Omitting control biopsy in paediatric coeliac disease: a follow-up study

AIM: To evaluate the practice of diagnosing coeliac disease with only one small-bowel mucosal biopsy in a selected group of children with suspected coeliac disease. METHODS: A retrospective review of medical records and a follow-up interview of 102 children (65 girls, 37 boys) at diagnosis of coeliac disease. The inclusion criteria were age >18 months, increased levels of serum antitissue transglutaminase IgA antibodies and pathologic small-bowel mucosal biopsy. Anthropometric data were calculated for children 1.5-11 years of age. RESULTS: The levels of serum antitissue transglutaminase IgA antibodies were either normal (92%) or slightly elevated (8%) in all children after 1 year on a gluten-free diet. The height-for-age Z score increased in 52 of 61 (85%) children, (median 0.26 SD, range -0.45 to 1.83 SD) and the weight-for-age Z score increased in 50 of 61 (82%) children (median 0.42 SD, range -0.77 to 2.24 SD). Sixty of 61 (98%) children showed normal or catch-up growth. Regression of symptoms after 1 year on a gluten-free diet was reported for 71 of 72 (98%) children. CONCLUSION: We propose that a control biopsy is not necessary for the diagnosis of coeliac disease in these children.     

Increasing incidence of childhood coeliac disease in Sweden. Results of a national study

A survey of the incidence of coeliac disease was carried out by asking all 43 paediatric departments in Sweden to report the number of children born between 1978 and 1987 in whom coeliac disease had been diagnosed. Thirty-four departments representing a population of 7.18 million reported 1944 cases of coeliac disease among 804,935 children born between 1978 and 1987. The cumulative incidence of coeliac disease was 1.7 per 1000 live births in children born between 1978 and 1982 and doubled to 3.5 per 1000 live births in children born after 1982. The highest incidence was found in the southern and south-eastern regions of the country. The observed increase may have been influenced by changes in infant feeding practices such as the postponed age of introduction of gluten from four to six months of age and an increase in gluten content of proprietary baby foods.     

Increasing prevalence of coeliac disease in Denmark: a linkage study combining national registries

Aim: To determine the prevalence and incidence of diagnosed coeliac disease (CD) in Danish children and adolescents and to describe trends over time. Methods: All children with a CD diagnosis registered in the Danish National Patient Registry (DNPR) were included in the study. Data were validated by combining this information with registrations of small‐bowel biopsies in the National Registry of Pathology (NRP) and with a selected sample of hospital records. Results: Data were obtained from 1996 to 2010. The prevalence of CD registered in DNPR increased from 43.2 [95% CI 39.3–47.1] to 83.6 [95% CI 78.4–88.7] per 100 000, and the incidence increased from 2.8 [95% CI 1.9–3.9] to 10.0 [95% CI 8.4–12.0] per 100 000; 56% of the children had at least one biopsy compatible with CD registered in NRP. The incidence of biopsy‐verified CD increased from 0.8 [95% CI 0.3–1.4] to 6.9 [95% CI 5.4–8.4] per 100 000. The mean age at diagnosis increased from 5.1 [95% CI 3.5–6.6] to 8.1 [95% CI 7.2–9.0] years of age. The proportion of children with associated diseases did not change over time. Conclusion: The prevalence of diagnosed CD in Danish children and adolescents has increased over the last 15 years.     

Down syndrome and coeliac disease: five new cases with a review of the literature

We report five new patients with coeliac disease and Down syndrome and review the 11 cases previously reported in the literature. In 14 of these 16 patients diarrhoea was the presenting symptom and in 2 failure to thrive in combination with anaemia. The frequency of coeliac disease in children with Down syndrome was calculated as being 43 times greater than in children without Down syndrome. Delay between first symptoms and diagnosis in patients with combined coeliac disease and Down syndrome was 2.5 years, while in the other children with coeliac disease it was only 8 months. This distinctive difference could be caused by an underestimation of the seriousness of gastro-intestinal complaints in patients with Down syndrome. It is stressed that coeliac disease should be strongly considered in all children with Down syndrome and either persistent diarrhoea or failure to thrive.     

Trichobezoar in a child with concomitant coeliac disease: a case report

We report on a case of childhood coeliac disease presenting with tricophagia and trichobezoar. The combination of obstructive symptoms, severe hypoalbuminaemia and a large abdominal mass detected on CT scan warranted diagnostic gastroscopy and laparotomy, resulting in removal of a large gastric trichobezoar. Surgical recovery was uneventful although serologic studies for coeliac disease were abnormal. Coeliac disease was confirmed by subsequent biopsy. CONCLUSION: Concomitant trichobezoar and coeliac disease in a child is reported for the first time. It is postulated that the trichobezoar was a result of coeliac disease-induced pica.     

IgG,IgA and IgE gliadin antibody determinations as screening test for untreated coeliac disease in children,a multicentre study

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. Antibodies against cow's milk proteins, though present in 72% of the 331 patients with CD, are of no therapeutic significance in CD and are of no value for its diagnosis.Abbreviations AB antibodies - CD coeliac disease - FIST fluorescent immunosorbent test     

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.     

Extraneous HLA antigens in severe combined immunodeficiency disease (SCID) survey of the literature and report of one new case

In a female infant with severe combined immunodeficiency disease extraneous HLA specificities were found which could neither have been inherited from the father nor the mother. The case is reported in detail and a survey of the literature with similar observations is given. The different explanations of this phenomenon are discussed.     

Serum antibodies against gliadin and reticulin in a family study of coeliac disease

The familial occurence of coeliac disease is well known. In every day practice, however, diagnosis of coeliac disease is not frequently established in the relatives of patients. As it did not seem practicable to biopsy all relatives, several tests were investigated in selecting individuals for intestinal biopsy in a family study. 55 index patients out of 54 families with biopsy-proven coeliac disease and 165 of their first grade relatives underwent the study. Immunofluorescent gliadin and reticulin antibodies were determined, and additionally laboratory tests were done. These included haemoglobin, serum iron, serum protein and albumin, serum immunoglobulins and blood xylose. The immunofluorescent gliadin antibody assay using red cells coated with gliadin proved to be superior to the other methods. False negatives came to 8.7%, and false positives 10.9%, in healthy relatives. Gliadin antibodies could be found five times more frequently in healthy relatives than in normal controls. This finding indicates a genetic predisposition to the formation of gliadin antibodies in coeliac families.Ninety-one percent of index coeliac children had IgG-antigliadin in their sera while on a normal diet. During gluten-free diet, and in adult patients, results were less convincing. All relatives with antigliadin titres greater than 8 have been biopsied, and all with titres above 64 were shown to have coeliac disease. The prevalence of coeliac disease found in this study was 5.5%. In the active state of coeliac disease in children, gliadin antibody determination thus is a valuable diagnostic tool but in selecting relatives for biopsy there are limitations to the wide application of the test. Although reticulin antibodies are more specific for coeliac disease than gliadin antibodies, determination of antireticulin proved to be much less sensitive.Supported by Deutsche Forschungsgemeinschaft Gr 278/6 and Ste 305/1     

Prevalence of coeliac disease in type I diabetes: a multicentre study

The aim of this study was to point out the prevalence ratio and the clinical presentation of coeliac disease (CD) in a large group of insulin-dependent diabetes mellitus (IDDM) patients. Patients and methods : 1114 patients affected by IDDM were screened for CD using antigliadin and antiendomysium antibodies. Patients who were positive for at least one test underwent an endoscopic biopsy of the descending duodenum in order to verify the presence of villous atrophy. Subjects with CD started a gluten-free diet and underwent a clinical follow-up. Results : Villous atrophy was found in 63 patients (5.6%). Among the Italian population, the rate was 7%. Twenty-four percent of coeliac patients presented with diarrhoea, while 22% were completely symptom-free. A significant correlation was found between the presence of villous atrophy and the duration and onset of diabetes. Conclusions : The prevalence of CD in IDDM is higher than previously reported, although the ratio range in different centres from 1.7 to 10%, probably due to both environmental and genetic factors. Twenty-two percent of coeliac patients were completely symptom-free. The prevalence seems to be significantly related to the duration and onset of IDDM.     

Immunofluorescent serum gliadin antibodies in children with coeliac disease and various malabsorptive disorders

An immunofluorescent gliadin antibody assay is described using pyruvic aldehyde-stabilized human erythrocytes coated with gliadin. Fifty coeliac children all had high serum IgG-antigliadin titres during a normal diet or a challenge with gluten. On a gluten-free diet (30 children), titres were much lower. In patients followed-up for one year on a gluten-free diet, an initial rise in titres was followed by a slow decline. On challenge, IgG-antigliadin titres showed a slow rise or persistence at the same level in most patients. Fifty-two percent of control children with malabsorptive disorders, but without the typical flat mucosal lesion on jejunal biopsy, were shown to have positive titres in their sera, as were 6% of normal children and 4% of adult blood donors. The fluorescent antibody technique was compared with methods commonly used to detect wheat-protein antibodies, and was found to be superior to all of them. The immunofluorescent gliadin antibody assay appears to be useful in following-up children with coeliac disease, and in selecting patients for jejunal biopsy, although it does not replace biopsy.Supported in part by Deutsche Forschungsgemeinschaft     

Prevalence of coeliac disease in diabetic children and their first-degree relatives in West Algeria: screening with serological markers

Atypical and relatively silent forms of coeliac disease (CD) have been described in insulin-dependent diabetes mellitus (IDDM). Our aim was to evaluate the prevalence of CD-IDDM with serological markers and to investigate the presence of CD in the IDDM first-degree relatives. During 1993 94 we explored 116 IDDM patients reported as new cases and 381 first-degree relatives of IDDM patients. Determination of IgA and IgG antigliadin antibodies (AGA) and IgA antiendomysium antibodies (AEA) was made. Jejunal biopsy was performed in symptomatic patients or in those with positive serological markers, (i) Nineteen IDDM-CD were identified and 5 were suspected. Thus, the prevalence of CD in IDDM patients was between 16.4 and 20%. AGA and/or AEA were abnormal in 13 and normal in 5. Sensitivity was 80% for the three tests when used simultaneously and specificity was 100%. (ii) In the family study, 26 sera of asymptomatic first-degree relatives of IDDM patients were positive for at least one of the serological markers; 13 of them had villous atrophy. Systematic serological screening in IDDM allowed us to detect CD and evaluate the true incidence.     

Bilateral calcifications in the basal ganglia, and frontal and parietal lobes of a patient with coeliac disease

Previous authors have described a specific syndrome of coeliac disease, bilateral cerebral calcifications and epileptic seizures. We report a 4-year-old boy with coeliac disease who had bilateral calcifications in the basal ganglia and frontal and parietal lobes, but did not exhibit epileptic seizures.     

Kawasaki Disease in a Father and Son

The pathogenesis and etiology of Kawasaki disease are unknown, but some studies suggest increased genetic susceptibility. The case is presented of an infant with Kawasaki disease whose father suffered from the same illness 21 years previously. The A, B and C loci of the HLA antigens were examined.     

Anti-endomysium antibody on human umbilical cord vein tissue: an inexpensive and sensitive diagnostic tool for the screening of coeliac disease

Anti-endomysium antibody (AEA) was evaluated in 136 subjects by indirect immunofluorescence using both cryosections of monkey oesophagus (MO) and the human umbilical cord vein (HUCV) as substrate. This human tissue gave results comparable to those of MO. In particular, the HUCV sections showed positive results in all 22 newly diagnosed cases of coeliac disease. Compared to the MO sections, the sensitivity, specificity and positive predictive values of HUCV tissue was 100%. Conclusion HUCV tissue can replace MO for AEA detection and can make the screening for coeliac disease easier both in at-risk and in normal populations, with a remarkable saving, both in terms of money and of monkeys. Received: 15 October 1996 and in revised form: 18 February 1997 / Accepted: 4 March 1997     

Small intestinal mucosa in coeliac disease and cow's milk protein intolerance: Morphometric and immunofluorescent studies

One hundred and twenty-five small intestinal biopsies from children with coeliac disease (CD), cow's milk protein intolerance (CMPI) and controls were compared by morphometric analysis, by counting intraepithelial lymphocytes (IEL) and by quantitative evaluation of immunoglobulin-containing cells of lamina propria. The double-stain immunofluorescent technique of Brandtzaeg and Baklien [2] was used, based on defined mucosal tissue units. A patchy enteropathy was found in 60% of CMPI, and in 14% of nonspecific changes, but never in CD. There was a significant difference in crypt depth between CD (360±80 m) and CMPI (217±92 m), even when lesions of equal grade were compared (P<0.015). IEL counts per 1000 epithelial cells showed even better discrimination between the groups (CD: 793±173, CMPI: 320±143, P<0.001). In CD, there was a relatively greater increase of IgM-cells (x4.9) and of IgG-cells (x4.2) than of IgA-cells (x2.6). Ig-cell changes outlasted the morphological lesion in CD on a gluten-free diet. In CMPI, IgM-cells (x2.3), IgG-cells (x2.5), and IgA-cells (x1.7) were proportionately increased, compared to controls. A special increase of IgE-cells in CMPI could not be substantiated.By computerized stepwise discriminant analysis based upon crypt depth, villus/crypt-ratio, IEL-count, and counts of IgM-, IgG-, IgA-containing cells of lamina propria, accurate classification of patient groups was accomplished, even when only the initial biopsy data were analysed.Supported by Deutsche Forschungsgemeinschaft Gr 278/6 and Ste 305/1     

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.     

Muscle abnormalities in coeliac disease: Studies on gross motor development and muscle fibre composition,size and metabolic substrates

In 11 children with coeliac disease gross motor development was assessed before and during diet treatment using the gross motor subscale of the Denver developmental screening test. ATP, creatine phosphate (CP), glycogen and lactate concentrations, muscle fibre size and fibre composition were measured in specimens obtained by needle biopsy from the vastus lateralis muscle.Before treatment, gross motor development was delayed. ATP, and to a lesser extent, CP and glycogen concentrations were lowered compared to a control group. After treatment, gross motor development was normal and no differences in ATP, CP or glycogen concentrations were found compared to the control group. Fibre size seemed unaffected by the disease. The percentage of type 1 fibres was significantly lower before treatment, compared to values obtained during treatment and from the control group. Whether these metabolic changes were due to the coeliac disease per se or the inactivity which it causes was not possible to establish. In humans, only altered neurogenic influence on the muscles has been previously shown to give changes in fibre composition.