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6 Chronic Abdominal Pain in Children 6 Chronic Abdominal Pain in Children Chronic Abdominal Pain in Children in Children Pain Abdominal Chronic Chronische buikpijn bij kinderen Carolien Gijsbers Carolien Gijsbers Carolien Chronic Abdominal Pain in Children Chronische buikpijn bij kinderen Carolien Gijsbers Promotiereeks HagaZiekenhuis Het HagaZiekenhuis van Den Haag is trots op medewerkers die fundamentele bijdragen leveren aan de wetenschap en stimuleert hen daartoe. Om die reden biedt het HagaZiekenhuis promovendi de mogelijkheid hun dissertatie te publiceren in een speciale Haga uitgave, die onderdeel is van de promotiereeks van het HagaZiekenhuis. Daarnaast kunnen promovendi in het wetenschaps­­magazine HagaScoop van het ziekenhuis aan het woord komen over hun promotieonderzoek. Chronic Abdominal Pain in Children Chronische buikpijn bij kinderen © Carolien Gijsbers 2012 Den Haag ISBN: 978-90-9027270-2 Vormgeving en opmaak De VormCompagnie, Houten Druk DR&DV Media Services, Amsterdam Printing and distribution of this thesis is supported by HagaZiekenhuis. All rights reserved. Subject to the exceptions provided for by law, no part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form by any means, electronic, mechanical, photocopying, recording or otherwise, without the written consent of the author. Chronic Abdominal Pain in Children Chronische buikpijn bij kinderen Carolien Gijsbers Proefschrift ter verkrijging van de graad van doctor aan de Erasmus Universiteit Rotterdam op gezag van de rector magnificus Prof.dr. H.G. Schmidt en volgens besluit van het College voor Promoties. De openbare verdediging zal plaatsvinden op donderdag 20 december 2012 om 15.30 uur door Carolina Francesca Maria Gijsbers geboren te Zierikzee Promotiecommisie Promotor: Prof.dr. H.A. Büller Copromotor: Dr. C.M.F. Kneepkens Overige leden: Prof.dr. D. Tibboel Prof.dr. A.J. van der Heijden Prof.dr. M.Y. Berger Table of contents 1 INTRODUCTION 8 2 OUTLINE OF THE THESIS 48 3 CLINicaL AND LABORATORY FINDINGS IN 220 CHILDREN WITH 50 RECURRENT ABDOMINAL paiN 4 RECURRENT ABDOMINAL paiN IN 200 CHILDREN: SOMATIC 62 caUSES AND DIAGNOSTIC CRITERIA 5 RAP AND ROME: vaLidaTION OF THE ROME III CRITERIA FOR 76 RECURRENT ABDOMINAL paiN 6 PROTOZOA AS caUSES OF RECURRENT ABDOMINAL paiN IN 88 CHILDREN 7 LacTOSE AND FRUCTOSE MALABSORPTION IN CHILDREN WITH 96 RECURRENT ABDOMINAL paiN: RESULTS OF Double-blINDED TESTING 8 OccULT CONSTipaTION: FAEcaL RETENTION AS A caUSE OF 106 RECURRENT ABDOMINAL paiN IN CHILDREN 9 SUMMARY AND DISCUSSION 116 10 SAMENvaTTING EN DISCUSSIE 126 11 DANKWOORD 138 12 CURRICULUM VITAE 142 Introduction 1 INTRODUCTION Recurrent abdominal pain Recurrent abdominal pain (RAP) was first defined in 1958 by Apley as “at least 3 bouts of pain, severe enough to affect activities, over a period of at least 3 months”(1) . This was a landmark publication with great impact, showing, that emotional disturbances played a role in many patients. Since then, several studies showed, that anxiety, depression or behavioural problems are present in patients with abdominal pain, in patients with organic causes of pain as well as in patients with supposed functional pain, as is described by Di Lorenzo et al. on behalf of NASPGHAN in an evidence based report on chronic abdominal pain in children (2). In other words, it can be suggested, that the psychological symptoms could be the result of the pain in stead of the cause. However, in many papers RAP is considered identical to functional abdominal pain, but it is clearly not; in fact RAP is a symptom, not a diagnosis and we should carefully analyse the patients before conclusions are drawn regarding aetiology. In a follow up study, Apley et al. stated, that only “with extremely rare exceptions organic disease can be satisfactorily ruled out from a carefully taken history, …” and that “Two facets of diagnosis are necessary and complementary: reasonable evidence against organic disease, together with evidence in favour of an emotional disturbance. It is prudent not to rely on either one alone, but on both” (3). This in fact is confirmed in more recent studies: based on data obtained from history and physical examination differentiation between organic and functional causes of pain is not possible, as is concluded by Di Lorenzo et al. in their authoritative, evidence based report (2). Therefore, it is reasonable to state, that the diagnosis “functional abdominal pain” can only be made with certainty when organic disease has been ruled out. Functional Gastrointestinal Pain Syndromes Around 1980 attempts have been made to find criteria for recognizing irritable bowel syndrome (IBS) in adult patients with abdominal pain without the need of exhaustive investigations, resulting in the Manning criteria and afterwards the criteria of Kruis (4;5). Validation of these criteria has been performed in several studies (6-8). Talley et al, using all 6 Manning criteria, found the Manning criteria to discriminate IBS from organic gastrointestinal disease with a sensitivity of 58% and a specificity of 74%(6) . Jeong et al. found the Manning criteria to discriminate from organic disease with a sensitivity of 67% and a specificity of 66%, using 3 or more criteria (7). Frigerio et al. validating the Kruis criteria found a sensitivity of 47 and 60% for men and women respectively and a specificity of 94 and 95%, but several important diagnoses were not identified and they considered the results as insufficient(8) . Around 1990 the Rome criteria for functional gastrointestinal disorders (FGIDs) have been published, that classified – amongst other – the functional gastrointestinal pain syndromes, followed by revisions (Rome II and Rome III criteria) in 1999 and 2006 (9-14). The diagnoses IBS, functional dyspepsia (FD), functional abdominal pain (FAP) and – newly introduced for Rome III criteria – functional abdominal pain syndrome (FAPS) can be made when patients present with the symptom clusters of the specific pain syndrome in the absence of alarm symptoms. Validation has been performed in several studies. Whitehead et al. found a percentage of 84% of patients who presented with IBS symptoms to have alarm symptoms and concluded, that incorporating these “red flags” into the Rome 9 1 Introduction criteria would not improve sensitivity and would result in too many missed IBS diagnoses. Using Rome II criteria with exclusion of the patients with red flags, they still found a low agreement with clinical diagnoses (sensitivity 54-60%, specificity 67-72%, positive prospective value 55-38% for primary care and gastrointestinal clinic patients respectively) (15). Ford et al. and Jellema et al. published a systematic review on the diagnostic performance of the symptom-based IBS criteria in diagnosing IBS (16;17). They found only one study on Rome I criteria; of several studies on Rome II criteria all but the study of Whitehead et al. had considerable methodological shortcomings (15;18). Spiller et al. and Camilleri published a “Pro Argument” and “Con Argument” respectively, with respect to the question if the symptom based IBS criteria lead to better diagnosis and treatment outcomes (19;20). Camilleri, referring to an article of Quigley with arguments against the use of the Rome criteria (21), concludes that the Rome criteria fall short on all expectations. Spiller et al. mention the improvement of the reproducibility of clinical trials in IBS by using the standardized entry criteria of IBS, but describe as the limitations of the criteria the unreliability of symptom-based criteria and absence of data on underlying psychological mechanisms; moreover, insufficient validation has been performed of Rome II and III criteria (19). For children, alarm symptoms have been published in several versions since 1984 – especially by the group of Rappaport – as a means to recognize organic disease in children with RAP (22;23). Boyle proposed differentiation of abdominal pain in 3 groups: 1. RAP presenting as paroxysmal periumbilical abdominal pain; 2. RAP associated with symptoms of dyspepsia; 3. RAP associated with altered bowel pattern (23). He stated that it is not sure whether these different presentations are the result of different disorders or variable expressions of the same disorder. Hyams et al. looked for IBS using adapted Rome-criteria in adolescents and found ‘abdominal pain in the last year’ to be present in 75% of students, of whom 17% of high school and 8% of middle school students had symptoms of IBS (24). Walker et al included children with RAP and a control group and performed a follow up after 5 years; the patients with RAP significantly more often (18%) fulfilled at least 3 Manning criteria of IBS than the control group (0%) (25). Shortly afterwards, with the publication of the Rome II criteria for adults in 1999, Rome criteria were formulated for the first time for children as well (26), followed by the Rome III criteria in 2006 (27). The process of defining the Rome criteria consisted of arriving at consensus, based on clinical experience. As in adults, a Rome diagnosis of one of the functional gastrointestinal pain syndromes can be made, when patients present with the symptom clusters of IBS, FD, FAP or FAPS in the absence of alarm symptoms. However, neither the alarm symptoms nor the Rome criteria for children have been validated. EPIDEMIOLOGY Recurrent abdominal pain was found by Apley in 1958 in 11% of 1000 schoolchildren between the ages of 3 and 15 years (girls 12%, boys 10%). Boys had a steady incidence of 10-12% from 5 to 10 years with a fall thereafter and a small peak at 14 years. In girls there was a similar incidence up to the age of 8 years; thereafter there was a marked rise to more than 25% of all 9 year old girls, followed by a steady decrease (1). Hyams et al (24) performed a study in 1996 in which 507 middle school and high school students (mean age 13 and 16 year respectively) participated using the Bowel Disease Questionnaire (28): abdominal pain was noted by 75% of all students, occurring at least weekly in 13 and 17% respectively and severe enough to affect activities in 21%.
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