FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2904016703> ?p ?o ?g. }

• W2904016703 endingPage "889" @default.
• W2904016703 startingPage "885" @default.
• W2904016703 abstract "PurposeThe purpose of this clinical practice update is to define key modalities in the diagnosis and monitoring of celiac disease (CD) in adults as well as in children and adolescents.MethodsThe recommendations outlined in this expert review are based on available published evidence, including cohort and case-control studies of the diagnostic process as well as controlled and descriptive studies of disease management.Best Practice Advice 1: Serology is a crucial component of the detection and diagnosis of CD, particularly tissue transglutaminase–immunoglobulin A (TG2-IgA), IgA testing, and less frequently, endomysial IgA testing.Best Practice Advice 2: Thorough histological analysis of duodenal biopsies with Marsh classification, counting of lymphocytes per high-power field, and morphometry is important for diagnosis as well as for differential diagnosis.Best Practice Advice 2a: TG2-IgA, at high levels (> ×10 upper normal limit) is a reliable and accurate test for diagnosing active CD. When such a strongly positive TG2-IgA is combined with a positive endomysial antibody in a second blood sample, the positive predictive value for CD is virtually 100%. In adults, esophagogastroduodenoscopy (EGD) and duodenal biopsies may then be performed for purposes of differential diagnosis.Best Practice Advice 3: IgA deficiency is an infrequent but important explanation for why patients with CD may be negative on IgA isotype testing despite strong suspicion. Measuring total IgA levels, IgG deamidated gliadin antibody tests, and TG2-IgG testing in that circumstance is recommended.Best Practice Advice 4: IgG isotype testing for TG2 antibody is not specific in the absence of IgA deficiency.Best Practice Advice 5: In patients found to have CD first by intestinal biopsies, celiac-specific serology should be undertaken as a confirmatory test before initiation of a gluten-free diet (GFD).Best Practice Advice 6: In patients in whom CD is strongly suspected in the face of negative biopsies, TG2-IgA should still be performed and, if positive, repeat biopsies might be considered either at that time or sometime in the future.Best Practice Advice 7: Reduction or avoidance of gluten before diagnostic testing is discouraged, as it may reduce the sensitivity of both serology and biopsy testing.Best Practice Advice 8: When patients have already started on a GFD before diagnosis, we suggest that the patient go back on a normal diet with 3 slices of wheat bread daily preferably for 1 to 3 months before repeat determination of TG2-IgA.Best Practice Advice 9: Determination of HLA-DQ2/DQ8 has a limited role in the diagnosis of CD. Its value is largely related to its negative predictive value to rule out CD in patients who are seronegative in the face of histologic changes, in patients who did not have serologic confirmation at the time of diagnosis, and in those patients with a historic diagnosis of CD; especially as very young children before the introduction of celiac-specific serology.ManagementBest Practice Advice 10: Celiac serology has a guarded role in the detection of continued intestinal injury, in particular as to sensitivity, as negative serology in a treated patient does not guarantee that the intestinal mucosa has healed. Persistently positive serology usually indicates ongoing intestinal damage and gluten exposure. Follow-up serology should be performed 6 and 12 months after diagnosis, and yearly thereafter.Best Practice Advice 11: Patients with persistent or relapsing symptoms, without other obvious explanations for those symptoms, should undergo endoscopic biopsies to determine healing even in the presence of negative TG2-IgA. The purpose of this clinical practice update is to define key modalities in the diagnosis and monitoring of celiac disease (CD) in adults as well as in children and adolescents. The recommendations outlined in this expert review are based on available published evidence, including cohort and case-control studies of the diagnostic process as well as controlled and descriptive studies of disease management. Best Practice Advice 1: Serology is a crucial component of the detection and diagnosis of CD, particularly tissue transglutaminase–immunoglobulin A (TG2-IgA), IgA testing, and less frequently, endomysial IgA testing. Best Practice Advice 2: Thorough histological analysis of duodenal biopsies with Marsh classification, counting of lymphocytes per high-power field, and morphometry is important for diagnosis as well as for differential diagnosis. Best Practice Advice 2a: TG2-IgA, at high levels (> ×10 upper normal limit) is a reliable and accurate test for diagnosing active CD. When such a strongly positive TG2-IgA is combined with a positive endomysial antibody in a second blood sample, the positive predictive value for CD is virtually 100%. In adults, esophagogastroduodenoscopy (EGD) and duodenal biopsies may then be performed for purposes of differential diagnosis. Best Practice Advice 3: IgA deficiency is an infrequent but important explanation for why patients with CD may be negative on IgA isotype testing despite strong suspicion. Measuring total IgA levels, IgG deamidated gliadin antibody tests, and TG2-IgG testing in that circumstance is recommended. Best Practice Advice 4: IgG isotype testing for TG2 antibody is not specific in the absence of IgA deficiency. Best Practice Advice 5: In patients found to have CD first by intestinal biopsies, celiac-specific serology should be undertaken as a confirmatory test before initiation of a gluten-free diet (GFD). Best Practice Advice 6: In patients in whom CD is strongly suspected in the face of negative biopsies, TG2-IgA should still be performed and, if positive, repeat biopsies might be considered either at that time or sometime in the future. Best Practice Advice 7: Reduction or avoidance of gluten before diagnostic testing is discouraged, as it may reduce the sensitivity of both serology and biopsy testing. Best Practice Advice 8: When patients have already started on a GFD before diagnosis, we suggest that the patient go back on a normal diet with 3 slices of wheat bread daily preferably for 1 to 3 months before repeat determination of TG2-IgA. Best Practice Advice 9: Determination of HLA-DQ2/DQ8 has a limited role in the diagnosis of CD. Its value is largely related to its negative predictive value to rule out CD in patients who are seronegative in the face of histologic changes, in patients who did not have serologic confirmation at the time of diagnosis, and in those patients with a historic diagnosis of CD; especially as very young children before the introduction of celiac-specific serology. Best Practice Advice 10: Celiac serology has a guarded role in the detection of continued intestinal injury, in particular as to sensitivity, as negative serology in a treated patient does not guarantee that the intestinal mucosa has healed. Persistently positive serology usually indicates ongoing intestinal damage and gluten exposure. Follow-up serology should be performed 6 and 12 months after diagnosis, and yearly thereafter. Best Practice Advice 11: Patients with persistent or relapsing symptoms, without other obvious explanations for those symptoms, should undergo endoscopic biopsies to determine healing even in the presence of negative TG2-IgA. The concept of Celiac disease (CD) has undergone significant expansion in recent years. At one side, there is increased public concern about the effects of gluten on health and the trend of gluten sensitivity at large; and on the other side, an increasing awareness of the multifaceted symptomatology and systemic effects of CD. CD is strongly genetically dependent and particularly related to the presence of HLA-DQ2/DQ8.1Kuja-Halkola R. Lebwohl B. Halfvarson J. et al.Heritability of non-HLA genetics in coeliac disease: a population-based study in 107 000 twins.Gut. 2016; 65: 1793-1798Crossref PubMed Scopus (67) Google Scholar Furthermore, it is increasingly recognized as a common disease with a prevalence in a number of adult and childhood populations close to 1%.1Kuja-Halkola R. Lebwohl B. Halfvarson J. et al.Heritability of non-HLA genetics in coeliac disease: a population-based study in 107 000 twins.Gut. 2016; 65: 1793-1798Crossref PubMed Scopus (67) Google Scholar, 2Rubio-Tapia A. Ludvigsson J.F. Brantner T.L. et al.The prevalence of celiac disease in the United States.Am J Gastroenterol. 2012; 107 (quiz 1537, 1545): 1538-1544Crossref PubMed Scopus (549) Google Scholar The scope of this article was to give a comprehensive update as to the options and uncertainties related to diagnosis and follow-up of CD. As CD may occur at all ages, a considerable portion of disease-compatible characteristics are universally applicable; whereas other aspects are specifically related to age groups. The diagnosis of CD is variably defined by 4 components: symptoms, the presence of HLA-DQ2/DQ8, celiac antibodies in serum, and duodenal histology. A crucial question3Hill P.G. Holmes G.K. Coeliac disease: a biopsy is not always necessary for diagnosis.Aliment Pharmacol Ther. 2008; 27: 572-577Crossref PubMed Scopus (184) Google Scholar is whether the diagnostic cornerstone, the duodenal biopsy with histological analysis, may be omitted in a proportion of patients who fulfill other diagnostic criteria for CD. Two recent papers in Gastroenterology present evidence on this issue in children.4Wolf J. Petroff D. Richter T. et al.Validation of antibody-based strategies for diagnosis of pediatric celiac disease without biopsy.Gastroenterology. 2017; 153: 410-419.e17Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar, 5Werkstetter K.J. Korponay-Szabo I.R. Popp A. et al.Accuracy in diagnosis of celiac disease without biopsies in clinical practice.Gastroenterology. 2017; 153: 924-935Abstract Full Text Full Text PDF PubMed Scopus (148) Google Scholar Symptoms and signs are an important component of every diagnostic effort, as they bring the patient to the doctor’s office and aid in preliminary problem sorting, even if symptoms are diffuse and multifaceted; as may be the case in CD. Symptoms of CD may be gastrointestinal (eg, diarrhea or constipation) or extraintestinal (eg, dermatitis herpetiformis). The aim is to increase the prevalence of celiac disease in the tested population from 1%, which is the population prevalence, to 5% to 10% or more, where serologic testing and histologic analysis have an increased positive predictive value.6Vermeersch P. Geboes K. Marien G. et al.Defining thresholds of antibody levels improves diagnosis of celiac disease.Clin Gastroenterol Hepatol. 2013; 11 (quiz e32): 398-403Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar Do all symptoms seen with CD carry similar sensitivity and specificity for the disease? Probably not. Data with reporting of different symptoms in a recent pediatric prospective study suggests that malabsorption symptoms (including failure-to-thrive) increase the accuracy of antibody testing from 98% to 100%.5Werkstetter K.J. Korponay-Szabo I.R. Popp A. et al.Accuracy in diagnosis of celiac disease without biopsies in clinical practice.Gastroenterology. 2017; 153: 924-935Abstract Full Text Full Text PDF PubMed Scopus (148) Google Scholar The coexistence of other diseases that are well-known risk factors for CD further supports the likelihood of suspected diagnosis. These include autoimmune diseases, such as type 1 diabetes, autoimmune thyroid disease, autoimmune liver disease and chromosome abnormalities, such as Down and Turner syndrome. Such co-occurrence is of diagnostic value; as CD is present in 5% to 10% of children with type 1 diabetes.7Craig M.E. Prinz N. Boyle C.T. et al.Prevalence of celiac disease in 52,721 youth with type 1 diabetes: international comparison across three continents.Diabetes Care. 2017; 40: 1034-1040Crossref PubMed Scopus (81) Google Scholar Familial occurrence is common, as asymptomatic first-degree relatives of patients with CD in a recent meta-analysis had a 7.5% risk of CD.8Singh P. Arora A. Strand T.A. et al.Global prevalence of celiac disease: systematic review and meta-analysis.Clin Gastroenterol Hepatol. 2018; 16: 823-836.e2Abstract Full Text Full Text PDF PubMed Scopus (625) Google Scholar The discovery of transglutaminase-2 as the major autoantigen in CD8Singh P. Arora A. Strand T.A. et al.Global prevalence of celiac disease: systematic review and meta-analysis.Clin Gastroenterol Hepatol. 2018; 16: 823-836.e2Abstract Full Text Full Text PDF PubMed Scopus (625) Google Scholar led to the development of assays for immunoglobulin (Ig)A transglutaminase antibodies (TG2-IgA). Serological testing for TG2-IgA has become important in the diagnosis of CD based on increasing quality and convenience of assays such as enzyme-linked immunosorbent assay, which are well-suited for automation and high-throughput testing. The IgA endomysial antibody test (EMA) based on fluorescence testing on primate esophagus or human umbilical cord is based on antibody reactivity to tissue-bound TG-2. EMA is more labor-intensive and depends on personal judgment and experience. Assays for deamidated gliadin peptide (DGP) antibodies have been shown to have reasonably high accuracy,8Singh P. Arora A. Strand T.A. et al.Global prevalence of celiac disease: systematic review and meta-analysis.Clin Gastroenterol Hepatol. 2018; 16: 823-836.e2Abstract Full Text Full Text PDF PubMed Scopus (625) Google Scholar although inferior to TG2-IgA. A multitude of commercial assays for TG2-IgA have been developed and standardized, with laboratories encouraged to participate in quality control measures on a national or international basis. TG2-IgA has been used as a screening test in multiple studies and in populations with a low incidence of CD.8Singh P. Arora A. Strand T.A. et al.Global prevalence of celiac disease: systematic review and meta-analysis.Clin Gastroenterol Hepatol. 2018; 16: 823-836.e2Abstract Full Text Full Text PDF PubMed Scopus (625) Google Scholar EMA is well suited for second-line confirmatory testing, as EMA has a high specificity.9Rostami K. Kerckhaert J.P. Tiemessen R. et al.The relationship between anti-endomysium antibodies and villous atrophy in coeliac disease using both monkey and human substrate.Eur J Gastroenterol Hepatol. 1999; 11: 439-442Crossref PubMed Scopus (81) Google Scholar Point-of-care tests have been advocated for screening purposes and results comparable with conventional testing have been obtained.10Korponay-Szabo I.R. Szabados K. Pusztai J. et al.Population screening for coeliac disease in primary care by district nurses using a rapid antibody test: diagnostic accuracy and feasibility study.BMJ. 2007; 335: 1244-1247Crossref PubMed Scopus (128) Google Scholar However, point of care tests may present difficulties with quality control when in the hands of inexperienced users and the advantage of rapid results is rarely decisive in the diagnosis of CD. Who should then be tested for CD and with what tests? A pretest probability of 5% to 10% seems advantageous to obtain significant accuracy,6Vermeersch P. Geboes K. Marien G. et al.Defining thresholds of antibody levels improves diagnosis of celiac disease.Clin Gastroenterol Hepatol. 2013; 11 (quiz e32): 398-403Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar which may be obtained by selecting patients with signs/symptoms consistent with CD or asymptomatic patients in the proper risk groups (eg, type 1 diabetes or first-degree relatives). Population screening data suggests that even in the general population TG2-IgA assays may give reasonable results.11Webb C. Norstrom F. Myleus A. et al.Celiac disease can be predicted by high levels of anti-tissue transglutaminase antibodies in population-based screening.J Pediatr Gastroenterol Nutr. 2015; 60: 787-791Crossref PubMed Scopus (35) Google Scholar CD is strongly influenced by genetic factors, as shown in twin studies,1Kuja-Halkola R. Lebwohl B. Halfvarson J. et al.Heritability of non-HLA genetics in coeliac disease: a population-based study in 107 000 twins.Gut. 2016; 65: 1793-1798Crossref PubMed Scopus (67) Google Scholar with most of the genetic dependence residing in HLA-DQ2 and -DQ8.12Sollid L.M. Markussen G. Ek J. et al.Evidence for a primary association of celiac disease to a particular HLA-DQ alpha/beta heterodimer.J Exp Med. 1989; 169: 345-350Crossref PubMed Scopus (827) Google Scholar A gene dose effect is present as the subtype HLA-DQ2.5 in a homozygous pattern, makes CD likely; whereas heterozygous HLA-DQ2.2, at the other side of the spectrum, makes CD unlikely. The absence of HLA-DQ2/DQ8 has primarily been used to exclude the disease with a high negative predictive value. Recent studies have shown that, in clinical practice, determination of HLA-DQ2/DQ8 is of no additional diagnostic value in cases with a high level of serum TG2-IgA antibodies.5Werkstetter K.J. Korponay-Szabo I.R. Popp A. et al.Accuracy in diagnosis of celiac disease without biopsies in clinical practice.Gastroenterology. 2017; 153: 924-935Abstract Full Text Full Text PDF PubMed Scopus (148) Google Scholar, 13Mitchell R.T. Sun A. Mayo A. et al.Coeliac screening in a Scottish cohort of children with type 1 diabetes mellitus: is DQ typing the way forward?.Arch Dis Child. 2016; 101: 230-233Crossref PubMed Scopus (24) Google Scholar In conclusion, determination of HLA-DQ2/DQ8 may be reserved for second-line evaluation of patients where the diagnosis is doubtful (eg, due to inconclusive celiac antibodies, histology, or prior gluten-free diet [GFD]). The analysis of duodenal biopsy specimens forms the classic diagnosis of CD, and represented an immense leap forward when it was introduced as the diagnostic criterion for CD in the 1950s. Today biopsies should be taken at esophagogastroduodenoscopy (EGD), which allows the possibility of multiple biopsies from different parts of the duodenum. Biopsies from the bulb should be included, taking into account Brunner glands and other variants that may disturb the histologic interpretation.14Mooney P.D. Kurien M. Evans K.E. et al.Clinical and immunologic features of ultra-short celiac disease.Gastroenterology. 2016; 150: 1125-1134Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar, 15TaavelaTaavela J. Kurppa K. Collin P. et al.Degree of damage to the small bowel and serum antibody titers correlate with clinical presentation of patients with celiac disease.Clin Gastroenterol Hepatol. 2013; 11: 166-171.e1Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar The duodenal biopsy has been regarded as the reference standard for the diagnosis of CD, but lack of sampling quality has been suggested in several comparative studies.15TaavelaTaavela J. Kurppa K. Collin P. et al.Degree of damage to the small bowel and serum antibody titers correlate with clinical presentation of patients with celiac disease.Clin Gastroenterol Hepatol. 2013; 11: 166-171.e1Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar, 16Corazza G.R. Villanacci V. Zambelli C. et al.Comparison of the interobserver reproducibility with different histologic criteria used in celiac disease.Clin Gastroenterol Hepatol. 2007; 5: 838-843Abstract Full Text Full Text PDF PubMed Scopus (211) Google Scholar In addition, criticism has been raised as to the quality of duodenal biopsy interpretation,17Arguelles-Grande C. Tennyson C.A. Lewis S.K. et al.Variability in small bowel histopathology reporting between different pathology practice settings: impact on the diagnosis of coeliac disease.J Clin Pathol. 2012; 65: 242-247Crossref PubMed Scopus (89) Google Scholar particularly from nonspecialized pathology departments. The process of placing the biopsy, the subsequent cutting, and formalin fixation demands time and expertise, which is not always available or followed.15TaavelaTaavela J. Kurppa K. Collin P. et al.Degree of damage to the small bowel and serum antibody titers correlate with clinical presentation of patients with celiac disease.Clin Gastroenterol Hepatol. 2013; 11: 166-171.e1Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar In practical terms, 5% of biopsies may lead to diagnostic uncertainty.5Werkstetter K.J. Korponay-Szabo I.R. Popp A. et al.Accuracy in diagnosis of celiac disease without biopsies in clinical practice.Gastroenterology. 2017; 153: 924-935Abstract Full Text Full Text PDF PubMed Scopus (148) Google Scholar Description of the biopsies including positioning, Marsh classification, villus-crypt ratio, and counting of lymphocytes (more than 25 per high power field) to define lymphocytosis is recommended. CD3 staining for T cells may be included.18Rostami K. Marsh M.N. Johnson M.W. et al.ROC-king onwards: intraepithelial lymphocyte counts, distribution & role in coeliac disease mucosal interpretation.Gut. 2017; 66: 2080-2086Crossref PubMed Scopus (46) Google Scholar Gamma/delta T-cell markers19Spencer J. Isaacson P.G. MacDonald T.T. et al.Gamma/delta T cells and the diagnosis of coeliac disease.Clin Exp Immunol. 1991; 85: 109-113Crossref PubMed Scopus (122) Google Scholar as well as IgA transglutaminase antibody deposits20Salmi T.T. Collin P. Korponay-Szabo I.R. et al.Endomysial antibody-negative coeliac disease: clinical characteristics and intestinal autoantibody deposits.Gut. 2006; 55: 1746-1753Crossref PubMed Scopus (215) Google Scholar may be supportive in the analysis. The classic algorithm for the diagnosis of CD in children and adults is to perform an EGD with duodenal biopsies on the background of symptoms attributable to malabsorption or to conditions associated with CD. The development of reliable antibody tests has led to a combination strategy. In adults, all guidelines, including the American College of Gastroenterology guidelines,21Rubio-Tapia A. Hill I.D. Kelly C.P. et al.ACG clinical guidelines: diagnosis and management of celiac disease.Am J Gastroenterol. 2013; 108: 656-676Crossref PubMed Scopus (1164) Google Scholar recommend screening with celiac antibody testing and, if positive, performing a biopsy in populations with a low prevalence (<5%) of CD. The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines from 200522Hill I.D. Dirks M.H. Liptak G.S. et al.Guideline for the diagnosis and treatment of celiac disease in children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.J Pediatr Gastroenterol Nutr. 2005; 40: 1-19Crossref PubMed Scopus (975) Google Scholar recommend performing a biopsy in all cases of suspected CD in children, whereas the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition guidelines from 201223Husby S. Koletzko S. Korponay-Szabo I.R. et al.European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease.J Pediatr Gastroenterol Nutr. 2012; 54: 136-160Crossref PubMed Scopus (1974) Google Scholar recommend using quantitative determination of TG2-IgA for first-line screening (Figure 1). If the antibody titer is above ×10 upper limit of normal in a symptomatic patient, the guidelines give the option to perform further tests (TG2-IgA, EMA, and HLA-DQ2/DQ8) in a second blood sample. If they all are confirmative, the child may be diagnosed with CD provided symptoms subside after the institution of a GFD. In practice, this strategy may reduce the need of EGD by 30% to 50%.5Werkstetter K.J. Korponay-Szabo I.R. Popp A. et al.Accuracy in diagnosis of celiac disease without biopsies in clinical practice.Gastroenterology. 2017; 153: 924-935Abstract Full Text Full Text PDF PubMed Scopus (148) Google Scholar In unclear cases, histological analysis is important, and even an approach with gluten challenge may be warranted. When patients have already started on a GFD before diagnosis, we suggest that the patient goes back on a normal diet with 3 slices of wheat bread daily for 1 to 3 months followed by TG2-IgA determination, although even a shorter period has been advocated. The management and follow-up of patients with CD is preferentially performed with a team-based approach in which the dietician has an important role in the practical advice on lifestyle and choice of foods.24See J.A. Kaukinen K. Makharia G.K. et al.Practical insights into gluten-free diets.Nat Rev Gastroenterol Hepatol. 2015; 12: 580-591Crossref PubMed Scopus (99) Google Scholar Most patients will comply satisfactorily with a GFD and experience relief of their symptoms, as well as decreasing celiac antibody levels. A reasonable follow-up schedule will be every 12 months. An open access or online service, perhaps aided with short message services, may improve adherence.25Sainsbury K. Mullan B. Sharpe L. A randomized controlled trial of an online intervention to improve gluten-free diet adherence in celiac disease.Am J Gastroenterol. 2013; 108: 811-817Crossref PubMed Scopus (63) Google Scholar In children and adolescents, a satisfactory increase in weight and height is an essential marker of the success of the GFD, whereas the adult patients may experience more subtle improvement. Lack of compliance in a GFD may lead to deterioration of quality of life.26Nachman F. del Campo M.P. Gonzalez A. et al.Long-term deterioration of quality of life in adult patients with celiac disease is associated with treatment noncompliance.Dig Liver Dis. 2010; 42: 685-691Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar Long-term side effects of a GFD may be related to lack of vitamins and fiber in the diet. Lack of adherence to GFD may result in symptoms and complications of CD, such as ongoing and worsening of malabsorption, anemia, and osteoporosis. In practice, most adult patients are not followed, as shown in a study from Olmsted County where 35% of patients were adherent to follow-up 4 years after diagnosis.27Herman M.L. Rubio-Tapia A. Lahr B.D. et al.Patients with celiac disease are not followed up adequately.Clin Gastroenterol Hepatol. 2012; 10: 893-899.e1Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar Societal circumstances may affect this percentage, with national differences. Concordantly, the frequency of therapy-resistant CD occurs in a significant proportion of adults (20%).28Rubio-Tapia A. Rahim M.W. See J.A. et al.Mucosal recovery and mortality in adults with celiac disease after treatment with a gluten-free diet.Am J Gastroenterol. 2010; 105: 1412-1420Crossref PubMed Scopus (281) Google Scholar Maybe not surprising, teenagers are less satisfied with the impact of CD on their lives and even less adherent to a GFD. Whether the diagnosis of CD is based on symptoms or objective screening tests seemingly does not influence long-term adherence to GFD.29Kivela L. Kaukinen K. Huhtala H. et al.At-risk screened children with celiac disease are comparable in disease severity and dietary adherence to those found because of clinical suspicion: a large cohort study.J Pediatr. 2017; 183: 115-121.e2Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar Notably, children who are lost to follow-up are more frequently nonadherent to GFD and are antibody-positive.30Barnea L. Mozer-Glassberg Y. Hojsak I. et al.Pediatric celiac disease patients who are lost to follow-up have a poorly controlled disease.Digestion. 2014; 90: 248-253Crossref PubMed Scopus (35) Google Scholar As to malnutrition and growth, routine testing for vitamin and mineral deficiencies seems unnecessary in the large majority of children who attend registered follow-up and grow and develop normally without any symptoms.31Wessels M.M. van Veen I.I. Vriezinga S.L. et al.Complementary serologic investigations in children with celiac disease is unnecessary during follow-up.J Pediatr. 2016; 169: 55-60Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar A key issue in the follow-up is the usefulness of serology; whether a decline in antibody levels is sufficient evidence for proper management. The usefulness of serology has been reported for children, best for EMA, and with a median time for mucosal healing of 2.2 years.32Vecsei E. Steinwendner S. Kogler H. et al.Follow-up of pediatric celiac disease: value of antibodies in predicting mucosal healing, a prospective cohort study.BMC Gastroenterol. 2014; 14: 28Crossref PubMed Scopus (32) Google Scholar In a recent meta-analysis, the positive predictive value and sensitivity of persistently positive TG2-IgA determination was fairly low; with a sensitivity at 0.38 for adults, higher (0.70) for children. The negative predictive value of serology in adult patients on a GFD for 1 year or more was higher, with a specificity of 0.80 for adults, and 0.87 for children.33Silvester J.A. Kurada S. Szwajcer A. et al.Tests for serum transglutaminase and endomysial antibodies do not detect most patients with celiac disease and persistent villous atrophy on gluten-free diets: a meta-analysis.Gastroenterology. 2017; 153: 689-701.e1Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar It may be concluded that the usefulness of serology at follow-up is limited for adults and better for children. A refinement of the TG2-IgA determination utilizing the detectable levels below the upper normal limit may add in the identification of patients with CD with mucosal healing.34Fang H. King K.S. Larson J.J. et al.Undetectable negative tissue transglutaminase IgA antibodies predict mucosal healing in treated coeliac disease patients.Aliment Pharmacol Ther. 2017; 46: 681-687Crossref PubMed Scopus (12) Google Scholar The intestinal biopsies from an EGD are an important tool in the follow-up of CD. Histological evaluation is in essence an evaluation of mucosal healing. If damage equating to at least Marsh 2 changes are still present, another biopsy is required, after 12 months. However, the correlation between symptoms, mucosal healing, and later outcome of CD is not clear. In one study in adults, factors predicting incomplete recovery were malabsorption (55% vs 41%, P = .003), high EMA (46% vs 25%, P < .001), and severe mucosal damage (total atrophy 32% vs 19%, P < .001) at diagnosis.35Pekki H. Kurppa K. Maki M. et al.Performing routine follow-up biopsy 1 year after diagnosis does not affect long-term outcomes in coeliac disease.Aliment Pharmacol Ther. 2017; 45: 1459-1468Crossref PubMed Scopus (24) Google Scholar Symptoms did not reliably predict lack of mucosal healing, and most patients with lack of healing were without symptoms.36Mahadev S. Murray J.A. Wu T.T. et al.Factors associated with villus atrophy in symptomatic coeliac disease patients on a gluten-free diet.Aliment Pharmacol Ther. 2017; 45: 1084-1093Crossref PubMed Scopus (40) Google Scholar However, in large studies, most adult patients did achieve complete mucosal healing.37Haere P. Hoie O. Schulz T. et al.Long-term mucosal recovery and healing in celiac disease is the rule - not the exception.Scand J Gastroenterol. 2016; 51: 1439-1446Crossref PubMed Scopus (46) Google Scholar Irreparable damage in the mucosa may lead to the rare but serious appearance of refractory CD type 1 and type 2, with the latter having a considerable mortality after 5 years.38Rubio-Tapia A. Malamut G. Verbeek W.H. et al.Creation of a model to predict survival in patients with refractory coeliac disease using a multinational registry.Aliment Pharmacol Ther. 2016; 44: 704-714Crossref PubMed Scopus (31) Google Scholar Although failure to heal the intestine was associated with an increased lymphoma risk, it was not associated with excess mortality. However, adequate studies in which all patients have had follow-up biopsies are inadequately powered to address long-term risk of rare events.28Rubio-Tapia A. Rahim M.W. See J.A. et al.Mucosal recovery and mortality in adults with celiac disease after treatment with a gluten-free diet.Am J Gastroenterol. 2010; 105: 1412-1420Crossref PubMed Scopus (281) Google Scholar Even though data are conflicting for adults with lack of mucosal healing; the large majority do well, but with a small risk of nonresponsive CD, which may lead to further complications. Significant changes have occurred in the diagnosis of CD in the past decade, with serology gaining greater clinical importance based on better assay performance. The diagnosis of CD relies on a combination of symptom recognition, serology, and histological analysis of duodenal biopsies. In children and adolescents, repeated serological testing with high TG2-IgA levels may render a gastroscopy with biopsy unnecessary. Cases with IgA deficiency deserve special recognition. Treatment consists foremost of a GFD. It is important not to initiate a GFD before measurement of antibodies and biopsy. Follow-up secures the avoidance of long-term side effects of the GFD and aids the adherence to the GFD. The utility of serology vs histology in follow-up has not been definitively settled. This update was produced by the AGA Institute. Author contributions: All authors contributed equally to the editing, research, and writing of the manuscript." @default.
• W2904016703 created "2018-12-22" @default.
• W2904016703 creator A5066621036 @default.
• W2904016703 creator A5073186855 @default.
• W2904016703 creator A5089464953 @default.
• W2904016703 date "2019-03-01" @default.
• W2904016703 modified "2023-10-17" @default.
• W2904016703 title "AGA Clinical Practice Update on Diagnosis and Monitoring of Celiac Disease—Changing Utility of Serology and Histologic Measures: Expert Review" @default.
• W2904016703 cites W1899913413 @default.
• W2904016703 cites W1953587749 @default.
• W2904016703 cites W1965007454 @default.
• W2904016703 cites W1975400911 @default.
• W2904016703 cites W1983428906 @default.
• W2904016703 cites W1988733464 @default.
• W2904016703 cites W2017600139 @default.
• W2904016703 cites W2019955754 @default.
• W2904016703 cites W2020626093 @default.
• W2904016703 cites W2024063803 @default.
• W2904016703 cites W2026680774 @default.
• W2904016703 cites W2030124936 @default.
• W2904016703 cites W2031954292 @default.
• W2904016703 cites W2042417593 @default.
• W2904016703 cites W2044202223 @default.
• W2904016703 cites W2048796508 @default.
• W2904016703 cites W2090331375 @default.
• W2904016703 cites W2094721384 @default.
• W2904016703 cites W2100548379 @default.
• W2904016703 cites W2102821497 @default.
• W2904016703 cites W2136359243 @default.
• W2904016703 cites W2137700281 @default.
• W2904016703 cites W2194658909 @default.
• W2904016703 cites W2260940905 @default.
• W2904016703 cites W2282837732 @default.
• W2904016703 cites W2395294369 @default.
• W2904016703 cites W2496585964 @default.
• W2904016703 cites W2515189025 @default.
• W2904016703 cites W2581875041 @default.
• W2904016703 cites W2590159237 @default.
• W2904016703 cites W2598348255 @default.
• W2904016703 cites W2607714548 @default.
• W2904016703 cites W2617859352 @default.
• W2904016703 cites W2619612092 @default.
• W2904016703 cites W2626971737 @default.
• W2904016703 cites W2744969343 @default.
• W2904016703 cites W2756086142 @default.
• W2904016703 cites W2792440444 @default.
• W2904016703 doi "https://doi.org/10.1053/j.gastro.2018.12.010" @default.
• W2904016703 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6409202" @default.
• W2904016703 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30578783" @default.
• W2904016703 hasPublicationYear "2019" @default.
• W2904016703 type Work @default.
• W2904016703 sameAs 2904016703 @default.
• W2904016703 citedByCount "148" @default.
• W2904016703 countsByYear W29040167032019 @default.
• W2904016703 countsByYear W29040167032020 @default.
• W2904016703 countsByYear W29040167032021 @default.
• W2904016703 countsByYear W29040167032022 @default.
• W2904016703 countsByYear W29040167032023 @default.
• W2904016703 crossrefType "journal-article" @default.
• W2904016703 hasAuthorship W2904016703A5066621036 @default.
• W2904016703 hasAuthorship W2904016703A5073186855 @default.
• W2904016703 hasAuthorship W2904016703A5089464953 @default.
• W2904016703 hasBestOaLocation W29040167032 @default.
• W2904016703 hasConcept C142724271 @default.
• W2904016703 hasConcept C159654299 @default.
• W2904016703 hasConcept C177713679 @default.
• W2904016703 hasConcept C203014093 @default.
• W2904016703 hasConcept C2779134260 @default.
• W2904016703 hasConcept C45189115 @default.
• W2904016703 hasConcept C71924100 @default.
• W2904016703 hasConceptScore W2904016703C142724271 @default.
• W2904016703 hasConceptScore W2904016703C159654299 @default.
• W2904016703 hasConceptScore W2904016703C177713679 @default.
• W2904016703 hasConceptScore W2904016703C203014093 @default.
• W2904016703 hasConceptScore W2904016703C2779134260 @default.
• W2904016703 hasConceptScore W2904016703C45189115 @default.
• W2904016703 hasConceptScore W2904016703C71924100 @default.
• W2904016703 hasFunder F4320323799 @default.
• W2904016703 hasIssue "4" @default.
• W2904016703 hasLocation W29040167031 @default.
• W2904016703 hasLocation W29040167032 @default.
• W2904016703 hasLocation W29040167033 @default.
• W2904016703 hasLocation W29040167034 @default.
• W2904016703 hasLocation W29040167035 @default.
• W2904016703 hasOpenAccess W2904016703 @default.
• W2904016703 hasPrimaryLocation W29040167031 @default.
• W2904016703 hasRelatedWork W1506200166 @default.
• W2904016703 hasRelatedWork W1995515455 @default.
• W2904016703 hasRelatedWork W2048182022 @default.
• W2904016703 hasRelatedWork W2080531066 @default.
• W2904016703 hasRelatedWork W2604872355 @default.
• W2904016703 hasRelatedWork W2748952813 @default.
• W2904016703 hasRelatedWork W2899084033 @default.
• W2904016703 hasRelatedWork W3031052312 @default.
• W2904016703 hasRelatedWork W3032375762 @default.
• W2904016703 hasRelatedWork W3108674512 @default.
• W2904016703 hasVolume "156" @default.
• W2904016703 isParatext "false" @default.

• next