Abdominal Pain-Associated Functional Gastrointestinal Disorder Prevalence in Children and Adolescents with Celiac Disease on Gluten-Free Diet: A Multinational Study

doi:10.1016/j.jpeds.2016.11.049

The Journal of Pediatrics

Volume 182, March 2017, Pages 150-154

https://doi.org/10.1016/j.jpeds.2016.11.049 Get rights and content

Objective

To test the hypothesis that children with celiac disease (CD) on gluten-free diet are at increased risk of abdominal pain (AP) associated-functional gastrointestinal disorders (FGIDs).

Study design

This was a multinational cross-sectional study performed from 2014 to 2015. Patients 4-18 years of age with CD on gluten-free diet for longer than 6 months were recruited from pediatric CD clinics in US and Italy. Control groups included siblings of children with CD (with normal tissue transglutaminase levels) and unrelated controls. Subjects or parents completed the Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III.

Results

Children (n = 289) were recruited (55% US, 45% Italy): 96 children with CD, 96 sibling controls, and 97 unrelated controls. Chronic AP was present in 30 (30.9%) subjects with CD, 22 (22.7%) sibling controls, and 21 (21.6%) unrelated controls (P = .26 patients with CD vs siblings; P = .18 patients with CD vs unrelated; P = .96 siblings vs unrelated). AP-FGIDs were present in 8 (8.2%) subjects with CD, 8 (8.2%) sibling controls, and 2 (2.1%) unrelated controls (P = 1.00 subjects with CD vs sibling controls; P = .06 subjects with CD vs unrelated controls; P = .06 sibling controls vs unrelated controls).

Conclusion

This multinational study evaluated the prevalence of chronic abdominal pain and AP-FGIDs in the pediatric population with CD. We found that subjects with CD and controls have a similar prevalence of chronic AP and AP-FGIDs. This suggests that not all types of gastrointestinal inflammation result in AP-FGIDs in children.

Section snippets

Methods

This international cohort study was conducted during 2014-2015 at 3 university hospitals in 3 cities: Chicago (US) and Messina and Verona (Italy). The study included 3 groups of 4- to 18-year-old children and adolescents: (1) children with CD on a GFD for more than 6 months; (2) sibling controls without CD; and (3) unrelated controls. The Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III (QPGS-RIII) was completed for each subject who consented to the study. The QPGS-RIII has been

Results

A total of 289 children participated in the study (96 with CD on a GFD, 96 sibling controls, and 97 unrelated controls); 53 subjects were recruited into each group from Chicago, 43 subjects were recruited into the CD and sibling groups from Italy, and 44 subjects were recruited into the unrelated control group from Italy (Table I). One subject in the Italian group with CD and their corresponding sibling were excluded because they were older than 18 years. The mean age of subjects in the groups

Discussion

This study investigated the prevalence of chronic AP and AP-FGIDs in children with CD on a GFD, sibling controls, and unrelated controls. We found no significant difference in prevalence in chronic AP or AP-FGIDs among children in the 3 groups. The relative risk of AP-FGIDs in CD compared with siblings was not significant. The relative risk of AP-FGIDs in CD compared with healthy controls, although it exceeded 4-fold, had a CI that crossed 1 and did not achieve significance. The findings of

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Cited by (16)

Functional Abdominal Pain Disorders and Constipation in Children on Gluten-Free Diet
2021, Clinical Gastroenterology and Hepatology
Citation Excerpt :
With the assumption that IBS would be expected in 4.2% of the general Italian pediatric population17 and in 7.3% of CD patients,18 we calculated that a sample of 371 children with CD would be required for the study to have 80% power based on a 2-sided type 1 error rate of 5%. This sample size has a 95% power based on a 2-sided type 1 error rate of 1% to identify a difference in the prevalence of FAPD in CD patients vs controls considering a prevalence of FAPD in 9% of controls17 and in 18% of CD patients.18–20 Risk models were developed using a decisional tree.
We studied the prevalence of functional abdominal pain disorders (FAPDs) and functional constipation (FC) in a large prospective cohort of children with celiac disease on a strict gluten-free diet (GFD).
We performed a prospective cohort study, from 2016 through 2018, in a tertiary care center in Italy, of 417 patients (37% male; mean age, 13.7 y) with a diagnosis of celiac disease (European Society for Paediatric Gastroenterology Hepatology, and Nutrition criteria) who had been on a strict GFD for more than 1 year and had negative results from serologic tests after being on the GFD. Parents and children (>10 y) were asked to fill in a questionnaire on pediatric gastrointestinal symptoms, according to Rome IV criteria. Patients’ closest siblings (or cousins) who had negative results from serologic test for celiac disease were used as controls (n = 373; 39% male; mean age, 13.5 y).
We found a higher prevalence of FAPDs among patients with celiac disease (11.5%) than controls (6.7%) (P < .05); the relative risk (RR) was 1.8 (95% CI, 1.1–3.0). Irritable bowel syndrome (IBS) and FC defined by the Rome IV criteria were more prevalent in patients with celiac disease (7.2% for IBS and 19.9% for FC) than controls (3.2% for IBS and 10.5% for FC) (P < .05 and P < .001, respectively); the RR for IBS was 2.3 (95% CI, 1.1–4.6) and the RR for functional constipation was 2.1 (95% CI, 1.4–3.2). We found no differences in the prevalence of other subtypes of FAPDs. A logistic regression showed that younger age (P < .05) and a higher level of anti–transglutaminase IgA at diagnosis (P < .04) were associated with FAPDs (in particular for IBS) irrespective of GFD duration.
Celiac disease is associated with an increased risk of IBS and FC. Strategies are needed to manage IBS and FC in patients with celiac disease.
Food protein-induced allergic proctocolitis in infants: Literature review and proposal of a management protocol
2020, World Allergy Organization Journal
Citation Excerpt :
Adult studies suggest that an abnormal mucosal milieu and neuro-immune interactions, caused by mast cell activation and nerve growth factor release, may be identified as crucial mechanisms in the pathophysiology of intestinal dysfunction resting to note that the kind of inflammation, as well as the period of life in which it occurs, are pivotal in defining its long-term effects.75 Two research groups have recently shown that with inflammatory bowel disease have an FGIDs prevalence like that of the general pediatric population.76–79 It was demonstrated that an early-life event of allergic/inflammatory origin may be the trigger for the onset of persistent digestive symptoms, particularly IBS.
Food protein-induced allergic proctocolitis (FPIAP) is a condition characterized by inflammatory changes in the distal colon in response to one or more foreign food proteins because of immune-mediated reactions.
FPIAP prevalence estimates range widely from 0.16% in healthy children and 64% in patients with blood in stools.
In clinical practice, FPIAP is diagnosed when patients respond positively to the elimination of a suspected triggering food allergen. Nevertheless, significant proportions of infants get misdiagnosed with IgE mediated allergy and undergo unnecessary dietary changes.
Diagnosis is based on clinical symptoms, a good response to an allergen-free diet and the recurrence of symptoms during the “allergy challenge test”. Sometimes clinical features may be non-specific and the etiology of rectal bleeding in childhood may be heterogeneous. Therefore, it is crucial to exclude a variety of other possible causes of rectal bleeding in the pediatric age group, including infection, anal fissure, intestinal intussusception and, in infants, necrotizing enterocolitis and very early onset inflammatory bowel disease. The diagnostic workup includes in those cases invasive procedures such as sigmoidoscopy and colonoscopy with biopsies.
The high prevalence of FPIAP contrasts with the lack of known information about the pathogenesis of this condition. For this reason and due to the absence of a review of the evidence, a literature review appears necessary to clarify some aspects of allergic colitis.
The aim of the review is to fill this gap and to lay the foundations for a subsequent evidence-based approach to the condition.
Prevalence of functional gastrointestinal disorders in children with celiac disease during the COVID-19 lockdown
2020, Digestive and Liver Disease
Nutrition Assessment, Interventions, and Monitoring for Patients with Celiac Disease: An Evidence Analysis Center Scoping Review
2020, Journal of the Academy of Nutrition and Dietetics
Citation Excerpt :
These studies assessed various outcomes, including adherence/management,35,38 gastrointestinal symptoms and conditions,35,36 immunology/serology measures,35,39 mental/cognitive health,35,37 and quality of life (Figure 4).35,37,39 Eight systematic review/meta-analysis,42-49 9 experimental trials,50-58 and 176 observational studies59-234 examined the effects of gluten-free diet. Most of the systematic reviews/meta-analyses44-49 were published between 201544,45 and 2018.48,49
The objectives of this scoping review were to identify and characterize studies examining nutrition assessment, interventions, and measures to monitor gluten-free diet (GFD) adherence/compliance in patients with celiac disease (CD). An electronic literature search of four databases (Cochrane Database for systematic reviews, CINAHL, Embase, and Ovid MEDLINE) was conducted to identify articles examining nutrition care in CD individuals. Except for narrative review, grey literature, and case study/report, all types of peer-reviewed articles published between January 2007 and August 2018 were eligible. There were a total of 10,823 records; 10,368 were excluded during the first round of screening due to irrelevancy and/or duplication. Of the 455 full-text articles that were assessed, 292 met the criteria and were included. Most of the studies were observational studies (n=212), followed by experimental trials (n=50), evidence-based practice guideline (EBPG)/report/statement (n=16), and systematic review (SR) (n=14). Nine original studies examined assessment, focusing mainly on different tools/ways to assess GFD adherence. The majority of the included original articles (n=235) were in the nutrition intervention category with GFD, oats, and prebiotics/probiotics as the top-three most studied interventions. There were eight SRs on GFD and five on oats. One SR and 21 original studies investigated the effectiveness of different measures to monitor GFD adherence/compliance. Although recent CD EBPGs were identified, different methods with varying levels of rigor, in terms of literature search and assessment of evidence strength, were used. Based on this scoping review, interventions focused on gluten-free diet and oats have been significantly covered by either SRs or EBPGs. Studies related to prebiotics/probiotics and education program/counseling focused interventions, as well as assessment, in CD patients have increased in recent years. Thus, it might be beneficial to conduct SRs/EBPGs focused on these topics to guide practitioners.
Allergic Proctocolitis Is a Risk Factor for Functional Gastrointestinal Disorders in Children
2018, Journal of Pediatrics
Citation Excerpt :
It is interesting to note that the type of inflammation, as well as the period of life in which it occurs, are crucial to defining its long-term effects. In fact, 2 research groups have recently showed that celiac patients on a gluten-free diet36 and patients with inflammatory bowel disease in clinical remission37-39 have an FGIDs prevalence similar to that of the general pediatric population. The pathogenesis of FGIDs remains elusive and is likely multifactorial.1
To test the hypothesis that allergic proctocolitis, a cause of self-limiting rectal bleeding in infants, can predispose to the development of functional gastrointestinal disorders (FGIDs) later in childhood.
We studied a cohort of 80 consecutive patients diagnosed with allergic proctocolitis. Their sibling or matched children presenting to the same hospital for minor trauma served as controls. Parents of the patients with allergic proctocolitis and controls participated in a telephone interview every 12 months until the child was at least 4 years old. At that time, they were asked to complete the parental Questionnaire on Pediatric Gastrointestinal Symptoms, Rome III version.
Sixteen of the 160 subjects (10.0%) included in the study met the Rome III criteria for FGIDs. Among the 80 patients with allergic proctocolitis, 12 (15.0%) reported FGIDs, compared with 4 of 80 (5.0%) controls (P = .035). After adjustment for age and sex, the OR for FGIDs in allergic proctocolitis group was 4.39 (95% CI, 1.03-18.68). FGIDs were significantly associated with iron deficiency anemia, duration of hematochezia, and younger age at presentation. In a multivariate analysis, only the duration of hematochezia was significantly associated with the development of FGIDs (OR, 3.14; 95% CI,1.72-5.74).
We have identified allergic proctocolitis as a new risk factor for the development of FGIDs in children. Our data suggest that not only infection, but also a transient early-life allergic inflammatory trigger may induce persistent digestive symptoms, supporting the existence of “postinflammatory” FGIDs.
Overlap between functional abdominal pain disorders and organic diseases in children
2018, Revista de Gastroenterologia de Mexico
Los trastornos funcionales de dolor abdominal tienen una alta prevalencia en los niños. Estos trastornos pueden estar presentes por sí solos o en combinación con enfermedades orgánicas, tales como la enfermedad celíaca y las enfermedades inflamatorias intestinales. La inflamación intestinal (infecciosa y no infecciosa) predispone a los niños al desarrollo de hipersensibilidad visceral que puede manifestarse como trastornos funcionales de dolor abdominal, entre ellos el síndrome de intestino irritable. La aparición de síntomas de síndrome de intestino irritable en un paciente con una enfermedad orgánica subyacente, como la enfermedad inflamatoria intestinal, es un reto clínico, dado que la misma sintomatología puede representar un periodo de exacerbación de la enfermedad inflamatoria intestinal o un trastorno de dolor abdominal funcional sobrepuesto. Así mismo, puede ser que los síntomas del síndrome de intestino irritable en un niño con diagnóstico de enfermedad celíaca ocurran por un inadecuado control de la enfermedad celíaca o por la sobreposición con un trastorno de dolor abdominal funcional. Existe poca investigación acerca de la sobreposición de los trastornos funcionales abdominales y las enfermedades orgánicas en niños. Los estudios sugieren que la sobreposición entre los trastornos funcionales de dolor abdominal y la enfermedad inflamatoria intestinal es más común en adultos que en niños. Las causas de estas diferencias de prevalencia son aún desconocidas. Solo se han publicado unos cuantos estudios que tratan el tema de la sobreposición entre la enfermedad celíaca y los trastornos funcionales abdominales en niños. El presente artículo proporciona una revisión de la literatura acerca de la sobreposición entre la enfermedad celíaca, la enfermedad inflamatoria intestinal, y los trastornos funcionales de dolor abdominal en niños, además de establecer comparaciones con estudios realizados en adultos.
Functional abdominal pain disorders are highly prevalent in children. These disorders can be present in isolation or combined with organic diseases, such as celiac disease and inflammatory bowel diseases. Intestinal inflammation (infectious and non-infectious) predisposes children to the development of visceral hypersensitivity that can manifest as functional abdominal pain disorders, including irritable bowel syndrome. The new onset of irritable bowel syndrome symptoms in a patient with an underlying organic disease, such as inflammatory bowel disease, is clinically challenging, given that the same symptomatology may represent a flare-up of the inflammatory bowel disease or an overlapping functional abdominal pain disorder. Similarly, irritable bowel syndrome symptoms in a child previously diagnosed with celiac disease may occur due to poorly controlled celiac disease or the overlap with a functional abdominal pain disorder. There is little research on the overlap of functional abdominal disorders with organic diseases in children. Studies suggest that the overlap between functional abdominal pain disorders and inflammatory bowel disease is more common in adults than in children. The causes for these differences in prevalence are unknown. Only a handful of studies have been published on the overlap between celiac disease and functional abdominal pain disorders in children. The present article provides a review of the literature on the overlap between celiac disease, inflammatory bowel disease, and functional abdominal pain disorders in children and establish comparisons with studies conducted on adults.

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: The authors declare no conflicts of interest.

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Original ArticlesAbdominal Pain-Associated Functional Gastrointestinal Disorder Prevalence in Children and Adolescents with Celiac Disease on Gluten-Free Diet: A Multinational Study

Objective

Study design

Results

Conclusion

Section snippets

Methods

Results

Discussion

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Rev Gastroenterol Méx

Gastroenterology

Gastroenterology

Gastroenterology

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Am J Gastroenterol

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Original Articles
Abdominal Pain-Associated Functional Gastrointestinal Disorder Prevalence in Children and Adolescents with Celiac Disease on Gluten-Free Diet: A Multinational Study