Faecal occult blood in children with coeliac disease

It has recently been suggested that in adults with coeliac disease, faecal blood loss may play a role in the development of iron deficiency. A group of 45 children diagnosed with coeliac disease during 1996 and 1997 were therefore prospectively evaluated for the presence of gluten in their diet, iron deficiency anaemia, and faecal occult blood. Sixty children admitted for elective surgery or asthma served as controls. Faecal occult blood was found in four iron deficient children on normal diet, of whom three were newly diagnosed. Occult blood loss disappeared in three of the four children when gluten was removed from their diet. Faecal occult blood was found in 26.7% of children on gluten-containing diet, but not in children on gluten-free diet (P=0.01), or in control children (P=0.001). Conclusion Our data suggest that the incidence of occult blood loss in coeliac disease occurs mainly in newly diagnosed cases and responds to a gluten-free diet. Occult blood testing may not be warranted in the absence of iron deficiency anaemia nor in children with iron deficiency anaemia who are on a gluten-free diet. Received: 23 September 1999 and in revised form: 3 April 2000 and 5 May 2000 / Accepted: 7 May 2000     

Erythropoiesis and stainable iron in bone marrow in malabsorptive states in children

Summary The haematological findings in twenty-five children with the malabsorption syndrome (15 with coeliac disease, 7 fibrocystic disease and 3 tropical sprue) have been analysed. 28% children did not show either anaemia or reduction in stainable marrow iron. 16% showed latent iron deficiency while 56% were anaemic. The predominant type of anaemia was hypochromic although two patients in each of the groups of coeliac disease, fibrocystic disease and tropical sprue showed dimorphic anaemia. The erythropoiesis was normoblastic in 66.6% and dimorphic in 33.3% patients. The stainable marrow iron was deficient in 68% of patients and adequate in 32%. Iron deficiency was less severe in patients with fibrocystic disease of the pancreas. From the Haematology Section, Department of Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh.     

Growth and adult height in atypical coeliac patients, with or without growth hormone deficiency

OBJECTIVE: To evaluate the effect of a gluten-free diet on growth and adult height, when available, in coeliac children without gastrointestinal symptoms. PATIENTS AND METHODS: Sixty-one coeliac children without gastro-intestinal symptoms were included in the study. The age at diagnosis was 9.50 +/- 3.3 years. Thirty-eight had short stature at diagnosis (< 10th percentile) and 23 had normal stature. Thirty-seven reached adult height. RESULTS: After beginning the diet an increase in growth velocity was seen in 30 patients (responders) (20 with initial short stature), while in 31 patients (18 with short stature) there was no catch-up growth (non-responders). Bone age at diagnosis was significantly more delayed in the responders than in the non-responders. Target height was significantly higher in children with normal stature at diagnosis than those with short stature. Growth hormone (GH) deficiency was found and confirmed after 6-12 months of diet in 12 of the 38 patients (32%) with short stature. In the group of the 30 'short' patients who attained final height, target height was attained or improved in 12 patients (40%): in eight of the 16 (50%) responders and in four of the 14 (29%) non-responders; in eight (all responders) out of 22 (36%) without GH deficiency, and in four out of eight (50%) patients with GH deficiency treated with GH (all non-responders). CONCLUSIONS: In children in whom coeliac disease is diagnosed because of short stature, a gluten-free diet will be successful if at diagnosis there is a delay of bone age and in the first year of diet there is an evident catch-up growth. When this does not occur, i.e. in half of the patients (18 out of 38), it may be because of an associated and transient GH deficiency. In these patients a period of GH replacement therapy as well as a gluten-free diet may improve their final height.     

Celiac disease diagnosis in misdiagnosed children

Antiendomysial antibodies (EMA) are today considered the most sensitive and specific serological marker of celiac disease (CD). The aim of the present study was to assess the occurrence of EMA of IgG isotype in EMA IgA negative children with clinical suspicion of malabsorption and their relationship with CD. Serum EMA IgG1 determination was performed on 30 EMA IgA negative children with clinical suspicion of CD. Total serum IgA levels were further investigated. Sixty children with gastroenterological diseases other than CD were used as control disease patients and 63 healthy children were evaluated as the control group. Eighteen out of 30 children in the study showed EMA IgG1 positivity in sera and a villous height/crypt depth ratio <3:1 as index of intestinal atrophy. It is noticeable that a selective IgA deficiency was present in only 9 of 18 EMA IgG1 positive children. In addition, clinical symptoms, EMA IgG1, and mucosal atrophy disappeared after 8-10 mo on a gluten-free diet. Neither EMA IgA nor EMA IgG1 were detected in the children in the control groups. The other 12 children in study group showed no histologic abnormalities and were EMA IgG1 negative. In this study, we reveal a group of EMA IgG1 CD children without IgA deficiency. The diagnosis was based on the presence of gluten-dependent typical serological and histologic features of CD. Our data suggest that EMA IgG1 determination could be a new tool in the diagnostic workup of CD, useful in avoiding possible misdiagnosis.     

Iron deficiency in coeliac disease is mild and it is detected and corrected by gluten-free diet

In 54 children with coeliac disease, mild iron deficiency anaemia or evidence of iron deficiency without anaemia were common at the time of diagnosis. Treatment with a gluten-free diet without iron medication eliminated all evidence of iron deficiency and completely normalized laboratory values. Subsequent challenge with gluten resulted in the rapid reappearance of suboptimal iron balance as evidenced by a decrease in serum ferritin concentration.     

Iron Deficiency in Coeliac Disease Is Mild and It Is Detected and Corrected by Gluten-free Diet

ABSTRACT. In 54 children with coeliac disease, mild iron deficiency anaemia or evidence of iron deficiency without anaemia were common at the time of diagnosis. Treatment with gluten-free diet without iron medication eliminated all evidence of iron deficiency and completely normalized laboratory values. Subsequent challenge with gluten resulted in the rapid reappearance of suboptimal iron balance as evidenced by decrease in serum ferritin concentration.     

Antiendomysial antibody detection in biopsy culture allows avoidance of gluten challenge in celiac children

OBJECTIVE: Antiendomysial antibody (EMA) production has been induced in vitro by the small bowel mucosa of celiac disease (CD) patients in clinical remission cultured in the presence of gliadin peptides. The aim of the present study was to use this in vitro system to determine whether it could be used to predict the clinical or histologic relapse to gluten challenge in CD children on a gluten-free diet (GFD). METHODS: Enrolled were 32 CD children and adolescents on GFD (group 1), and 80 controls (group 2) who underwent in vitro gliadin challenge. Subsequently, 24 group 1 CD children underwent in vivo gluten challenge to confirm the diagnosis. Biopsy cultures, with and without gliadin, morphometric analysis, immunoglobulin (Ig)A and IgG1 EMA detection, both in sera and culture supernatants, were performed. RESULTS: Of the 32 group 1 CD patients, 23 were IgA EMA positive in culture supernatants. The other nine were IgG1 EMA positive. All 24 children who had in vivo gluten challenge showed clinical or histologic relapse. All culture supernatants from disease controls belonging to group 2 were both IgA and IgG1 EMA negative, irrespective of gliadin challenge. CONCLUSIONS: Organ culture with in vitro gliadin challenge is able to reproduce the results of in vivo challenge. This system could reduce the need for gluten challenge in celiac children.     

Frequency of coeliac disease in Hungarian children with type 1 diabetes mellitus

Coeliac disease and type 1 diabetes mellitus can frequently coexist, presumably due to a common genetic predisposition. The present study was designed to evaluate the frequency of coeliac disease among Hungarian diabetic children and to study the effect of gluten-free diet on glycaemic control. A total of 205 diabetic children (age range 2.0-17.0 years, median 11.6 years) were screened for coeliac disease by determination of IgA-endomysium (EMA) antibodies. In the positive cases, a jejunal biopsy was performed and, in addition to routine histology, the number of intraepithelial gamma/delta T-cells was also determined. Insulin requirement, glycosylated haemoglobin level and body mass index of diabetic children with coeliac disease were determined before and 3 months after the introduction of gluten-free diet. IgA-EMA was positive in 24 cases, 17 of them (8.3% of all diabetic children) had a subtotal villous atrophy and thus coeliac disease was diagnosed. In all but two of these children, the mean number of gamma/delta T-cells was elevated (above 7 cells/mm). Of the remaining seven patients with positive EMA but normal villous structure, five (2.4%) had elevated number of epithelial gamma/delta T-cells, indicating probable latent coeliac disease. The insulin requirement of the children had significantly increased 3 months after the introduction of gluten-free diet (median values 0.64 versus 0.48 U/kg per day, P<0.05). Median body mass indices also showed significant elevation after this period (16.8 versus 14.2 kg/m(2), P<0.05) Conclusion: the frequency of coeliac disease was high in the studied group. Introduction of a gluten-free diet improved the somatic development of these children. A latent form of coeliac disease is also frequent in children with type 1 diabetes mellitus.     

Antigliadin and antiendomysium antibody determination for coeliac disease.

The value of IgG and IgA gliadin antibodies (AGA) was compared with that of IgA endomysium antibodies (EMA) for the diagnosis of coeliac disease. Three hundred and six of 340 (90%) children with untreated coeliac disease (flat mucosa) had EMA and 338/340 (99.4%) had IgG AGA and/or IgA AGA. Only 1/340 (a 7 year old boy with selective IgA deficiency) had neither AGA nor EMA. Absence of EMA is more frequent in coeliac patients younger than 2 years than in older patients (32/277 compared with 1/62). EMA were present in 4/211 (2%) of comparison subjects (normal mucosa), IgA AGA in 12/211 (6%), and IgG AGA in 74/211 (35%). The specificity of AGA cannot be calculated from these figures as they are biased. The combined determination of AGA and EMA, taking advantage of the high sensitivity of AGA and the high specificity of EMA, gives an excellent prediction of the condition of the mucosa: 247/248 patients (99.6%) with positive EMA and positive IgG AGA and IgA AGA had a flat mucosa, whereas 136/137 patients (99.3%) with neither AGA nor EMA had a normal mucosa. During a gluten free diet EMA and AGA disappear. Their presence or absence is therefore an indicator of dietary compliance. After reintroduction of gluten into the diet 110/134 (82%) of the patients who had a flat mucosa at diagnosis relapsed, but 24/134 still had a normal mucosa after 2-15 years of challenge. All these patients without a morphological relapse were less than 2 years old at diagnosis so we conclude that patients who are young at diagnosis should be challenged. AGA often reappear earlier than EMA. After one month of challenge 93% of patients are AGA and 69% EMA positive. After more than three years of gluten intake the percentage of AGA positive patients decreased to about 50% whereas the percentage of EMA positive sera was then highest (93%). Therefore EMA are more sensitive for the detection of 'silent' relapse after prolonged periods of gluten intake.     

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.     

Helicobacter pylori infection with iron deficiency anaemia and subnormal growth at puberty

The purpose of this study was to determine whether Helicobacter pylori infection can contribute to growth deficit, especially in pubescent children who need large amounts of iron for growth. A structured questionnaire was sent to the parents of 532 healthy children aged 10 to 15 years (mean 12.9) to obtain demographic information on the parents and the environment. Of the 532 questionnaires sent out, 375 (70.5%; 170 girls and 205 boys) were returned. After collecting blood samples from participants, haemoglobin, serum iron, total iron binding capacity, serum ferritin, and serum IgG antibodies to H pylori were measured. The effects of risk factors such as H pylori infection, iron deficiency anaemia, sex, socioeconomic status, type of house, and crowding index on growth were analysed using multiple regression analysis. Of 63 H pylori positive children, 18 (28.6%) were below the 25th centile values for height, compared with 63 of 312 (20.2%) H pylori negative children. The prevalence rate of H pylori infection was 15.5% (53 of 343) in children without iron deficiency anaemia and 31.3% (10 of 32) in those affected. The relative risk of short stature was 2.2 (95% confidence interval (CI), 1.0 to 4.8) for iron deficiency anaemia, and 1.4 (95% CI, 0.8 to 2.4) for H pylori infection. The mean height was significantly lower in the group having both H pylori infection and iron deficiency anaemia. Therefore, H pylori infection accompanied by iron deficiency anaemia, rather than H pylori infection per se, might delay pubertal growth.     

Helicobacter pylori infection with iron deficiency anaemia and subnormal growth at puberty.

The purpose of this study was to determine whether Helicobacter pylori infection can contribute to growth deficit, especially in pubescent children who need large amounts of iron for growth. A structured questionnaire was sent to the parents of 532 healthy children aged 10 to 15 years (mean 12.9) to obtain demographic information on the parents and the environment. Of the 532 questionnaires sent out, 375 (70.5%; 170 girls and 205 boys) were returned. After collecting blood samples from participants, haemoglobin, serum iron, total iron binding capacity, serum ferritin, and serum IgG antibodies to H pylori were measured. The effects of risk factors such as H pylori infection, iron deficiency anaemia, sex, socioeconomic status, type of house, and crowding index on growth were analysed using multiple regression analysis. Of 63 H pylori positive children, 18 (28.6%) were below the 25th centile values for height, compared with 63 of 312 (20.2%) H pylori negative children. The prevalence rate of H pylori infection was 15.5% (53 of 343) in children without iron deficiency anaemia and 31.3% (10 of 32) in those affected. The relative risk of short stature was 2.2 (95% confidence interval (CI), 1.0 to 4.8) for iron deficiency anaemia, and 1.4 (95% CI, 0.8 to 2.4) for H pylori infection. The mean height was significantly lower in the group having both H pylori infection and iron deficiency anaemia. Therefore, H pylori infection accompanied by iron deficiency anaemia, rather than H pylori infection per se, might delay pubertal growth.     

Changing pattern of childhood coeliac disease in Finland

In the Tampere region in Finland, the incidence of childhood coeliac disease was 1:1,096 between 1964 and 1973 and 1:3,214 from 1974 to 1983. The clinical picture of coeliac disease had changed to milder forms, resulting in an upward shift of age at diagnosis. Coeliac disease was found in older children and adolescents, manifesting itself mostly in minor abdominal symptoms, short stature, delayed puberty, anaemia and joint complaints, and in children with diabetes mellitus. Long breast-feeding seemed to postpone the symptoms but the introduction of gluten was of no significance. The low incidence for 1974 to 1983 was thought to be due to the estimated 20 cases born in 1979 to 1983 who were not detected. We do not believe that coeliac disease has disappeared but that it will be found during the next decade in the patients who were not diagnosed in school age and adolescence.     

Changing Pattern of Childhood Coeliac Disease in Finland

ABSTRACT. In the Tampere region in Finland, the incidence of childhood coeliac disease was 1:1096 between 1964 and 1973 and 1:3214 from 1974 to 1983. The clinical picture of coeliac disease had changed to milder forms, resulting in an upward shift of age at diagnosis. Coeliac disease was found in older children and adolescents, manifesting itself mostly in minor abdominal symptoms, short stature, delayed puberty, anaemia and joint complaints, and in children with diabetes mellitus. Long breast-feeding seemed to postpone the symptoms but the introduction of gluten was of no significance. The low incidence for 1974 to 1983 was thought to be due to the estimated 20 cases born in 1979 to 1983 who were not detected. We do not believe that coeliac disease has disappeared but that it will be found during the next decade in the patients who were not diagnosed in school age and adolescence.     

Iron and folate status in Gambian children with malaria.

Iron and folate status were evaluated in a group of 106 Gambian children with malaria and variable degrees of anaemia. In children with malaria, normal or increased levels of red cell folate were found in 75 patients at presentation and in 15 patients 1-2 weeks after treatment with anti-malarials alone, despite the presence of giant metamyelocytes and megaloblasts in the bone marrow in some cases. Twenty-eight per cent of patients were found to have deficient bone marrow iron stores but malaria could not be directly implicated as the cause of this deficiency. Iron deficiency could also not be implicated as the sole cause of dyserythropoiesis in patients with malarial anaemia. Excess storage iron and the presence of ring sideroblasts were found in the bone marrow in some cases. It is concluded that the morphological changes including dyserythropoiesis, occasional megaloblasts, giant metamyelocytes and ring sideroblasts seen in the bone marrows of these children are manifestations of disturbed marrow function in malaria and are not related to haematinic deficiency. Because of the high rate of iron deficiency found in these patients it is recommended that Gambian children with severe anaemia should receive iron therapy after adequate treatment of malaria.     

An iron treatment trial in an Aboriginal community: Improving non-adherence

OBJECTIVE: To compare supervised vs unsupervised oral iron treatment in anaemic Aboriginal children living in a remote community with a 40% prevalence of iron deficiency anaemia. METHODOLOGY: A randomised unblinded clinical trial in children < 6 years presenting to a remote Health Centre with anaemia. Oral iron prescribed as a daily unsupervised dose (group A) was compared to twice weekly supervised administration (group B) over 12 weeks. Parenteral iron (group C) was reserved for failure of oral treatment. RESULTS: Only 3 of 25 children in group A responded to treatment compared to 23 of 26 children in group B (odds ratio = 7.7, 95% confidence interval 2.6-25.0). After six weeks of treatment, the mean haemoglobin rise was 0.96 g/L in group A compared to 10.9 g/L in group B and 12.4 g/L in group C. On entry to the study, 29.4% of subjects were underweight, 33.3% stunted and 35.3% microcephalic. The mean catch-up in weight/height on iron treatment over the study was only 0.28 (0.08, 0.48) Z-scores. CONCLUSIONS: Oral iron as directly observed twice weekly treatment is superior to unsupervised therapy. In view of the poor compliance with unsupervised treatment and the high prevalence of iron deficiency anaemia (along with stunting and microcephaly) in Aboriginal children in northern Australia, we propose to undertake in partnership with communities a nutritional intervention program with a high energy weaning food fortified with micronutrients (iron, vitamin A, zinc, folate) as the most effective strategy to address these nutritional problems in the weaning period.     

Iron status of young Vietnamese children in Australia

OBJECTIVE: The aim of this study was to estimate the prevalence of iron deficiency in Vietnamese children living in Australia and to identify risk factors associated with iron deficiency. METHODS: A cohort of healthy term Vietnamese infants, were followed from birth (n = 210) to 18 months (n = 174) with anthropometry, dietary intake and feeding practices measured at seven time points. Socio-demographic data were collected from the parents at the first home visit. At 18 months iron status was examined by full blood count and plasma ferritin concentration in 129/152 (85%) of the eligible children. Iron depletion was defined as a plasma ferritin level < 10 microg/L. Iron deficiency without anaemia was defined as iron depletion plus MCV < 70fl and iron deficiency anaemia was defined as iron deficiency anaemia plus Hb < 110 g/L. RESULTS: The prevalence of iron deficiency was iron depletion 19.4% (95% CI: 13.0%, 27.3%), iron deficiency without anaemia 3.1% (95% CI: 0.9%, 7.8%) and iron deficiency anaemia 3.9% (95% CI: 1.3%, 8.8%). Multiple regression analysis showed three significant predictors of iron deficiency: cows milk intake (negative effect), meat, fish or poultry intake (positive effect) and weight gain (negative effect). A cows milk intake > or = 650 mL/day was a risk factor for iron deficiency. CONCLUSION: Prevalence of iron deficiency at 18 months was high despite appropriate infant feeding practices during the first year. Modification of the diet in the second year of life may decrease the risk of iron deficiency in Vietnamese children.     

Negative results of antiendomysial antibodies: long term follow up

Fifteen patients with intestinal villous atrophy, but simultaneously negative results of antiendomysial antibodies (EMA) were studied. Two patients were finally diagnosed as having coeliac disease. The predictive value of negative results of EMA assessment in children suspected of coeliac disease is high, approaching 86.7%.     

Negative results of antiendomysial antibodies: long term follow up.

Fifteen patients with intestinal villous atrophy, but simultaneously negative results of antiendomysial antibodies (EMA) were studied. Two patients were finally diagnosed as having coeliac disease. The predictive value of negative results of EMA assessment in children suspected of coeliac disease is high, approaching 86.7%.     

Celiac disease in children with Down syndrome: Importance of follow-up and serologic screening

BACKGROUND: Celiac disease, also known as gluten-sensitive enteropathy, is a chronic inflammation disease of the small intestinal mucosa. Detection of Ig-A antigliadin antibodies (AGA) and antiendomysial antibodies (EMA) in serum is important in the diagnosis and screening for celiac disease. Antiendomysial antibodies have greater sensitivity compared to antigliadin antibodies. It has been reported that the prevalence of celiac disease is higher in children with Down syndrome than the other autoimmune conditions. The aim of the present study was to investigate the incidence of celiac disease in children with Down syndrome, to assess the availability of Ig-A AGA and EMA for serologic screening, and to highlight the importance of follow-up for children with Down syndrome. METHODS: Forty-seven children with Down syndrome without known celiac disease were tested for total blood count, thyroid function tests, immunoglobulin values, Ig-A AGA and EMA. Duodenal biopsy was performed on eight patients who showed at least one serologically positive marker. RESULTS: The ages of the children with Down syndrome ranged from 2 to 18 years (30 boys/17 girls). The mean age was 6.55 +/- 3.88. Total blood count and immunoglobulin values were normal. Eleven of the 47 patients (23.40%) were found to be serologically positive, 10 (21.28%) having antigliadin antibody concentrations above normal; and six (12.77%) being positive for antiendomysial antibody. In five patients (10.64%), both Ig-A AGA and EMA concentrations were high and positive. Duodenal biopsies of three of eight cases (37.50%) revealed villous atrophy, lymphocyte infiltration and crypt hyperplasia. Three cases with abnormal biopsy results (100%) were below the 10th percentile for weight and height. Hypo-thyroidism was detected in one of 11 cases where at least one serologic marker was positive. CONCLUSION: Children with Down syndrome should be carefully examined in their follow up, and celiac disease should be considered in cases with growth retardation. Ig-A antigliadin antibodies and EMA are non-invasive, cheap and readily available serologic screening tests for celiac disease, and the positivity of both markers gives the most reliable result.