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Guideline for the Diagnosis and Treatment of Celiac Disease in Children: Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition
Abstract
Celiac disease is an immune-mediated enteropathy caused by a permanent sensitivity to gluten in genetically susceptible individuals. It occurs in children and adolescents with gastrointestinal symptoms, dermatitis herpetiformis, dental enamel defects, osteoporosis, short stature, delayed puberty and persistent iron deficiency anemia and in asymptomatic individuals with type 1 diabetes, Down syndrome, Turner syndrome, Williams syndrome, selective immunoglobulin (Ig)A deficiency and first degree relatives of individuals with celiac disease. The Celiac Disease Guideline Committee of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition has formulated a clinical practice guideline for the diagnosis and treatment of pediatric celiac disease based on an integration of a systematic review of the medical literature combined with expert opinion. The Committee examined the indications for testing, the value of serological tests, human leukocyte antigen (HLA) typing and histopathology and the treatment and monitoring of children with celiac disease. It is recommended that children and adolescents with symptoms of celiac disease or an increased risk for celiac disease have a blood test for antibody to tissue transglutaminase (TTG), that those with an elevated TTG be referred to a pediatric gastroenterologist for an intestinal biopsy and that those with the characteristics of celiac disease on intestinal histopathology be treated with a strict gluten-free diet. This document represents the official recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition on the diagnosis and treatment of celiac disease in children and adolescents.
... The adoption of GFD should be initiated only after confirmed diagnosis [16,17], as it is a lifelong commitment with challenges of compliance and barriers to access to gluten-free foods [18,19], and most importantly, it is economically burdensome [19]. Children with CD should be monitored for symptom improvement, compliance, and quality of life [20]. ...
... A strict diet excluding all gluten-containing foods [24,52] is the only treatment for CD [51,57]. In addition to its therapeutic role, it helps confirm the diagnosis [17,72,73] and completely eliminate the symptoms of the disease [74]. Despite the spectacular results of the GFD [15,75], particularly in children [15], and its relative simplicity [15], in practice, it is restrictive, difficult to follow [15,16], and presents real challenges [74]. ...
... Good GFD compliance leads to rapid clinical improvement [22,24,79], enhances quality of life [80,81], reduces the occurrence of complications [14,75], and guarantees a normal life expectancy [82]. This clinical improvement after GFD is used to assess the effectiveness of the treatment [17,22,24]. Clinical improvement is observed in 70%-95% of patients with CD [65]. ...
A gluten-free diet (GFD) is the only scientifically proven treatment for celiac disease (CD). Strict adherence to this diet in children yields excellent results in terms of the clinical symptoms present at the time of diagnosis. Despite the constraints associated with following this diet, it remains the only hope for children with CD to have a better quality of life and life expectancy.
Methods: A retrospective descriptive cohort study was carried out on children diagnosed with CD in the pediatrics department of the Hassan II University Hospital in Fez, Morocco. The children were followed up for 18 months, during which time they were seen as outpatients at different frequencies depending on their clinical condition and degree of compliance with the diet.
Results: Only half of the diagnosed children continued to follow our structure. Compliance with the gluten-free diet varied from 58.7% (n = 84) of children who strictly followed the GFD to 3.5% (n = 5) of children who never followed the diet. Compliance was significantly correlated with the child's age, with adolescents being the least compliant (p = 0.03). Similarly, a correlation was observed between compliance with the diet and the disappearance of symptoms (p <0.01), the persistence of certain symptoms (p = 0.02), and the occurrence of complications (p = 0.01). The majority of children (87.3%) had their clinical symptoms resolved within a mean delay of 6.4±3.6 months, with a mode of three months. The speed of symptom resolution differed from one symptom to another but remained statistically correlated with the degree of GFD compliance (p = 0.03).
Conclusion: Despite the excellent results of a GFD on clinical symptoms in children, the discrepancies observed between compliance and non-compliance call for close follow-up of children with CD to avoid complications and repercussions on the vital prognosis in adulthood.
... The detection of CD -speci c IgA autoantibodies against the enzyme tissue transglutaminase (tTG IgA) is an accurate screening tool to diagnose or identify patients at risk for CD (14). Given the relatively high prevalence of IgA de ciency in relation to other autoimmune diseases in patients with CD, evaluation of this de ciency and use of CD-speci c antibodies is recommended by current guidelines (15). The objective of the present study was to investigate the prevalence of IgA de ciency and tTG IgA antibodies in a large JIA cohort compared to healthy autoimmunity free controls. ...
... N: There were no differences in tTG positivity between cases and controls after strati cation by sex or race/ethnicity. Abbreviations DISCUSSION Celiac disease, de ned as a sensitivity to gluten in wheat and related proteins found in barley and rye, occurs in genetically susceptible individuals and manifests as an immune-mediated enteropathy as de ned by changes seen on intestinal histology (15). The prevalence of CD in persons older than 6 years of age and younger than 20 years has been estimated to be 1.2% for non-Hispanic whites, 0.2% for Hispanics, and 0.1% for non-Hispanic blacks (17). ...
... Treatment consists of lifelong exclusion of gluten from the diet. Since asymptomatic individuals with some autoimmune disorders and chromosomal abnormalities can have a higher prevalence of CD, screening is recommended for speci c populations (15,18). ...
Background: The prevalence of Celiac Disease (CD) in Juvenile Idiopathic Arthritis (JIA) has been reported to be 0.1% to 7% in various small studies. As a result of the limited number of research and their inconclusive results there are no clear recommendations for routine CD screening in asymptomatic patients with JIA. Our aim is to estimate the prevalence of IgA deficiency and tissue transglutaminase (tTG) IgA in a cohort of JIA followed in two large academic medical centers.
Methods: Serum was collected and stored from all subjects and analyzed in a reference laboratory for total IgA (Quantitative Nephelometry) and tTG IgA antibody levels (Semi-Quantitative Enzyme-Linked Immunosorbent Assay). Fisher’s exact tests were performed for statistical significance. Risk estimates (odds ratios) with 95% confidence intervals were calculated.
Results: 808 JIA and 140 controls were analyzed. Majority were non-Hispanic whites (72% vs 68% p=ns). A total of 1.2% of cases were IgA deficient compared to none of the controls (p=0.373). After excluding IgA deficient subjects, 2% of cases had tTG IgA >4u/mL compared to 3.6% of controls (p=0.216) (OR = 0.5; 95% C.I= 0.1-1.4); and 0.8% of cases had tTG IgA >10u/mL compared to 1.4% of controls (p=0.627) (OR=0.5; 95%C.I=0.1-2.9).
Conclusions: Using the largest JIA cohort to date to investigate prevalence of celiac antibodies, the prevalence of positive tTG IgA was 0.8% and of IgA deficiency was 1.2%. The results did not demonstrate a higher prevalence of abnormal tTG IgA in JIA. The study did not support the routine screening of asymptomatic JIA patients for Celiac Disease (CD).
... The detection of CD -specific IgA autoantibodies against the enzyme tissue transglutaminase (tTG IgA) is an accurate screening tool to diagnose or identify patients at risk for CD [13]. Given the relatively high prevalence of IgA deficiency in relation to other autoimmune diseases in patients with CD, evaluation of this deficiency and use of CD -specific IgA autoantibodies against the enzyme tissue transglutaminase (tTG IgA) is recommended by current North American Society for Pediatric Gastroenterology, Hepatology and Nutrition guidelines [14]. ...
... Celiac disease, defined as a sensitivity to gluten in wheat and related proteins found in barley and rye, occurs in genetically susceptible individuals and manifests as an immune-mediated enteropathy as defined by changes seen on intestinal histology [14]. The prevalence of CD in persons older than 6 years of age and younger than 20 years has been estimated to be 1.2% for non-Hispanic whites, 0.2% for Hispanics, and 0.1% for non-Hispanic blacks [15]. ...
... Treatment consists of lifelong exclusion of gluten from the diet. Since asymptomatic individuals with some autoimmune disorders and chromosomal abnormalities can have a higher prevalence of CD, screening is recommended for specific populations [14,16]. ...
Background
The prevalence of Celiac Disease (CD) in Juvenile Idiopathic Arthritis (JIA) has been reported to be 0.1–7% in various small studies. As a result of the limited number of research and their inconclusive results there are no clear recommendations for routine CD screening in asymptomatic patients with JIA. Our aim is to estimate the prevalence of IgA deficiency and tissue transglutaminase (tTG) IgA in a cohort of JIA followed in two large academic medical centers.
Methods
Serum was collected and stored from all subjects and analyzed in a reference laboratory for total IgA (Quantitative Nephelometry) and tTG IgA antibody levels (Semi-Quantitative Enzyme-Linked Immunosorbent Assay). Fisher’s exact tests were performed for statistical significance. Risk estimates (odds ratios) with 95% confidence intervals were calculated.
Results
808 JIA cases and 140 controls were analyzed. Majority were non-Hispanic whites (72% vs. 68% p = 0.309). A total of 1.2% of cases were IgA deficient compared to none of the controls (p = 0.373). After excluding IgA deficient subjects, 2% of cases had tTG IgA ≥ 4u/mL compared to 3.6% of controls (p = 0.216) (OR = 0.5; 95% C.I = 0.1–1.4); and 0.8% of cases had tTG IgA > 10u/mL compared to 1.4% of controls (p = 0.627) (OR = 0.5; 95%C.I = 0.1–2.9).
Conclusions
Using the largest JIA cohort to date to investigate prevalence of celiac antibodies, the prevalence of positive tTG IgA was 0.8% and of IgA deficiency was 1.2%. The results did not demonstrate a higher prevalence of abnormal tTG IgA in JIA. The study did not support the routine screening of asymptomatic JIA patients for CD.
... This complex is perceived as an antigen and proinflammatory cytokines form. As a result of inflammation created in the small intestine mucosa by cytokines, hyperplasia and villous atrophy develop in the intestinal crypts [7]. Celiac disease is seen more often in those with a family history, especially in a first-degree relative, and in those with diseases such as immunoglobulin A(IgA) deficiency, autoimmune thyroiditis, and type 1 diabetes mellitus [7]. ...
... As a result of inflammation created in the small intestine mucosa by cytokines, hyperplasia and villous atrophy develop in the intestinal crypts [7]. Celiac disease is seen more often in those with a family history, especially in a first-degree relative, and in those with diseases such as immunoglobulin A(IgA) deficiency, autoimmune thyroiditis, and type 1 diabetes mellitus [7]. The clinical findings of celiac disease are seen in a wide spectrum. ...
... Typical findings in children are abdominal pain, diarrhea, abdominal swelling, constipation, weight loss and retarded growth [8]. Atypical findings may include osteoporosis, dermatitis herpetiformis, listlessness, anemia, short stature, delayed puberty, and moderately elevated liver enzymes [7]. Tissue transglutaminase (TG) IgA antibody level has 99% sensitivity in the diagnosis of celiac disease [8], but small intestine biopsy is accepted as the gold standard in diagnosis [7]. ...
... Most of the patients have minimum of 1 of Human Leukocyte Antigen (HLA) DQ2/DQ8 alleles (4). It was reported that celiac disease is observed more frequently among those having celiac disease history of first-degree relatives and those having conditions such as immunoglobulin A (IgA) deficiency, autoimmune thyroiditis, and type 1 diabetes mellitus (DM) (6). Clinical findings range in a wide spectrum from asymptomatic disease to severe malnutrition and celiac attack. ...
... Atypical symptoms are mode commonly seen among adults. Atypical symptoms include osteoporosis, dermatitis herpetiformis, exhaustion, anemia, short stature, delayed puberty, and moderately high level of liver enzymes (6). Celiac disease diagnosis has 99% sensitivity to the tissue transglutaminase IgA (tTG IgA) antibody level (7). ...
... Celiac disease diagnosis has 99% sensitivity to the tissue transglutaminase IgA (tTG IgA) antibody level (7). Small intestine biopsy is still considered as the golden standard for the diagnosis (6). In the present study, anthropometric, clinical, and laboratory findings of pediatric cases diagnosed within 2-year period in a tertiary healthcare facility in the Southeastern Anatolian region, where celiac disease is widely seen in Turkey, and the pathological results of endoscopic biopsies were retrospectively examined. ...
Background: The aim of this study is to evaluate the medical parameters of celiac disease cases in the preschool age group in terms of public health and to make recommendations to health professionals, policy makers and the society. Materials and Methods: This study was conducted between February 2017 and December 2018 in Şanlıurfa Education and Research Hospital, Pediatric Gastroenterology Clinic. Clinical and laboratory findings of preschool children diagnosed with celiac disease were retrospectively analyzed. Anamnesis, physical examination findings, laboratory findings, endoscopic biopsies and pathology results of pati-ents were evaluated. Results: The most common presenting complaint was growth retardation (96.3%), followed by chronic diarrhea (32.5%) and constipation (27.5%). Height-for-age and weight-for-age values were found to be lower in patients with chronic diarrhea and duodenitis compared to those without (p<0.05). Patients with strong positive tissue transglutaminase-IgA (tTG IgA) levels had significantly higher Marsh scores (p<0.05). Conclusions: For preschool-age children, initiating the diet via early diagnosis and ensuring adherence to diet are the main objectives. Children adhering to the diet have a higher success in elementary school and a shorter adaptation period.
... (1,2). Currently, the only known treatment for controlling the symptoms and complications of this disease is a glutenfree diet (2).Untreated CD is associated with an increased risk of many complications associated with the impaired nutritional status of patients (3)(4)(5)(6). ...
... . Currently, the only known treatment for controlling the symptoms and complications of this disease is a glutenfree diet (2). ...
... In this regard, studies have shown that even after the healing of the small intestinal mucosa, the recovery of iron stores may take a relatively long time. Thus, iron deficiency may be an important nutritional problem in CD patients (2,15). In addition, although mandatory wheat flour fortification has been applied on a global scale, these rules do not apply to gluten-free flour. ...
Aim:
This study aimed to assess the status of iron stores and the frequency of iron deficiency anemia in Celiac disease (CD) patients referred to the Golestan Research Center of Gastroenterology and Hepatology, Gorgan, Iran.
Background:
Studies have shown that nutritional deficiencies affect 20-38% of patients with CD due to malabsorption and as a result of a gluten-free diet.
Methods:
In this study, 59 out of 100 CD patients were assessed. The presence and severity of anemia were determined using the concentration of serum hemoglobin according to WHO criteria. The status of body iron stores was also assessed based on serum ferritin levels.
Results:
Mean and SD of age, duration of disease, serum hemoglobin, ferritin, TIBC, and serum iron were 39.9±11.9 years, 69.8±45.4 months, 12.6±1.99 g/dl, 54.3±55.3 mg/dL, 365.9±49.1 μg/dL, and 84.1±37.1 μg/dL, respectively. 68.42% had no anemia, 19.3% had mild anemia, 8.77% had moderate anemia, and 3.51% had severe anemia. 25.42% of patients had depleted iron stores, 71.19% had normal iron stores, and 3.39% were exposed to iron overload. There was a statistically significant correlation between serum hemoglobin and the duration of disease diagnosis (P=0.037, r=0.302).
Conclusion:
In this study, 31.58% of CD patients on a gluten-free diet had some degree of anemia. In addition, 25.42% of patients had depleted iron stores. These results suggest that CD patients should be evaluated for iron status, even with a gluten-free diet.
... If a patient has high levels of Anti tTG-IgA, a duodenal biopsy is typically recommended as the gold standard for confirming a diagnosis of CD (9). The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), the National Institute for Health and Care Excellence (NICE), and the North American Society for Paediatric Gastroenterology Hepatology and Nutrition (NASPHGAN) have all recognized that certain "at-risk" groups have a higher prevalence of CD (10)(11)(12). Individuals with type 1 diabetes, unexplained anemia, Trisomy 21 (Down syndrome), delayed growth, and autoimmune thyroid disease are considered to be at higher risk for CD, and are recommended to be screened for the condition (10)(11)(12). ESPGHAN has established diagnostic criteria for CD in children, with a shift towards non-invasive and more accurate serological testing. ...
... The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), the National Institute for Health and Care Excellence (NICE), and the North American Society for Paediatric Gastroenterology Hepatology and Nutrition (NASPHGAN) have all recognized that certain "at-risk" groups have a higher prevalence of CD (10)(11)(12). Individuals with type 1 diabetes, unexplained anemia, Trisomy 21 (Down syndrome), delayed growth, and autoimmune thyroid disease are considered to be at higher risk for CD, and are recommended to be screened for the condition (10)(11)(12). ESPGHAN has established diagnostic criteria for CD in children, with a shift towards non-invasive and more accurate serological testing. The updated ESPGHAN guidelines, released in 2020, now allow for serological diagnosis of CD in children who meet certain clinical, genetic, and serologic criteria, without the need for biopsy confirmation (11). ...
... AlNababteh et al. 10.3389/fped.2023.1197612 ...
Introduction
Celiac disease (CD) is an autoimmune disorder that is provoked by the consumption of gluten in genetically vulnerable individuals. CD affects individuals worldwide with an estimated prevalence of 1% and can manifest at any age. Growth retardation and anemia are common presentations in children with CD. The objective of this study is to estimate the prevalence of CD in multiple “at risk groups” and to characterize children with CD, presented to a tertiary hospital in Dubai, United Arab Emirates (UAE).
Methods
The study reviewed medical charts of all patients <18 years who had received serologic testing for CD. The study was conducted at Al Jalila Children's Specialty Hospital in Dubai, UAE, from January 2018 to July 2021. Extracted information from medical records included sociodemographics, laboratory findings, clinical presentation, and any associated co-morbidities. The European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) criteria were used to identify patients with CD.
Results
During the study period, 851 paediatric patients underwent serological screening for CD, out of which, 23 (2.7%) were confirmed with CD. Of the 23 patients diagnosed with CD, 43.5% had no gastrointestinal symptoms. Diabetes type 1 (30.4%) followed by iron deficiency anaemia (30%) and Hashimoto thyroiditis (9%) were the most commonly associated comorbidities. The prevalence of CD among paediatric patients with autoimmune thyroiditis (12.5%) was 1.92-times higher than that among paediatric patients with diabetes type 1 (6.5%).
Conclusion
The results of this study show that almost three out of every 100 paediatric patients who were screened for CD were confirmed to have the condition. These findings highlight the importance of screening children who are at risk or present symptoms suggestive of CD, to ensure early diagnosis and appropriate management.
... Initial screening for CD with serum tissue transglutaminase (tTG) immunoglobulin A (IgA) levels is the current recommendation by most consensus authorities (4)(5)(6). Additionally, current international guidelines suggest that together with anti-tTG IgA antibodies, a total IgA serum level must also be measured to exclude an IgA deficiency that could cause a false-negative anti-tTG IgA result (7). Although having a positive tTG IgA level is both sensitive (99%) and specific (75%) for CD, the precise tTG IgA value does not correlate with the extent of luminal or extra-luminal disease severity according to the published literature (5). ...
... Timely access to endoscopy also represents a challenge in readily confirming a CD diagnosis. If there is a delay in a child receiving an endoscopy, symptoms may persist causing discomfort for the child as guidelines recommend treatment only after a diagnosis has been confirmed (4). Treatment for CD involves a strict adherence to a gluten-free diet for life, and patients with CD who are still ingesting gluten for long periods of time may be at risk for many health concerns (2,4). ...
... If there is a delay in a child receiving an endoscopy, symptoms may persist causing discomfort for the child as guidelines recommend treatment only after a diagnosis has been confirmed (4). Treatment for CD involves a strict adherence to a gluten-free diet for life, and patients with CD who are still ingesting gluten for long periods of time may be at risk for many health concerns (2,4). ...
... In approximately 75% of celiac disease patients, a gluten-free diet (GFD) results in complete or significant regeneration of the damaged intestinal mucosa [13]. Currently, strict adherence to a lifelong GFD is the only accepted treatment for celiac disease [14]. However, 10% to 19% of patients do not respond to a GFD and represent the non-responsive form of celiac disease [15]. ...
... Примерно у 75% пациентов с целиакией безглютеновая диета (БГД) приводит к полному или значительному восстановлению поврежденной слизистой оболочки кишечника [13]. В настоящее время строгое пожизненное соблюдение БГД является единственным общепринятым методом лечения целиакии [14]. Однако от 10 до 19% пациентов не отвечают на БГД и у них диагностируют резистентную форму целиакии [15]. ...
Background and Objective. Celiac disease (CeD) is an autoimmune condition characterized by specific serological and tissue characteristics resulting from gluten consumption in genetically predisposed individuals. The only currently treatment available for CeD is strict lifelong adherence to a gluten-free diet (GFD), which leads to remission. This study aimed to evaluate leptin and ghrelin serum levels in celiac patients before and after treatment with a gluten-free diet. Patients and Methods. Thirty patients aged 3 to 50 years with CeD and 30 age- and gender-matched healthy controls were included in the study. Serum levels of leptin and ghrelin in patients before GFD and after four months of GFD treatment were measured using ELISA kits. Results. The mean serum ghrelin concentration in celiac cases decreased from 653.6 pg/ml to 483.2 pg/ml after GFD treatment (p < 0.001). Although the mean serum ghrelin concentration before treatment was not significantly different between the case and control groups, it was significantly lower in celiac patients than in the control group after treatment (p < 0.001). The average concentration of serum leptin in the control group was significantly higher than before and after the treatment of celiac patients, but the average concentration of serum leptin in celiac patients did not change significantly after GFD treatment (p = 0.298). Conclusion. In conclusion, this study suggests that a GFD can positively affect the levels of leptin and ghrelin hormones in celiac patients. Key words: celiac disease, leptin, ghrelin, gluten-free diet
... The screening and diagnosis of CD in T1D children are challenging. According to the guidelines of the American Diabetes Association (ADA) [29], the International Society for Pediatric and Adolescent Diabetes (ISPAD) [12], and the NASPGHAN [9,30], T1D children should be screened by TGA and/or EMA at the time of diagnosis and at different time points thereafter. With persistent CD antibodies, children should be referred to intestinal biopsy. ...
... It is important to make an accurate CD diagnosis in T1D in order to start a gluten-free diet (GFD) when necessary. Depending on ADA, ISPAD or NASPGHAN, a GFD should be started in symptomatic or even in asymptomatic T1D children with CD [9,12,29,30]. It is well known that a GFD can have psychological consequences, but T1D patients with CD have an increased risk of diabetic retinopathy, cardiovascular complications, and a reduced life expectancy in comparison to non-CD T1D patients. ...
Background and Objectives: Patients with type 1 diabetes (T1D) are considered at high-risk for developing celiac disease (CD). The purpose of our study was to determine the prevalence of CD among children who were followed in our unit for T1D using the latest ESPGHAN guidelines, and avoiding intestinal biopsies in some of the children. Materials and Methods: We performed a prospective monocentric study, which included 663 T1D children between June 2014 and June 2016. We considered CD according to serological (tissue transglutaminase (TGAs) and endomysium antibodies) results. Children were included either at the time of T1D diagnosis or during their follow up. We looked for clinical and biochemical signs of CD, and for T1D characteristics. Results: The children’s ages ranged from 11 months to 18 years. CD was confirmed in 32 out of 663 patients with T1D, with a prevalence of 4.8%. CD was excluded in 619 children and remained uncertain for 12 children, who had positive TGAs without the required criteria. We found that 95% of T1D children express HLA-DQ2 and/or -DQ8, which was 2.4 times higher than in the general population. Conclusions: An intestinal biopsy could be avoided to confirm CD in the majority of T1D children. Silent forms of CD are frequent and screening is recommended for all patients. Importantly, repeated TGA assessment is required in HLA genetically predisposed T1D patients, while it is unnecessary in the 5% who are HLA-DQ2 and -DQ8 negative.
... La pacienţii adulţi cu celiachie, ce nu se află sub tratament, sunt dovezi că transaminazele hepatice au valori crescute (alanin aminotransferaza şi aspartat aminotransferaza) (7). Sunt studii efectuate la pacienţii adulţi care consideră că peste 9% dintre pacienţii cu origine necunoscută a sindromului de hepatocitoliză dezvoltă o formă silenţioasă a bolii celiace (8). ...
... Iniţierea dietei fără gluten este recomandată după confirmarea histologică a diagnosticului. Leziunile histologice la copil se remit de obicei după 3 sau 6 luni de la începerea dietei (7). Rapiditatea şi amploarea remisiei leziunilor histologice apar invariabil după îmbunătăţirea stării clinice. ...
Celiac disease is an autoimmune disorder of the gastrointestinal tract. The condition may develop at any age, triggered by exposure to dietary gluten in genetically susceptible individuals. The most frequent intestinal manifestations include diarrhea and weight loss. Common extradigestive manifestations include iron deficiency anemia, dermatitis herpetiformis. The authors presents a clinical case diagnosed with celiac disease expressed with gastrointestinal and extradigestive symptoms, such as abdominal pain, flatulence, anemia, impaired hepatic function and dermatitis herpetiformis.
... The prevalence of Down syndrome is independent of geographic location. The CD Guideline Committee of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) recommends CD screening for asymptomatic Down syndrome children [53], and the American Academy of Pediatrics recommends testing for CD in Down syndrome children with CD-related symptoms [54]. According to the latest recommendations of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) from 2012, HLA-DQ2 and HLA-DQ8 typing should be the first line of screening for CD in cases of Down syndrome [55]. ...
... If the diagnosis is delayed, failure to thrive, irritability, and severe malnutrition can be seen. Gastrointestinal symptoms, such as diarrhea, nausea, vomiting, abdominal pain, abdominal distension, weight loss, and constipation, may occur in older children, depending on the gluten intake [53,119]. Extraintestinal symptoms are frequent in adult CD cases and may appear associated with other digestive symptoms, such as asthenia, oral sores, osteoporosis, or skin lesions [117,120]. ...
Celiac disease is an autoimmune disease primarily affecting the small intestine that is caused by the ingestion of gluten in genetically susceptible individuals. The development of celiac disease is based on a complex immune response to gluten proteins. The global average prevalence in the general population is about 1%. In recent years, it has become clear that celiac disease is not less common in Asian countries than in Western countries but often remains undiagnosed. Although the number of patients with celiac disease in Asia is expected to increase with improving disease recognition and advances in diagnostic techniques, there remain few reports of celiac disease in the Far East region of Asia, especially in Japan. In this paper, we outline the epidemiology, diagnosis, and treatment of celiac disease. In addition, we summarize the reported Japanese cases of celiac disease with an overview in Japan.
... For this systematic review, we considered a diagnosis of CeD when the diagnosis of CeD was established on the basis of positive anti-tissue transglutaminase antibodies (anti-tTG Ab) and/or anti-endomysial antibodies (anti-EMA Ab) and the presence of villous abnormality on duodenal biopsy [23][24][25][26]. The diagnosis of CeD was also made in the presence of high anti-tTG Ab titers (≥ 10x) with the presence of anti-EMA Ab [27]. ...
Objective
In recent years, patients with celiac disease (CeD) have been reported to have a high prevalence of fatty liver and metabolic syndrome. We conducted a systematic review and meta-analysis to assess the prevalence of fatty liver and metabolic syndrome in patients with CeD and effect of gluten-free diet in them.
Methods
The PubMed, Embase and the Cochrane Library databases were searched for original studies upto November 18, 2022. We included full-text articles published in the English language after 1990 that used well-defined criteria for CeD, fatty liver and metabolic syndrome. A random effects model was used to calculate pooled prevalence.
Results
Of 350 studies identified, 11 studies (n = 2578) were included in the analysis. On analysis of both cross-sectional and longitudinal studies, pooled prevalence of fatty liver and metabolic syndrome in treatment-naïve patients with CeD were 18.2% (95% CI 8.3–30.8%, n = 1237) and 4.3% (95% CI 2.4–6.7, n = 1239) and in those on GFD of varying duration was 28.2% (95% CI 20.7–36.4%, n = 1368) and 21.3% (95% CI 11.7–32.9%, n = 2193), respectively. There was no difference in the prevalence of fatty liver and metabolic syndrome between low- or high-income group countries.
Conclusions
Patients with CeD have a high prevalence of fatty liver and metabolic syndrome which increases further with the initiation of GFD. Patients with CeD should thus be screened and monitored for development of fatty liver and metabolic syndrome. They should be counselled appropriately regarding their diet and inclusion of physical activity in their lifestyle.
Graphical Abstract
... Histological evaluation typically shows a spectrum of disease, ranging from intraepithelial lymphocytosis to total mucosal damage characterized by atrophy and loss of villi, hyperplasia of the crypts, and increased apoptosis of the epithelium [3]. The pathogenesis of CD includes gluten antigens presented on the surface of HLA complexes, mainly of haplotypes DQ2 or DQ8 [36]. ...
... По данным метаанализа, соотноше ние выявленных и недиагностированных случаев заболева ния составляет 1:7-8 [25]. Известно, что поздняя диагности ка целиакии может привести к многочисленным осложнени ям, таким как нутритивная недостаточность и дефицитные состояния (например, анемия и остеопороз), сопровождает ся высоким риском внекишечных проявлений аутоиммунно го характера, а также развития лимфомы тонкой кишки [26,27]. ...
Objective. To assess the level of awareness of celiac disease, its timely diagnosis and effective treatment among primary care
and hospital physicians.
Patients and methods. A total of 207 physicians from the Republic of Uzbekistan participated in the study. The questionnaire
included 17 questions about clinical manifestations, diagnosis, identification of risk groups and treatment of celiac disease.
Results. Only 31.9% of respondents were aware of the autoimmune mechanism of celiac disease. More than 71% of
physicians, especially primary care, know well about the typical manifestations of celiac disease (diarrhea, underweight), but исслеquite
rarely consider constipation (25.1%), abdominal pain of unknown etiology (46.9%), common colds (24.6%) as a manifestation
of celiac disease. Low awareness of the association of celiac disease with autoimmune thyroiditis (20.8%), type 1
diabetes (14.9%), and infertility (34.3%) was shown. Only 43.9% of physicians use to anti-tissue transglutaminase antibodies
as serological markers of celiac disease, 30.9% continue to focus on anti-gliadin antibodies. Only 32.9% of patients with
suspected celiac disease are referred to a gastroenterologist for evaluation.
Conclusion. The results of the study demonstrate a rather low level of awareness of clinical manifestations, methods of
diagnosis and treatment of celiac disease among physicians in the Republic of Uzbekistan. It is necessary to develop additional
educational programs and introduce modern research methods, especially in remote regions of the country, for timely diagnosis
and treatment of celiac disease.
Key words: celiac disease, diagnosis, treatment, physicians, survey
... Признаки и симптомы заболевания у разных людей иногда сильно отличаются, что в свою очередь затрудняет диагностику [23]. Для диагностики глютеновой болезни медицинские работники обычно используют несколько подходов, включая клиническое обследование, сбор анамнеза (история болезни), тестирование на человеческий лейкоцитарный антиген (human leukocyte antigens, HLA), гистопатологию (биопсия тонкой кишки) и серологию (анализы крови) [24]. ...
Celiac disease is a chronic autoimmune disorder that affects the small intestine. It is triggered in genetically predisposed individuals by consumption of gluten, a protein found in wheat, barley and rye. Celiac disease typically manifests in young pediatric patients as malabsorption of nutrients, gastrointestinal symptoms, and other health complications, which is associated with partial or total villous atrophy of the proximal small intestine. Food allergy, on the other hand, is an abnormal immune response to a specific food protein that causes inflammation and a range of symptoms, from mild hives to life-threatening anaphylaxis. Although the mechanisms behind celiac disease and food allergy are different, both conditions involve an immune response to food proteins. The current study revealed the possibility of IgE-A coexistence in celiac disease and food allergy screening should be considered for people with celiac disease, especially when symptoms persist even after implementing a gluten-free. However, the relationship between celiac disease and food allergy is not fully understood, and more research is needed to explore this link. This review aims to examine the available literature for the occurrence of food allergy in subjects with celiac disease.
... 16,17 The no-biopsy strategy has not been accepted by the North American Society For Pediatric Gastroenterology, Hepatology and Nutrition, which, in its 2005 guidelines and a clinical report in 2016, recommends that the diagnosis of coeliac disease be confirmed by the demonstration of characteristic changes in the histology of the small intestinal mucosa. 18,19 A primary concern regarding the no-biopsy approach is the incorrect diagnosis of coeliac disease in children and the substantial consequences for these children and their families. However, a US study of 3555 paediatric participants indicated the feasibility of avoiding duodenal biopsy in the diagnosis of coeliac disease in children when substituted by the detection of high serum antitissue transglutaminase IgA (tTG-IgA). ...
Background:
Whether coeliac disease in adults can be diagnosed with serology alone remains controversial. We aimed to evaluate the accuracy of serum anti-tissue transglutaminase IgA (tTG-IgA) in the diagnosis of coeliac disease.
Methods:
In this multicentre, prospective cohort study, adult participants (aged ≥18 years) with suspected coeliac disease without IgA deficiency who were not on a gluten-free diet and who had a local serum tTG-IgA measurement, were enrolled from Feb 27, 2018, to Dec 24, 2020, by 14 tertiary referral centres (ten from Europe, two from Asia, one from Oceania, and one from South America) to undergo local endoscopic duodenal biopsy. Local serum tTG-IgA was measured with 14 different test brands and concentration expressed as a multiple of each test's upper limit of normal (ULN), and defined as positive when greater than 1 times the ULN. The main study outcome was the reliability of serum tests for the diagnosis of coeliac disease, as defined by duodenal villous atrophy (Marsh type 3 or Corazza-Villanacci grade B). Histology was evaluated by the local pathologist, with discordant cases (positive tTG-IgA without duodenal villous atrophy or negative tTG-IgA with duodenal villous atrophy) re-evaluated by a central pathologist. The reliability of serum tests for the prediction of duodenal villous atrophy was evaluated according to sensitivity, specificity, positive predictive value, negative predictive value, and the area under the receiver operating characteristic curve (AUC) for categorical and continuous data.
Findings:
We enrolled 436 participants with complete local data on serum tTG-IgA and duodenal histology (296 [68%] women and 140 [32%] men; mean age 40 years [SD 15]). Positive serum tTG-IgA was detected in 363 (83%) participants and negative serum tTG-IgA in 73 (17%). Of the 363 participants with positive serum tTG-IgA, 341 had positive histology (true positives) and 22 had negative histology (false positives) after local review. Of the 73 participants with negative serum tTG-IgA, seven had positive histology (false negatives) and 66 had negative histology (true negatives) after local review. The positive predictive value was 93·9% (95% CI 89·2-98·6), the negative predictive value was 90·4% (85·5-95·3), sensitivity was 98·0% (95·3-100·0), and specificity was 75·0% (66·6-83·4). After central re-evaluation of duodenal histology in 29 discordant cases, there were 348 true positive cases, 15 false positive cases, 66 true negative cases, and seven false negative cases, resulting in a positive predictive value of 95·9% (92·0-99·8), a negative predictive value of 90·4% (85·5-95·3), a sensitivity of 98·0% (95·3-100·0), and a specificity of 81·5% (73·9-89·1). Either using the local or central definition of duodenal histology, the positive predictive value of local serum tTG-IgA increased when the serological threshold was defined at increasing multiples of the ULN (p<0·0001). The AUC for serum tTG-IgA for the prediction of duodenal villous atrophy was 0·87 (95% CI 0·81-0·92) when applying the categorical definition of serum tTG-IgA (positive [>1 × ULN] vs negative [≤1 × ULN]), and 0·93 (0·89-0·96) when applying the numerical definition of serum tTG-IgA (multiples of the ULN). Additional endoscopic findings included peptic gastritis (nine patients), autoimmune atrophic gastritis (three), reflux oesophagitis (31), gastric or duodenal ulcer (three), and Barrett's oesophagus (one). In the 1-year follow-up, a midgut ileum lymphoma was diagnosed in a woman on a gluten-free diet.
Interpretation:
Our data showed that biopsy could be reasonably avoided in the diagnosis of coeliac disease in adults with reliable suspicion of coeliac disease and high serum tTG-IgA.
Funding:
None.
... Indeed, evidence in children was so strong that the no-biopsy principle was incorporated by the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) into the guidelines for CeD diagnosing in children 15,16 . The no-biopsy strategy has not been accepted by the North American Society For Pediatric Gastroenterology, Hepatology & Nutrition (NASPGHAN) which still recommends in its 2005 guidelines and a clinical report in 2016 that the diagnosis of CeD be confirmed by demonstration of characteristic changes in the histology of the small intestinal mucosa 17,18 . A primary concern is the incorrect diagnosis of CeD in a child and the highly significant consequences for the child and their families. ...
ABSTRACT
Background. It remains controversial whether coeliac disease (CeD) in adults can be diagnosed using only serology. We conducted a prospective study investigating this point focusing on serum antitissue transglutaminase IgA (anti-tTG IgA).
Methods. Patients with suspected CeD were enrolled by 14 centres and underwent local anti-tTG IgA measurements and endoscopic duodenal biopsy. Anti-tTG IgA was expressed as a multiple of each test’s upper limit of normal range (xULN) and defined high when > 1. CeD diagnosis was defined as the presence of villous duodenal atrophy. Histology was evaluated by local pathologist and the central pathologist in discordant cases (high anti-tTG IgA without duodenal villous atrophy or non-high antitTG IgA with duodenal villous atrophy). Anti-tTG IgA was measured in a subgroup of patients by the central lab.
Findings. Local data were complete for 436 patients. CeD prevalence was 79.6% by local centre histology and 81.4% after re-evaluation of 30 discordant cases; high anti-tTG IgA prevalence was 83.3%. Positive predictive value of duodenal villous atrophy increased with higher anti-tTG IgA levels using local data (from 9.6% for ≤1 xULN to 97.8% for >15 xULN, P <0.001) and after central re-evaluation (9.6% for ≤1 xULN to 100% for >15 xULN, P <0.001). Using the > x10 ULN cut-off for anti-tTG for the serological diagnosis of CeD, this study correctly identified 161 (99.4%) of 162
patients without needing a biopsy. For the whole cohort, 36.9% would have avoided biopsy.
Interpretation. Our data showed that biopsy could be reasonably avoided in adult CeD patients with anti-tTG IgA >10x ULN
... The diagnosis of celiac disease typically involves a combination of serological testing for specific antibodies to gluten, and confirmation through biopsy of the small intestine [7]. Treatment for celiac disease involves strict adherence to a gluten-free diet, which allows for the restoration of the intestinal lining and alleviation of symptoms [8,9]. The present document has been produced and adopted by the bodies identified above as authors. ...
preDQ is a software tool for peptide binding prediction to HLA‐DQ2 and HLA‐DQ8 proteins specially designed and developed for the European Food Safety Authority. The tool is able to identify peptides binding to HLA‐DQ2 and/or HLA‐DQ8 proteins and to predict their binding affinities. The tool is used to assess the risk of novel proteins to cause celiac disease.
Predictions made by preDQ are based on five models and the risk assessment is reported by five outputs. The models are developed using datasets of known peptides binding and non‐binding to HLA‐DQ2 and HLA‐DQ8 proteins. The datasets are compiled from the literature and curated. Ligand‐based and structure‐based methods are applied in the development of the computational models. The models are validated by internal cross‐validation procedures and by external test sets. Only the best performing models are selected and included in preDQ.
preDQ is a comprehensive, user friendly and reliable tool for assessing the binding affinity of peptides to HLA‐DQ2 and HLA‐DQ8 and the capacity of the origin proteins to cause celiac disease.
... The diagnosis of celiac disease typically involves a combination of serological testing for specific antibodies to gluten, and confirmation through biopsy of the small intestine [7]. Treatment for celiac disease involves strict adherence to a gluten-free diet, which allows for the restoration of the intestinal lining and alleviation of symptoms [8,9]. ...
... This clinical need is growing, given the increasingly popular gluten-free lifestyle in the western world [26,27], or for first degree relatives, who frequently initiate a GFD when a household member is diagnosed with CeD. For the latter, the high risk of developing CeD has been proven in many studies [28,29] and surveillance for CeD is even recommended for first-degree relatives of a diagnosed patient where carriage of a risk gene has not been excluded [30,31]. Work herein might be the first step towards identifying such cases, without a conventional burdening gluten re-challenge, since characteristic changes in cytokine expression in gliadin-specific CD4 + T-cells in the peripheral blood are present. ...
To demonstrate and analyze the specific T-cell response following barrier disruption and antigen translocation, circulating food antigen-specific effector T-cells isolated from peripheral blood were analyzed in patients suffering from celiac disease (CeD) as well as inflammatory bowel disease (IBD). We applied the antigen-reactive T-cell enrichment (ARTE) technique allowing for phenotypical and functional flow cytometric analyses of rare nutritional antigen-specific T-cells, including the celiac disease-causing gliadin (gluten). For CeD, patient groups, including treatment-refractory cases, differ significantly from healthy controls. Even symptom-free patients on a gluten-free diet were distinguishable from healthy controls, without being previously challenged with gluten. Moreover, frequency and phenotype of nutritional antigen-specific T-cells of IBD patients directly correlated to the presence of small intestinal inflammation. Specifically, the frequency of antigen specific T-cells as well as pro-inflammatory cytokines was increased in patients with active CeD or Crohn's disease, respectively. These results suggest active small intestinal inflammation as key for the development of a peripheral food antigen-specific T-cell response in Crohn's disease and celiac disease.
... 1,2 CD is a lifelong disease that can occur at any age. 3 It is a systemic disorder with multifactorial pathogenesis with clinical manifestations including both classic gastrointestinal symptoms such as chronic diarrhea and weight loss, but also the more common nonspecific symptoms such as bloating, vomiting, and abdominal pain. Moreover, extraintestinal manifestations include a broad spectrum of symptoms involving several organs. ...
Introduction:
Previous studies have indicated that patients with celiac disease (CD) may have an increased risk of developing neuropsychiatric disorders. However, large-scale epidemiologic studies on the topic are still scarce. We aimed to examine the association between CD and development of neuropsychiatric disorders during an 18-year follow-up period.
Methods:
We conducted a prospective cohort study. All Danish patients with an incident diagnosis of CD (ICD-10 K90.0) from 2000 to 2018 were identified in nationwide registries and compared with birthdate- and sex-matched controls (variable 1:10 ratio) for the development of a neuropsychiatric disease. Individual neuropsychiatric diseases were also examined. The absolute risk was calculated by the cumulative incidence, and the relative risk was estimated in Cox regression models.
Results:
We identified a cohort of 6329 patients with CD diagnosed from 2000 to 2018 and 63,287 matches at risk for developing incident neuropsychiatric disorders. The cumulative incidence of development of any neuropsychiatric disorder was 3.9%, 14.9%, 24.8%, 35.9% after 1, 5, 10, and 15 years of follow-up, respectively, in patients with CD compared with 1.8%, 9.3%, 18.3%, and 27.0% in controls. Gray's test for equality p < 0.001. The relative risk was HR = 1.58 (95% confidence interval: 1.49-1.68) in CD patients compared with matches. For the individual outcomes, CD was associated with an increased relative risk of developing anxiety, depression, eating disorders, epilepsy, migraine, and stress. We also found indications of an increased relative risk of ADHD, alcoholism, bipolar disorders, and drug abuse, although the associations were less clear. No associations were found between CD and dementia, Parkinson's disease, and schizophrenia.
Conclusions:
In this nationwide study including more than 6000 patients with CD, we found an increased risk of development of a neuropsychiatric disorder compared with age- and sex-matched controls. The causes and the clinical relevance of these associations remain to be elucidated.
... Celiac disease (CD) is an autoimmune chronic disease that develops in individuals who are genetically sensitive to gluten, a protein found in wheat, rye, and barley, which leads to widespread villous atrophy and lymphocyte infiltration of the small intestinal mucosa due to persistent intolerance to polypeptide fragments of this protein [1][2][3]. People with HLA class II DQ2 and DQ8 haplotypes are known to have an increased risk of developing the disease [4]. ...
Objectives
To evaluate the nutritional and oral health status of children with previously diagnosed celiac disease (CD) who follow a gluten-free diet and recently diagnosed CD patients.
Materials and methods
Previously and recently diagnosed groups were formed from children with CD, aged 4 to 15 years. A questionnaire was completed about the children’s dental history and nutritional and oral hygiene habits. All the children underwent an oral examination, and dmft-DMFT indices were determined. Dental plaque status, periodontal health, and dental enamel defects were recorded. Oral soft tissues were examined for the presence of lesions. Unstimulated salivary flow rate and pH value were evaluated.
Results
A statistically significant difference was determined between the previously and recently diagnosed patients in terms of toothpaste preference (p=0.003), frequency of going to the dentist (p=0.039), and the types of dental treatment they had received (p=0.001). A statistically significant difference was determined between the previously and recently diagnosed patient groups in terms of dmft values (p=0.005).
Conclusions
Children with CD should be directed to a pediatric dentist to improve oral and dental health, relieve the symptoms of oral mucosal lesions, be informed about enamel defects, and be encouraged to use gluten-free oral care products.
Clinical relevance
The collaboration of pediatric gastroenterologists and pediatric dentists can prevent the progression of oral symptoms in children with CD and eliminate long-term complications in terms of both oral health and multisystemic problems.
... 16,17 The no-biopsy strategy has not been accepted by the North American Society For Pediatric Gastroenterology, Hepatology and Nutrition, which, in its 2005 guidelines and a clinical report in 2016, recommends that the diagnosis of coeliac disease be confirmed by the demonstration of characteristic changes in the histology of the small intestinal mucosa. 18,19 A primary concern regarding the no-biopsy approach is the incorrect diagnosis of coeliac disease in children and the substantial consequences for these children and their families. However, a US study of 3555 paediatric participants indicated the feasibility of avoiding duodenal biopsy in the diagnosis of coeliac disease in children when substituted by the detection of high serum antitissue transglutaminase IgA (tTG-IgA). ...
... When the typical/atypical symptoms of our patient group were evaluated, typical symptoms were observed in 65.1% of boys and 64.6% of girls, 34.9% of boys and 35.4% of girls had atypical symptoms, and typical symptoms in both genders /atypical symptom rates were found to be similar. Similarly, in the guideline published by the North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition for the diagnosis and treatment of CD in children, it was stated that the most common findings of CD are related to the gastrointestinal system (12). When the studies conducted in our country were examined, Soylu et al. reported that the most common symptoms in children with CD were abdominal pain, abdominal swelling, and diarrhea, which were seen in approximately 60% of the patients (7). ...
Objective: Celiac disease (CD) is an autoimmune disorder among genetically predisposed subjects exposed to gluten-containing foods. It is now appreciated that CD is now recognized as a common condition among persons of various ethnic groups and both adults and children, and that affects many organ systems. This study was conducted to evaluate the demographic and clinical characteristics of pediatric celiac patients. Patients and Methods: A total of 122 individuals diagnosed with CD by serologic and histologic assessments between January 2010 and December 2016 were enrolled in the study. Results: Forty-three patients were boys (35.2%), and seventy-nine were girls (64.8%). The mean age was 12.6±5.7 years, and the mean age at diagnosis was 8.8±5.1 years. The most frequent presenting symptoms were abdominal pain (41%), failure to thrive (36.1%), and diarrhea (34.4%). Adherence to a gluten-free diet was 67.2%. Family history of CD was positive in 2.5% of patients. The most frequent comorbidities were iron deficiency anemia (36.1%), vitamin D deficiency (12.3%), and type-1 diabetes mellitus (7.4%). Endoscopic assessments revealed dentations in 61.5% of cases, and histologic evaluations told that Marsh 3b was the most frequent histologic grade (27.9%). IgA and IgG transglutaminase antibody levels were decreased significantly following the initiation of the gluten-free diet. Conclusion: Celiac disease faces a very varied picture in terms of clinic and laboratory at the time of diagnosis and in the follow-up. Early diagnosis of CD is critical to prevent long-term complications; currently, the only effective treatment is a lifelong gluten-free diet.
... The prevalence of CD, as detected by screening programmes using specific antibodies, is substantially increased in several risk groups as compared with the general population. High-risk groups for CD include: first-degree relatives of individuals with CD (range: 5% to 7.5%), second-degree relatives of individuals with CD (range: 2-3%), and individuals with T1DM (range: 5-10%), Down syndrome (range: 5-12%), or autoimmune thyroid disease (range: 2-7%); in addition, CD is also associated with Turner syndrome (range: 4-8%), Williams syndrome, and selective immunoglobulin A deficiency (each with 8% risk) [14,[57][58][59][60][61][62][63]. Thus, because of their increased risk, routine screening for CD is recommended in asymptomatic children with these conditions. ...
Celiac disease (CD) is a chronic autoimmune disorder of the small bowel that is triggered by exposure to dietary gluten. In paediatric, CD commonly presents with intestinal manifestations, while in adults, many present with more subtle symptoms and extraintestinal manifestations, such as anaemia, fatigue, dermatitis, and headaches. The main scope of this chapter is to explore and present the prevalence of CD worldwide as well as trends in diagnosis over recent years. The prevalence of CD is approximately 0.5–1% in different regions of the world. However, exact prevalence rates may vary substantially in specific populations. Although CD was formerly believed to affect solely individuals of European ancestry, more recent studies indicate that the disease may have been either under-reported or undiagnosed in other populations. Moreover, it is possible that the increasing popularity of Western dietary practices may have an impact on the recent trend of increased rates of CD in non-Western populations. Certain population groups are also at high risk of developing CD, including first- or second-degree relatives of individuals with CD and those with diabetes or autoimmune disorders. Serological screening and HLA typing are therefore highly recommended for asymptomatic children in whom such risk factors are present.
... CD usually occurs in children up to 2 years old. The symptoms commonly experienced are diarrhea, abdominal pain, anorexia and failure to thrive (19). ...
Background: The prevalence of eosinophilic esophagitis (EoE) has increased in recent decades. Recent studies have found that the prevalence of EoE in patients with celiac disease (CD) is much higher compared with the general population. In this study, the prevalence of EoE in children with CD was calculated and their clinical symptoms, endoscopic and histopathological findings were compared. Methods: This was a retrospective study conducted on the data records of the patients diagnosed with celiac disease during 2012-2020, and registered at Imam Hossein Children's Hospital and the Institute of the Celiac Association in Isfahan, Iran. Clinical findings, endoscopic reports, serological and histopathological data of the patients were recorded and analyzed. Results: A total of 80 children with CD were included in the study. The mean age of the patients with CD and EoE (n=8) was 7.75± 3.99 years, and in children with CD alone (n=72), the mean age was 7.85± 3.83. The most common clinical findings were abdominal pain, anorexia, diarrhea and constipation. There were no significant differences in the symptoms of either group. The most common endoscopic view was duodenal scalloping and esophagitis; and 50% of EoE patients had a normal endoscopic view of the esophagus. With regards to serological findings, the level of TTG-IgA (U/ml) in the CD and EoE group was higher than the CD group (183.73 ± 101.54 vs. 117.07 ± 95.34 U/ml); however, no statistically significant difference was observed. Conclusion: Our study found that the prevalence of EoE in children with CD appears to be higher than in previous studies. We have also shown that the presence of EoE cannot be detected solely based on clinical and even endoscopic results. Therefore, an esophageal biopsy is recommended in celiac patients.
... Çölyak hastalığı tanısında en duyarlı testlerden biri olan ve immünofloresan yöntemi ile bakılan Anti -endomisyal antikor (EMA) testi uygulanma zorluğu, maliyet yüksekliği ve nedeniyle çok gerekli olmadıkça tercih edilmemektedir (12). ...
AMAÇ: Çölyak Hastalığı, gluten içeren yiyeceklerin tüketilmesi ile oluşan ve ince bağırsakta otoimmün olaylarla karakterize bir enteropatidir. Çalışmamızda, çölyak hastalığında diyet uyumsuzluğu ile artış gösteren aktivasyon kriterleri ile delta nötrofil indeks arasındaki ilişkinin gösterilmesi amaçlandı.GEREÇ VE YÖNTEM: Bu çalışmada, Ocak 2019 ve Aralık 2019 tarihleri arasında Dr. Sami Ulus Kadın Doğum ve Çocuk Hastanesi pediatrik gastroenteroloji polikliniğine başvuran önceden çölyak hastalığı tanısı almış olan 99 çocuk ve ergen (18 yaş altı) dahil edildi.BULGULAR: Çalışmaya 45’i kız (% 45.5), 54’ü erkek (% 54.5) olmak üzere 3 - 17 yaş arası toplam 99 çölyak hastası dahil edildi. Delta Nötrofil İndeksi (DNI) ile tanı süresi arasında (p=0,094 r=0,169), dTGA ile (p=0,256 r=0,115), dTGG ile (p=0,359 r=-0,094) ve IgA ile anlamlı bir ilişki saptanmadı (p=0,259 r=0,115).SONUÇ: Çölyak hastalığının erken tanınıp tedavi edilmesi çok önemlidir çünkü glütensiz diyet sonrası hem semptomlar gerilemekte hem de daha ciddi çölyak ilişkili hasarların gelişmesi önlenebilmektedir. Hastaların takipte diyet uyumunu belirlemek için kullanılan serolojik testler, bir çok inflamatuar durumda kullanılan ve rutin hemogram parametrelerinden biri olan DNI düzeyi ile karşılaştırıldı ancak istatistiksel olarak anlamlı ilişki saptanmadı. Çölyak hastalarının takibinde diyet uyumu ileri çalışmalar ile belirlenebilir.
... Структурные дефекты зубной эмали могут проявляться как функциональными в виде гипоплазии, так и качественными нарушениями -гипоминерализацией [15]. Согласно рекомендациям Североамериканского общества детской гастроэнтерологии, гепатологии и питания (NASPGHAN) специфические дефекты зубной эмали отнесены к предикторам риска развития целиакии [16,17]. ...
The high prevalence of non-carious manifestations in patients with celiac disease is described by numerous authors, who are considered as a diagnostic key to atypical forms of celiac disease. The manifestations closely associated with celiac disease include: defects in tooth enamel, pathological tooth abrasion, as a violation of the mineralization of dental crowns, and morphofunctional defects in the hard tissues of the teeth.
Materials and methods . We examined 45 patients aged 23 to 36 years with a diagnosis of celiac disease, established on the basis of the results of clinical anamnestic, genetic, instrumental studies, morphological study of a biopsy specimen of the intestinal mucosa.
Result . Examination of the dentition of the patients showed that 100% of the examined had pathological abrasion of tooth enamel. Crowded teeth were found in 32 patients. Partial symmetric congenital adentia was diagnosed in 5 patients.
Conclusion . The revealed dentoalveolar anomalies can be attributed to oral manifestations of celiac disease, which is a diagnostic criterion for suspected disease.
... 22 These patients have a more complex dietary program and consequently lower compliance. 23,24 In 2003, Liu et al indicated that the level of atTG fluctuated over time in DM 1 and CD-susceptible patients. They indicated that the antibody normalization was seen even with a gluten-containing diet and recommended a higher threshold of the antibody titer for diagnosis of CD. 25 In our study, the mean atTG normalization interval was less than nondiabetics, although it was not statistically significant (25.62 vs. 31.29 months). ...
A very limited amount of data are available regarding the follow-up of celiac disease (CD) treatment in Iran. The aim of this study is to investigate antitissue transglutaminase (atTG) normalization interval and the associated factors in CD patients. This retrospective study included CD patients enrolled in Children's Medical Center, Tehran University of Medical Sciences. The initial atTG titer and histological evaluation (with Marsh grade ≥2) were recorded. The atTG titer was assessed in each follow-up until the time of normalization where children were strictly on gluten-free diet. The age at the time of diagnosis, gender, Marsh grade at the time of diagnosis, other comorbidities, and family history of CD patients were recorded to determine the association of these factors with antibody normalization interval. In total, 71 patients were recruited in the study of which 34 (47.89%) subjects had atTG level below 20 U/mL at the average interval of 31.36 ( ± 2.89) months (95% confidence interval: 25.7–37.02). There was no significant difference between the antibody normalization interval and different age ranges and Marsh grade. Cox regression demonstrated that gender, age ranges, Marsh grade, positive family history of CD, and the presence of comorbidities did not significantly predict longer antibody normalization interval.
Introduction: Increasing cardiovascular risk in celiac disease (CD) may be attributed to the chronic systemic inflammation and unfavorable biochemical profile leading to accelerated atherosclerosis. Carotid intimal medial thickness (CIMT) has emerged as a direct marker of the early atherosclerosis as compared to traditional biochemical markers. Objectives: The aim of this study was to evaluate the CIMT in children with CD aged 1–16 years. Materials and Methods: A cross-sectional observational study was conducted at the department of Pediatrics and Radio Diagnosis in a tertiary care hospital of New Delhi. Thirty-six children with CD with age- and sex-matched controls were enrolled. CIMT for the anterior and posterior walls on each side was measured, and the mean CIMT was obtained for all the enrolled children. Results: The mean right-sided CIMT was significantly higher in cases (0.053±0.009 cm vs. 0.039±0.007 cm, p=0.000). The mean left-sided CIMT did not significantly differ between the groups (0.051±0.009 cm vs. 0.048±0.055 cm, p=0.702). The mean CIMT (right and left together), although higher in Celiacs, was not significantly different from controls (0.052±0.008 cm and 0.044±0.029 cm, p=0.114). However, a significant positive correlation between the age of the patients, age at the onset of symptoms, and CIMT was noted. Conclusion: Although we could not demonstrate statistically significant results, the mean CIMT and the right-sided measurements were significantly higher in cases than in controls.
El "Pediatría General Tomo 14" se alza como una obra imprescindible en el campo de la pediatría, ofreciendo una visión integral y actualizada de los aspectos fundamentales del cuidado infantil. Compilado por un equipo de expertos en pediatría, este tomo aborda una amplia gama de temas relevantes para la práctica clínica pediátrica, desde el nacimiento hasta la adolescencia. Con un enfoque práctico y orientado a la resolución de problemas, cada capítulo de este tomo proporciona una revisión exhaustiva de los principales trastornos pediátricos, incluyendo su etiología, manifestaciones clínicas, diagnóstico y manejo. Además, se abordan temas importantes como el desarrollo infantil, la nutrición pediátrica, la inmunización y la salud mental en la infancia y la adolescencia.
Celiac disease (CD) is main gastrointestinal disease initiated by an immune reaction to gluten in genetically susceptible people. The objective of this analysis attempted to evaluate the nature as well as effect of systemic cytokine and adipokines levels within the pathophysiology of CD and also the role of therapy with gluten completely free diet on the status of its. Cytokine assays had been carried out on fifty children patients with effective CD and positive TTG IgA antibodies, and the effects were compared with healthy controls. Individuals with active CD with positive antibodies had significantly greater degrees of pro inflammatory cytokines, for example interferon-γ, tumor necrosis factor-α, IL-4 and IL-6,IL-8, and the Th-2 cytokines for example IL-5 and IL-10, in contrast to controls. Additionally, a statistically significance correlation involving levels of TTG IgA titters as well as serum levels of Th-2 cytokines IL-4 (p < 0.001), IL-10 (p < 0.001) along with inflammatory cytokines including IL-12 (p < 0.001) had been recognized, No impact on cytokine levels between the 2 organizations on and off gluten free diet (GFD) was discovered for TNF, IL-1, IL-8 and IL-, IL-4. Immediately after gluten free diet, levels of IL-5, IL-10 and IL-12 decreased significantly (P < 0.001) and IFN-γ levels have been decreased (P < 0.05). In addition children with celiac disease off of a GFD exhibited larger ghrelin levels than children on a GFD. Adiponectin levels were not age, sex or GFD-dependent. Therapy with GFD had no effect on the adiponectin and leptin levels in children with CD, nonetheless, a GFD reduced extremely higher ghrelin levels in pre-pubertal children.
Bu çalışma, Türkiye’de satılan glütensiz ürünler ile bu ürünlerin glüten içeren eşdeğerlerinin besin ögesi içeriği ve kalitesi ile maliyeti yönünden değerlendirmesi amacıyla gerçekleştirilmiştir. Çalışmaya 29 ürün grubu ve toplam 176 ürün dahil edilmiştir. Ürünler enerji, toplam yağ, doymuş yağ, şeker, protein, tuz, lif ve sodyum içeriği, Nutri-Score değerleri ve satış fiyatları açısından incelenmiştir. Glütensiz ekmek, makarna, şehriye, tuzlu gevrek ve bisküvinin glütenli eşdeğerlerinden daha düşük protein içerdiği saptanmıştır (p
Gluten challenge is an essential clinical tool that involves reintroducing or increasing the amount of gluten in the diet to facilitate diagnostic testing in celiac disease (CD). Nevertheless, there is no consensus regarding the applications of gluten timing, dosing, and duration in children. This review aims to summarize the current evidence, discuss practical considerations, and proposes a clinical algorithm to help guide testing in pediatric patients.
Childhood development, social circumstances and long-term health concerns must be considered when identifying a candidate for gluten challenge. Based on previous studies, the authors suggest baseline serology followed by a minimum of 3-6 grams of gluten per day for over 12 weeks to optimize diagnostic accuracy for evaluation of CD. A formal provider check-in at 4-6 weeks is essential so the provider and family can adjust dosing or duration as needed. Increasing the dose of gluten further may improve diagnostic yield if tolerated, although in select cases a lower dose and shorter course (6-12 weeks) may be sufficient.
There is consensus that mild elevations in celiac serology (<10 times the upper limit of normal) or symptoms, while supportive are not diagnostic for CD. Current North American Society for Pediatric Gastroenterology, Hepatology and Nutrition guidelines recommend histologic findings of intraepithelial lymphocytosis, crypt hyperplasia, and villous atrophy as the accurate and most appropriate endpoint for gluten challenge.
The present investigation was conducted to develop a technology for the manufacture of a gluten-free chhana cake. Refined wheat flour was substituted with blend of three flours viz., barnyard millet, amaranth and little millet (consisting of 31.86% barnyard millet, 32.69% amaranth and 35.45% little millet) were subjected to heat moisture treatment. In order to select the most suitable heat moisture treatment the millet blend was subjected to three heat moisture treatments. Based on the results the selected heat moisture treatment was: Adjusting the moisture content of millet flour blend to 25% and keeping it at 4°C for 24 h in an air tight plastic container followed by heating the moisture adjusted flour at 100°C for 3 h in a hot air oven and finally drying it at 40°C till a final moisture content of about 9% was obtained. In the second part of the study, the rate of addition of baking powder and glycerol monostearate was optimized using Response Surface Method (RSM) i.e., Design Expert 13.0.5.0. The optimized solution was 1.40% baking powder and 1.66% glycerol monostearate. The desirability of this model was 0.93.
A presença de glúten na dieta pode ser desencadeante de vários processos fisiopatológicos que culminam em doenças neuropsiquiátricas além dos problemas gastrointestinais. Nos chamados “sensíveis ao glúten não celíacos”, os dados da literatura são divergentes. Objetivo: avaliar o efeito dos tratamentos de diferentes dietas relacionadas ao teor de glúten, sobre parâmetros comportamentais e bioquímicos. Métodos: camundongos C56bl/6j (fêmeas, N:7-10) foram submetidos a testes comportamentais de doenças neuropsiquiátricas. Os animais foram divididos em grupos: G1/ ração enriquecida 75% de glúten (DEG), G2/dieta normal (Nuvilab®- DNN) e G3/dieta isenta de glúten (DIG). Para os testes de depressão e ansiedade, foram introduzidos dois grupos adicionais (controles – positivos) que receberam respectivamente Fluoxetina (20mg/kg mg), Diazepam (0.75mg/kg e galantamina (4mg kg/kg). Após o período de tratamento os animais foram submetidos aos testes comportamentais: Open field (Campo aberto), Suspensão pela cauda (TSC), labirinto em cruz elevada (LCE) e esquiva inibitória (TEI). Foram realizados ensaios bioquímicos para verificar a influência da DEG sobre os parâmetros bioquímicos (ALT, AST, glicose de jejum, colesterol total, HDL, TG). Resultados: Os resultados demonstraram que DEG desencadeou comportamentos de ansiedade e depressão nos animais, além de déficits de memória. Promoveu também hiperglicemia, aumento do peso corporal, diminuição do HDL e aumento do LDL. Podendo levar à um mau funcionamento das funções hepáticas (AST e ALT). Conclusão: Os resultados em conjunto
confirmam os efeitos deletérios causado pelo glúten.
Palavras-chave: Glúten. Depressão. Ansiedade. Memória. Ensaios pré-clinicos. Camundongos.
Aim: Estimated serum Pentraxine-3(PTX3) levels, Lipid profile, and BMI in Iraqi patients with celiac disease with and without GFD in order to validate their role in the exacerbation of celiac disease symptoms. Method: One hundred Iraqi patients with celiac disease (aged from 20-55 years) were sign up in the current study. The Patients group were divided according to the period of the disease forP (n=48) (male=16, female=32) with a period less than one year and G (N=52) (male=24, female=28) with a period from (1-10 years) The G group was further subdivided in the form of G1 (gluten-free diet (GFD)=29) and G2 (non-gluten free diet (Non-GFD=23). Diagnosis is based on clinical examination. The Patients' group matched with a control group (C, n=51) (male=25, female=26). Serum PTX3 and Lipid profile levels were resolute for each participant. Results: The outcomes obtained from our study indicate a highly significant increase (p=0.000) in serum anti-TtG and PTX3 as compared with a control group. A significant increase was found in LDL, VLDL, and TG levels in G1 as compared with G2 and control groups while a significant decrease in BMI was found in G1 and G2 as compared to the control group. Conclusion: High serum PTX3 are associated with CD with and without gluten free diet (GFD), while high serum LDL, TG and VLDL are associated with long life gluten free diet.
Background:
Celiac disease is an immunological reaction provoked by gluten digestion in genetically vulnerable individuals in response to unknown environmental factors. It affects 0.7% of the world's population and occurs at a rate of 1% in most nations. We aimed to assess the clinical, laboratory, and histopathological characteristics of patients with a presumable diagnosis of celiac disease and to investigate the coexistence of autoimmune disorders.
Methods:
In this retrospective study, data were gathered from the medical files of a total of 493 individuals with a preliminary diagnosis of celiac disease who underwent endoscopic biopsies. Analysis was carried out for clinical, biochemical, and histological results, as well as the presence of autoimmune disease.
Results:
Per the results of serological tests used in the diagnosis of celiac disease in this series, gliadin IgA and IgG positivities were found in 33.7% (n = 54/160) and 39.4% (n = 69/175) of patients; endomysium IgA and IgG positivities were detected in 37% (n = 88/238) and 18% (n = 30/167) of patients, while tissue transglutaminase IgA and IgG positivities were detected in 47.3% (n = 115/243) and 16.3% (n = 15/92) of patients, respectively. The incidence of patients with a CD3 level of ≥30% was 69.1% in 152 patients whose CD3 levels were tested.
Conclusion:
The general public and healthcare professionals need to be more aware of the prevalence and many signs of celiac disease. There is still a need to conduct the necessary research in this area. By boosting awareness, early diagnosis, and diet, it will be possible to prevent symptoms and negative consequences.
Objectives:
Patients with Trisomy 21 (T21) commonly have gastrointestinal symptoms and diseases that prompt evaluation with esophagogastroduodenoscopy (EGD). Our objective is to characterize duodenal histological abnormalities in these patients when undergoing EGD. A secondary aim is to explore associations of histologic findings with different therapies.
Methods:
Patients 30 years old or younger with T21 who underwent EGD from 2000-2020 at six hospitals were included in this retrospective cohort study. Duodenal biopsies were categorized based on reported histopathology findings as normal or abnormal. Abnormal pathology reports were reviewed and categorized into villous atrophy (VA), and duodenitis without VA. The VA group was further categorized based on the presence or absence of celiac disease (CD).
Results:
We identified 836 patients with T21 who underwent EGD, 419 (50.1%) of whom had duodenal histologic abnormalities. At the time of the first (index) abnormal duodenal biopsy, 290/419 had VA and of those, 172/290 met CD diagnostic criteria, while 118/290 did not meet CD criteria (non-specific VA). Among the patients with an abnormal biopsy, acid suppression at the time of the index biopsy was less common in patients with VA-CD compared to patients without VA or patients with non-specific VA (12.2% vs. 45.7% vs. 44.9%).
Conclusions:
Half of the T21 patients in this cohort had abnormal duodenal biopsies including a subgroup with non-specific VA. In this cohort, acid suppression use was more prevalent in patients with abnormalities other than celiac disease.
The prevalence of pediatric serological negative celiac disease (SNCD) is poorly described, with few recognized clinical predictors beyond IgA deficiency or reduced gluten intake. The purpose of this retrospective review was to describe the prevalence of SNCD at the Stollery Children's Hospital and identify clinical features to help in recognition of these cases. Patients with a positive biopsy and negative serology (SNCD) were compared to those with positive biopsy and serology (SPCD). SNCD diagnosis required clinical correlation and either confirmatory genetics or follow up endoscopy on a gluten free diet. Of the 424 patients who met celiac disease (CD) criteria, 4.7% (n=20) fulfilled our criteria for SNCD. There was a significant difference in the rates of IgA deficiency between the two groups, but no other clinical features were found that allowed for ready identification of SNCD patients.
Objectives:
Mucosal injury in celiac disease (CD) patients can be patchy, and up to 12% of CD patients can have mucosal changes limited to the duodenal bulb. Hence, recent guidelines recommend obtaining bulb biopsies in addition to distal duodenum. This study aimed to describe a cohort of children with isolated bulb CD and assess the benefit of separating bulb biopsies.
Methods:
A retrospective chart review between 01/2011 and 01/2022 at two medical centers was conducted. We included children with CD who underwent endoscopy with separated biopsies from the bulb and distal duodenum. A blinded pathologist performed Marsh-Oberhuber grading on selected cases.
Results:
We identified 224 CD patients, of which 33 (15%) had histologically confirmed isolated bulb CD. Patients with isolated bulb CD were older at diagnosis (10 vs. 8 years; p=0.03). Median anti-TTG IgA level was lower in isolate bulb CD (2.8 vs. 16.7 times the upper limit of normal [ULN], p<0.001). Almost 88% (29/33) of isolated bulb CD patients had an anti-TTG IgA value of less than 10 times the ULN. Time to anti-TTG IgA normalization (mean 14 months) was similar between the two groups. A pathologist review of diagnostic biopsies could not distinguish between the bulb and distal duodenum biopsies in approximately one-third of the reviewed samples.
Conclusions:
Separating bulb from distal duodenum biopsies can be considered during CD diagnosis, particularly in children with anti-TTG IgA levels less than 10 time the ULN. Larger prospective cohorts are needed to decide whether isolated bulb CD is a unique cohort or an early stage of the conventional CD.
Unlabelled:
To evaluate the ordering practices of celiac disease (CD) serologies by providers at a tertiary, academic, Children's Hospital and compare them to guidelines and best practices.
Methods:
We analyzed celiac serologies ordered in 2018 by provider type (pediatric gastrointestinal (GI) specialists, primary care providers (PCPs), and nonpediatric GI specialists), and identified causes for variability and nonadherence.
Results:
The antitissue transglutaminase antibody (tTG) IgA was ordered (n = 2504) most frequently by gastroenterologists (43%), endocrinologists (22%), and other (35%). Total IgA was ordered with tTG IgA for screening purposes in 81% of overall cases, but endocrinologists ordered it only 49% of the time. The tTG IgG was ordered infrequently (1.9%) compared with tTG IgA. Antideaminated gliadin peptide (DGP) IgA/IgG levels were also infrequently ordered (5.4%) compared with tTG IgA. The antiendomysial antibody was ordered sparingly (0.9%) compared with tTG IgA, but appropriately by providers with expertise in CD, similar to ordering for celiac genetics (0.8%). Of the celiac genetic tests, 15% were ordered in error. The positivity rate of the tTG IgA ordered by PCPs was 4.4%.
Conclusions:
The tTG IgA was appropriately ordered by all types of providers. Endocrinologists inconsistently ordered total IgA levels with screening labs. DGP IgA/IgG tests were not commonly ordered but were inappropriately ordered by one provider. The low number of ordered antiendomysial antibody and celiac genetic tests suggests under-utilization of the nonbiopsy approach. The positive yield of tTG IgA ordered by PCPs was higher compared with previous studies.
Background: Celiac disease (CD) is a multifactorial, immune-mediated enteropathic disorder that may occur at any age with heterogeneous clinical presentation. In the last years, unusual manifestations have become very frequent, and currently, it is not so uncommon to diagnose CD in subjects with overweight or obesity, especially in adults; however, little is known in the pediatric population. This systematic review aims to evaluate the literature regarding the association between CD and overweight/obesity in school-age children. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. An electronic database search of articles published in the last 20 years in English was carried out in Web of Sciences, PubMed, and Medline. The quality of the included studies was assessed by using the STrengthening the Reporting of OBservational studies in Epidemiology statement. Results: Of the 1396 articles identified, 9 articles, investigating overweight/obesity in children/adolescents affected by CD or screening CD in children/adolescents with overweight/obesity, met the inclusion criteria. Overall, the results showed that the prevalence of overweight or obesity in school-age children (6-17 years) affected by CD ranged between 3.5% and 20%, highlighting that the coexistence of CD with overweight/obesity in children is not uncommon as previously thought. Conclusion: Although CD has been historically correlated with being underweight due to malabsorption, it should be evaluated also in children with overweight and obesity, especially those who have a familiar predisposition to other autoimmune diseases and/or manifest unusual symptoms of CD.
This guideline presents an update to the 2013 American College of Gastroenterology Guideline on the Diagnosis and Management of Celiac Disease with updated recommendations for the evaluation and management of patients with celiac disease (CD). CD is defined as a permanent immune-mediated response to gluten present in wheat, barley, and rye. CD has a wide spectrum of clinical manifestations that resemble a multisystemic disorder rather than an isolated intestinal disease, and is characterized by small bowel injury and the presence of specific antibodies. Detection of CD-specific antibodies (e.g., tissue transglutaminase) in the serum is very helpful for the initial screening of patients with suspicion of CD. Intestinal biopsy is required in most patients to confirm the diagnosis. A nonbiopsy strategy for the diagnosis of CD in selected children is suggested and discussed in detail. Current treatment for CD requires strict adherence to a gluten-free diet (GFD) and lifelong medical follow-up. Most patients have excellent clinical response to a GFD. Nonresponsive CD is defined by persistent or recurrent symptoms despite being on a GFD. These patients require a systematic workup to rule out specific conditions that may cause persistent or recurrent symptoms, especially unintentional gluten contamination. Refractory CD is a rare cause of nonresponsive CD often associated with poor prognosis.
The incidence of celiac disease in first-degree relatives of affected individuals is higher than in the general population, yet the clinical characteristics of this unique subset of patients has not been well described. Through a retrospective review of patients seen in a tertiary care pediatric celiac disease clinic, we identified 49 patients diagnosed with celiac disease following screening due to an affected first-degree relative. Although 51% of patients screened due to an affected first-degree relative were asymptomatic, their disease histology was as severe as those screened for symptoms suggestive of celiac disease. These findings support current recommendations to screen all first-degree relatives of patients with celiac disease regardless of clinical symptoms.
BACKGROUND
In selective IgA deficiency (IgAD), there is no reliable screening test for coeliac disease (CD).AIMTo evaluate the usefulness of IgG1 antiendomysium and IgG antitissue transglutaminase tests for CD diagnosis in IgAD.METHODS
IgA and IgG antigliadin antibodies (IgA- and IgG-AGA), IgA and IgG1antiendomysium antibodies (IgA- and IgG1-EMA), and IgA and IgG antitissue transglutaminase (IgA- and IgG-anti-tTG) were assayed in: (a) 20 untreated IgAD/CD patients; (b) 34 IgAD/CD patients on a strict gluten free diet (GFD); (c) 10 IgAD/CD patients not on a strict GFD; (d) 11 untreated CD patients without IgAD; (e) 10 healthy IgAD patients; and (f) 25 healthy controls.RESULTSIn all untreated IgAD/CD patients, IgG1-EMA, IgG-anti-tTG, and IgG-AGA were positive whereas IgA antibodies against these antigens were negative. IgAD/CD patients on a strict GFD did not produce IgG-AGA or IgG1-EMA but four of 34 produced IgG anti-tTG. IgAD/CD subjects not on a strict GFD produced IgG-AGA whereas 5/10 and 4/10 were IgG1- EMA and IgG-anti-tTG negative, respectively. Untreated CD patients without IgAD were AGA (IgA and IgG), EMA (IgA and IgG1), and anti-tTG (IgA and IgG) positive. Healthy controls were AGA and EMA negative whereas two of 10 apparently healthy IgAD subjects and one of 25 healthy negative control were IgG-anti-tTG positive.CONCLUSIONS
Both IgG1-EMA and IgG-anti-tTG tests appear to be useful for identification of IgAD/CD patients whereas they are less satisfactory for monitoring dietary compliance in these subjects. In addition, our findings seem to suggest that IgG-EMA autoantibodies produced by coeliac patients are mainly of the IgG1 subtype.
Two hundred and seventy-eight duodenal biopsy specimens taken consecutively from children using either a single port paediatric Crosby capsule or a double port modification were examined both histologically and by dissecting microscopy, in order to determine the incidence of patchy mucosal lesions. One hundred and six specimens were abnormal and 49 of these were patchy. Patchy lesions occurred most commonly in cow's milk sensitive enteropathy where 66% of 33 specimens were patchy; in comparison all children with undiagnosed coeliac disease taking a normal diet showed a uniformly flat mucosa. Twenty-two per cent of specimens taken using the double port and 10% using the single port capsule were patchy, a statistically significant difference (P = 0.01) using standard errors. Where lesions were uniform, grading by dissecting microscopy correlated well with histological grading; 18 (37%) of specimens were, however, recognised as patchy only on gross appearance. The high incidence of patchy lesions of the proximal small intestine reflected the prevalence of cow's milk protein intolerance and the postenteritis syndrome in these children. The use of the double port capsule and of dissecting microscopy also contributed to the high incidence found.
The incidence and degree of patchiness of mucosal abnormality in both coeliac disease (CD) and dermatitis herpetiformis (DH) is documented. As judged by both stereomicroscopy and subjective histology, patchiness occurred frequently in both CDand DH patients. In most cases the difference of abnormality was of only one grade, but in approximately 25% as assessed by stereomicroscopy and 10% as assessed by histology the difference was of two or more grades. In control subjects with normal small bowel mucosa the variation of the mucosal appearance between the duodenum and proximal jejunum was studied. Contrary to popular belief, no significant difference of villous and crypt measurements or of apparent villous "bridging" and "branching" between these two sites was found, if only well-orientated sections were studied. The stereomicroscopic appearances were also similar at these two sites, although villi tended to be broader in the duodenal biopsies. The duodenal-jejunal variation was also studied in CD and DH patients and although by both stereomicroscopy and subjective histology the appearances were similar in most patients, in approximately 33% the duodenal abnormality was the most severe and, surprisingly, the jejunal abnormality was more severe in approximately 15%. It is concluded that multiple, precisely located biopsies of both the duodenum and proximal jejunum are invaluable in the investigation of small bowel disease and in assessing response to treatment.
This article examines associations between gluten, polymorphisms of the major histocompatibility complex, and mucosal pathology representative of the spectrum of gluten sensitivity. Sequences of wheat, rye, and barley prolamins contain recurring tetrapeptide motifs that are predicted to have beta-reverse-turn secondary structure and that, with in vitro assays, appear active. Structural polymorphisms of major histocompatibility complex subloci identify codon switches within the second exon that control the third hypervariable region in the outer domain of the beta chain. Observations of the intestinal response to gluten reveal five interrelated lesions (preinfiltrative, infiltrative, hyperplastic, destructive, and hypoplastic) that are interpretable as cell-mediated immunologic responses. These responses originate in the lamina propria, where a series of antigen-specific inflammatory processes has now been identified. There is no evidence that celiac sprue is a disease of jejunal enterocytes. Furthermore, the role of intraepithelial space lymphocytes in pathogenesis, if relevant, needs further experimental dissection. Also awaiting further definition are polymorphisms of the celiac lymphocyte antigen receptor and their relationship to gliadin oligopeptide(s) and predisposing genes. The nature and basis of nonresponsive celiac sprue require more thoughtful initiatives to elucidate the immunologic mechanism(s) of unresponsiveness and evaluate possible means of reversal. Finally, a more sensible definition of gluten sensitivity (unhampered by qualitative morphological imagery) is ultimately called for in order to accommodate the biomolecular advances addressed in this review.
To investigate the extent to which the detection of antibodies to gliadin, endomysium, and jejunum predicts the eventual diagnosis of coeliac disease according to the revised ESPGAN diagnostic criteria in a group of patients in whom there is a high suspicion of coeliac disease.
Clinical assessment and laboratory analysis of patients with suspected coeliac disease.
Gastroenterology department of teaching hospital.
96 adults with suspected coeliac disease attending for jejunal biopsy.
Diagnosis of coeliac disease with the revised criteria of the European Society of Paediatric Gastroenterology and Nutrition in patients with and without antibodies associated with coeliac disease.
28 patients had a clinical diagnosis of coeliac disease, seven of other gastrointestinal diseases, and 12 of miscellaneous diseases; 49 had no diagnosis. Gliadin IgA detected by ELISA was found in all patients with coeliac disease and none of those without, giving a sensitivity, specificity, positive and negative predictive values, and predictive efficiency of 100% for diagnosing coeliac disease within the group. Endomysial IgA was found in 25 (89%) patients with coeliac disease and jejunal IgA in 21 (75%); neither IgA was found in patients without coeliac disease.
Detection of gliadin IgA by ELISA and to a lesser extent the endomysial IgA should allow better selection of patients for jejunal biopsy and thus make diagnosing coeliac disease simpler and more efficient.
The value of IgG and IgA gliadin antibodies (AGA) was compared with that of IgA endomysium antibodies (EMA) for the diagnosis of coeliac disease. Three hundred and six of 340 (90%) children with untreated coeliac disease (flat mucosa) had EMA and 338/340 (99.4%) had IgG AGA and/or IgA AGA. Only 1/340 (a 7 year old boy with selective IgA deficiency) had neither AGA nor EMA. Absence of EMA is more frequent in coeliac patients younger than 2 years than in older patients (32/277 compared with 1/62). EMA were present in 4/211 (2%) of comparison subjects (normal mucosa), IgA AGA in 12/211 (6%), and IgG AGA in 74/211 (35%). The specificity of AGA cannot be calculated from these figures as they are biased. The combined determination of AGA and EMA, taking advantage of the high sensitivity of AGA and the high specificity of EMA, gives an excellent prediction of the condition of the mucosa: 247/248 patients (99.6%) with positive EMA and positive IgG AGA and IgA AGA had a flat mucosa, whereas 136/137 patients (99.3%) with neither AGA nor EMA had a normal mucosa. During a gluten free diet EMA and AGA disappear. Their presence or absence is therefore an indicator of dietary compliance. After reintroduction of gluten into the diet 110/134 (82%) of the patients who had a flat mucosa at diagnosis relapsed, but 24/134 still had a normal mucosa after 2-15 years of challenge. All these patients without a morphological relapse were less than 2 years old at diagnosis so we conclude that patients who are young at diagnosis should be challenged. AGA often reappear earlier than EMA. After one month of challenge 93% of patients are AGA and 69% EMA positive. After more than three years of gluten intake the percentage of AGA positive patients decreased to about 50% whereas the percentage of EMA positive sera was then highest (93%). Therefore EMA are more sensitive for the detection of 'silent' relapse after prolonged periods of gluten intake.
Altogether 38 postpubertal children with coeliac disease were rebiopsied. Mucosal abnormality in nine (24%) of them indicated poor adherence to the diet. Gluten challenge with a diet containing a normal amount of gluten was performed in those 29 patients with a normal mucosa. During challenge, rebiopsy was done when reticulin antibodies turned positive (mean 0.6 years, range 0.2-2.0) or at the end of the two year study. Histologically a clear relapse into coeliac disease was seen in all 23 patients who were positive for reticulin antibodies. At this time gliadin antibodies were positive in all but two. Sixteen (70%) of those who relapsed were completely asymptomatic. Three girls and one boy did not relapse within two years, indicating the possible recovery from coeliac disease to be 11%. All four had undergone gluten challenge earlier in childhood, after initial diagnosis and mucosal recovery, and this had resulted in mucosal relapse. To establish definite postpubertal recovery from coeliac disease in cases with normal mucosa at two years from challenge, further follow up studies of reticulin antibodies and later rebiopsy are needed. The reticulin antibody test seems to be suitable for prediction of mucosal relapse in coeliac disease.
Two hundred and ten patients with coeliac disease previously reported from this unit were reviewed at the end of 1985 after a further 11 years of follow up. The initial review at the end of 1974 could not demonstrate that a gluten free diet (GFD) prevented these complications, probably because the time on diet was relatively short. The same series has therefore been kept under surveillance with the particular aim of assessing the effects of diet on malignancy after a further prolonged follow up period. Twelve new cancers have occurred: of which one was a carcinoma of the oesophagus and two lymphomas. Thirty nine cancers developed in 38 patients and of 69 deaths, 33 were the result of malignancy. A two-fold relative risk (RR) of cancer was found and was because of an increased risk of cancer of the mouth and pharynx (RR = 9.7, p less than 0.01, 95% confidence interval (CI) = 2.0-28.3), oesophagus (RR = 12.3, p less than 0.01, CI = 2.5-36.5), and of non-Hodgkin's lymphoma (RR = 42.7, p less than 0.001, CI = 19.6-81.4). The results indicate that for coeliac patients who have taken a GFD for five years or more the risk of developing cancer over all sites is not increased when compared with the general population. The risk is increased, however, in those taking a reduced gluten, or a normal diet, with an excess of cancers of the mouth, pharynx and oesophagus (RR = 22.7, p < 0.001), and also of lymphoma (RR = 77.8, p < 0.001). A significant decreasing trend in the excess morbidity rate over increasing use of a GFD was found. The results are suggestive of a protective role for a GFD against malignancy in coeliac disease and give further support for advising all patients to adhere to a strict GFD for life.
Celiac sprue is a life-long inflammatory condition of the gastrointestinal tract that affects the small intestine in genetically susceptible individuals. The prevalence in Northern Europe is approximately 1:300, whereas in the United States it occurs less frequently. A small intestinal biopsy is mandatory to confirm the diagnosis. Treatment involves a strict gluten-free diet that excludes wheat, rye, and barley and that should be supervised by a dietician. Follow-up is important because of potential long-term complications.
An association between celiac disease and other autoimmune disorders-such as insulin-dependent diabetes, Addison's disease, systemic lupus erythematous, rheumatoid arthritis, alopecia areata, and autoimmune endocrine diseases-has been described. The aim of this study was to evaluate the prevalence of celiac disease in 100 patients with autoimmune thyroid disease. Moreover, the monitoring of patients with concomitant celiac and autoimmune thyroid diseases, after a gluten-free diet or a gluten-containing diet, can give important insights into the effect of dietary habits in thyroid autoantibodies modulation. In our study, the prevalence of celiac disease in patients with autoimmune thyroid disease was 2%. In these two celiac patients, the serologic markers became undetectable 6 months after beginning a gluten-free diet. However, thyroid autoantibodies did not positively correlate with dietary habits.
Serum gliadin antibodies (IgA/IgG) were determined in 191 consecutive children (median age, 2.75 years; range, 0.33-15.5 years) admitted for a small-intestinal biopsy on suspicion of celiac disease. The test was a diffusion-in-gel enzyme-linked immunosorbent assay (DIG-ELISA). Of these 191, 14 (7.3%) appeared to have untreated celiac disease. Depending on the choice of cut-off value of the test (combined determination of IgA and IgG), the sensitivity was 86-100%, the specificity was 97-99%, and the positive/negative predictive values were 70-92% and 99-100%, respectively. No variation according to age was found. Gliadin antibodies were determined in 47 children who had well-treated celiac disease. Fourteen of these children were also investigated when challenged with gluten. Gliadin antibodies (IgA or IgG) decreased significantly in 13 of 13 cases when the patients shifted from a gluten-containing diet to a gluten-free one. During the gluten challenge, the IgG and IgA increased in 14 of 14 and 11 of 14 cases, respectively (two patients suffered from IgA deficiency). In eight patients who later appeared to be free of celiac disease, the gliadin antibodies were determined on gluten-free diet and during gluten challenge; no significant differences in gliadin antibodies were found. We conclude that this test is useful in selecting patients with symptoms suggesting celiac disease for a small-intestinal biopsy. The test seems to be of some value in monitoring the effects of a gluten-free diet and during gluten challenge.
Thirty-five subjects treated with a gluten-free diet for a chronic gastrointestinal disorder (no biopsy performed) in early childhood were re-examined 14-38 (median, 28) years later. Twenty-one accepted jejunal biopsy at re-examination. None of those studied were on a gluten-free diet at the time of the study. Ten of 21 biopsy specimens were abnormal—6 with flat mucosa and very low disaccharidase levels, indicating coeliac disease, and 4 with low disaccharidase activity but morphologically normal mucosa. Three of the six subjects with flat mucosa showed a slight fat and lactose malabsorption, but their clinical condition did not suggest serious intestinal disease. Ingestion of gluten throughout most of childhood did not appear to affect growth, as evaluated by final height. Jejunal biopsy is recommended in all patients with gastrointestinal symptoms that are not otherwise explainable if their medical history shows a period of gluten-free diet for a chronic gastrointestinal disorder in childhood.
HLA-DRB1, -DQA1, and -DQB1 genomic typing of 50 patients with dermatitis herpetiformis and of 290 healthy blood donors was performed. Genes encoding the DQ (α1*0501, (β1*02) heterodimer were carried by 43 (86%) of the patients and 72 (25%) of the controls. Of die remaining seven patients six (12% of all the patients) carried genes encoding the DQ (α1*03, β1*0302) heterodimer. These HLA associations are very similar to those observed in patients with celiac disease. We thus conclude that dermatitis herpetiformis and celiac disease are associated to the very same HLA-DQαβ heterodimers.
The relationship between celiac disease and many autoimmune disorders has been explained by the sharing of a common genetic factor. In a multicenter national study, we examined the relationship between the prevalence of autoimmune disorders in celiac disease and the duration of exposure to gluten.
Over a 6-month period, 909 patients with celiac disease (group A; mean age, 16.1 +/- 3.8 years; grouped according to age at diagnosis into three subgroups [group A1, <2 years; group A2, 2-10 years; and group A3, >10 years]), 1268 healthy controls (group B; mean age, 20.8 +/- 4.5 years), and 163 patients with Crohn's disease (group C; mean age, 28.8 +/- 10 years) were evaluated for the presence of autoimmune disorders.
Prevalence of autoimmune disorders in group A was significantly higher than in group B (14% vs. 2.8%; P < 0.000001) but not higher than in group C (12.9%). Prevalence of autoimmune disorders in celiac disease increased with increasing age at diagnosis: 5.1% in group A1, 17% in group A2, and 23.6% in group A3 (P = 0.000001). In group A3, the prevalence of autoimmune disorders was significantly higher than in group C. In a logistic regression model, age at diagnosis was the only significant predictor variable of the odds of developing an autoimmune disorder (r = 0.3; P < 0.000001).
Our data show for the first time that the prevalence of autoimmune disorders in celiac disease is related to the duration of exposure to gluten.
A prospective study of risks in upper intestinal endoscopy, liver biopsy, proctosigmoidoscopy, rectal biopsy, esophageal motility, intraesophageal pH probe tests and liver biopsy was conducted at 25 medical centers during an 18 month period from April 1, 1978 to October 1, 1979. 5,840 procedures were reported: 2046 upper intestinal endoscopies; 1,120 small intestinal biopsies; 1,400 proctosigmoidoscopies; 842 rectal biopsies; 432 esophageal motility and Tuttle tests, and 584 liver biopsies. Completeness of reporting varied from 88 to 99% of all procedures at participating centers. Total numbers of procedures varied from 5 to 50 per month. Some centers did not do all procedures. 20 of 25 institutions reported doing all the procedures. 5 of 25 did no esophageal function tests. Complications occurred in 1.7% of upper intestinal endoscopies; .5% of small intestinal biopsies; .2% of proctosigmoidoscopies; 1% of rectal biopsies, .3% of esophageal function tests and 4% of liver biopsies. Bronchospasm, transient respiratory arrest and phlebitis secondary to sedation were the commonest complications in those undergoing endoscopy; fever and sedation complications were commonest in small intestinal biopsy;only 1 hemorrhage requiring transfusion and 1 perforation were reported in this group. Fever and perforation of the rectum were the only serious complications at proctosigmoidoscopy. Rectal bleeding requiring transfusion and fever were the only complications in rectal biopsy and aspiration pneumonia and transient respiratory arrest the only ones in esophageal function tests. Liver biopsy had the greatest risk of complication with bleeding, pneumothorax and pain the 3 major complications.Invasive diagnostic procedures in pediatric gastroenterology patients may be done with a low risk of complications. Information gained outweighs risk of procedures.
Background: Unrecognized celiac disease (CD) may be found in a substantial proportion of patients with type 1 diabetes mellitus.
Methods: A cohort of 403 Austrian children and adolescents with type 1 diabetes mellitus (210 males and 193 females; age range, 1-22 years) was screened for celiac disease using the IgA anti-endomysium antibody test (EMA) and the immunoglobulin (Ig)G anti-gliadin (AGA-IgG) and IgA anti-gliadin (AGA-IgA) antibody test.
Results: Twelve patients' sera (2.98%) yielded positive EMA results and two patients' sera (0.49%) with IgA deficiency had high AGA-IgG values. All but one of these patients underwent intestinal biopsy. Six (1.49%) had clear histologic evidence of CD (flat mucosa), whereas three (0.74%) showed minor histologic changes (increase in intraepithelial lymphocytes) and four (0.99%), including the EMA-negative patients with IgA deficiency, had a normal mucosa. When the cases with silent and potential CD were combined, the overall prevalence in the current cohort was 2.98%. There was no difference in the hemoglobin (Hb)A1c level between antibody-positive and -negative patients, and subsequent gluten-free diet did not change this metabolic parameter.
Conclusion: The prevalence of clinically unrecognized CD, found by EMA screening, is much higher in Austrian children with diabetes than in a comparable population without diabetes. The prevalence of CD in diabetic children in Austria is distinctly lower, however, than in several other countries.
Background: A multicenter research study of Down syndrome patients was carried out to estimate the prevalence of celiac disease in patients with Down syndrome and to show clinical characteristics and laboratory data of Down syndrome patients.
Methods: The authors studied 1,202 Down syndrome patients. Fifty-five celiac disease patients (group 1) were compared with 55 immunoglobulin A antigliadin-positive antiendomysium antibodies-negative patients (group 2) and with 57 immunoglobulin A antigliadin-negative antiendomysium antibodies-negative patients (group 3).
Results: Celiac disease was diagnosed in 55 of 1,202 Down syndrome patients (4.6%). In group 1, weight and height percentiles were shifted to the left, whereas these parameters were normally distributed in groups 2 and 3. In celiac patients, diarrhea, vomiting, failure to thrive, anorexia, constipation, and abdominal distension were higher than in the other two groups. Low levels of hemoglobinemia, serum iron, and calcium were observed more frequently in group 1. The diagnosis of celiac disease was made after a mean period of 3.8 years from the initiation of symptoms. Sixty-nine percent of patients showed a classic presentation, 11% had atypical symptoms, and 20% had silent celiac disease. Autoimmune disorders were more frequent (30.9%) in group 1 than in the other two groups examined (15%;P < 0.05).
Conclusions: This study reconfirms a high prevalence of celiac disease in Down syndrome. However, the diagnostic delay, the detection of atypical symptoms or silent form in one third of the cases, and the increased incidence of autoimmune disorders suggest the need for the screening of celiac disease in all Down syndrome patients.
Duodenal or jejunal biopsies are needed to establish the diagnosis of celiac disease. It is widely advocated that these biopsies be taken from the distal duodenum.
After finding two index cases with diagnostic biopsies taken from the duodenal bulb, we retrospectively analyzed biopsies from the descending duodenum and the duodenal bulb of 51 patients with suspected or diagnosed celiac disease. The diagnosis of celiac disease and classification of the histological changes were performed by one pathologist.
In the two index cases the diagnosis of celiac disease could only be established by taking the biopsies from the duodenal bulb, and not from the descending duodenum. In the retrospective analysis the number of intraepithelial lymphocytes was on average higher, but not significantly, in the descending part of the duodenum.
Most patients with celiac disease show similar mucosal changes in biopsies taken from the descending part of the duodenum and from the duodenal bulb. But in patients who have already been on a gluten-free diet in childhood and later abandoned their diet, an additional duodenal bulb biopsy should be done.
Celiac disease is an autoimmune gastrointestinal disorder characterized by mucosal atrophy of the jejunum on exposure to gluten, a protein found in grains. The purpose of our study was to determine the prevalence of celiac disease in children with Downs syndrome in a U.S.-based Caucasian population. The 97 Downs syndrome children were screened for celiac disease using serum IgA-anti-endomysial antibody testing, which is highly specific and sensitive for the disorder. Children with titers greater than 1:5 (using the IgA endomysial antibody [EMA] test; EMA+) were considered affected. Ten children (10.3%) were EMA+. We examined their HLA DQA1 DQB1 genotype, karyotype, clinical characteristics, and the prevalence of celiac disease in their first-degree relatives. The nine available karyotypes were trisomy 21. Downs syndrome-specific mean height percentile was 64% ± 26% (range <5–99%) and weight percentile was 43% ± 28% (range 5–95%). Presence of diarrhea, constipation, vomiting, and abdominal pain was similar for children with and without celiac disease. Only bloating symptoms were significantly more frequent in those with celiac disease (EMA+). Seven of eight (88%) genotyped EMA+ children had the celiac disease-associated high-risk HLA DQA1*0501 DQB1*0201 genotype as compared with 13/80 (16%) of EMA− children. Five of 48 (10%) first-degree relatives of the celiac disease (EMA+) children were EMA+. In conclusion, celiac disease, as diagnosed by positive endomysial antibody tests, has an increased prevalence in children with Downs syndrome in the U.S. as compared with the general population (1/250). Clinical and growth characteristics do not distinguish between children with and without celiac disease. Based on these observations, it is recommended that children with Downs syndrome be screened for celiac disease. © 2001 Wiley-Liss, Inc.
Stenhammar, L. (Department of Paediatrics, Central Hospital, Norrköping, Sweden). Transient gastro-intestinal disorders during infancy and early childhood–a follow-up study with special reference to coeliac disease. Acta Paediatr Scand, 70:383, 1981.–In a reappraisal study of coeliac disease (CD) 38 children and adolescents were studied: 20 (group A) had a previous diagnosis of CD from early childhood but had been lost to follow-up, 18 (group B) had in infancy or early childhood been hospitalized for more than 1 month for different gastro-intestinal symptoms without receiving a diagnosis of CD. In the present study the patients had a clinical examination and Hb, serum IgA and folate were analysed. These investigations did not prove helpful in selecting coeliac cases. Intestinal biopsy revealed CD in 8 patients in group A and in 6 patients in group B. Thus the frequency of CD was almost the same in the two groups. All 14 patients with CD had very few complaints, when a careful medical history was taken before biopsy. The present study shows the importance of performing intestinal biopsy on liberal indications on patients with an infancy or early childhood history of malabsorption-related symptoms. Among these patients many coeliacs are likely to be found.
The prevalence of hypertransaminasemia and the effect of gluten-free diet (GFD) were evaluated in 158 consecutive adult celiac patients, 127 women and 31 men, aged 18 to 68 years (mean, 32). At diagnosis, 67 patients (42%) had raised aspartate and/or alanine transaminase levels (AST and ALT; mean, 47 IU/L, range, 30 to 190; and 61 IU/L, range, 25 to 470, respectively), whereas 91 patients had normal liver function tests (LFT). Patients with and without hypertransaminasemia were comparable for epidemiological data, body mass index (18.5 vs. 19.6), and severity of intestinal histological involvement. All patients were given a strict GFD and were followed for 1 to 10 years (median, 4). At 1 year, a highly significant improvement in intestinal histology was observed in both groups (P < .0001). In the 67 patients with raised transaminase levels body mass index (BMI) also increased significantly (from 18.5 to 21.0, P < .001), and transaminase levels normalized in 60 (95%). In the other seven cases liver biopsy showed fatty infiltration in two and chronic active hepatitis (CAH) in the other five, related to chronic infection with hepatitis B virus in three and hepatitis C virus in one, and to autoimmune type in the fifth. We conclude that in adult celiac patients elevated serum transaminases are a frequent finding and normalize in most cases after GFD. When they persist, liver biopsy is mandatory to further investigate hepatic involvement, which in our series was mainly attributable to CAH. (Hepatology 1995; 22:833–836.)
The aims of this study were to estimate the prevalence of coeliac disease (CD) in Czech children with insulin dependent diabetes mellitus (IDDM), and to determine the contribution of HLA-DQA1 and DQB1 to CD susceptibility among diabetic children. We screened 345 children with IDDM (186 boys and 159 girls, aged 0 to 18 y) for coeliac disease using the IgA endomysial antibodies (EMA) test. In all EMA-positive children, small bowel biopsy was performed to confirm CD. To determine the role of the HLA-DQA1*05-DQB1*0201 (DQ2) and the DQA1*03-DQB 1*0302 (DQ8) molecules in CD susceptibility among diabetic children, the HLA-DQA1-DQB1 was genotyped in all EMA-positive, and in 186 of EMA-negative diabetic patients. EMA positivity was found in 15/345 (4.3%) diabetic children. The diagnosis of CD was established in 14/345 (4.1%) children based on a bioptic finding of villous atrophy, while the remaining EMA-positive patient had a normal bioptic finding, being diagnosed as a potential CD. The HLA DQA1*05-DQB1*0201 (DQ2) molecule conferred a significant risk of CD among diabetic children (odds ratio = 4.1, CI 95% 1.1–15), being found more frequently in diabetic children with CD (80%) than in diabetic children without CD (49%).
Conclusion: The high prevalence of CD (4.1%) found in Czech children with IDDM emphasizes the need for their regular screening. We suggest that this CD screening protocol may be individualized according to the DQA1*05-DQB 1*0201 positivity.
There have been anecdotal reports of an association between coeliac disease and epilepsy with cerebral calcifications that resemble those of the Sturge-Weber syndrome. A series of patients who had epilepsy with calcifications, in whom coeliac disease (CD) was incidentally observed, prompted us to study this association. 43 patients (15 male, age range 4·6-30·7 years) were selected from two series. 31 patients with cerebral calcifications of unexplained origin and epilepsy (series A) underwent intestinal biopsy. 12 patients with CD and epilepsy (series B) underwent computed tomography. Antibodies to gluten, folic acid serum concentrations, were measured, and H LA typing was done in most patients. 24 of the series A patients were identified as having CD on the basis of a flat intestinal mucosa (15/22 with a high concentration of serum antigluten), and 5 series B patients showed cerebral calcifications, giving a total of 29 cases with the combination of CD, epilepsy, and cerebral calcifications (CEC). In 27 of these CEC patients, calcifications were located in the parieto-occipital regions. Only 2 of the series A patients had gastrointestinal symptoms at the time of intestinal biopsy; most patients had recurrent diarrhoea, anaemia, and other symptoms suggestive of CD in the first 3 years of life. The epilepsy in CEC patients was poorly responsive to antiepileptic drugs. Gluten-free diet beneficially affected the course of epilepsy only when started soon after epilepsy onset. Cases of "atypical Sturge-Weber syndrome" (characterised by serpiginous cerebral calcifications and epilepsy without facial port-wine naevus) should be reviewed, and CD should be ruled out in all cases of epilepsy and cerebral calcifications of unexplained origin.
Objective:
Tissue transglutaminase (tTG) is the main autoantigen recognized by endomysial antibodies. The aim of this study was to assess sensitivity, specificity, and predictive value of IgA and IgG antibodies to tTG in the diagnosis of celiac disease compared with endomysial antibodies.
Study design:
We established enzyme-linked immunosorbent assay procedures to measure IgA and IgG antibodies to tTG in sera from 48 untreated and 33 treated patients with celiac disease and from 63 patients with gastrointestinal disease who were in a control group. Sera from 10 patients with celiac disease were examined at various times after gluten was reintroduced into the patients' diet.
Results:
Both IgA and IgG to tTG were significantly (P <.001) higher in serum of untreated patients with celiac disease versus those in the control group; IgA but not IgG was significantly (P <.001) higher in untreated versus treated patients with celiac disease. IgA and IgG antitissue tTG had a diagnostic sensitivity, specificity, and positive predictive value of 92% and 21%, 98% and 97%, and 98% and 83%, respectively. The concordance rate of IgA anti-tTG with IgA antiendomysial antibodies was 95%. In 5 of the 10 patients undergoing gluten challenge, IgA antiendomysium antibodies were detected earlier than IgA anti-tTG antibodies.
Conclusions:
tTG-based enzyme-linked immunosorbent assay is an effective diagnostic test, although immunofluorescent-based assays are more sensitive, particularly during gluten challenge.
It should be recognized that these guidelines should not be deemed inclusive of all proper methods of care or exclusive of methods of care reasonably directed to obtaining the same results. The ultimate judgement regarding the propriety of any specific guideline must be made by the physician in light of all the circumstances presented by the individual patient.
The clinical spectrum of adults with celiac disease in the United States, where the disease is considered rare, is not known. We sought this information by distributing a survey.
A questionnaire was distributed by way of a celiac newsletter, directly to celiac support groups, and through the Internet.
Respondents (1,612) were from all United States except one. Seventy-five percent (1,138) were biopsy proven. Women predominated (2.9:1). The majority of respondents were diagnosed in their fourth to sixth decades. Symptoms were present a mean of 11 yr before diagnosis. Diarrhea was present in 85%. Diagnosis was considered prompt by only 52% and 31% had consulted two or more gastroenterologists. Improved quality of life after diagnosis was reported by 77%. Those diagnosed at age > or = 60 yr also reported improved quality of life. Five respondents had small intestinal malignancies (carcinoma 2, lymphoma 3) accounting for a relative risk of 300 (60-876) for the development of lymphoma and 67 (7-240) for adenocarcinoma.
Patients with celiac disease in the United States have a long duration of symptoms and consider their diagnosis delayed. Improved quality of life after diagnosis is common. An increased risk of developing small intestine malignancies is present.
Of 58 children with suspected malabsorption, 27 were shown to have subtotal or partial atrophy, and 31 had normal mucosal histology. Oral glucose tolerance tests, faecal fat excretion, D-xylose excretion tests, Prosparol absorption studies, haematological investigations, and radiological examination of the small bowel failed to distinguish these two groups and frequently gave misleading results. It is concluded that in suspected coeliac disease small intestinal biopsy should be performed as a primary investigation.
This study characterizes by serological and molecular methods the HLA class I and class II alleles in a group of celiac disease children, their parents and a control group of Sardinian descent. We found the DR3-DQw2 haplotype in all patients which was, in almost all cases (84%), associated with the HLA-A30, B18, DR3, DRw52, DQw2 extended haplotype named "Sardinian haplotype" because of its frequency (12-15%) in this Caucasian population. This is the first time that this DQw2-linked haplotype has been reported with such a high frequency in CD. However, no different distribution of "Sardinian haplotype" was found comparing CD patients with 91 haplotyped DQw2-positive controls. This finding indicates that the DQw2 antigen in Sardinians is almost always associated with the A30, B18, DR3, DRw52, DQw2 extended haplotype. The DQA1 and DQB1 second exon sequence analysis of the B18,DR3 and B8,DR3 haplotypes showed the DQA1*0501 and DQB1*0201 alleles which shared the already published sequences. DPB1 subtyping showed the DPB1*0301 allele more frequently (p less than 0.005) in CD patients but this difference was no longer significant when patients and controls, both heterozygous for the DR3-DQw2 haplotype, were compared. We suggest that the divergent HLA extended haplotypes and DP allele associated with CD, described in different Caucasian populations, can be explained by the particular DQw2 linkage disequilibrium in each population.
There have been anecdotal reports of an association between coeliac disease and epilepsy with cerebral calcifications that resemble those of the Sturge-Weber syndrome. A series of patients who had epilepsy with calcifications, in whom coeliac disease (CD) was incidentally observed, prompted us to study this association. 43 patients (15 male, age range 4.6-30.7 years) were selected from two series. 31 patients with cerebral calcifications of unexplained origin and epilepsy (series A) underwent intestinal biopsy. 12 patients with CD and epilepsy (series B) underwent computed tomography. Antibodies to gluten, folic acid serum concentrations, were measured, and HLA typing was done in most patients. 24 of the series A patients were identified as having CD on the basis of a flat intestinal mucosa (15/22 with a high concentration of serum antigluten), and 5 series B patients showed cerebral calcifications, giving a total of 29 cases with the combination of CD, epilepsy, and cerebral calcifications (CEC). In 27 of these CEC patients, calcifications were located in the parieto-occipital regions. Only 2 of the series A patients had gastrointestinal symptoms at the time of intestinal biopsy; most patients had recurrent diarrhoea, anaemia, and other symptoms suggestive of CD in the first 3 years of life. The epilepsy in CEC patients was poorly responsive to antiepileptic drugs. Gluten-free diet beneficially affected the course of epilepsy only when started soon after epilepsy onset. Cases of "atypical Sturge-Weber syndrome" (characterised by serpiginous cerebral calcifications and epilepsy without facial port-wine naevus) should be reviewed, and CD should be ruled out in all cases of epilepsy and cerebral calcifications of unexplained origin.
A significant increase in the prevalence of selective IgA deficiency has been observed in patients with autoimmune disorders such as systemic lupus erythematosus and rheumatoid arthritis. Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease and susceptibility to both IDDM and IgA deficiency is associated with HLA DQB1 alleles encoding non-Asp amino acids at position 57. In order to assess whether the prevalence of selective IgA deficiency is increased in IDDM, we have screened a homogeneous series of adult patients with IDDM for selective IgA deficiency. One patient (1:261) was found to have a selective IgA deficiency. The prevalence of selective IgA deficiency among adult French blood donors is 1:1400. Thus, although IDDM and selective IgA deficiency are both associated with the presence of non-Asp amino acids at position 57 of the HLA DQ beta chain, the frequency of this immunodeficiency in adult IDDM patients is not significantly increased.
Twenty-five children and adults with concomitant coeliac disease and selective IgA deficiency are described. IgG-class reticulin antibodies were positive in 94% The clinical course of coeliac disease did not differ from that of patients with normal serum IgA level. Patients with IgA deficiency also had other concomitant diseases, especially autoimmune diseases. Patients with selective IgA deficiency have at least a tenfold risk of coeliac disease compared with the population in general. © 1992 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
Celiac disease (CD) has been recently reported to be primarily associated with the DQ(alpha 1*0501, beta 1*0201) heterodimer encoded in cis on DR3 haplotype and in trans in DR5,7 heterozygous individuals. The high incidence of DR5,7 heterozygotes, reflecting the high frequency of the DR5 allele in Italy, makes the analysis of the Italian CD patients critical. Polymerase chain reaction-amplified DNA from 50 CD patients and 50 controls, serologically typed for DR and DQw antigens, was hybridized with five DQA1-specific oligonucleotide probes detecting DQA1*0101 + 0102 + 0103, DQA1*0201, DQA1*0301 + 0302, DQA1*0401 + 0501 + 0601, and DQA1*0501 and a DQB1-sequence-specific oligonucleotide probe recognizing DQB1*0201 allele. As expected by the DR-DQ disequilibria, DQA1*0201 [62% in patients versus 26% in controls, relative risk (RR) = 5] and DQA1*0501 (96% versus 56%, RR = 19) show positive association with the disease. Of CD patients, 92% (50% DR3 and 42% DR5,7) compared to 18% of the controls carry both DQA1*0501 and DQB1*0201 alleles, so that the combination confers an RR of 52, higher than both the risks of the single alleles (DQA1*0501 RR = 19, DQB1*0201 RR = 30), confirming the primary role of the dimer in determining genetic predisposition to CD both in DR3 and in DR5,7 subjects.
Essentially all patients with dermatitis herpetiformis (DH) and dermal granular IgA deposits have a gluten-sensitive enteropathy as seen in coeliac disease. A gluten-free diet would normally restore mucosal morphology within months. The dapsone medication required to suppress the skin lesions could be gradually reduced and/or finally discontinued in most patients if they constantly adhere to the diet. The immunological reactions may also be reduced. The gluten-free diet could thus be successful both concerning manifestations from the skin and the gut. Although well known in dermatological literature, diet therapy in DH has attracted little interest in journals of nutrition. A survey of this causal diet therapy for the disease therefore seems appropriate.
A cohort of 123 patients with coeliac disease, diagnosed in the first three years of life and followed up for at least 10 years, was reevaluated during the teenage period in terms of compliance with the diet and clinical state. Mucosal structure and lymphocytes were assessed in small intestinal biopsy specimens obtained from 36 subjects, by computerised image analysis. Of these adolescents with coeliac disease, 65% were adhering to a strict gluten free diet, 11.4% were on a gluten free diet but with occasional gluten intake, and 23.6% were on a gluten containing diet. Clinical symptoms occurred more frequently in patients on a gluten containing diet, but not in patients on a semi-strict diet. Occasional intake of small amounts (0.06-2 g/day) of gluten did not produce increased concentrations of antigliadin antibodies but resulted in an appreciably increased crypt epithelial volume and expanded crypt intraepithelial lymphocyte population.
Serum IgA antigliadin antibodies (IgAAGA) assay, cellobiose/mannitol sugar permeability test (ST), and carotenemia were evaluated prospectively as diagnostic tests in 60 consecutive adult patients with suspected celiac disease (CD). CD was confirmed histologically in 26 patients. IgAAGA, ST, and carotenemia had a sensitivity of 65.4%, 96.2%, and 76.9%, a specificity of 97.1%, 73.5%, and 70.6%, and positive likelihood ratio of 22.2, 3.6, and 2.6, respectively. Multivariate logistic regression showed that IgAAGA and ST had a sensitivity and specificity of 96.2% and 70.6% and a positive likelihood ratio of 47.3 if both were positive. Assuming a prevalence of CD of 1:2000 in the general population, for every 89 positive IgAAGA and 549 altered ST there would be one celiac patient, whereas, if both tests were positive, the patient was certain to have CD. We conclude that, of the tests studied, IgAAGA and ST are respectively the most specific and the most sensitive and that, used together, they can diagnose CD.
The teeth of 40 adults aged 19 to 67 yr with celiac disease (CD) were examined for dental enamel defects (ED). A total of 33 of the 40 adults with CD (83%) had systematic ED in contrast to only 5 of the 112 clinical controls (4%). Unspecific enamel lesions were found in both groups, but they were more common in the control group (80% vs. 18%). Altogether 69% of the permanent teeth in adults with CD were found to be defected, in clinical controls only 19%. In adults with CD the ED were in contrast to those in controls symmetrically and chronologically distributed in all four sections of dentition. The present study clearly shows that symmetrically and chronologically distributed enamel defects are strongly associated with CD. Therefore in the absence of symptoms and signs of malabsorption dentists could easily select the right patients possibly suffering from CD for gastroenterologic consultations.
We have estimated lactose absorption indirectly by the breath H test to see if disaccharide exclusion is necessary for untreated celiac children. Lactose at 2 g/kg body weight (maximum 50 g) was administered to 42 infants and children (ranging in age from 9 months to 12 years) with flat small intestinal mucosa. Later, different amounts of lactose were given to determine the quantities tolerated and absorbed. One hundred percent of patients expired hydrogen more than 20 ppm over the baseline after an oral lactose load of 2 g/kg (maximum 50 g). Thirty-eight percent of them did not tolerate this quantity. Thirty-seven subjects aged 0-6 years absorbed and tolerated 0.5-1.5 g/kg (5-12.5 g total), and five patients aged 6-12 years absorbed and tolerated 0.5-0.6 g/kg (12-16.2 g total). We conclude that in many subjects with untreated celiac disease, lactase activity is sufficient for absorption and tolerance of the amount of lactose present in 250-300 ml cow's milk. Because of lactose's nutritional value, it should not be excluded unless necessary.
The diagnostic value of gliadin IgG, IgA and IgE antibody (AB) determinations using the fluorescent immunosorbent test was examined in 586 children with malabsorptive disorders and/or failure to thrive. All patients underwent jejunal biopsy and were on a gluten-containing diet. IgG AB were found in all patients (331/331) with untreated coeliac disease (CD) in our study, but IgA AB in only 295/331 (89%). Therefore a screening test based only on IgA AB determinations is not recommended. By contrast, 203 (80%) of 255 children with other malabsorptive disorders had no gliadin AB, 43 (16.5%) had only IgG AB and only 9 (3.5%) had IgG and IgA AB. IgE AB proved to be of no additional value as a diagnostic tool because they were found in a quarter of the children without CD. Statistical evaluation of combined IgG and IgA AB determination showed at least 96% sensitivity and a specificity of 97%. The subjective ("Bayesian") probability that an actual patient with a given AB test result has CD, is considered: a patient very probably has CD in the case of positive IgG and IgA AB, and no CD in the case of a negative AB result. In the case of negative IgA AB but positive IgG AB the physician's judgement ("prior probability") influences the ("posterior") probability of CD for an actual patient. In contrast to IgG AB, IgA AB decline rapidly after the introduction of a gluten-free diet and may be used for diet control after diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)
This study was designed to determine (1) whether the site of biopsy within the proximal small bowel affects the ability to assess mucosal architecture in general, or to confirm a diagnosis of celiac sprue specifically; and (2) whether endoscopic small bowel biopsy using standard forceps can obtain adequate biopsy specimens to detect or exclude mucosal abnormalities. Three-hundred fifty-two biopsy specimens were obtained prospectively from 26 patients (8 sprue, 2 nonspecific changes, 16 normal) with "jumbo" and standard forceps from jejunum, ligament of Treitz, fourth, third, and second portions of the duodenum. There was no difference in biopsy specimen quality from different locations. All celiac sprue patients had at least one good or excellent specimen from each location, thereby allowing the diagnosis to be made equally well from second, third, and fourth portions of the duodenum, as well as at the ligament of Treitz and jejunum. No false-positive diagnoses of celiac sprue were made. Finally, the standard biopsy forceps provided good or excellent specimens in all patients.