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Functional Abdominal Pain Disorders and Constipation in Children on Gluten-Free Diet

Published:September 02, 2020DOI:https://doi.org/10.1016/j.cgh.2020.09.001

      Background & Aims

      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).

      Methods

      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).

      Results

      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.

      Conclusions

      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.

      Keywords

      Abbreviations used in this paper:

      CD (celiac disease), EMA (endomysial antibodies), ESPGHAN (European Society for Paediatric Gastroenterology Hepatology, and Nutrition), FAPD (functional abdominal pain disorder), FC (functional constipation), FGID (functional gastrointestinal disorder), GFD (gluten-free diet), IBS (irritable bowel syndrome), RR (relative risk), TTG (transglutaminase)
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      References

        • Husby S.
        • Koletzko S.
        • Korponay-Szabó I.R.
        • et al.
        European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease.
        J Pediatr Gastroenterol Nutr. 2012; 54: 136-160
        • Koppen I.J.
        • Nurko S.
        • Saps M.
        • et al.
        The pediatric Rome IV criteria: what's new?.
        Expert Rev Gastroenterol Hepatol. 2017; 11: 193-201
        • Hyams J.S.
        • Di Lorenzo C.
        • Saps M.
        • et al.
        Functional disorders: children and adolescents.
        Gastroenterology. 2016; 150: 1456-1468
        • Hookway C.
        • Buckner S.
        • Crosland P.
        • et al.
        Irritable bowel syndrome in adults in primary care: summary of updated NICE guidance.
        BMJ. 2015; 350: h701
        • Irvine A.J.
        • Chey W.D.
        • Ford A.C.
        Screening for celiac disease in irritable bowel syndrome: an updated systematic review and meta-analysis.
        Am J Gastroenterol. 2017; 112: 65-76
        • Sainsbury A.
        • Sanders D.S.
        • Ford A.C.
        Prevalence of irritable bowel syndrome-type symptoms in patients with celiac disease: a meta-analysis.
        Clin Gastroenterol Hepatol. 2013; 11: 359-365
        • Cristofori F.
        • Fontana C.
        • Magistà A.
        • et al.
        Increased prevalence of celiac disease among pediatric patients with irritable bowel syndrome: a 6-year prospective cohort study.
        JAMA Pediatr. 2014; 168: 555-560
        • Mulak A.
        • Waszczuk E.
        • Paradowski L.
        Anorectal function and visceral hypersensitivity in celiac disease.
        J Clin Gastroenterol. 2010; 44: 249-252
        • Usai P.
        • Usai Satta P.
        • Lai M.
        • et al.
        Autonomic dysfunction and upper digestive functional disorders in untreated adult coeliac disease.
        Eur J Clin Invest. 1997; 27: 1009-1015
        • Buyse I.
        • Decorte R.
        • Baens M.
        • et al.
        Rapid DNA typing of class II HLA antigens using the polymerase chain reaction and reverse dot blot hybridisation.
        Tissue Antigens. 1993; 41: 1-14
        • Oberhuber G.
        • Granditsch G.
        • Vogelsang H.
        The histopathology of coeliac disease: time for a standardised report scheme for pathologists.
        Eur J Gastroenterol Hepatol. 1999; 11: 1185-1194
        • Biagi F.
        • Bianchi P.I.
        • Marchese A.
        • et al.
        A score that verifies adherence to a gluten-free diet: a cross-sectional, multicentre validation in real clinical life.
        Br J Nutr. 2012; 108: 1884-1888
        • Di Lorenzo C.
        • Nurko S.
        • Drossman D.A.
        • et al.
        Rome IV-Pediatric Functional gastrointestinal disorders-disorders of gut brain interaction.
        The Rome Foundation, Raleigh, NC2016
        • Caplan A.
        • Walker L.
        • Rasquin A.
        Development and preliminary validation of the questionnaire on pediatric gastrointestinal symptoms to assess functional gastrointestinal disorders in children and adolescents.
        J Pediatr Gastroenterol Nutr. 2005; 41: 296-304
        • Caplan A.
        • Walker L.
        • Rasquin A.
        Validation of the pediatric Rome II criteria for functional gastrointestinal disorders using the questionnaire on pediatric gastrointestinal symptoms.
        J Pediatr Gastroenterol Nutr. 2005; 41: 305-316
        • Tabbers M.M.
        • DiLorenzo C.
        • Berger M.Y.
        • et al.
        Evaluation and treatment of functional constipation in infants and children: evidence-based recommendations from ESPGHAN and NASPGHAN.
        J Pediatr Gastroenterol Nutr. 2014; 58: 258-274
        • Scarpato E.
        • Kolacek S.
        • Jojkic-Pavkov D.
        • et al.
        Prevalence of functional gastrointestinal disorders in children and adolescents in the Mediterranean region of Europe.
        Clin Gastroenterol Hepatol. 2018; 16: 870-876
        • Turco R.
        • Boccia G.
        • Miele E.
        • et al.
        The association of coeliac disease in childhood with functional gastrointestinal disorders: a prospective study in patients fulfilling Rome III criteria.
        Aliment Pharmacol Ther. 2011; 34: 783-789
        • Saps M.
        • Sansotta N.
        • Bingham S.
        • et al.
        Abdominal pain-associated functional gastrointestinal disorder prevalence in children and adolescents with celiac disease on gluten-free diet: a multinational study.
        J Pediatr. 2017; 182: 150-154
        • Saps M.
        • Adams P.
        • Bonilla S.
        • et al.
        Abdominal pain and functional gastrointestinal disorders in children with celiac disease.
        J Pediatr. 2013; 162: 505-509
        • Green P.H.
        • Stavropoulos S.N.
        • Panagi S.G.
        • et al.
        Characteristics of adult celiac disease in the U.S.A.: results of a national survey.
        Am J Gastroenterol. 2001; 96: 126-131
        • Pensabene L.
        • Talarico V.
        • Concolino D.
        • et al.
        Post infectious functional gastrointestinal disorders in children: a multicenter prospective study.
        J Pediatr. 2015; 166: 903-907
        • Zimmerman L.A.
        • Srinath A.I.
        • Goyal A.
        • et al.
        The overlap of functional abdominal pain in pediatric Crohn’s disease.
        Inflamm Bowel Dis. 2013; 19: 826-831
        • Diederen K.
        • Hoekman D.R.
        • Hummel T.Z.
        • et al.
        The prevalence of irritable bowel syndrome-type symptoms in paediatric inflammatory bowel disease, and the relationship with bio-chemical markers of disease activity.
        Aliment Pharmacol Ther. 2016; 44: 181-188
        • Watson Jr., K.L.
        • Kim S.C.
        • Boyle B.M.
        • et al.
        The prevalence and impact of functional abdominal pain disorders in children with inflammatory bowel diseases (IBD-FAPD).
        J Pediatr Gastroenterol Nutr. 2017; 65: 212-217
        • Langshaw A.H.
        • Rosen J.M.
        • Pensabene L.
        • et al.
        Overlap between functional abdominal pain disorders and organic diseases in children.
        Rev Gastroenterol Mex. 2018; 83: 268-274
        • O’Leary C.
        • Wieneke P.
        • Buckley S.
        • et al.
        Celiac disease and irritable bowel-type symptoms.
        Am J Gastroenterol. 2002; 97: 1463-1467
        • Verdu E.F.
        • Armstrong D.
        • Murray J.A.
        Between celiac disease and irritable bowel syndrome: the "no man's land" of gluten sensitivity.
        Am J Gastroenterol. 2009; 104: 1587-1594
        • Kakar S.
        • Nehra V.
        • Murray J.A.
        • et al.
        Significance of intraepithelial lymphocytosis in small bowel biopsy samples with normal mucosal architecture.
        Am J Gastroenterol. 2003; 98: 2027-2033
        • Rubio-Tapia A.
        • Rahim M.W.
        • See J.A.
        • et al.
        Mucosal recovery and mortality in adults with celiac disease after treatment with a gluten-free diet.
        Am J Gastroenterol. 2010; 105: 1412-1420
        • Spiller R.
        • Garsed K.
        Postinfectious irritable bowel syndrome.
        Gastroenterology. 2009; 136: 1979-1988
        • Chang M.S.
        • Green P.H.
        A review of rifaximin and bacterial overgrowth in poorly responsive celiac disease.
        Therap Adv Gastroenterol. 2012; 5: 31-36
        • Rubio-Tapia A.
        • Barton S.H.
        • Rosenblatt J.E.
        • et al.
        Prevalence of small intestine bacterial overgrowth diagnosed by quantitative culture of intestinal aspirate in celiac disease.
        J Clin Gastroenterol. 2009; 43: 157-161
        • Tursi A.
        • Brandimarte G.
        • Giorgetti G.
        High prevalence of small intestinal bacterial overgrowth in celiac patients with persistence of gastrointestinal symptoms after gluten withdrawal.
        Am J Gastroenterol. 2003; 98: 839-843
        • Sanz Y.
        Microbiome and gluten.
        Ann Nutr Metab. 2015; 67: 28-41
        • Barbara G.
        • Feinle-Bisset C.
        • Ghoshal U.C.
        • et al.
        The intestinal microenvironment and functional gastrointestinal disorders.
        Gastroenterology. 2016; (Epub ahead of print)
        • Rodiño-Janeiro B.K.
        • Vicario M.
        • Alonso-Cotoner C.
        • et al.
        A review of microbiota and irritable bowel syndrome: future in therapies.
        Adv Ther. 2018; 35: 289-310
        • Wacklin P.
        • Laurikka P.
        • Lindfors K.
        • et al.
        Altered duodenal microbiota composition in celiac disease patients suffering from persistent symptoms on a long-term gluten-free diet.
        Am J Gastroenterol. 2014; 109: 1933-1941
        • Barone M.
        • Della Valle N.
        • Rosania R.
        • et al.
        A comparison of the nutritional status between adult celiac patients on a long-term, strictly gluten-free diet and healthy subjects.
        Eur J Clin Nutr. 2016; 70: 23-27
        • De Palma G.
        • Nadal I.
        • Collado M.C.
        • et al.
        Effects of a gluten-free diet on gut microbiota and immune function in healthy adult human subjects.
        Br J Nutr. 2009; 102: 1154-1160
        • De Angelis M.
        • Vannini L.
        • Di Cagno R.
        • et al.
        Salivary and fecal microbiota and metabolome of celiac children under gluten-free diet.
        Int J Food Microbiol. 2016; 239: 125-132
        • Di Cagno R.
        • Rizzello C.G.
        • Gagliardi F.
        • et al.
        Different fecal microbiotas and volatile organic compounds in treated and untreated children with celiac disease.
        Appl Environ Microbiol. 2009; 75: 3963-3971
        • Nazareth S.
        • Lebwohl B.
        • Tennyson C.A.
        • et al.
        Dietary supplement use in patients with celiac disease in the United States.
        J Clin Gastroenterol. 2015; 49: 577-581
        • Barratt S.M.
        • Leeds J.S.
        • Robinson K.
        • et al.
        Reflux and irritable bowel syndrome are negative predictors of quality of life in coeliac disease and inflammatory bowel disease.
        Eur J Gastroenterol Hepatol. 2011; 23: 159-165
        • Dorn S.D.
        • Hernandez L.
        • Minaya M.T.
        • et al.
        Psychosocial factors are more important than disease activity in determining gastrointestinal symptoms and health status in adults at a celiac disease referral center.
        Dig Dis Sci. 2010; 55: 3154-3163
        • Usai P.
        • Manca R.
        • Cuomo R.
        • et al.
        Effect of gluten-free diet and co-morbidity of irritable bowel syndrome-type symptoms on health-related quality of life in adult coeliac patients.
        Dig Liver Dis. 2007; 39: 824-828