Subclinic cardiac involvement in paediatric patients with celiac disease: a novel sign for a case finding approach.

The aim of the present work was to assess the prevalence of early cardiac involvement in children with celiac disease (CD), and the impact of a gluten free diet (GFD) on this issue. Sixty CD children was compared with a control group of 45 healthy children by an echocardiographic examination. CD patients were re-evaluated 1-year after 1-year GFD. Main outcome measures were ejection fraction (EF), fractional shortening (FS), left ventricular end-diastolic diameter (LVDD), left ventricular end-systolic diameter (LVSD), any regurgitating valve lesions. Mild cardiac involvement was found in 13 CD children and in one control (21.7% vs. 2.2%; p=0.003), and was secondary to regurgitation of mitral valve, aortic valve, pulmonary and tricuspid valve, or to impaired ejection fraction. CD children as compared to controls had significantly lower contractility indices, and higher left ventricular dimensions. In patients adhering to the GFD all valve regurgitations resolved, and the echocardiographic parameters significantly improved. Subclinical cardiac involvement in CD children is quite frequent, and GFD may exert a beneficial effect on the overall cardiac performance.

Coeliac disease diagnosis: ESPGHAN 1990 criteria or need for a change? Results of a questionnaire.

BACKGROUND AND OBJECTIVES: A revision of criteria for diagnosing coeliac disease (CD) is being conducted by The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). In parallel, we have performed a survey aimed to evaluate present practices for CD among paediatric gastroenterologists and to learn their views on the need for modification of present criteria for CD diagnosis. PATIENTS AND METHODS: Questionnaires were distributed to experienced paediatric gastroenterologists (ESPGHAN members) via the Internet. RESULTS: Overall, 95 valid questionnaires were available for analysis, pertaining to 28 different countries, with the majority of responders treating patients with CD for >15 years. Only about 12% of the responders comply with present criteria, noncompliance being related mainly to the challenge policy. Approximately 90% request a revision and modification of the present criteria. Forty-four percent want to omit the small bowel biopsy in symptomatic children with positive anti-tissue transglutaminase immunoglobulin (Ig) A or endomysial IgA antibodies, especially if they are DQ2/DQ8 positive. For silent cases detected by screening with convincingly positive anti-tissue transglutaminase IgA or EMA IgA, about 30% consider that no small bowel biopsy should be required in selected cases. Adding human leukocyte antigen typing in the diagnostic workup was asked for by 42% of the responders. As for gluten challenge, a new policy is advocated restricting its obligation to cases whenever the diagnosis is doubtful or unclear. CONCLUSIONS: Based on these opinions, revision of the ESPGHAN criteria for diagnosing CD is urgently needed.

European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease.

OBJECTIVE: Diagnostic criteria for coeliac disease (CD) from the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) were published in 1990. Since then, the autoantigen in CD, tissue transglutaminase, has been identified; the perception of CD has changed from that of a rather uncommon enteropathy to a common multiorgan disease strongly dependent on the haplotypes human leukocyte antigen (HLA)-DQ2 and HLA-DQ8; and CD-specific antibody tests have improved. METHODS: A panel of 17 experts defined CD and developed new diagnostic criteria based on the Delphi process. Two groups of patients were defined with different diagnostic approaches to diagnose CD: children with symptoms suggestive of CD (group 1) and asymptomatic children at increased risk for CD (group 2). The 2004 National Institutes of Health/Agency for Healthcare Research and Quality report and a systematic literature search on antibody tests for CD in paediatric patients covering the years 2004 to 2009 was the basis for the evidence-based recommendations on CD-specific antibody testing. RESULTS: In group 1, the diagnosis of CD is based on symptoms, positive serology, and histology that is consistent with CD. If immunoglobulin A anti-tissue transglutaminase type 2 antibody titers are high (>10 times the upper limit of normal), then the option is to diagnose CD without duodenal biopsies by applying a strict protocol with further laboratory tests. In group 2, the diagnosis of CD is based on positive serology and histology. HLA-DQ2 and HLA-DQ8 testing is valuable because CD is unlikely if both haplotypes are negative. CONCLUSIONS: The aim of the new guidelines was to achieve a high diagnostic accuracy and to reduce the burden for patients and their families. The performance of these guidelines in clinical practice should be evaluated prospectively.

Prevalence of celiac disease in Egyptian children disputes the east-west agriculture-dependent spread of the disease.

OBJECTIVES: Celiac disease (CD) seems to be a common disorder in north Africa; however, to our knowledge no data are yet available on its prevalence in Egypt. This study was undertaken to investigate the frequency of CD in Egyptian children. PATIENTS AND METHODS: We investigated a sample of the general pediatric population (1500 individuals, 656 girls and 844 boys, age range 7 months to 18 years, median age 8.0 years) (group A); 150 children (age range 6 months to 13 years, median age 16 months) admitted for diarrhea or failure to thrive (group B); and 250 children and adolescents with type 1 diabetes (group C). The screening test was serum class A anti-transglutaminase (anti-tTG) antibody; immunoglobulin A (IgA) antiendomysium, total IgA, and IgG anti-tTG, and small bowel biopsy was performed for confirmation of diagnosis. RESULTS: In group A, 8 of 1500 children fulfilled the criteria for CD diagnosis; the prevalence of CD was at least 1 in 187 individuals (0.53%; 95% CI 0.17%-0.89%). In group B, 7 of 150 children had CD (4.7%, 95% CI 1.4-7.9). In group C, 16 of 250 sera showed positive results to both the IgA anti-tTG and the IgA antiendomysium test (6.4%; 95% CI 3.4-9.4). CONCLUSIONS: Celiac disease is a frequent disorder among Egyptian children, both in the general population and in at-risk groups. Therefore, our data do not support the theory of a Middle East-Europe CD prevalence gradient secondary to the pattern of agriculture spreading from the so-called Fertile Crescent.

Inflammatory bowel disease in children and adolescents in Italy: data from the pediatric national IBD register (1996-2003).

BACKGROUND: The purpose was to assess in Italy the clinical features at diagnosis of inflammatory bowel disease (IBD) in children. METHODS: In 1996 an IBD register of disease onset was established on a national scale. RESULTS: Up to the end of 2003, 1576 cases of pediatric IBD were recorded: 810 (52%) ulcerative colitis (UC), 635 (40%) Crohn's disease (CD), and 131 (8%) indeterminate colitis (IC). In the period 1996-2003 an increase of IBD incidence from 0.89 to 1.39/10(5) inhabitants aged <18 years was observed. IBD was more frequent among children aged between 6 and 12 years (57%) but 20% of patients had onset of the disease under 6 years of age; 28 patients were <1 year of age. Overall, 11% had 1 or more family members with IBD. The mean interval between onset of symptoms and diagnosis was higher in CD (10.1 months) and IC (9 months) versus UC (5.8 months). Extended colitis was the most frequent form in UC and ileocolic involvement the most frequent in CD. Upper intestinal tract involvement was present in 11% of CD patients. IC locations were similar to those of UC. Bloody diarrhea and abdominal pain were the most frequent symptoms in UC and IC, and abdominal pain and diarrhea in CD. Extraintestinal symptoms were more frequent in CD than in UC. CONCLUSIONS: The IBD incidence in children and adolescents in Italy shows an increasing trend for all 3 pathologies. UC diagnoses exceeded CD.

Coeliac disease: oral ulcer prevalence, assessment of risk and association with gluten-free diet in children.

AIMS: Oral mucosal lesions may be markers of chronic gastrointestinal disorders, such as those causing malabsorption. Our objectives were to assess the prevalence of recurrent oral aphthous-like ulcers in coeliac disease patients living in the Mediterranean area, and to evaluate the impact of a gluten-free diet. METHODS: A test group of 269 patients (age range 3-17 years) with coeliac disease confirmed both serologically and histologically was compared with a control group of 575 otherwise clinically healthy subjects for the presence, or a positive history of aphthous-like ulcers. Coeliac disease patients with aphthous-like ulcers were re-evaluated 1-year after starting a gluten-free diet. RESULTS: Aphthous-like ulcers were found significantly more frequently in coeliac disease, in 22.7% (61/269) of patients with coeliac disease versus 7.1% (41/575) of controls (p=<0.0001; chi-square=41.687; odds ratio=4.3123; 95% confidence interval=2.7664:6.722). Most coeliac disease patients with aphthous-like ulcers and adhering strictly to gluten-free diet (71.7%; 33/46) reported significant improvement on gluten-free diet, with no or reduced episodes of aphthous-like ulcers (p=0.0003; chi-square=13.101; odds ratio=24.67; 95% confidence interval=2.63:231.441). CONCLUSIONS: The epidemiological association found between coeliac disease and aphthous-like ulcers suggests that recurrent aphthous-like ulcers should be considered a risk indicator for coeliac disease, and that gluten-free diet leads to ulcer amelioration.

Anti-human versus anti-guinea pig tissue transglutaminase antibodies as the first-level serological screening test for coeliac disease in the general population.

BACKGROUND: So far the reliability of the anti-guinea pig and anti-human tissue transglutaminase antibodies for the coeliac disease diagnosis has been evaluated in selected groups of patients. AIM: To compare the diagnostic accuracy of anti-human versus anti-guinea pig tissue transglutaminase in the coeliac disease screening of the general population. SUBJECTS: Two healthy Italian populations living in Marche region and in Western Sardinia. METHODS: Both anti-guinea pig and anti-human tissue transglutaminase were determined using an enzyme-linked immunosorbent assay-based commercially available kit (Eu-tTG, Eurospital, Trieste, Italy). RESULTS: During the period 1999-2001, 3541 subjects (1500 from "continental" Italy and 2041 from Sardinia) were screened for coeliac disease using both anti-guinea pig and anti-human tissue transglutaminase as first-level tests. Both these tests were negative in 3439/3541 sera, while 29 resulted positive for both of them and 73 showed discordant results. Overall, 50 intestinal biopsies were performed in 22, 21 and 7 subjects with positivity to both screening tests, to anti-guinea pig and to anti-human tissue transglutaminase alone, respectively. A coeliac disease diagnosis was made in 25 subjects giving an overall prevalence of 1:126 individuals. The anti-tissue transglutaminase specificity and sensitivity were 98 and 92% for guinea pig and 99.6 and 96% for human tissue transglutaminase, respectively. CONCLUSIONS: The anti-human tissue transglutaminase test should definitely replace the anti-guinea pig-derived one as first-level screening tool for identifying all subjects who need the second-level investigations (small intestinal biopsy).

Coeliac disease in Middle Eastern countries: a challenge for the evolutionary history of this complex disorder?

About 10,000 years ago domestication and farming of wheat and other cereals developed in the 'Fertile Crescent', an area including modern Turkey, Iraq and Iran. Agriculture then slowly spread from Middle East to Europe. Coeliac disease is the permanent intolerance to dietary gluten, the major protein component of wheat. It has been until relatively recently hypothesised that wheat consumption exerted a negative selective pressure on genes predisposing to coeliac disease, eventually leading to higher coeliac disease frequency in Northeastern Europe because of lack of exposure to cereals. This theory is at variance with recent studies showing that coeliac disease is as common in Middle Eastern countries as in Europe. High prevalence of coeliac disease has been found in Iran, in both the general population and at-risk groups, e.g. patients with irritable bowel syndrome or type 1 diabetes. Clinical manifestations of coeliac disease vary markedly with the age of the patient, the duration and the extent of disease. Clinical studies showed that presentation with non-specific symptoms or no symptoms is as common in the Middle East as in Europe. Wheat represented a major component of the Iranian diet for many centuries and it may be argued that the continuous and high level of exposure to wheat proteins has induced some degree of immune tolerance, leading to milder symptoms that may be misdiagnosed as irritable bowel syndrome or unexplained gastrointestinal disorders. The gluten-free diet represents a real challenge to both patients and clinicians in this area. This is particularly difficult in the absence of any supply for gluten-free diet in Middle Eastern countries.

Prevalence of coeliac disease: unexplained age-related variation in the same population.

BACKGROUND: The aims of this work were (a) to evaluate the prevalence of coeliac disease (CD) in a large sample of the Brazilian general population and (b) to compare CD prevalence between children and adults. METHODS: The study group comprised 4405 subjects (2629 F and 1776 M). Age distributions were 2034 (1-14 years), 848 (15-29), 584 (30-44), 667 (45-59) and 272 above 60. The immunoglobulin A antiendomysial antibody (IgA-EMA) test was used as the serological screening tool. All sera were submitted to turbidimetric measurement of IgA levels and those with IgA deficiency to the IgG antigliadin (IgG-AGA) test. The small intestinal biopsy was recommended for subjects showing either (a) IgA-EMA positivity or (b) selective IgA deficiency (SigAD) and IgG-AGA positivity. RESULTS: There were 16 EMA positive out of 4405 sera tested. SigAD was found in five cases (one adult and four children). Two of these children tested positive for IgG-AGA and underwent jejunal biopsy that, in both cases, disclosed a normal mucosa. Overall, 17 out of 18 eligible subjects performed the small intestinal biopsy. The prevalence of biopsy-proven CD in this study group was 3.41 per 1000 individuals. If all 18 EMA-positive patients were included, the overall prevalence would become 3.63 per 1000. The prevalence in adults and children was 2.11 per 1000 and 5.44 per 1000, respectively. CONCLUSION: This work supports previous findings showing that CD is not a rare disorder in Brazil and that there is an unexplained difference in the prevalence of CD between adults and children.

[Celiac disease; a world in exploration]. / La celiachia: un mondo in esplorazione.

Celiac disease (CD) or gluten-sensitive enteropathy is an autoimmune disorder triggered by gluten ingestion in genetically predisposed subjects. The presence of gluten in these patients leads to a self-perpetuating mucosal damage, while the elimination of gluten results in a full mucosal recovery. The prevalence of CD in the general population is between 0.3% and 1%. The clinical manifestation of CD is variable; in addition to the classical gastrointestinal form a variety of other clinical manifestation of the disease have been described, including atypical and asymptomatic form. The diagnosis of CD is still based on the small intestinal biopsy findings, but can be suspected using serological testing, e.g. the antigliadin antibody (AGA), the antiendomysial antibody (EMA) and the anti-tissue transglutaminase antibody (tTG). The keystone treatment of CD patients is a life-long gluten-free diet.

[Treatment of childhood obesity. Long-term outcome and predictive factors of success in a group of 130 subjects]. / Trattamento dell'obesità infantile. Risultati a lungo termine e fattori predittivi di successo in una casistica di 130 pazienti.

BACKGROUND: In the last years the prevalence of childhood obesity has notably increased. The treatment of this condition is very difficult, because of the frequent relapses. The aim of our study was to examine the long-term outcomes of different dietary treatments (1200 or 1400 calories or chetogenic diet, derived from the protein sparing modified fast) in children and adolescents with primary obesity, in order to show factors predictive of the long-term success. METHODS: A group of 130 obese children previously undergoing a dietary treatment have been re-evaluated after a 3, 5 and 7 years period from the beginning of the diet. RESULTS: Ninety-seven out of 130 contacted patients (52 males and 45 females; mean age: 16+/-3 years) participated in this study. An overall improvement of the weight indexes has been observed (relative DBMI mean value: -10.5%). About 1/5 of the whole study-group is not overweight anymore. The statistical analysis (ANOVA and multiple regression analysis) showed that the factors positively affecting the long-term outcome were the following: use of chetogenic diet, initial success of the treatment, older age and strong motivation at the beginning of the diet, gender (male) and lack of familiarity for obesity. CONCLUSIONS: It is important, in the clinical practice, to consider the above factors that can predict the long-term success of the dietary treatment, in order to individualize the therapy.

Antiendomysial antibody test reliability in children with frequent diarrhea and malnutrition: is it celiac disease?

BACKGROUND: The aim of this study was to evaluate the specificity of the immunoglobulin A (IgA) antiendomysial antibody test in the diagnosis of celiac disease in a group of malnourished children with acute diarrhea, chronic diarrhea, or parasitosis, because the reliability of this test has been questioned when applied to this specific group of patients. METHODS: Serum IgA level, IgA antiendomysial antibody (EMA) test, and stool examination were performed in 315 children, ranging in age 6 months to 13 years (range, 41 +/- 2.9 months), affected by malnutrition, isolated or in association with diarrhea or parasitosis. Independent of results, 33 children with a strong suspicion of celiac disease, also underwent IgA antitransglutaminase antibody test and jejunal biopsy. RESULTS: The EMA test was negative in 313 children, including the 43 with parasitosis, being positive in two patients in whom biopsy disclosed typical celiac mucosal abnormalities (1:157). The 31 children with negative EMA test who underwent biopsy also showed negative antitransglutaminase antibody results. Their biopsies disclosed normal mucosa in 1 patient, variable degree of jejunal atrophy (grade 1 and 2) in 27 patients, and grade 3 abnormalities in 3 patients. One of these three children, showing severe jejunal atrophy, died. The diagnosis of celiac disease was apparently not confirmed by a protracted gluten challenge in the other two children. CONCLUSIONS: The specificity of the EMA test seems to be high also in children with chronic malnutrition and diarrhea. However, the possibility of false-negative tests among immunologically compromised children cannot be excluded. In doubtful cases, the gluten challenge is required in malnourished children with clinical picture, biopsy finding, and evolution suggestive of celiac disease.

Prevalence and clinical picture of celiac disease in italian down syndrome patients: a multicenter study.

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.

Coeliac disease: a potentially treatable health problem of Saharawi refugee children.

OBJECTIVE: To characterize the clinical and nutritional impact of coeliac disease (gluten-sensitive enteropathy) among Saharawi children living as refugees in Algeria. METHODS: A total of 65 Saharawi children with coeliac disease were compared with 71 age-matched non-coeliac controls. For each participant, the clinical history was taken and a clinical examination, non-quantitative 24-hour dietary recall, anthropometric and skinfold measurements, bioelectric impedance analysis (BIA) of body composition, and venous blood sampling for haemoglobin determination were performed. RESULTS: Gluten-containing food, especially bread, was the staple diet of Saharawi children. Abdominal pain and distension were significantly commoner among children with coeliac disease than in controls (P < 0.05). The mean height-for-age was significantly lower in such children than in controls (-2.5 +/- 1.4 units vs -1.8 +/- 1.3 units, respectively, P < 0.01). No significant differences were found for either skinfold or BIA measurements. Haemoglobin values tended to be lower in children with coeliac disease than in controls. CONCLUSIONS: Coeliac disease has a negative effect on the health status of Saharawi refugee children. Because of the high prevalence of the condition in the Saharawi, a specific programme for treating all affected individuals should be established. Further studies are required to quantify the impact of coeliac disease in other areas of the developing world.

The serum IgA class anti-tissue transglutaminase antibodies in the diagnosis and follow up of coeliac disease. Results of an international multi-centre study. International Working Group on Eu-tTG.

OBJECTIVES: So far the reliability of the anti-tissue transglutaminase (anti-tTG) test for the diagnosis of coeliac disease has mostly been evaluated using slightly different enzyme-linked immunosorbent assays (ELISAs) in selected and usually small groups of patients. The aims of this study were: (1) to evaluate the reliability of the IgA anti-tTG antibodies for the diagnosis of coeliac disease; and (2) to define the sensitivity and specificity of a commercially available kit for the anti-tTG antibodies' quantitative determination. DESIGN: Each centre in this international multi-centre study collected sera from three groups of subjects: coeliac disease patients at the onset of (1) or on a gluten-free diet for at least 12 months (2); disease and healthy controls (3). METHODS: The anti-tTG antibodies were determined in duplicate using an ELISA-based commercially available kit (Eu-tTG Eurospital, Trieste, Italy). RESULTS: The following overall cases and controls have been enrolled: (1) 399 subjects with active coeliac disease; (2) 351 treated coeliac disease cases; (3) 432 controls. The centralized re-testing was performed on: (1) group a: 176 patients with active coeliac disease (mean anti-tTG, 21 arbitrary units [AU]); (2) group b: 172 treated coeliac disease cases (mean anti-tTG, 5 AU); (3) group c: 206 controls (mean anti-tTG, 3 AU). In active coeliacs, the anti-tTG antibodies showed a significant progressive decrease with age, while in controls an opposite trend was found. In active coeliac disease patients, the anti-tTG antibodies were significantly higher in coeliacs with a grade III enteropathy than in those showing a grade II lesion. In treated coeliacs, the mean anti-tTG values were significantly lower in patients strictly adhering to a gluten-free diet than in those reporting dietary transgressions. The sensitivity and the specificity of the Eu-tTG assay were 90% and 96%, respectively. CONCLUSION: The results of this study show that the commercially available test for the anti-tTG antibodies' determination is a reproducible and valuable tool for the diagnosis and follow up of coeliac disease.

[The global village of celiac disease]. / Il villaggio globale della celiachia.

Recent data suggest that celiac disease, or gluten-sensitive enteropathy, is a common disorder not only in populations of European ancestry, but also in developing areas, such as North Africa, Middle East and India. The world distribution of celiac disease apparently relates to the consumption of gluten-containing cereals. In the Arab people of Saharawi, the prevalence of celiac disease in children is so high (more than 5%) that this condition represents a primary health problem. In developing countries the clinical picture of celiac disease is often typical, characterized by chronic diarrhea, malnutrition, stunting and increased mortality, especially in younger children. The high prevalence of celiac disease in areas showing a poor sanitary condition could be explained by a protective role of the celiac enteropathy (against intestinal infections) in the context of a low gluten consumption. The problem of celiac disease in developing countries should by approached by a multifaceted strategy, based on (1) increasing disease awareness and diagnostic facilities and (2) a "flexible" dietary intervention that takes into account the nutritional habits and local food availability.

Current approaches to diagnosis and treatment of celiac disease: an evolving spectrum.

Celiac disease (CD) is a syndrome characterized by damage of the small intestinal mucosa caused by the gliadin fraction of wheat gluten and similar alcohol-soluble proteins (prolamines) of barley and rye in genetically susceptible subjects. The presence of gluten in these subjects leads to self-perpetuating mucosal damage, whereas elimination of gluten results in full mucosal recovery. The clinical manifestations of CD are protean in nature and vary markedly with the age of the patient, the duration and extent of disease, and the presence of extraintestinal pathologic conditions. In addition to the classical gastrointestinal form, a variety of other clinical manifestations of the disease have been described, including atypical and asymptomatic forms. Therefore, diagnosis of CD is extremely challenging and relies on a sensitive and specific algorithm that allows the identification of different manifestations of the disease. Serologic tests developed in the last decade provide a noninvasive tool to screen both individuals at risk for the disease and the general population. However, the current gold standard for the diagnosis of CD remains histologic confirmation of the intestinal damage in serologically positive individuals. The keystone treatment of CD patients is a lifelong elimination diet in which food products containing gluten are avoided.