Thrombocytopenic purpura and coeliac disease

In a child with immune thrombocytopenic purpura (ITP) the findings of circulating reticulin antibodies and IgA and IgG gliadin antibodies suggested the diagnosis of coeliac disease. This was verified by small intestinal biopsy. In spite of a gluten-free diet the thrombocytopenia persisted. The association of ITP and coeliac disease was previously described in adults but to our knowledge this is the first report of the coexistence of ITP and coeliac disease in a child.     

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.     

Anti-endomysium and anti-gliadin antibodies as serological markers for coeliac disease in childhood: a clinical study to develop a practical routine

Anti-gliadin and anti-endomysium antibodies were analysed in 174 children with suspected or verified coeliac disease with the aim of developing a practical routine. The biopsy was performed without knowledge of the antibody levels. To screen for coeliac disease is children younger than 2 years, we suggest the use of IgA anti-gliadin antibodies, giving a sensitivity of 100% and a specificity of 86%. In older children both tests should be used in parallel, i.e. a biopsy should be performed if at least one of the tests is positive, giving a sensitivity of 98% and a specificity of 81%. To avoid unnecessary biopsy before mucosal relapse can be demonstrated during gluten challenge in a child without clinical symptoms, we suggest that the tests are used as serial testing, i.e. a biopsy should be performed if both tests are positive.     

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     

Serological screening (antigliadin and antiendomysium antibodies) for non-overt coeliac disease in children of short stature

This study aimed to assess the value of IgA-antigliadin and antiendomysium antibodies for coeliac disease screening in children with short stature. In 118 children with height less than the 3rd percentile for age preliminary work-up included absorption, hormonal and genetic studies, sweat test. X-ray for bone age, serum immunoglobulin levels and antigliadin antibodies. In 65 patients antiendomysium antibody and a small-intestinal biopsy were performed. Forty-three children had a normal mucosa and 22 a subtotal villous atrophy. Three coeliac children were negative for both antigliadin and antiendomysium antibodies; one further 11-year-old boy was negative only for antiendomysium antibodies. Sensitivity and specificity for antigliadin antibodies were 94.75% and 93%, respectively, and for antiendomysium antibodies 88.3% and 90.5%. Our results show that the use of antiendomysium antibodies as a confirmatory test to select patients for biopsy could result in coeliac disease going undiagnosed in adolescents.     

Nachweis von präcipitierenden Antikörpern gegen wäßrige Mehlextrakte bei Cöliakie

A method is described whereby the presence of precipitating antibodies to aqueous extracts of flour (wheat, barley, oats and rye) can be detected. The demonstration of these antibodies forms the basis of a sensitive and specific diagnostic test in coeliac disease. 15 children with coeliac disease have been investigated with the help of this technique. All patients had precipitating antibodies to extracts of wheat and barley. Antibodies to oats were present in 13, and antibodies to rye in 10 patients. In none of 60 control sera precipitins to the aqueous extract of the cereals could be detected. The demonstration of these antibodies may not only be a diagnostic tool but may also elucidate the immunological mystery of coeliac disease.     

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.     

Results of coeliac disease screening in Estonia in 1990–1994

In the period 1990–94, 2895 individuals (629 children with suspicion of coeliac disease selected throughout Estonia; 700 consecutively hospitalized children; 105 children with atopic dermatitis; 1461 inhabitants of a small Estonian town) were serologically screened for coeliac disease. The enzyme-linked immunosorbent assay was used for antigliadin antibody determinations and R 1-type antireticulin antibodies were detected using an indirect immunofluorescence method. Coeliac disease was diagnosed according to recent criteria recommended by the European Society for Paediatric Gastroenterology and Nutrition. Antigliadin antibody testing was positive in 44 (3.1%) of 1434 children studied, and in 33 of whom coeliac disease was confirmed. In all the coeliac patients R 1-type antireticulin antibody test was positive. However, 52 (3.5%) of 1461 adults studied who did not have coeliac disease had positive antigliadin antibody test but negative antireticulin antibody test. Thus, in Estonia, the antigliadin antibody test can be used in screening for coeliac disease in children but not in adults.     

Postpubertal gluten challenge in coeliac disease.

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.     

IgA endomysium antibodies. Detection in children with celiac disease]

BACKGROUND: Epidemiology of coeliac disease gives rise to the search for a non-invasive, reliable screening test. METHODS: We looked for IgA anti-endomysial antibodies (IgA-EmA) in 103 sera of 90 children (age: 2 months-13.9 years) using an indirect immunofluorescence method on monkey oesophagus sections. In 44 patients, the diagnosis of coeliac disease was confirmed fulfilling new criteria of the European Society of Pediatric Gastroenterology and Nutrition. RESULTS: All 24 coeliac disease patients with an initial flat mucosa had IgA-EmA (sensitivity 100%). In 36% of coeliac disease patients adhering to a gluten-free diet we found IgA-EmA. None of 46 patients in whom coeliac disease had been excluded by jejunal biopsy had IgA-EmA (specificity 100%). The sera of 102 blood-donors were used as controls and showed a test specificity of 99%. In coeliac disease patients, the titer of IgA-EmA declined during gluten-free diet by 0.66 steps/month on average, and rose 1.76 steps/month during gluten challenge. CONCLUSIONS: These results confirm the diagnostic significance of IgA-EmA for patients with suspected coeliac disease and their value for monitoring treatment even in young children (below 2 years).     

Antibodies to gliadin as a screening test for coeliac disease. A prospective study.

The diagnostic value of gliadin antibody determination using the fluorescent immunosorbent test was examined in a prospective study of 57 children with gastrointestinal disease. Antibodies to gliadin were found in all 20 patients with active coeliac disease, whereas 7 of these children (37%) had a normal xylose absorption test despite a flat small gut mucosa. Only 4 (14%) of 28 children with other gastrointestinal conditions had antibodies to gliadin, invariably in low titre. After at least 2 years on a gluten-free diet none of 9 children with coeliac disease in remission had demonstrable gliadin antibodies. The gliadin antibodies disappear slowly, within 6 to 24 months, after withdrawal of gliadin from the diet. 0.8% (5/606) of a healthy control group of children, adolescents and adults (not biopsied) had gliadin antibodies in low titre. Increased mean cow's milk antibody titres were demonstrable in 8 (40%) of 20 patients with active coeliac disease as well as in 9 (32%) of 28 patients with other gastrointestinal lesions. Our studies show that determination of circulating gliadin antibodies is a worthwhile screening test in suspected cases of coeliac disease. In patients so selected there is a definite indication for small intestinal biopsy to confirm the diagnosis.     

Documented latent coeliac disease in a child with insulin-dependent diabetes mellitus

The histological development of coeliac disease has been documented in a child with insulin-dependent diabetes mellitus (IDDM). Serum antigliadin IgG was temporarily present at the onset of IDDM. It is assumed that IDDM may exert a trigger effect on the development of coeliac disease.     

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     

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.     

Thrombocytopenic purpura during the incubation period of rubella

A child with idiopathic thrombocytopenic purpura (ITP) which started eight days before the appearance of rubella rash is described. All previous reports described ITP after or occasionally simultaneous with the onset of rubella rash. The onset of purpura in this patient was during the incubation of rubella before the initiation of immune response, suggesting that in some patients the mechanism of platelet damage in ITP associated with rubella is through a direct effect of the virus, rather than by circulating antibodies.     

Unmasking anti-endomysial antibodies in coeliac subjects positive for anti-smooth muscle antibodies

Anti-endomysial antibodies assayed by indirect immunofluorescence presently represent the most advanced in vitro method for diagnosing coeliac disease. While testing the serum of patients affected by coeliac disease for anti-endomysial antibodies, we noticed in some samples the presence of anti-smooth muscle antibodies. This led us to the hypothesis that anti-smooth muscle antibodies might mask the presence of anti-endomysial antibodies. The aim of our research was to develop a method that could confirm our hypothesis. Here we show that the AEA response can be effectively unmasked by increasingly diluting anti-smooth muscle antibodies-positive serum.     

Antiretikulin-Antikörper und präcipitierende Antikörper gegen Nahrungsmittelproteine im Serum von Kindern mit Cöliakie

Zusammenfassung Antiretikulin-Antikörper im Serum wurden mit der Methode der indirekten Immunfluorescenz an frischen Rattennierenschnitten bei 11/13 Kindern (85%) mit florider Cöliakie, 7/17 Kindern (41%) mit klinisch und biochemisch stummem, bioptisch nachgewiesenem Cöliakie-Rezidiv und 0/16 Kindern mit behandelter Cöliakie nachgewiesen. Präcipitierende Antikörper im Serum gegen Weizenmehl bzw. Kuhmilch wurden mit Hilfe einer Kombination aus Elektrophorese und Immundiffusion bei 3/13 Kindern (23%) bzw. 2/13 Kindern (15%) mit florider Cöliakie und bei 1/16 Kindern (6%) mit behandelter Cöliakie gefunden. Bei den 17 Kindern mit stummem Cöliakie-Rezidiv fiel die Untersuchung auf präcipitierende Antikörper negativ aus. 40 Kontrollkinder wiesen weder Antiretikulin-Antikörper noch präcipitierende Antikörper gegen Weizenmehl oder Kuhmilch auf. Die Bedeutung des Antiretikulin-Antikörper-Nachweises für Screening-Untersuchungen und für die Verlaufskontrolle wird diskutiert.

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Antireticulin antibodies and precipitating antibodies to food proteins in the sera of children with coeliac disease

Summary Sera from 41 children suffering with histologically proven coeliac disease and from 40 healthy control children were investigated for the presence of antireticulin antibodies and precipitating antibodies to a watery extract of wheat flour and to cow's milk. Antireticulin antibodies were demonstrated by means of indirect immunofluorescence using sections of fresh rat kidney as substrat. For the detection of precipitating antibodies a combination of electrophoresis and immunodiffusion was used. Serum antireticulin antibodies were found in 11/13 children (85%) with active coeliac disease, in 7/17 children (41%) with clinically and biochemically silent coeliac relapse and in 0/16 children with treated coeliac disease. Serum precipitating antibodies to wheat flour and cow's milk were found respectively in 3/13 children (23%) and 2/13 children (15%) with active coeliac disease and in 1/16 children (6%) with treated coeliac disease. Precipitating antibodies could not be detected in the sera of 17 patients with silent relapse of coeliac disease. In the sera of 40 controls neither antireticulin nor precipitating antibodies were detectable. The presence of antireticulin antibodies in serum did not correspond to the presence of serum precipitins to wheat flour and cow's milk. The significance of serum antireticulin antibodies for sereening investigations and for follow-up studies is discussed.

A. Odenthal (Universitäts-Kinderklinik Bonn), E. Schmitz (Medizinische Universitätsklinik Bonn-Venusberg)     

Salivary IgA antigliadin antibody as a marker for coeliac disease.

In recent years, serum antibodies to gliadin (AGA) have been reported to be useful markers of coeliac disease. IgA AGA have also been found in intestinal secretions and saliva in coeliac disease and may offer a convenient, non-invasive screening test. In order to test this hypothesis, salivary and serum AGA were measured in children with coeliac disease proved by biopsy and compared with several control groups. Measurement of salivary IgA AGA provided excellent discrimination between those children with coeliac disease and the control groups, and our study suggests that it may provide a rapid, non-invasive method of screening for this disease before intestinal biopsy.     

Mass screening for coeliac disease using antihuman transglutaminase antibody assay.

AIMS: To determine coeliac disease prevalence by an anti-transglutaminase antibody assay in a large paediatric population; to evaluate acceptance of the screening programme, dietary compliance, and long term health effects. METHODS: Cross-sectional survey of 3188 schoolchildren (aged 6-12) and prospective follow up of diagnosed cases. Main outcome measures were: prevalence of coeliac disease defined by intestinal biopsy or positivity to both human tissue transglutaminase and anti-endomysium antibodies in HLA DQ2-8 positive subjects; percentage of children whose families accepted screening; dietary compliance as defined by negativity for anti-transglutaminase antibodies; and presence of clinical or laboratory abnormalities at 24 month follow up. RESULTS: The families of 3188/3665 children gave their consent (87%). Thirty biopsy proven coeliacs were identified (prevalence 1:106). Three other children testing positive for both coeliac related autoantibodies and HLA DQ2-8 but refusing biopsy were considered as having coeliac disease (prevalence 1:96). Of 33 cases, 12 had coeliac related symptoms. The 30 biopsy proven coeliacs followed a gluten-free diet. Of 28 subjects completing 18-24 months follow up, 20 (71.4%) were negative for anti-transglutaminase antibodies, while eight were slightly positive; symptoms resolved in all 12 symptomatic children. CONCLUSIONS: Prevalence of coeliac disease is high in Italian schoolchildren. Two thirds of cases were asymptomatic. Acceptance of the programme was good, as was dietary compliance. Given the high prevalence and possible complications of untreated coeliac disease, the availability of a valid screening method, and evidence of willingness to comply with dietary treatment population mass screening deserves careful consideration.     

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.