Consequences of testing for celiac disease
2005; Elsevier BV; Volume: 128; Issue: 4 Linguagem: Inglês
10.1053/j.gastro.2005.02.019
ISSN1528-0012
AutoresAnn Cranney, Alaa Rostom, Richmond Sy, Catherine Dubé, Navaz Saloogee, C Garritty, David Moher, Margaret Sampson, Li Zhang, Fatemeh Yazdi, Vasil Mamaladze, Irene Pan, Joanne MacNeil,
Tópico(s)Helicobacter pylori-related gastroenterology studies
ResumoPopulation 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. 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. Recent, large, screening programs have noted a high prevalence of celiac disease (CD) in the general population and, of those who test positive, up to two thirds are asymptomatic.1Tommasini A. Not T. Kiren V. et al.Mass screening for celiac diseaes using antihuman transglutaminase antibody assay.Arch Dis Child. 2004; 89: 15Crossref Scopus (195) Google Scholar Prior to recommending population screening for CD, the consequences of testing and risk of long-term complications in individuals with clinical silent CD, especially those with low-grade histologic lesions on small bowel biopsy, need to be clarified. Our objective was to conduct a systematic review of trials evaluating the expected consequences of testing for CD in (1) patients with symptoms suggestive of CD, (2) asymptomatic at-risk populations, and (3) general population. This paper was part of a multipart systematic review conducted for the Agency for Healthcare Research and Quality (AHRQ). A comprehensive literature search was conducted by the National Library of Medicine in collaboration with the University of Ottawa Evidence-Based Practice Center (UO-EPC). The searches were run in MEDLINE (1996–October 2003), EMBASE (1974 to December 2003), PsychINFO (1840–2003), AGRICOLA (1970–2003), CAB (1972–December 2003), and Sociological Abstracts (1963–2003). Reference lists from eligible studies were reviewed for other relevant studies. The comprehensive search strategy included potential studies that dealt with consequences of testing for celiac disease; 1199 potentially relevant citations were identified. Study selection was performed by 2 independent reviewers, using 3 levels of screening with gradually increasing stringent criteria to ensure that all relevant articles were captured. Articles were excluded if they did not identify one of the consequences of screening for celiac disease such as false-positives, cases diagnosed, or response to treatment. Studies were excluded if there was no control group, unless the studies were a before-after design. Studies that used antigliadin (AGA) without commercial ELISA or that were published before 1990 were excluded. After 3 levels of screening, 51 published studies met the eligibility criteria. Full data extraction was conducted by 2 independent reviewers (R.S. and A.C.). Quality of case control and cohort studies was evaluated with the Ottawa-Newcastle Scale.2Wells G.A. Shea B. O'Connell D. Peterson J. Welch V. Tugwell P. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Symposium on Systematic Reviews: Beyond the Basics. 2000Google Scholar Outcomes included test performance and outcomes related to identifying patients and the subsequent response to the gluten-free diet (GFD), including (1) body composition and anthropometrics, nutritional status, and diabetic control; (2) compliance with a gluten-free diet; and (3) costs, factures/osteoporosis, and mortality. The search strategy did not identify studies that allowed us to address specific benefits and harms of testing with different strategies for CD. Many of the included studies relevant to response to treatment dealt with small populations of symptomatic individuals. Most studies did not report outcomes according to clinical presentation, so it was difficult to ascertain whether outcomes differed in asymptomatic or silent CD cases when compared with symptomatic CD cases. Few studies correlated the histologic grade at biopsy with outcomes, such as improvements in bone mineral density (BMD), anemia, and diabetic control. We did not pool results from the observational trials because of differences in methodologies and the potential for selection bias and heterogeneity.3Egger M. Schneider M. Smith G.D. Meta-analysis spurious precision? Meta-analysis of observational studies.BMJ. 1998; 316: 140-144Crossref PubMed Scopus (791) Google Scholar The search identified 1121 citations from bibliographic databases, and 123 potentially relevant citations were nominated by reviewers. Twenty-nine duplicate records were removed, resulting in 1199 potential citations that were evaluated for inclusion. Out of 1199 citations, 1164 failed to meet the specified inclusion criteria; 1148 were not about the consequences of testing, and 7 were review articles. Thirty-six articles satisfied the inclusion criteria.4Kemppainen T.A. Kosma V.M. Janatuinen E.K. Julkunen R.J. 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It is important to determine whether clinical outcomes vary according to the clinical presentation. Most studies included in this review were studies that assessed the response to treatment in newly diagnosed patients after commencing a gluten-free diet (GFD). False-positive results and cases diagnosed with testing are dealt with extensively in the paper of serologic testing by Rostom et al.55Dubé C. Rostom A. Sy R. Cranney A. Saloojee N. Garritty C. Sampson M. Zhang L. Yazdi F. Mamaladze V. Pan I. MacNeil J. Mack D. Patel D. Moher D. The prevalence of celiac disease in average risk and at-risk western European populations a systematic review.Gastroenterology. 2005; 128: S57-S67Abstract Full Text Full Text PDF PubMed Scopus (523) Google Scholar However, it is important to emphasize that the prevalence of CD in the test populations has an important impact on the diagnostic parameters of the screening tests used. For example, the sensitivity of screening tests is lower for histologic grades below Marsh IIIa by approximately 30%.55Dubé C. Rostom A. Sy R. Cranney A. Saloojee N. Garritty C. Sampson M. Zhang L. Yazdi F. Mamaladze V. Pan I. MacNeil J. Mack D. Patel D. Moher D. The prevalence of celiac disease in average risk and at-risk western European populations a systematic review.Gastroenterology. 2005; 128: S57-S67Abstract Full Text Full Text PDF PubMed Scopus (523) Google Scholar In addition, the prevalence of CD in study populations in which the diagnostic test studies of serologic testing were conducted is higher than the prevalence of CD in most clinical situations. The positive predictive value, which is influenced by both the specificity and prevalence of CD, falls from the reported value to much lower values in typical clinical populations, resulting in an increased chance of false-positives. Conversely, the negative predictive value increases as the prevalence of CD decreases but will remain over 90%, provided the sensitivity of the test is >50%. Although currently recommended serologic screening tests (EMA, tissue transglutaminase IgA antibody [tTG]), have a high specificity in low-prevalence populations, the use of these tests results in much higher false-positive rates (as high as 30%–35%) in low-prevalence populations. Four studies evaluated diabetes and celiac disease in children.5Amin R. Murphy N. Edge J. Ahmed M.L. Acerini C.L. Dunger D.B. A longitudinal study of the effects of a gluten-free diet on glycemic control and weight gain in subjects with type 1 diabetes and celiac disease.Diabetes Care. 2002; 25: 1117-1122Crossref PubMed Scopus (110) Google Scholar, 14Westman E. Ambler G.R. Royle M. Peat J. Chan A. Children with coeliac disease and insulin dependent diabetes mellitus—growth, diabetes control and dietary intake.J Pediatr Endocrinol Metab. 1999; 12: 433-442Crossref PubMed Scopus (74) Google Scholar, 16Arato A. Korner A. Veres G. Dezsofi A. Ujpal I. Madacsy L. Frequency of coeliac disease in Hungarian children with type 1 diabetes mellitus.Eur J Pediatr. 2002; 162: 1-5PubMed Google Scholar, 27Saukkonen T. Vaisanen S. Akerblom H.K. Savilahti E. Coeliac disease in children and adolescents with type 1 diabetes a study of growth, glycemic control, and experiences of families.Acta Pediatrica. 2002; 91: 297-302Crossref PubMed Google Scholar Two were case-control studies,5Amin R. Murphy N. Edge J. Ahmed M.L. Acerini C.L. Dunger D.B. A longitudinal study of the effects of a gluten-free diet on glycemic control and weight gain in subjects with type 1 diabetes and celiac disease.Diabetes Care. 2002; 25: 1117-1122Crossref PubMed Scopus (110) Google Scholar, 14Westman E. Ambler G.R. Royle M. Peat J. Chan A. Children with coeliac disease and insulin dependent diabetes mellitus—growth, diabetes control and dietary intake.J Pediatr Endocrinol Metab. 1999; 12: 433-442Crossref PubMed Scopus (74) Google Scholar and 2 studies had CD patients act as their own controls.16Arato A. Korner A. Veres G. Dezsofi A. Ujpal I. Madacsy L. Frequency of coeliac disease in Hungarian children with type 1 diabetes mellitus.Eur J Pediatr. 2002; 162: 1-5PubMed Google Scholar, 27Saukkonen T. Vaisanen S. Akerblom H.K. Savilahti E. Coeliac disease in children and adolescents with type 1 diabetes a study of growth, glycemic control, and experiences of families.Acta Pediatrica. 2002; 91: 297-302Crossref PubMed Google Scholar All studies assessed the impact of a GFD (range, 3–12 months) on the diabetic control of type 1 diabetics. The United Kingdom study5Amin R. Murphy N. Edge J. Ahmed M.L. Acerini C.L. Dunger D.B. A longitudinal study of the effects of a gluten-free diet on glycemic control and weight gain in subjects with type 1 diabetes and celiac disease.Diabetes Care. 2002; 25: 1117-1122Crossref PubMed Scopus (110) Google Scholar included 230 type 1 diabetics who were screened for celiac disease with serologic tests. Children with positive serology had small bowel biopsies. Eleven children were diagnosed with celiac disease and followed longitudinally. Controls included type 1 diabetic children with negative serology, and 2 controls per case were matched for age, sex, and duration of diabetes. Baseline weight standard deviation score (SDS), body mass index (BMI) SDS, and HbA1c of the cases were statistically lower than the controls. No statistical difference was noted for height SDS, C-peptide level, and insulin requirements. Cases received significantly less intensive insulin regimens compared with controls. Six type 1 diabetic children with celiac disease participated in the GFD. After 12 months of a GFD, the differences seen in the BMI SDS reversed between the cases and controls. HbA1c levels did not improve significantly on the GFD, and insulin requirements were not statistically different between cases and controls. An Australian study14Westman E. Ambler G.R. Royle M. Peat J. Chan A. Children with coeliac disease and insulin dependent diabetes mellitus—growth, diabetes control and dietary intake.J Pediatr Endocrinol Metab. 1999; 12: 433-442Crossref PubMed Scopus (74) Google Scholar identified children and adolescents with coexisting type 1 diabetes and biopsy-proven celiac disease from a database at a diabetes center. Twenty patients were enrolled, and 40 age- and sex-matched controls were selected. At baseline, the current height SDS, weight SDS, BMI SDS, and HbA1c did not differ significantly from controls. Compliance with GFD was based on dietary records. Thirty percent were classified as following a strict GFD, 30% had trace gluten, and 40% had a significant amount of gluten in their diet. No differences in growth parameters or HbA1c based on compliance with a GFD were noted. A Hungarian study16Arato A. Korner A. Veres G. Dezsofi A. Ujpal I. Madacsy L. Frequency of coeliac disease in Hungarian children with type 1 diabetes mellitus.Eur J Pediatr. 2002; 162: 1-5PubMed Google Scholar included 205 children with type 1 diabetes, randomly selected from children screened for celiac disease. Twenty-four children had positive antiendomysial IgA antibody (EMA) results, and 17 (10 girls) children had subtotal villous atrophy. At baseline, the height of the children with CD and type 1 diabetes was normal compared with control children with type 1 diabetes. The BMI of the 17 children was significantly lower (14.2 vs. 16.3 [kg/m2]) than controls, and, after 3 months of GFD, BMI significantly increased. Significant increases in insulin requirements occurred after a GFD. The percentage of HbA1c did not change on a GFD compared with baseline (7.82% vs 7.67%). Saukkonen et al27Saukkonen T. Vaisanen S. Akerblom H.K. Savilahti E. Coeliac disease in children and adolescents with type 1 diabetes a study of growth, glycemic control, and experiences of families.Acta Pediatrica. 2002; 91: 297-302Crossref PubMed Google Scholar screened 776 children with type 1 diabetes over a 2.7-year period with serology and biopsy. Eighteen (2.3%) children had biopsy-confirmed CD. HbA1c levels did not change after introduction of a GFD. Six studies assessed body composition after starting a GFD, and 4 were conducted in pediatric populations.6Bardella M.T. Fredella C. Prampolini L. Molteni N. Giunta A.M. Bianchi P.A. Body composition and dietary intakes in adult celiac disease patients consuming a strict gluten-free diet.Am J Clin Nutr. 2000; 72: 937-939PubMed Google Scholar, 7Barera G. Mora S. Brambilla P. Ricotti A. Menni L. Beccio S. Bianchi C. Body composition in children with celiac disease and the effects of a gluten-free diet a prospective case-control study.Am J Clin Nutr. 2000; 72: 71-75PubMed Google Scholar, 8Boersma B. Houwen R.H.J. Blum W.F. vanDoorn J. Wit J.M. Catch-up growth and endocrine changes in childhood celiac disease.Horm Res. 2002; 58: 57-65Crossref PubMed Scopus (57) Google Scholar, 9Rea F. Polito C. Marotta A. Di Toro A. Iovene A. Collini R. Rea L. Sessa G. Restoration of body composition in celiac children after one year of gluten-free diet.J Pediatr Gastroenterol Nutr. 1996; 23: 408-412Crossref PubMed Scopus (60) Google Scholar, 26Poddar U. Thapa B.R. Nain C.K. Prasad A. Singh K. Celiac disease in India are they true cases of celiac disease?.J Pediatr Gastroenterol Nutr. 2002; 35: 508-512Crossref PubMed Scopus (58) Google Scholar, 28Smecuol E. Gonzalez D. Mautalen C. Siccardi A. Cataldi M. Niveloni S. Mazure R. Vazquez H. Pedreira S. Soifer G. Boerr L.A. Maurino E. Bai J.C. Longitudinal study on the effect of treatment on body composition and anthropometry of celiac disease patients.Am J Gastroenterol. 1997; 92: 639-643PubMed Google Scholar Bardella et al6Bardella M.T. Fredella C. Prampolini L. Molteni N. Giunta A.M. Bianchi P.A. Body composition and dietary intakes in adult celiac disease patients consuming a strict gluten-free diet.Am J Clin Nutr. 2000; 72: 937-939PubMed Google Scholar in a case control study evaluated 212 t
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