Occult constipation: faecal retention as a cause of recurrent abdominal pain in children

Eur J Pediatr (2014) 173:781 785 DOI 10.1007/s00431-013-2257-3 ORIGINAL ARTICLE Occult constipation: faecal retention as a cause of recurrent abdominal pain in children Carolien F. M. Gijsbers & C. M. Frank Kneepkens & Yvonne Vergouwe & Hans A. Büller Received: 18 September 2013 /Accepted: 17 December 2013 /Published online: 3 January 2014 # Springer-Verlag Berlin Heidelberg 2014 Abstract Recurrent abdominal pain (RAP) in children is generally believed to be functional. In practice, many children with RAP become pain-free with laxative therapy. The aims of the study were to establish the role of (occult) constipation in RAP and to investigate whether patients diagnosed with (occult) constipation could be identified by history and physical examination. During 2 years, all patients (age 4 16 years, secondary referral) fulfilling Apley criteria of RAP were included. After exclusion of gastrointestinal infections and food intolerance, laxatives were advised when pain persisted. (Occult) constipation was defined as abdominal pain disappearing with laxative treatment and not reappearing within a 6 month follow up period ; occult constipation was diagnosed in patients who did not fulfil the Rome criteria of constipation. Two hundred children (87 M; median age 8.8 years) were evaluated. (Occult) constipation was found in 92 patients (46 %). Of these, 18 had considerable relief of pain when treated for a somatic cause but experienced complete relief only after laxative measures; they were considered to have two diagnoses. Using multivariate C. F. M. Gijsbers (*) Department of Pediatric Gastroenterology, Juliana Children s Hospital/Haga Teaching Hospital, Sportlaan 600, 2566 MJ The Hague, The Netherlands e-mail: cfm.gijsbers@planet.nl C. F. M. Gijsbers e-mail: c.gijsbers@hagaziekenhuis.nl C. M. F. Kneepkens Department of Pediatric Gastroenterology, VU University Medical Centre, De Boelelaan 1117, 1081 HVAmsterdam, The Netherlands Y. Vergouwe Department of Public Health, Erasmus Medical Centre, Dr Molewaterplein 60, 3015 GJ Rotterdam, The Netherlands H. A. Büller Department of Pediatric Gastroenterology, Sophia Children s Hospital/Erasmus Medical Centre, Dr Molewaterplein 60, 3015 GJ Rotterdam, The Netherlands analysis, a simple model was developed with cystitis in past history, early satiety and flatulence as predictors for (occult) constipation. The risk of (occult) constipation ranged from 18/ 58 if no predictor was present to 4/4 if all three were present. Conclusion: Laxatives played a pivotal role in the recovery of patients with RAP. We developed a simple model to identify patients at risk of having (occult) constipation. Keywords Chronic abdominal pain. Functional abdominal pain. Constipation. Occult constipation. Children Introduction Recurrent abdominal pain (RAP) as defined by Apley [1] isfoundin10 15 % of 4 16-year-old children, with considerable morbidity. RAP often has a great impact on the life of the child and his family and frequently causes much anxiety [2]. In most patients, RAP is considered a functional problem. Conventional therapy, consisting of reassurance and advice on lifestyle and feeding habits, has only limited success [6]. In the 1990 s, the first Rome criteria for functional gastrointestinal disorders (FGIDs), including functional abdominal pain and functional constipation, were published in order to come to more uniform patient groups as a basis for research, followed by specific criteria for children in the second version of the Rome criteria ( Rome II criteria ). This has resulted in an enormous increase in research, which until now, however, did not lead to satisfactory advice on therapy for patients with functional abdominal pain [3]. The relation between abdominal pain and constipation remains a matter of controversy. While some consider constipation a frequent (and treatable) cause of abdominal pain, others feel that the diagnosis of constipation should be confined to children who fulfil the Rome criteria. Studies with respect to constipation and laxative therapy in relation to

782 Eur J Pediatr (2014) 173:781 785 abdominal pain are remarkably scarce [2,4,10,15]. We found that even patients with abdominal pain without diagnostic clues for functional constipation according to the Rome criteria could become pain-free with laxative therapy. For this condition we reintroduced the term occult constipation [8]. As this was in line with an early report showing that many children with RAP become pain-free with laxatives [10], we evaluated the effect of laxatives in children with RAP who participated in a comprehensive study on the somatic causes of RAP [7,8]. The first aim of this study was to establish the role of (occult) constipation in RAP. The second aim was to investigate whether patients diagnosed with (occult) constipation could be identified based on history and physical examination. Materials and methods From May 2002 until May 2004, all consecutive patients (ages 4.0 16.0 years) referred by general practitioners to a secondary paediatric centre (CFMG) with RAP (which was defined by the Apley criteria: abdominal pain for at least 3 months; at least three bouts of pain, severe enough to interfere with daily activities) as the main presenting symptom, were included in the study. Somatic causes were excluded by evaluation in a standardized way as described previously (Table 1), resulting in the establishment of preliminary diagnoses and diagnostic clues, such as protozoan infection, celiac disease and lactose intolerance [8,9]. A causal relation of these with the abdominal pain was assumed when the patient fulfilled the criteria described in Table 2 [8]. In order to avoid bias in case of more than one diagnostic clue, interventions were performed in a fixed order, without clinical interpretation or weighing of history or Table 1 Diagnostic work-up Standardized history Physical examination Ancillary tests Blood: Blood cell count, liver enzymes, creatinine, amylase, albumin, calcium, phosphate, RAST for a panel of food allergens, anti-tissue transglutaminase antibodies (IgA) and total IgA, Yersinia serology (immunoblot) Urine: Screening, culture Faeces: Culture, Helicobacter pylori antigen, Triple Faeces Test (for protozoa) Hydrogen breath tests Lactose and fructose breath tests Radiology: Plain abdominal X-ray, abdominal ultrasound physical findings. As the first step, gastrointestinal infections and food allergy/intolerance, respectively, were treated if present. In case of persistent symptoms following these interventions, somatic causes were assumed to be sufficiently excluded (for the time being). As the second step, a trial with laxatives was performed, combined with advice on diet and toilet training, irrespective of history, physical examination or the outcome of plain abdominal X-ray [8]. Oral macrogol 4000 (polyethylene glycol 4000) was prescribed in a daily dose of 1 g/kg (maximum 40 g), the parents being advised to adjust the dose according to the resulting defaecation pattern. Some patients used other laxatives, especially lactulose or lactitol, as to their preference, with the same instructions. Frequent telephone contacts were used to support the parents with respect to laxative dosage. In case of insufficient result of oral laxatives, lavage of the colon was performed with polyethylene glycol electrolyte solution. (Occult) constipation was considered to be the cause of RAP when the pain disappeared with laxative treatment for a period of at least 6 months (Table 2). Constipation was diagnosed in those children who fulfilled the Rome II criteria for functional constipation (Table 3) [12]. Occult constipation was diagnosed in children who did not fulfil the Rome II criteria for functional constipation but had relieve of their symptoms with laxative treatment [8]. Rome II criteria for functional constipation were used because Rome III criteria were not yet published at the time of inclusion of patients. Table 2 Criteria for diagnoses General Based on intervention and follow-up, a causal relation of a specific disease or condition with abdominal pain is supposed if the following criteria are fulfilled: 1. Elimination of the cause of the pain (by therapeutic intervention) should lead to disappearance of the pain 2. The pain should disappear at an adequate moment after intervention (different per diagnosis) for optimal prevention of mistaking spontaneous recovery for the supposed diagnosis 3. The diagnosis should hold during a follow-up of at least 6 months (RAP does not reappear within a 6-month follow-up period or RAP reappears within 6 months, apparently due to the same cause and eliminated in the same way) for optimal exclusion of placebo effect Constipation and occult constipation Abdominal pain disappears with (laxative measures leading to) production of more faeces than before, regardless the kind of the measures. Treatment may need to be continued throughout the follow-up period. Pain may return upon reduction or discontinuation of treatment but disappears again with laxative treatment Constipation: those children who fulfil the Rome II criteria for functional constipation Occult constipation: those children who do not fulfil the Rome II criteria for functional constipation but show relieve of symptoms with laxative treatment

Eur J Pediatr (2014) 173:781 785 783 Table 3 Rome II criteria: functional constipation Scybalous, pebble-like, hard stools for a majority of stools, or Firm stools 2 per week; and No evidence of structural, endocrine or metabolic disease Statistical analysis Some patient characteristics were relatively rare. We therefore used Fisher s exact test to assess the univariate association for the 18 variables with (occult) constipation [5]. We combined the three variables that showed the strongest association with (occult) constipation in a simple model. Each included variable was assigned an equal weight (a score of 1). The total score was related to the observed proportion of (occult) constipation. Results Two hundred twenty children were enrolled, of whom 20 were lost to follow-up, leaving 200 patients (113 girls, 87 boys; median age 8.8 [range 4.1 16.0], for analysis. Laxative therapy was advised to 111 patients and was successful in 92 patients (83 %; 59 girls, 33 boys), patients being pain-free with therapy. In 14 patients, laxatives were not successful, and in 5 patients, no conclusion was possible because they performed the therapeutic measures insufficiently. Of the 14 patients in whom laxative therapy was not successful, 6 patients had a somatic diagnosis, 3 were considered to have stress-related abdominal pain, 2 recovered spontaneously and 3 had no certain diagnosis or had their pain unresolved. Eighteen of the 92 patients had had previous treatment for a somatic cause, including gastrointestinal infection (15 patients) and food allergy (2 patients), or had discontinued medication (1 patient; amitriptyline), which had led to persistent considerable relief of symptoms; but as they only had complete relief of pain after additional treatment with laxatives, they were considered to have two diagnoses. All 92 patients were pain-free with laxative treatment for at least 6 months and therefore, according to our definition, were considered to have constipation or occult constipation as the cause of the abdominal pain. Most children needed 20 30 g of macrogol per day, but there was considerable variation in the time (up to 4 weeks) and laxative dose (up to 70 g per day) needed to obtain success; 8 patients needed colonic lavage to obtain sufficient result. The median follow-up period of the patients with (occult) constipation was 11 (range 6 48) months. Of the 92 children who were successfully treated with laxatives, as proven by a 6-month pain-free follow-up, 24 fulfilled Rome II criteria for functional constipation and therefore were considered to have functional constipation. The other 68 children, who were pain-free with laxatives but did not fulfil the Rome II criteria for functional constipation, by definition were considered to have occult constipation. Of the 46 patients who fulfilled the Rome II criteria for functional constipation, 9 had a somatic diagnosis for the abdominal pain; they became pain-free with intervention for a somatic disorder without laxative treatment. Table 4 shows the univariate association of the patient characteristics with (occult) constipation. Cystitis (past history), early satiety, flatulence, change in consistency at the onset of pain, the sensation of incomplete evacuation and the sensation of abdominal fullness were more common in patients with (occult) constipation than in patients without constipation. The three manifestations with the strongest association, i.e. cystitis (past history), early satiety and flatulence, were combined in a model, resulting in a scoring system. Table 5 shows the link between the scores and (occult) constipation. Higher scores were related to higher risks of (occult) constipation: 18 of 58 patients with a score of 0 had (occult) constipation compared to 4 of the 4 patients with a score of 3. Discussion The present study is part of a comprehensive research program aiming at finding definite diagnoses for RAP in a large group of children. In this study, resolution of abdominal pain was obtained in 198 (99 %) of 200 patients [8]. In 92 of these patients (46 %), a diagnosis of functional or occult constipation was made, according to preset criteria. It should be realised that a diagnosis of functional constipation according to the Rome criteria does not guarantee a causal relation with the abdominal pain: as in other diagnoses that potentially can cause RAP, such as celiac disease or parasites, the causal relation has to be made plausible by therapeutic intervention and a pain-free follow-up period. In this study, we found 9 out of the 46 patients who fulfilled the Rome II criteria of functional constipation to have a somatic cause of their abdominal pain instead of constipation; this is about the same percentage as in the total population (34 patients, 17 %). Faecal retention in (part of) the colon with subsequent bowel distension with or without visceral hypersensitivity could very well explain why laxatives were successful in these RAP patients [9]. Clinical studies investigating occult constipation in relation with abdominal pain are very scarce. Eidlitz-Markus et al. [4] found 29 of 68 patients with RAP to have occult constipation, which was defined as no complaints or symptoms of constipation, but hard stools on rectal examination or distended large intestines at plain abdominal X-ray. Boccia et al. [2] found functional constipation in 67 % of patients with functional dyspepsia (both according to the

784 Eur J Pediatr (2014) 173:781 785 Table 4 Prevalence of symptoms and odds ratio Symptoms (Occult) Other b Odds ratio c constipation a (n=92) (n=108) (Occult) constipation versus other b OR 95 % CI a (Occult) constipation including patients with both somatic disease and (occult) constipation b Other:somaticdisease(34), spontaneous recovery (54), uncertain diagnosis (13), stress (5), unresolved abdominal pain (2) c Fisher s exact test: (occult) constipation, including patients with both somatic cause and (occult) constipation, versus other patients Pain at awakening 37/92 41/107 1.1 0.6 2.0 Pain with/after meals 25/92 28/107 1.1 0.5 2.1 Pain with physical exercise 37/92 39/108 1.2 0.6 2.2 More pain before defaecation 34/91 33/107 1.3 0.7 2.5 Pain relieved by defaecation 43/88 48/106 1.2 0.6 2.1 Frequently small amounts of faeces 9/92 17/108 0.6 0.2 1.5 Varying consistency of stool 29/92 24/108 1.6 0.8 3.2 Change in frequency at the onset of pain 22/87 27/103 1.0 0.5 1.9 Change in consistency at the onset of pain 35/88 28/106 1.8 1.0 3.4 Flatulence 44/92 35/108 1.9 1.0 3.5 Mucus 19/90 18/107 1.3 0.6 2.9 Feeling of incomplete evacuation 64/92 60/107 1.8 1.0 3.4 Anorexia 52/92 60/107 1.0 0.6 1.9 Early satiety 55/88 44/107 2.4 1.3 4.4 Feeling of abdominal fullness 57/88 52/102 1.8 0.9 3.3 Cystitis in past history 15/91 7/108 2.8 1.0 8.6 Abdominal distension 10/92 14/108 0.8 0.3 2.1 Abdominal/rectal faecal mass 65/92 69/108 1.4 0.7 2.6 Rome II criteria), symptoms of both functional constipation and functional dyspepsia diminishing significantly with laxatives in these patients, as did the gastric emptying time. The functional dyspepsia was supposed to be the result of constipation-induced cologastric brake [14]. Keuzenkamp-Jansen et al. [10] retrospectively investigated clinical symptoms and outcome of treatment in 244 children diagnosed with constipation as assessed by plain abdominal X-ray. Of these children, 75 presented with hard and infrequent stools, while 77 had abdominal pain as the presenting symptom. It is noteworthy that, in our study, a considerable discrepancy is found between the clinical diagnosis of (occult) constipation as the cause of RAP, based on successful laxative therapy (92 patients), and functional constipation as defined bytheromeiicriteria(24/92).theromecriteriaare Table 5 Numbers of patients having up to three symptoms to predict (occult) constipation as the cause of abdominal pain Number of symptoms per patient ( three-symptom score ) 0 1 2 3 Total Patients with (occult) constipation (n=92) 18 38 32 4 92 Other (n=108) 40 50 18 0 108 Total 58 88 50 4 200 Symptoms: cystitis (past history), early satiety and flatulence primarily designed as the starting point of research, for which sharp definitions are necessary. In clinical practice, however, accepting broader criteria for starting laxative therapy obviously leads to recovery in a higher percentage of children with abdominal pain. In our study, Rome II criteria for functional constipation were used because Rome III criteria were not yet published at the time of inclusion of the patients. The Rome III criteria for functional constipation (for children with a developmental age of at least 4 years) combine the criteria of functional constipation and functional faecal retention of Rome II with some adjustments. Although this may change the numbers of patients to be categorised with functional constipation,this has no implications for the total number of patients diagnosed with (occult) constipation in this study, because the diagnosis was based exclusively on the results of laxative therapy. Obviously, independent whether they fitted into the Rome definition of functional constipation or were diagnosed with occult constipation, the children are suffering from a functional gastrointestinal disorder. While patients with functional constipation can be identified by symptoms according to the Rome criteria, no signs and symptoms are recognised so far that point to occult constipation. We sought to identify combinations of symptoms and signs that could lead to a diagnosis of occult and functional constipation as the cause of abdominal pain. Eighteen gastrointestinal or related variables, other than those of the Rome II

Eur J Pediatr (2014) 173:781 785 785 and III criteria of functional constipation, were analysed as to their relation with (occult) constipation. Univariate analysis showed that several of these signs and symptoms were more frequent in patients with (occult) constipation than in other patients (Table 4). Combining the three most related symptoms in a model indicated the patients with lower and higher risks of having (occult) constipation (Table 5). We suggest that at least patients with two or three of these signs and symptoms should be given laxative therapy as a therapeutic trial with regard to (occult) constipation as the cause of abdominal pain. However, the numbers are small, and a certain number of patients having none of these characteristics were found to have (occult) constipation as well. Separate analysis comparing the symptoms of patients with functional and occult constipation did not reveal any significant differences. We would like to conclude, therefore, that constipation can be diagnosed in patients lacking Rome symptoms for functional constipation; they may be considered to have occult constipation. This is the first exploratory study on risk factors for (occult) constipation. These results may serve as input for further research. The strength of this study is the systematic way in which all children referred to secondary care with RAP after having excluded gastrointestinal infections and food allergy or intolerance were treated with laxatives in order to obtain a diagnosis of (occult) constipation according to preset criteria. An important limitation is the fact that our study is an observational study, without a control group. RAP patients may have been recovered spontaneously or due to a placebo effect. In a meta-analysis, Krogsbøll et al. found average relative contributions of spontaneous improvement and of placebo to the effect of active treatment of 24 and 20 %, respectively [11]. Spiller reported placebo effects to last for approximately 12 weeks before they start to recede; by about 6 months, placebo effect is suggested to have disappeared [13]. We tried to prevent mistaking of spontaneous recovery for the supposed diagnosis by requiring disappearance of RAP in relation with the intervention, and we diminished the placebo effect as much as possible by requiring persistence of the therapeutic effect during a follow-up period of at least 6 months. Conclusion In 200 children with RAP, abdominal pain disappeared with laxative therapy and did not recur for at least 6 months in about half of the patients. They were considered to have constipation as the cause of the abdominal pain. Three quarters of these patients did not fulfil the criteria for functional constipation and therefore were considered to have occult constipation. We propose a model to identify patients at presentation to be at higher risk of having (occult) constipation, who might benefit from laxative treatment; however, no strong associations could be found between patient characteristics and (occult) constipation. Conflict of interest Funding References No financial support. No conflict of interest. 1. Apley J, Naish N (1958) Recurrent abdominal pains: a field survey of 1,000 school children. Arch Dis Child 33:165 170 2. Boccia G, Buonavolonta R, Coccorullo P, Manguso F, Fuiano L, Staiano A (2008) Dyspeptic symptoms in children: the result of a constipation-induced cologastric brake? Clin Gastroenterol Hepatol 6:556 560 3. Di Lorenzo C, Colletti RB, Lehmann HP, Boyle JT, Gerson WT, Hyams JS, Squires RH Jr, Walker LS, Kanda PT (2005) Chronic abdominal pain in children: a technical report of the American Academy of Pediatrics and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 40:249 261 4. Eidlitz-Markus T, Mimouni M, Zeharia A, Nussinovitch M, Amir J (2004) Occult constipation: a common cause of recurrent abdominal pain in childhood. Isr Med Assoc J 6:677 680 5. Fisher RA (1922) On the interpretation of chi square from contingency tables, and the calculation of P. J R Stat Soc 85:87 94 6. Gieteling MJ, Bierma-Zeinstra SM, Passchier J, Berger MY (2008) Prognosis of chronic or recurrent abdominal pain in children. J Pediatr Gastroenterol Nutr 47:316 326 7. Gijsbers CFM, Benninga MA, Büller HA (2011) Clinical and laboratory findings in 220 children with recurrent abdominal pain. Acta Paediatr 100:1028 1032 8. Gijsbers CFM, Kneepkens CMF, Schweizer JJ, Benninga MA, Büller HA (2011) Recurrent abdominal pain in 200 children: somatic causes and diagnostic criteria. Acta Paediatr 100:e208 e214 9. Kellow JE, Azpiroz F, Delvaux M, Gebhart GF, Mertz HR, Quigley EM, Smout AJ (2006) Applied principles of neurogastroenterology: physiology/motility sensation. Gastroenterology 130:1412 1420 10. Keuzenkamp-Jansen CW, Fijnvandraat CJ, Kneepkens CM, Douwes AC (1996) Diagnostic dilemmas and results of treatment for chronic constipation. Arch Dis Child 75:36 41 11. Krogsbøll LT, Hróbjartsson A, Gøtzsche PC (2009) Spontaneous improvement in randomised clinical trials: meta-analysis of threearmed trials comparing no treatment, placebo and active intervention. BMC Med Res Methodol 9:1 10 12. Rasquin-Weber A, Hyman PE, Cucchiara S, Fleisher DR, Hyams JS, Milla PJ, Staiano A (1999) Childhood functional gastrointestinal disorders. Gut 45(Suppl 2):II60 II68 13. Spiller RC (1999) Problems and challenges in the design of irritable bowel syndrome clinical trials: experience from published trials. Am J Med 107:91S 97S 14. Tjeerdsma HC, Smout AJ, Akkermans LM (1993) Voluntary suppression of defecation delays gastric emptying. Dig Dis Sci 38:832 836 15. Wilschanski M, Branski D (2004) Recurrent abdominal pain in children: is constipation an issue? Isr Med Assoc J 6:697 698