IgA-antigliadin antibodies, IgA-antiendomysium antibodies., ABBREVIATIONS. DS, Down syndrome; CD, celiac disease; AGA, antigliadin antibodies; EMA, antiendomysium antibodies; AU, arbitrary units. Down syndrome (DS), or trisomy 21, has many clinical implications. DS has been reported [...]

Objective. An immunoglobulin A (IgA) anti-tissue transglutaminase antibody assay (anti-tTG) was compared with the conventional IgA anti-endomysium antibody assay (EMA) to assess its reliability as a screening test for celiac disease (CD) in a pediatric population. Methods. Seventy-five IgA-sufficient and 2 IgA-deficient children who were scheduled for small intestinal biopsy for the evaluation of history or symptoms suggesting a diagnosis of CD were prospectively evaluated and enrolled in this study (gastrointestinal [GI] patients). In addition, 16 children with type I diabetes mellitus (DM) who had a positive EMA and a small bowel biopsy were included as a separate cohort. IgA anti-tTG was measured by enzyme-linked immunosorbent assay (ELISA), and IgA-EMA titers were determined by indirect immunofluorescence on cryopreserved sections of monkey esophagus. Results. Nine of the 75 IgA-sufficient GI patients had a small bowel biopsy consistent with the diagnosis of CD. Eight of 9 IgA-sufficient patients with a positive small bowel biopsy had positive anti-tTG and EMA tests. Four IgA-sufficient patients had a false-positive anti-tTG ELISA and 2 had a false-positive IgA-EMA assay. In the IgA-sufficient patients, the sensitivity was 89% and the negative predictive value was 98% for either assay. The specificities of the IgA anti-tTG and the IgA-EMA tests were 94% and 97%, respectively (not significant). The positive predictive value of the IgA anti-tTG was 67%, compared with 80% for the IgA-EMA (not significant). In the 2 IgA-deficient children, one of whom had biopsyproved CD, both tests were negative. In the 16 DM children 12 true- and 4 false-positive IgA anti-tTG and IgA-EMA results were identified. Three of 12 complained of GI symptoms. In follow-up, thus far, none of the DM patients with a false-positive anti-tTG have developed CD. Conclusions. The IgA anti-tTG antibody assay is equivalent to the IgA-EMA assay as a screening test for CD in IgA-sufficient pediatric patients. Intestinal biopsy remains the gold standard for the diagnosis of CD. Pediatrics 2001;107(1). URL: http://www.pediatrics.org/ cgi/content/full/107/1/e8; celiac disease, tissue transglutaminase, endomysium antibody, diagnosis, screening tests.

Objective. The study was designed to investigate the prevalence of celiac disease (CD) among 2.5-year-old children in a Swedish urban population with a high incidence of CD. Material and Methods. Six hundred ninety apparently healthy children, born in the 12-month period of July 1992 through June 1993, were screened for immunoglobulin A (IgA) antigliadin antibodies and IgA antiendomysium antibodies, and those antibody-positive at repeated testing were further investigated with intestinal biopsy. Results. Of the 690 children, 6 were both IgA antigliadin antibody- and IgA antiendomysium antibody-positive, and 7 were antiendomysium antibody-positive but antigliadin antibody-negative. Jejunal biopsy, performed in 12 cases, manifested partial or total villous atrophy in 8 cases. Thus, together with an additional child whose parents declined the offered biopsy, but whose response to a gluten-free diet confirmed the presence of CD, the prevalence of CD in the study series was 1.3% (9/690; 95% confidence interval: .4-2.2). However, independent of the study, an additional 22 cases of symptomatic, biopsy-verified CD have already been detected in the birth cohort of 3004 children. Conclusions. The prevalence of CD in our study series was high, at least 1.0%, but may be as high as 2.0% if the frequency of silent CD is as high as we have found in the remaining unscreened cohort. These findings confirm that CD is one of the most common chronic disorders. Pediatrics 2001;107:42-45; celiac disease, immunoglobulin A antigliadin antibodies, immunoglobulin A antiendomysium antibodies., ABBREVIATIONS. CD, celiac disease; IgA, immunoglobulin A; AGA, IgA antigliadin antibody; EMA, IgA antiendomysium antibody; AU, arbitrary units; CI, confidence interval; SD, standard deviation. The incidence of celiac disease (CD) [...]

Serological testing for immunoglobulins to gluten constituents may effectively improve the accuracy of pediatric celiac disease diagnosis. Celiac disease is a gastrointestinal condition caused by an immune system intolerance to the gluten in wheat and other grains. Researchers performed serum antigliadin and antiendomysium antibody tests on 95 children with suspected celiac disease. One or both tests identified every child with celiac disease, which was confirmed by duodenal biopsy. Antibody testing may prevent unnecessary biopsies in children with gastrointestinal symptoms not caused by celiac disease., Objective. To prospectively evaluate and compare the sensitivity, specificity, and positive and negative predictive values of serum antigliadin (AGA) and antiendomysium antibodies (EMA) in predicting the initial diagnosis of celiac disease. Design. Sera were tested prospectively for IgA and IgG AGA by enzymed-linked immunosorbent assay and IgA EMA by immunofluorescence techniques on monkey esophagus and human umbilical cord sections in 95 pediatric patients referred for duodenal biopsies. Patients. Ninety-five pediatric patients were referred for duodenal biopsies, with a clinical suspicion of celiac disease; 24 of those patients had celiac disease by criteria of the European Society for Pediatric Gastroenterology and Nutrition. Setting. A pediatric gastroenterology clinic of a tertiary care pediatric university hospital. Results. EMA testing on human umbilical cords was the most specific but was also the least sensitive. All the patients with biopsy-proven celiac disease were identified by either one or both serologic tests (100% combined sensitivity). The combination of AGA and EMA on monkey esophagus resulted in a negative predictive value of 100% accuracy. Conclusions. A combination of AGA and EMA tests resulted in 100% sensitivity and 100% negative predictive value, useful in selecting patients for duodenal biopsy. Pediatrics 1999;104:75--78; endomysial antibodies, gliadin antibodies, serologic screening, celiac disease., ABBREVIATIONS. AGA, antigliadin antibodies; EMA, antiendomysial antibodies. The diagnosis of celiac disease, or gluten-sensitive enteropathy, is established by the histologic demonstration of small-intestinal villus atrophy with inflammation and hyperplastic crypts [...]

OBJECTIVES. Our goal was to evaluate the possible correspondence between antitissue transglutaminase of immunoglobulin A class levels and stage of mucosal damage in patients affected by celiac disease. In addition, we assessed clinical use of antitissue transglutaminase values to predict biopsy results. METHODS. One thousand eight hundred eighty-six consecutive patients with symptoms suggestive of celiac disease and 305 healthy controls underwent determination of serum levels of immunoglobulin A and antitissue transglutaminase. An intestinal biopsy was performed in subjects with antitissue transglutaminase levels [greater than or equal to]4 IU/mL and in subjects with negative antitissue transglutaminase levels but with clinical suspicion of celiac disease. Histologic grading of celiac disease was consistent with the Marsh classification. RESULTS. One hundred eighty-six subjects with positive antitissue transglutaminase levels and 91 patients with negative antitissue transglutaminase levels were submitted to biopsy. In all healthy subjects, antitissue transglutaminase results were negative. Histologic evaluations in patients with positive antitissue transglutaminase levels gave the following results: type 0 in 25 patients, type 1 in 3 patients, type 2 in 4 patients, type 3a in 22 patients, type 3b in 74 patients, and type 3c in 58 patients. None of the patients with negative antitissue transglutaminase levels showed histologic findings suggestive of celiac disease. The mean antitissue transglutaminase values in patients without mucosal atrophy were significantly lower than in patients with mucosal atrophy. Antitissue transglutaminase values [greater than or equal to]20 IU/mL were found in only 1 patient without mucosal atrophy. CONCLUSIONS. Our study found a strong correspondence between antitissue transglutaminase levels and stage of mucosal injury; antitissue transglutaminase values >20 IU/mL seemed to be strongly predictive of mucosal atrophy. KEYWORDS. celiac disease, antitissue transglutaminase, Marsh classification., PEDIATRICS 2006;118:e1696-e1700. URL: www.pediatrics.org/cgi/doi/10.1542/peds.2006-0604 Antonella Diamanti, MD, Franco Colistro, MD, Angelica Calce, PhD, Rita Devito, MD, Francesca Ferretti, MD, Antonio Minozzi, PhD, Alexandra Santoni, PhD, Massimo Castro, [...]

CELIAC DISEASE IS now recognized as a relatively common disease. The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition subcommittee on celiac disease recently published recommendations for testing and [...]

Objectives. We sought to characterize the clinical features at presentation as well as the associated disorders, family history, and evaluation of compliance with a gluten-free diet in children with celiac disease from across Canada. Study Design. All members (n = 5240) of the Canadian Celiac Association were surveyed with a questionnaire. Of the 2849 respondents with biopsy-confirmed celiac disease, 168 who were Results. The mean age when surveyed was 9.1 [+ or -] 4.1 years, and 58% were female. Median age at diagnosis was 3.0 years with a range of 1 to 15 years. Presenting symptoms included abdominal pain (90%), weight loss (71%), diarrhea (65%), weakness (64%), nausea/vomiting (53%), anemia (40%), mood swings (37%), and constipation (30%). Almost one third of families consulted [greater than or equal to] 2 pediatricians before confirmation of the diagnosis. Before the recognition of celiac disease, other diagnoses received by these children included anemia (15%), irritable bowel syndrome (11%), gastroesophageal reflux (8%), stress (8%), and peptic ulcer disease (4%). A serological test was performed to screen for celiac disease in 70% of those in this population. Eight percent had either type 1 diabetes mellitus or a first-degree relative with celiac disease. Almost all respondents (95%) reported strict adherence to a gluten-free diet, and 89% noted improved health. Reactions after accidental gluten ingestion developed in 54% of the children between 0.5 and 60 hours after ingestion with a median of 2.0 hours. Reactions included abdominal discomfort (87%), diarrhea (64%), bloating (57%), fatigue (37%), headache (24%), and constipation (8%), and most displayed >1 symptom. Although most adjusted well to their disease and diet, 10% to 20% reported major disruptions in lifestyle. Twenty-three percent felt angry all or most of the time about following a gluten-free diet. Only 15% avoided traveling all or most of the time, and during travel, 83% brought gluten-free food with them all of the time. More than half of the families avoided restaurants all or most of the time. Twenty-eight percent of the respondents found it extremely difficult to locate stores with gluten-free foods, and 27% reported extreme difficulty in finding gluten-free foods or determining if foods were free of gluten. Sixty-three percent of the respondents felt that the information supplied by the Canadian Celiac Association was excellent. Gastroenterologists provided excellent information to 44%o, dietitians to 36%, and the family physician to 11.5%. When asked to select 2 items that would improve their quality of life, better labeling of gluten-containing ingredients was selected by 63%, more gluten-free foods in the supermarket by 49%, gluten-free choices on restaurant menus by 49%, earlier diagnosis of celiac disease by 34%, and better dietary counseling by 7%. Conclusions. In Canada, children with celiac disease present at all ages with a variety of symptoms and associated conditions. Delays in diagnosis are common. Most children are compliant with a gluten-free diet. A minority of these children experience difficulties in modifying their lifestyles, and gluten-free foods remain difficult to obtain. celiac, gluten, survey.

In this issue of Pediatrics, Barera et al (1) expand on the significant, recognized relationship between type 1 diabetes and celiac disease (CD). The authors confirm the increased prevalence of [...]

Objective. The association of celiac disease (CD) and type 1 diabetes is now clearly documented. Immunoglobulin A (IgA) antitransglutaminase antibodies were measured to determine the prevalence of celiac disease in a diabetic population of children and to determine the temporal relationship between type 1 diabetes onset and CD. Methods. We measured IgA antitransglutaminase antibodies using human recombinant antigen in parallel with classical markers (IgA and IgG antigliadin, IgA antiendomysium) in 284 children with diabetes. Results. In the population studied, the prevalence of CD was 3.9% (11 of 284). Two cases of CD were diagnosed before the onset of diabetes, and in 8 patients, the diagnoses of CD and diabetes were concomitant, suggesting that CD was present before the onset of diabetes. In 1 case, a girl who presented with thyroiditis, serology for CD became positive after diabetes had been diagnosed. Conclusion. An excellent correlation was observed between IgA antiendomysium and IgA antitransglutaminase antibodies. We therefore propose using IgA antitransglutaminase as a screening test for practical reasons. Furthermore, IgA antitransglutaminase levels and mucosa abnormalities were closely correlated. The presence of antitransglutaminase antibodies should alert pediatricians to the atypical forms of CD. This study indicates that CD is most often present before the onset of diabetes. Pediatrics 2004;113:e418-e422. URL: http: //www.pediatrics.org/cgi/content/full/113/5/e418; celiac disease, type 1 diabetes, children, screening test, antitransglutaminase autoantibodies, prevalence, autoimmune diseases.