Dental enamel defects and screening for coeliac disease

Specific dental enamel defects (DEDs) in permanent teeth are frequently observed in coeliac patients. We examined the permanent teeth in 6949 secondary school children living in Trieste (78% of 8724 children born between 1978 and 1982). Children with DEDs were tested for serum antigliadin antibodies (AGAs) and antiendomysium antibodies (AEAs), and those positive for serum AGAs and/or AEAs underwent intestinal biopsy. Specific DEDs were observed in 52 children (0.59% of the total population examined). Serum AGAs and/or AEAs were positive in 10 cases. Nine patients underwent intestinal biopsy (one refused) and in four cases a flat mucosa was documented (one with short stature, three completely asymptomatic). The known incidence of CD in the study area was 1:1000 before the study programme and 1:670 (an increase of 44%) after it. Dental enamel inspection may be utilized for detecting undiagnosed coeliac disease in symptom–free schoolchildren. This clinical test is probably less sensitive than serum AGA screening test, but deserves some consideration because it is cheap, easy to perform and well accepted by the population.     

Oral aphthous ulcers and dental enamel defects in children with coeliac disease

AIM: Coeliac disease is characterized by oral manifestations, such as dental enamel defects and recurrent oral aphthae. In this study we compared the prevalence of enamel defects and recurrent aphthous stomatitis (RAS) between patients diagnosed with coeliac disease and healthy controls. METHODS: A total of 72 patients with coeliac disease were studied together with 162 normal healthy subjects as controls to individualize the prevalence of enamel defects and recurrent aphthous stomatitis (RAS) in this disease. RESULTS: Dental enamel defects were found in 14/70 (20%) coeliac patients and in 9/159 (5.6%) controls. In particular, 13/53 (24.5%) coeliac patients with mixed or permanent dentition and 1/17 (5.8%) coeliac children with deciduous dentition had enamel defects. Altogether, 9/145 (6.2%) control subjects with mixed or permanent dentition had dental enamel defects. None of the controls with deciduous dentition had enamel defects. Thus, the enamel defects occurred more frequently in coeliac patients (p < 0.001). Regarding RAS, 24/72 (33.3%) coeliac patients and 38/162 (23.4%) control subjects had aphthous ulcers. Statistically significant differences were not observed between the two groups (p > 0.05). One in three coeliac subjects suffering from RAS received benefit from a gluten-free diet. CONCLUSION: In the present study, the prevalence of enamel defects was found to be greater in coeliac patients than healthy controls. Even though the prevalence of RAS in coeliac subjects varied from healthy controls, the difference was not statistically significant. However, more than 1/3 coeliac subjects suffering from RAS benefited from a gluten-free diet.     

Coeliac disease in children of short stature without gastrointestinal symptoms

Eighty-seven children with short stature (height more than 2 SD below the mean for age and sex) were investigated by small intestinal biopsy. There was no obvious reason for their growth retardation found by routine examination and they had no gastrointestinal symptoms. Coeliac disease was found in two children and probable coeliac disease in two children. Although the prevalence of coeliac disease was comparatively low in this study of Swedish children with short stature, it emphasizes the fact that coeliac disease must be considered in a child with short stature even in the absence of gastrointestinal symptoms.     

Coeliac disease in children in Christchurch,New Zealand:Presentation and patterns from 2000-2010

AIM: To evaluate the presentation patterns of a cohort of children diagnosed with coeliac disease(CD) at Christchurch Hospital, New Zealand.METHODS: Children aged 16 years or less diagnosed with CD at Christchurch Hospital, Christchurch, New Zealand, over the 11 year period between 2000 and 2010 were identified retrospectively. Diagnosis of CD was based upon standard histological criteria of endoscopically-obtained duodenal biopsies. Overlapping search methods were used to identify all relevant diagnoses within the time period. Endoscopy reports and histology findings were reviewed to confirm diagnosis. The numbers of diagnoses per year were calculated and changes in annual rates over the study period were delineated. Available records were reviewed to ascertain presenting symptoms, baseline anthropometry and the indication for referral for each child. In addition, the results of relevant investigations prior to diagnosis were accessed and reviewed. These key investigations included the results of coeliac serology testing(including tissue transglutaminase and endomysial antibodies) as well as the results of tests measuring levels of micronutrients, such as iron. In addition, the histological findings of concurrent biopsies in the oesophagus and stomach were reviewed. RESULTS: Over the 11 year study period, 263 children were diagnosed with CD at this New Zealand paediatric facility. Children were diagnosed from late infancy to 16.9 years: the largest subgroup of children(n = 111) were diagnosed between 5 and 12 years of age. The numbers of children diagnosed each year increased from 13 per year to 31 per year over the 11 years(P = 0.0095).Preschool children(aged less than 5 years) were more likely to have low weight, and to have diarrhoea and abdominal pain prior to diagnosis. Older children(over 5 years of age) most commonly presented with abdominal pain. Fifty-six(21.6%) of the 263 children were diagnosed following screening in high risk groups, with 38 of these children having no symptoms at diagnosis. Mean weight Z scores were lower in children aged less than five years than children aged 5-12 years or older children(-0.4096 ± 1.24, vs 0.1196 ± 0.966 vs 0.0901 ± 1.14 respectively: P = 0.0033). CONCLUSION: Increasing numbers of children were diagnosed with CD in this New Zealand centre over this time, with varied presentations and symptoms.     

Coeliac disease in children: a social epidemiological study in Sweden

Aim: Little is known on the possible existence of socioeconomic and geographical differences in early coeliac disease (CD) risk. Therefore, we investigated these aspects in children before age two. Methods: Linking the Swedish Medical Birth Registry to several other national registries, we identified all singletons born in Sweden from 1987 to 1993 (n = 792 401) and followed them until 2 years of age to identify cases of CD. Applying multilevel logistic regression analysis, we investigated the association between socioeconomic position (SEP) and CD in children and also whether a possible geographical variation in CD risk was explained by individual characteristics. Results: Low SEP was associated with CD in boys OR 1.37 (95% CI 1.03–1.82), but not in girls OR 0.87 (95% CI 0.68–1.12). We found a considerable geographical variation in disease risk (i.e. intra‐municipality correlation ≈ 10%) that was not explained by individual characteristics. Conclusions: Low SEP is associated with CD in boys but not in girls. Also, CD appears to be conditioned by geographical area of residence. While our study represents an innovative contribution to the epidemiology of CD in children, the reasons for the observed geographical and socioeconomic differences could be speculated but are still unknown.     

Serum Gliadin Antibodies for Detection and Control of Childhood Coeliac Disease

Serum gliadin antibodies of the IgA and IgG isotypes were determined by means of the diffusion-in-gel enzyme-linked immunosorbent assay (DIG-ELISA) in children during different phases of coeliac disease. Fourteen children were studied before onset of dietary treatment, 16 during a period of gluten-free diet and 16 during gluten challenge. The control groups consisted of 44 children with other gastrointestinal diseases and 14 children without gastrointestinal disorders. All of the children studied had been subjected to small-intestinal biopsy. On the basis of the results obtained in this study the diagnostic sensitivity with regard to untreated coeliac disease was found to be 100 % and the diagnostic specificity 97 %. In 10 coeliac children followed during the phases of diagnostic evaluation antibody levels decreased in all during dietary treatment and increased in 8 during a subsequent gluten challenge. It is suggested that determination of IgA and IgG gliadin antibodies by means of DIG-ELISA may be used as a diagnostic test for coeliac disease in children and that this test may be useful in monitoring the dietary treatment in children with known coeliac disease. Moreover, the DIG-ELISA is an inexpensive and technically simple method     

Coeliac disease is associated with intrauterine growth and neonatal infections

To investigate whether factors in the fetal or neonatal period influence the risk of later development of coeliac disease we conducted a population-based register study. The Swedish Medical Birth Register was linked with the Hospital Discharge Register and identified 3392 singleton infants born in the period 1987-97 who developed coeliac disease. Perinatal data for these children were compared with all children born in these years. Exposure variables: Maternal age, parity and smoking habits in early pregnancy, preeclampsia, pregnancy duration and birthweight, birthweight by gestational week, Apgar score, neonatal icterus, neonatal infections, maternal-fetal blood group incompatibility, exchange transfusion, phototherapy. Odds ratios and test-based confidence intervals were calculated. Analyses were made with stratification for year of birth and other risk factors. The risk of developing coeliac disease decreased with maternal age and was lower in first-born than in second-born children. Maternal smoking in early pregnancy was a weak risk factor, as was low birthweight. The most evident risk factors were being exposed to neonatal infections (OR = 1.52, confidence limits 1.19; 1.95) and being small for gestational age (OR = 1.45, confidence limits 1.20; 1.75). These risk factors were independent of each other.

Conclusions: We have demonstrated that the intrauterine environment, mainly as mirrored by a low birthweight for gestational age and, independently, neonatal infection diagnosis, is associated with the risk of developing coeliac disease, supporting the idea of a multifactorial aetiology of the disease.     

Late Mucosal Relapse in a Boy with Coeliac Disease and Cow's Milk Allergy

ABSTRACT. A case of coeliac disease where exceptionally long gluten challenge was needed to produce mucosal relapse is presented. An initial diagnosis of intestinal cow's milk allergy with total villous atrophy was made at the age of 3.5 months. The lesion healed after the child was put on a diet free of cow's milk and gluten. After 4.3 years on a normal diet his jejunal structure was still normal but at the age of 10.9 years, after 8.7 years of gluten ingestion, total villous atrophy was again observed. On a gluten-free diet the small intestinal structure is completely normal at the age of 17.1 years.     

High prevalence of coeliac disease in siblings of children with type 1 diabetes

Coeliac disease has been shown to occur more frequently among first-degree relatives of diabetic patients than in the general population. Our objective was to assess the prevalence of endomysium antibodies (EMA) in non-diabetic siblings of Czech diabetic children and to evaluate the effects of HLA-DQ polymorphisms in determining the genetic susceptibility to coeliac disease (CD) in these subjects. We investigated 240 siblings of diabetic children from 213 families (125 males and 115 females, aged 12.6±4.9 years, mean ± SD). All subjects were tested for the total IgA level to exclude IgA deficiency, and for endomysium IgA to disclose CD. In five IgA-deficient subjects, anti-gliadin IgG was used instead. Small bowel biopsy was offered to subjects with confirmed positive EMA. The HLA-DQA1, -DQB1 genotypes were determined using PCR-SSP. Positive EMA were found in 9/240 (3.8%) subjects (three males, six females). The biopsy confirmed CD in six children, two had a normal mucosal finding and one refused the biopsy. The HLA-DQ2 polymorphism was more frequent among siblings with EMA (seven of nine) than in siblings without EMA (33%), corrected P =0.031. Conclusion:The 3.8% frequency of coeliac disease found in siblings of diabetic children is close to the 4.3% found previously in Czech children with type 1 diabetes mellitus and is substantially higher than the rate in the healthy children population.     

Coeliac disease and malignancies

When compared with the general population, patients with coeliac disease (CD) have an increased risk of developing enteropathy-associated T-cell lymphoma (EATCL), esophageal and pharyngeal squamous carcinomas and small intestinal adenocarcinomas. The prevalence of histologically confirmed CD in Edinburgh and the Lothians in 1979 was 61 per 100000. The National Health Service Central Records of all 653 subjects registered at that time have been flagged, allowing us to analyse mortality in CD. At a mean of 13.5 years, mortality overall was 1.9-fold that of the general population (115 deaths observed, 61.8 expected; p < 0.0001). For both sexes the early mortality was much greater than expected, but the excess steadily diminished with time from diagnosis. Much of the increased mortality from malignant disease was accounted for by deaths from lymphoproliferative disease and esophageal cancer. Interim re-analysis after a further 9 years shows that the pattern of later deaths is consistent with these trends. Clinical and pathological features of lymphomas in CD are described. In serum samples of 41 patients with normal villus architecture while taking a normal diet, but with minor pathological and/or immunological abnormalities, i.e. potential CD, IgA antiendomysium antibodies were positive in 7 with dermatitis herpetiformis but in only 3 others.     

Neutropenia, granulocytic hypersegmentation and coeliac disease

A 7-year-old girl was admitted to hospital with a 2-month history of profound weakness. Anaemia, marked neutropenia and hypersegmentation of the granulocytes were the major laboratory findings. These abnormal haematological data were due to significant folate deficiency caused by active coeliac disease diagnosed by both the presence of antigliadin and endomysium antibodies and typical histological features of the small intestine. The haematological abnormalities resolved within 3 weeks following a gluten-free diet and iv supplementation of folic acid.     

Human leucocyte class I and II antigens in coeliac disease: a study in an Austrian paediatric population

Regional variations in the human leucocyte antigen (HLA) distribution patterns of coeliac disease (CD) have been reported. This study focuses on phenotype frequencies of a cohort of Austrian paediatric CD patients in comparison with those recorded in the literature. HLA class I and II typing was performed in 136 CD patients and 667 healthy controls from the general population of the same geographical area. The HLA phenotypes of our controls agreed with those published for Caucasians. In our patients the relative risks (RR) were 6.43 for DR3 and 2.52 for DR7, the aetiologic fractions being 0.58 respectively 0.24. The highest RR (7.78) was found for DR3/DR7 heterozygotes. The RR for DR5 was increased in heterozygosities, either with DR3 (3.34) or DR7 (5.53), yet not for DR5 alone. Of our patients, 10% were lacking both DR3 and DR7 as well as B8, 82% of them were positive for DQw3. In these DR3 and DR7 negative patients, DR4 and DR5 were significantly more frequent than in the others. DR5 was also significantly more common in these patients compared to controls lacking the same antigens, whereas this did not hold true for DR4. Prospective studies are required to determine any link between these HLA heterogeneities and long-term progression of the disease.     

Non-malignant complications of coeliac disease

Patients with coeliac disease are at increased risk of developing complications which increase morbidity and mortality. Emphasis on malignant complications has often overshadowed the non-malignant risks, which have received relatively little attention, although some of these can be very troublesome and even life-threatening. This article points out that a large population of unidentified or neglected coeliac patients is at potential risk. The challenge is to identify this group by case-finding or screening programmes in selected populations, so that they can be offered a gluten-free diet and other treatments which will not only improve general health but may also prevent or reduce the development of health problems. The non-malignant risks are outlined and bone and neuropsychiatric disturbances considered in more detail because of recent developments in these areas.     

Coeliac disease in children and adolescents with type 1 diabetes: a study of growth,glycaemic control,and experiences of families

The aim of this study was to evaluate whether coeliac disease affects growth, glycaemic control, and general well-being of children and adolescents with type 1 diabetes. Eighteen subjects were found to have coeliac disease by a screening program. Gastrointestinal symptoms, changes in growth and the levels of glycated haemoglobin (GHbA1) were analysed, as well as subjective well-being before and after diagnosis of coeliac disease. Overt gastrointestinal symptoms and deterioration of growth prior to disclosure of coeliac disease were seen only in one patient who had both of these conditions. Retrospectively, most subjects reported mild gastrointestinal complaints, which resolved on a gluten-free diet. Introduction of a gluten-free diet did not have any positive effect on glycaemic control, but was associated with an increase in weight-for-height (from 4.3 ±18.1 to 8.2 ±15.4% deviation from population median, p = 0.02). This increase in weight-for-height was inversely correlated with changes in GHbA1 ( r =-0.574, p = 0.02).

Conclusion : Coeliac disease is rarely associated with signs of malabsorption in children and adolescents with type 1 diabetes. Introduction of a gluten-free diet may be associated with excess weight gain. We recommend intensified follow-up for these subjects.     

A boy with coeliac disease and obesity

AIM: To report the case of a 14-y-old boy with coeliac disease and obesity. METHODS AND RESULTS: A 14-y-old boy presented with episodic diarrhoea associated with eating spaghetti. His body mass index (BMI) at presentation was 37.2 kg/m2 (>99.9th centile). Both antigliadin and anti-endomysial antibodies were positive, and coeliac disease was diagnosed by jejunal biopsy. His diarrhoea ceased and the gliadin and endomysial antibodies disappeared after starting gluten-free diet. At 17 y, his BMI increased to 42.7 kg/m2 despite dietary support. CONCLUSION: Obesity in a child does not exclude the diagnosis of coeliac disease, especially if presenting with suggestive symptoms.     

Coexistent coeliac disease,Graves' disease and diabetes mellitus type 1 in a patient with Down syndrome

A 17-year-old girl with Down syndrome is presented who developed coeliac disease, Graves' disease and diabetes type 1. Her HLA type was A3, A9, B8, B15, DR3, DR5.     

Serological screening for coeliac disease: methodological standards and quality control

To establish methodological standards for serological investigation and screening of coeliac disease, a joint venture has been launched by the European Medical Research Council and the European Society for Paediatric Gastroenterology and Nutrition. Before general screening can be recommended, robust methods and technical standards ought to be introduced. Joint test protocols were defined: an enzyme-linked immunosorbent assay for IgG and IgA gliadin antibodies and an immunofluorescent test for IgA endomysium antibodies. Protocols have now been tested prospectively by one laboratory. Eighty-eight Tuebingen patients were studied (47 coeliac disease on normal diet, 22 coeliac disease on a gluten–free, and 19 disease controls). Single tests did not produce acceptable levels, but combinations of IgA gliadin antibodies and IgA endomysium antibodies showed 98% sensitivity, 100% specificity and 98% predictive efficiency. Only standardized and refereed methods established by ring testing can serve as a reliable basis for serological coeliac screening.     

Coeliac disease and alopecia areata in childhood

Coeliac disease is a genetic, immunologically mediated small bowel enteropathy that causes malabsorption. The immune inflammatory response to gluten frequently causes damage to many other tissues of the body. We report the association of coeliac disease and alopecia areata in two children, a 13-year-old girl and a 29-month-old girl. Both of our patients had immunoglobulin A (IgA) class endomysial antibodies, IgA and immunoglobulin G (IgG) antigliadin antibodies and subtotal villous atrophy on jejunal biopsy. Administration of a gluten-free diet to our patients resulted in complete hair growth and improved the gastrointestinal symptoms.