| Bonamico et al. Prevalence and clinical picture of celiac disease in Italian down syndrome patients: A multicenter study. 2001. Journal of Pediatric Gastroenterology and Nutrition 33[2], 139-143United States. | Study type:
Prospective cohort
Evidence level:
2+
Study aim:
To estimate the prevalence of coeliac disease (CD) in patients with Down syndrome and to define the clinical characteristics of CD among Down Syndrome patients | 1202 patients
Inclusion criteria:
Down's syndrome
Exclusion criteria:
IgA deficiency
Setting:
Community | 1202 patients
609 males
1110 children
age range: 15 months to 18 years
92 adults
age range 18 to 46 years
Country:
Italy
- -
Group 1: 55 CD patients diagnosed by ESPGHAN Criteria (36 males, aged 4 to 46 years) - -
Group 2: 55 IgA AGA-positive EMA negative DS patients (33 males, aged 3 to 40 years) - -
Group 3: 57 IgA AGA-negative EMA-negative DS patients (34 males, aged 4 to 38 years)
| Tests:
- -
Coeliac disease: Revised European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) criteria Patients selected for intestinal biopsy on the basis of EMA positivity, AGA IgA positivity, or both in children < 2 years of age (AGA: antigliadin antibodies; EMA: antiendomysium antibodies; IgA: immunoglobulin A) - -
Down syndrome: confirmed by cariotype in all cases
| Signs/symptoms (%):
- -
Group 1 (n=55): Growth failure 52.7 Diarrhoea 41.8 Vomiting 20 Anorexia 18.2 Constipation 29.1 Distended abdomen 23.6
- -
Group 2 (n=55): Growth failure 10.9 Diarrhoea 1.8 Vomiting 1.8 Anorexia 1.8 Constipation 14.5 Distended abdomen 14.5
- -
Group 3 (n=57): Growth failure 7 P < 0.001 Diarrhoea 6.9 P < 0.001 Vomiting 1.7 P < 0.001 Anorexia 3.4 P < 0.01 Constipation 8.8 P < 0.05 Distended abdomen 15.5 NS
P values are the results of comparing group 1 vs. group 2 and group 3 | Additional information from study
Levels of IgA AGA were measured by enzymelinked immunosorbent assay by the Alfa-gliatest (Eurospital, Trieste, Italy). Levels of EMA IgA were evaluated by an indirect immunofluorescence method (Eurospital, Trieste, Italy). Sections from the distal portion of monkey oesophagus were used as a substrate, and fluorescein-labeled goat antihuman IgA antibody was used as the second antibody. The patients' serum was diluted 1:5 in phosphate buffer at pH 7.2. The presence of a brilliant green network pattern under a fluorescence microscope was taken as a positive result. Intestinal biopsies performed by Watson capsule or by paediatric or adult endoscopes
Patients selected for intestinal biopsy on the basis of both EMA positivity and AGA IgA positivity in children < 2 years of age, because in this age group, EMA positivity may have a false-negative result
A detailed questionnaire was completed to obtain information about familial gastroenterologic history with special attention to feeding habits (breast milk or formula, age of introduction of gluten-containing foods); gastrointestinal function, particularly the features of CD, such as chronic diarrhoea, vomiting, failure to thrive, and anorexia; presence of autoimmune or neoplastic conditions
All patients were receiving a gluten-containing diet. Weight and height were evaluated using Down syndrome percentile charts (DSPC)
The clinical features of 55 CD patients diagnosed by ESPGHAN Criteria (group 1) were compared with those observed in 55 IgA AGA-positive EMA negative DS patients (group 2) and in 57 IgA AGA-negative EMA-negative DS patients (group 3). Group 2 and group 3 patients were selected randomly from among the screened patients to be age and gender matched to group 1.
18 symptomatic patients belonging to group 2 underwent intestinal biopsy and showed normal small bowel mucosa
Parents of 8 EMA positive children and 2 EMA-positive adults did not give permission for intestinal biopsy to be performed and were not included among the 55 CD patients
Reviewer comments:
It is unclear whether some patients had EMA and others had AGA IgA measured alternatively, or whether all patients had both EMA and AGA IgA measured at the same. This considered it is also unclear why only IgA AGA-positive EMA-negative patients and IgA AGA-negative EMA-negative patients were chosen as control groups and there is no mention of the EMA-positive IgA AGA-negative group
Source of funding: Not stated |
| Bingley et al. Undiagnosed coeliac disease at age seven: Population based prospective birth cohort study. 2004. British Medical Journal 328[7435], 322-323United Kingdom. | Study type:
Prospective cohort
Evidence level:
2+
Study aim:
to establish the prevalence of undiagnosed coeliac disease in the general population at age seven and to look for any associated clinical features | 5470 children
Inclusion criteria:
Children aged 7.5 years participating In the Avon Longitudinal Study of Parents and Children (ALPASC), a population based birth cohort study established in 1990
Exclusion criteria:
Not stated
Setting:
Community | 5470 children
age: 7.5 years
gender not reported
Country:
UK | Tests:
- -
Coeliac disease: Two stage screening: Sensitive initial radioimmunoassa y for antibodies to tissue transglutaminase (endomysial antigen) (tTG antibodies) If positive to previous, serum IgA antiendomysial antibodies (IgA-EMA) by indirect inmunofluorescence
- -
Constipation: Clinical variables
| Any constipation reported at age 6.75 years (No, %):
- -
tTG antibody negative controls (n=4285 questionnaires): 435 (10) - -
IgA-EMA positive (n=42 questionnaires): 6 (14)
Other symptoms reported at age 6.75 years (No, %):
- -
tTG antibody negative controls (n=4285 questionnaires): - -
IgA-EMA positive (n=42 questionnaires): any diarrhoea: 21 (50) odds ratio (95% CI): 1.96 (1.06 to 3.59) any vomiting: 23 (55) odds ratio (95% CI): 1.47 (0.80 to 2.71) any stomach pains: 28 (66) odds ratio (95% CI): 1.35 (0.71 to 2.57) ≥3 GI symptoms: 17 (40) odds ratio (95% CI): 2.45 (1.33 to 4.5)
| Additional information from study
Children with tTG antibodies < 97.5th centile were defined as antibody negative
Details of gastrointestinal symptoms and special diets collected by routine questionnaire at age 6.75 years
Total tTG antibody negative controls (n=5333 children). Total IgA-EMA positive children (n=54) (1.0%; 95% confidence interval 0.8 to 1.4)
4324 children (79%) returned questionnaires
An additional 137 children were tTG antibody positive, but Ig-EMA negative
IgA-EMA were more common in girls (OR 2.12; 1.20 to 3.75). IgA-EMA positive children were shorter and weighted less than those who tested negative for tTG antibody (p<0.0001 for all comparisons)
Since ALPASC is an observational study based on analysis of anonymous samples, confirmatory biopsy was not possible
Reviewer comments:
Unclear how the symptom “constipation” was defined in the first place
No data regarding clinical symptoms at 6.75 years for 21% of the total sample
Sources of funding:
Coeliac UK, Medical Research Council, Wellcome Trust, UK government departments, and various charitable organisations and commercial companies, ALSPAC is part of the WHO initiated European Longitudinal Study on Pregnancy and Childhood |
| Cataldo et al. Epidemiological and clinical features in immigrant children with coeliac disease: An Italian multicentre study. 2004. Digestive and Liver Disease 36[11], 722-729United States. | Study type:
Retrospective case series
Evidence level:
3
Study aim:
To evaluate the prevalence of immigrant children with coeliac disease (CD) in Italy, the clinical findings in these patients and the possible relationship between immigration, dietary habits and CD in childhood | 1917 children
Inclusion criteria:
Italian and immigrant children consecutively diagnosed as having CD between January 1999 to December 2001
Exclusion criteria:
Not stated
Setting:
Hospital (multicentre) | Total: 1917 children with CD
36 immigrant children with CD 15 males age range 6 months to 15 years (mean 7.3)
1881 Italian children 891 males age range 6 months to 16 years (mean 7.9)
Country:
Italy | Test:
- -
coeliac disease: diagnosis based on the revised criteria of the European Society of Paediatric Gastroenterology and Nutrition (ESPGAN): Finding of a flat small intestinal mucosa with the features of hyperplastic villous atrophy on histological examination of a biopsy specimen, while the patient is eating adequate amounts of gluten Clear cut clinical remission on a strict gluten free diet with relief of all symptoms of the disease. This response should be reasonably rapid occurring within a matter of weeks rather than many months The finding of circulating antibodies (IgA gliadin, antireticulin, and antiendomysiun) at time of diagnosis and their disappearance when the patient is taking a gluten free diet add weight to the diagnosis
| Clinical pattern and presenting symptoms at diagnosis (n=36)
- -
Classical forms (25/36) (69.4%): No child with constipation reported - -
Atypical forms (9/36) (25%): Abdominal pain with constipation: 2/9 - -
Silent forms (2/36) (5.5%): No child with constipation reported
| Additional information from study
Classical forms not clearly defined, but included the following symptoms: chronic diarrhoea, weight loss, abdominal distension and vomit
Atypical forms included: iron-deficiency anaemia, short stature, delayed puberty, recurrent oral aphtae
Silent forms included: serological screening of first degree relative, loss of Kerckring folds at endoscopy
Clinical patterns in Italian children were similar to those of immigrant children
Reviewer comments:
Unclear how the symptom “constipation” was defined in the first place
Presenting symptoms at diagnosis were not reported for Italian children
Source of funding: Study supported by grants of Ministero dell'Universita e della Ricerca Scientifica e Tecnologica (MURST) 60% di F.C. |
| Egan-Mitchell et al. Constipation in childhood coeliac disease. 1972. Archives of Disease in Childhood 47[252], 238-240 | Study type:
Retrospective case series
Evidence level:
3
Study aim:
To assess the incidence of constipation in coeliac disease | 112 children
Inclusion criteria:
Coeliac disease
Exclusion criteria:
Not stated
Setting:
Regional and university hospitals | 112 children
12 children with constipation: 6 males, age range 6 to 102 months
Country:
Ireland | Tests:
- -
Coeliac disease Clinical variables: undernutrition and retarded growth. Jejunal biopsy: Grade 2/3 or grade 3 jejunal mucosal damage
- -
Constipation: Clinical variables: passage of stools of harder consistency than normal, or the clinical observation of impaction of abnormal amounts of hard (usually pale) faeces in colon and rectum
| Incidence of constipation:
12 children constipated at some stage before diagnoses:
- -
9 of those children presented with constipation and faecal impaction, of these 5 had intermittent diarrhoea and constipation but 4 never had diarrhoea. Of these 4, 3 children presented at around 1 year of age with anorexia, failure to thrive and faecal impaction - -
the 3 children who did not have faecal impaction when investigated had histories of constipation alternating with mild diarrhoea and all had been given laxatives frequently for their constipation
| Additional information from study
Growth retardation assessed on the graphs of Tanner and Whitehouse (1959) and subsequently confirmed by catch-up growth following treatment with gluten-free diet
Mucosal damage according to authors' classification (normal mucosa grade 0; mild non-specific change grade 1; grade 2 and 3 correspond to moderate and severe villous atrophy)
Reviewer comments:
Unclear whether authors' classification system for jejunal mucosa damage has been validated
Source of funding: The main author was receiving a grant from the Medical Research Council of Ireland |
