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For children and adolescents with strong clinical suspicion for celiac disease, repeated transglutaminase-2-IgA (TG2-IgA) levels that are more than 10 times higher than the upper limit of normal often suffices for diagnosis, according to an American Gastroenterological Association clinical practice update and expert review.
This approach precludes the need for esophagogastroduodenoscopy (EGD) in about 30%-50% of cases, wrote Steffen Husby, MD, PhD, of Odense University Hospital (Denmark), together with his associates in Gastroenterology. “When such a strongly positive TG2-IgA is combined with a positive endomysial antibody in a second blood sample, the positive predictive value for celiac disease is virtually 100%.” But for adults, they recommend confirmatory histologic analysis of duodenal biopsies with Marsh classification, counting of lymphocytes per high-power field, and morphometry.
Transglutaminase-2 is the major autoantigen present in celiac disease and can now be assessed with accurate, convenient, high-throughput tests, such as enzyme-linked immunosorbent assays. To maximize test TG2-IgA accuracy, Dr. Husby and his associates recommend testing patients who have compatible signs and symptoms of celiac disease or are asymptomatic but have other risk factors, such as confirmed autoimmune diseases (type 1 diabetes, autoimmune thyroid or liver diseases), chromosome abnormalities (Down or Turner syndrome), or first-degree relatives with celiac disease.
Several other serologic tests are available but have a more limited role in diagnosing celiac disease, according to the practice update. Perhaps most useful is the endomysial antibody (EMA) test, which evaluates tissue-bound TG2-IgA. This test is highly specific but labor-intensive and user-sensitive and thus is best used to confirm a positive TG2-IgA result. Deamidated gliadin peptide antibody assays are less accurate than TG2-IgA, while HLA-DQ2/DQ8 testing is best reserved for cases where the diagnosis is complicated by a prior gluten-free diet or inconclusive antibody titers or histology.
For adults from populations with less than a 5% prevalence of celiac disease, all guidelines recommend following serology with confirmatory biopsy, and the experts concur. If biopsy was part of the initial work-up, they recommend performing confirmatory serology before starting a gluten-free diet. If the biopsy was negative but celiac disease is strongly suspected, they recommend TG2-IgA testing followed by repeat biopsies, when possible, either at the same time or in the future.
For children with suspected celiac disease, the North American Society for Pediatric Gastroenterology Hepatology and Nutrition recommends starting with biopsy, while the European Society for Paediatric Gastroenterology Hepatology and Nutrition suggests starting with quantitative TG2-IgA testing, followed by TG2-IgA, EMA, or HLA-DQ2/DQ8 assays if TG2-IgA is 10 times higher than the upper limit of normal. However, EGD with biopsies and even a gluten challenge may be needed if serology results are unclear, the experts state. They recommend against gluten-free or low-gluten diets prior to diagnosis, since these can lower the sensitivity of both histology and serology. If a patient has unclear test results and is already on a gluten-free diet, they suggest resuming eating three slices of wheat bread daily for 1-3 months, followed by TG2-IgA testing.
A small but important subgroup of patients have strong suspicion for celiac disease but are negative on IgA isotype tests because of IgA deficiency. In such suspected cases, the experts recommend measuring total IgA, IgG deamidated gliadin antibodies, and TG2-IgG levels. They note that IgG isotype testing for TG2 antibodies is not celiac specific outside the setting of IgA deficiency.
Serology has a useful but more limited role in managing celiac disease, according to the practice update. Negative TG2-IgA and other serology does not guarantee that the intestinal mucosa has healed, so patients with ongoing or relapsing symptoms without another obvious cause should have repeat biopsies. However, serology that stays positive over time usually indicates ongoing mucosal damage and gluten exposure, so these follow-up tests are appropriate 6 and 12 months after diagnosing celiac disease and yearly thereafter.
Dr. Husby reported receiving grant support from the University of Southern Denmark, the Region of Southern Denmark, and the Novo Nordisk Research Fund. He also reported receiving payments from Thermo Fisher Scientific and an advisory relationship with Inova. Two coauthors reported ties to Alba Therapeutics, Celimmune, Intrexon, GlaxoSmithKline, and several other pharmaceutical companies.
SOURCE: Husby S et al. Gastroenterology. 2018 Dec 19. doi: 10.1053/j.gastro.2018.12.010.
For children and adolescents with strong clinical suspicion for celiac disease, repeated transglutaminase-2-IgA (TG2-IgA) levels that are more than 10 times higher than the upper limit of normal often suffices for diagnosis, according to an American Gastroenterological Association clinical practice update and expert review.
This approach precludes the need for esophagogastroduodenoscopy (EGD) in about 30%-50% of cases, wrote Steffen Husby, MD, PhD, of Odense University Hospital (Denmark), together with his associates in Gastroenterology. “When such a strongly positive TG2-IgA is combined with a positive endomysial antibody in a second blood sample, the positive predictive value for celiac disease is virtually 100%.” But for adults, they recommend confirmatory histologic analysis of duodenal biopsies with Marsh classification, counting of lymphocytes per high-power field, and morphometry.
Transglutaminase-2 is the major autoantigen present in celiac disease and can now be assessed with accurate, convenient, high-throughput tests, such as enzyme-linked immunosorbent assays. To maximize test TG2-IgA accuracy, Dr. Husby and his associates recommend testing patients who have compatible signs and symptoms of celiac disease or are asymptomatic but have other risk factors, such as confirmed autoimmune diseases (type 1 diabetes, autoimmune thyroid or liver diseases), chromosome abnormalities (Down or Turner syndrome), or first-degree relatives with celiac disease.
Several other serologic tests are available but have a more limited role in diagnosing celiac disease, according to the practice update. Perhaps most useful is the endomysial antibody (EMA) test, which evaluates tissue-bound TG2-IgA. This test is highly specific but labor-intensive and user-sensitive and thus is best used to confirm a positive TG2-IgA result. Deamidated gliadin peptide antibody assays are less accurate than TG2-IgA, while HLA-DQ2/DQ8 testing is best reserved for cases where the diagnosis is complicated by a prior gluten-free diet or inconclusive antibody titers or histology.
For adults from populations with less than a 5% prevalence of celiac disease, all guidelines recommend following serology with confirmatory biopsy, and the experts concur. If biopsy was part of the initial work-up, they recommend performing confirmatory serology before starting a gluten-free diet. If the biopsy was negative but celiac disease is strongly suspected, they recommend TG2-IgA testing followed by repeat biopsies, when possible, either at the same time or in the future.
For children with suspected celiac disease, the North American Society for Pediatric Gastroenterology Hepatology and Nutrition recommends starting with biopsy, while the European Society for Paediatric Gastroenterology Hepatology and Nutrition suggests starting with quantitative TG2-IgA testing, followed by TG2-IgA, EMA, or HLA-DQ2/DQ8 assays if TG2-IgA is 10 times higher than the upper limit of normal. However, EGD with biopsies and even a gluten challenge may be needed if serology results are unclear, the experts state. They recommend against gluten-free or low-gluten diets prior to diagnosis, since these can lower the sensitivity of both histology and serology. If a patient has unclear test results and is already on a gluten-free diet, they suggest resuming eating three slices of wheat bread daily for 1-3 months, followed by TG2-IgA testing.
A small but important subgroup of patients have strong suspicion for celiac disease but are negative on IgA isotype tests because of IgA deficiency. In such suspected cases, the experts recommend measuring total IgA, IgG deamidated gliadin antibodies, and TG2-IgG levels. They note that IgG isotype testing for TG2 antibodies is not celiac specific outside the setting of IgA deficiency.
Serology has a useful but more limited role in managing celiac disease, according to the practice update. Negative TG2-IgA and other serology does not guarantee that the intestinal mucosa has healed, so patients with ongoing or relapsing symptoms without another obvious cause should have repeat biopsies. However, serology that stays positive over time usually indicates ongoing mucosal damage and gluten exposure, so these follow-up tests are appropriate 6 and 12 months after diagnosing celiac disease and yearly thereafter.
Dr. Husby reported receiving grant support from the University of Southern Denmark, the Region of Southern Denmark, and the Novo Nordisk Research Fund. He also reported receiving payments from Thermo Fisher Scientific and an advisory relationship with Inova. Two coauthors reported ties to Alba Therapeutics, Celimmune, Intrexon, GlaxoSmithKline, and several other pharmaceutical companies.
SOURCE: Husby S et al. Gastroenterology. 2018 Dec 19. doi: 10.1053/j.gastro.2018.12.010.
For children and adolescents with strong clinical suspicion for celiac disease, repeated transglutaminase-2-IgA (TG2-IgA) levels that are more than 10 times higher than the upper limit of normal often suffices for diagnosis, according to an American Gastroenterological Association clinical practice update and expert review.
This approach precludes the need for esophagogastroduodenoscopy (EGD) in about 30%-50% of cases, wrote Steffen Husby, MD, PhD, of Odense University Hospital (Denmark), together with his associates in Gastroenterology. “When such a strongly positive TG2-IgA is combined with a positive endomysial antibody in a second blood sample, the positive predictive value for celiac disease is virtually 100%.” But for adults, they recommend confirmatory histologic analysis of duodenal biopsies with Marsh classification, counting of lymphocytes per high-power field, and morphometry.
Transglutaminase-2 is the major autoantigen present in celiac disease and can now be assessed with accurate, convenient, high-throughput tests, such as enzyme-linked immunosorbent assays. To maximize test TG2-IgA accuracy, Dr. Husby and his associates recommend testing patients who have compatible signs and symptoms of celiac disease or are asymptomatic but have other risk factors, such as confirmed autoimmune diseases (type 1 diabetes, autoimmune thyroid or liver diseases), chromosome abnormalities (Down or Turner syndrome), or first-degree relatives with celiac disease.
Several other serologic tests are available but have a more limited role in diagnosing celiac disease, according to the practice update. Perhaps most useful is the endomysial antibody (EMA) test, which evaluates tissue-bound TG2-IgA. This test is highly specific but labor-intensive and user-sensitive and thus is best used to confirm a positive TG2-IgA result. Deamidated gliadin peptide antibody assays are less accurate than TG2-IgA, while HLA-DQ2/DQ8 testing is best reserved for cases where the diagnosis is complicated by a prior gluten-free diet or inconclusive antibody titers or histology.
For adults from populations with less than a 5% prevalence of celiac disease, all guidelines recommend following serology with confirmatory biopsy, and the experts concur. If biopsy was part of the initial work-up, they recommend performing confirmatory serology before starting a gluten-free diet. If the biopsy was negative but celiac disease is strongly suspected, they recommend TG2-IgA testing followed by repeat biopsies, when possible, either at the same time or in the future.
For children with suspected celiac disease, the North American Society for Pediatric Gastroenterology Hepatology and Nutrition recommends starting with biopsy, while the European Society for Paediatric Gastroenterology Hepatology and Nutrition suggests starting with quantitative TG2-IgA testing, followed by TG2-IgA, EMA, or HLA-DQ2/DQ8 assays if TG2-IgA is 10 times higher than the upper limit of normal. However, EGD with biopsies and even a gluten challenge may be needed if serology results are unclear, the experts state. They recommend against gluten-free or low-gluten diets prior to diagnosis, since these can lower the sensitivity of both histology and serology. If a patient has unclear test results and is already on a gluten-free diet, they suggest resuming eating three slices of wheat bread daily for 1-3 months, followed by TG2-IgA testing.
A small but important subgroup of patients have strong suspicion for celiac disease but are negative on IgA isotype tests because of IgA deficiency. In such suspected cases, the experts recommend measuring total IgA, IgG deamidated gliadin antibodies, and TG2-IgG levels. They note that IgG isotype testing for TG2 antibodies is not celiac specific outside the setting of IgA deficiency.
Serology has a useful but more limited role in managing celiac disease, according to the practice update. Negative TG2-IgA and other serology does not guarantee that the intestinal mucosa has healed, so patients with ongoing or relapsing symptoms without another obvious cause should have repeat biopsies. However, serology that stays positive over time usually indicates ongoing mucosal damage and gluten exposure, so these follow-up tests are appropriate 6 and 12 months after diagnosing celiac disease and yearly thereafter.
Dr. Husby reported receiving grant support from the University of Southern Denmark, the Region of Southern Denmark, and the Novo Nordisk Research Fund. He also reported receiving payments from Thermo Fisher Scientific and an advisory relationship with Inova. Two coauthors reported ties to Alba Therapeutics, Celimmune, Intrexon, GlaxoSmithKline, and several other pharmaceutical companies.
SOURCE: Husby S et al. Gastroenterology. 2018 Dec 19. doi: 10.1053/j.gastro.2018.12.010.
FROM GASTROENTEROLOGY