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Recurrent Abdominal Pain in Children: A Review

Introduction

The symptom of abdominal pain in childhood is very common. More than one-third of elementary and middle school children complain of weekly abdominal pain. Children with recurrent abdominal pain (RAP) and their families often suffer with this frustrating situation. However, the majority of children with RAP (almost 90%) do not have a serious disease.1Campo JV. Functional Recurrent Abdominal Pain in Children and Adolescents.International Foundation for Functional Gastrointestinal Disorders (IFFGD).  

Recurrent abdominal pain was first described in 1958,2Plunkett A, Beattie RM. J R Soc Med 2005; 98:101-6.   and is considered as a symptom and not a diagnosis. The seminal work of Apley and Naish, who studied 1000 school children in Bristol, England, used a pragmatic definition of recurrent abdominal pain as, '3 episodes over 3 months, severe enough to affect daily activity'.3Bremner AR, Sandhu BK. Indian Pediatr 2009;46: 375-9.  

Prevalence

In Apley's original study, the prevalence of recurrent abdominal pain in a population of school children was 10%. In subsequent studies using his criteria the prevalence ranged from 11- 45%. The width of this range has been suggested due to differences in age, geographical area and social factors and methodology. In the majority of studies, girls are more affected than boys. In the present day Western setting, irritable bowel syndrome (IBS) is the commonest cause of functional RAP in children, accounting for 52% of cases.3Bremner AR, Sandhu BK. Indian Pediatr 2009;46: 375-9.  

Children with functional abdominal pain as well as their parents have obviously diminished quality of life. School-aged children with abdominal pain miss their school days by the average of 2.3 days and 10% of the parents miss their day works.4Pourmoghaddas Z, Saneian H, Roohafza H, Gholamrezaei A. BioMed Research International. 2014, pp:1-6.  

Presentation

Clinically, these episodes are characterised by vague abdominal pain that may be dull or crampy, lasts for less than 1 hour and is poorly localised or periumbilical. It is associated with autonomic and functional symptoms like nausea, vomiting, pallor and other painful conditions like headache and limb pains. It had been noted that children with RAP are more likely, as compared to children without RAP, to have headache, joint pain, anorexia, vomiting, nausea, excessive gas and altered bowel habits.5Banez GA. Recurrent abdominal pain in children and adolescents: classification, epidemiology, and etiology/conceptual models from UNC.  6Devanarayana NM, Rajindrajith S, De Silva HJ. Indian Pediatrics 2009; 46: 389-9.  

Aetiology & Pathophysiology

The origin of abdominal pain is complex. Most cases of chronic abdominal pain in children are functional in nature. However, advances in medical diagnostics, have led to an increase in the identification of organic causes.

  1. RAP with no clear organic cause
  2. Psychological distress accompanies recurrent abdominal pain and stressful life events have been associated with an increased incidence of the condition. Paediatric patients with recurrent abdominal pain are mostly found to suffer with anxiety and depressive disorders. It has been postulated that psychological stress leads to changes in the 'brain-gut axis', altering the perception of visceral sensation. This may lead to a phenomenon known as 'visceral hyperalgesia'.2Plunkett A, Beattie RM. J R Soc Med 2005; 98:101-6.  

  3. Organic diseases causing RAP
  4. Numerous organic disorders lead to abdominal pain. In most of the cases, the pathophysiology is related to infection (e.g. urinary tract infection), inflammation (e.g. Crohn's disease) or distension or obstruction of a hollow viscus (e.g. obstructive uropathy) (see Table I).2Plunkett A, Beattie RM. J R Soc Med 2005; 98:101-6.   6Devanarayana NM, Rajindrajith S, De Silva HJ. Indian Pediatrics 2009; 46: 389-9.   7Available at: http://contemporarypediatrics.modernmedicine.com/contemporary-pediatrics/news/modernmedicine/modern-medicine-news/ managing-chronic-abdominal-pain-chi?page=full   A study in Bristol found an organic cause, in as many as 30% of children presenting with recurrent abdominal pain.2Plunkett A, Beattie RM. J R Soc Med 2005; 98:101-6.  8El-Matary W, Spray C, Sandhu B. Eur J Pediatr 2004;163:584-8  

    Several etiological studies in India have recognised intestinal parasitic infections, including giardiasis, as the leading cause for RAP. It is also important to realize that the organic and non-organic causes for RAP can co-exist in some patients.

  5. Functional gastrointestinal disorders causing RAP

Chronic abdominal pain or RAP in most children, is functional, that is, without demonstrable evidence of a pathologic condition, such as an anatomic, metabolic, infectious, inflammatory or neoplastic disorder. According to Rome II criteria, abdominal pain related conditions in children were classified into five categories; (see Box 1). To overcome drawbacks in Rome II criteria, the revised and modified Rome III criteria were developed in 2006. Table 2 summarizes the Rome III criteria for paediatric functional gastrointestinal 6 disorders (FGID) leading to abdominal pain.

The pathophysiology of functional abdominal pain (FAP) is thought to involve abnormalities in the enteric nervous system, a rich and complex nervous system that envelops the entire gastrointestinal tract. The enteric nervous system is also known as the "gut brain" or the "little brain in the gut". The enteric nervous system interacts with the central nervous system, allowing bidirectional communication. A dysregulation of this brain-gut communication plays an important role in the pathogenesis of functional abdominal pain.6Devanarayana NM, Rajindrajith S, De Silva HJ. Indian Pediatrics 2009; 46: 389-9.  

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Most of the research on childhood visceral pain in the 1980s and early 1990s focused on the role of motility disorders and psychiatric abnormalities. Recently, however, more sophisticated diagnostic techniques have failed to identify motor abnormalities severe enough to account for these patient's symptoms. It is now believed that children with functional bowel disorders, rather than having a baseline motility disturbance, may have an abnormal bowel reactivity to physiologic stimuli (meal, gut distension, hormonal changes), noxious stressful stimuli (inflammatory processes) or psychologic stressful stimuli (parental separation, anxiety).9Chronic Abdominal Pain in Children: A Clinical Report. JPGN 40:245-8, 2005  

Assessment of Recurrent Abdominal Pain

The evaluation of the child with abdominal pain is directed primarily to determine the likelihood of serious pathology and to direct investigations appropriately. The 'red flag' signs have long been used by clinicians to identify children who need further investigations (Table 3).

History, clinical examination and the presence of red flags or alarm symptoms help discriminate between organic and non-organic causes of the pain and provide indications for further testing. Only basic urine, stool and blood examinations are recommended to exclude organic causes in the diagnosis of RAP (Table 4).

The American Academy of Pediatrics technical report concluded that there is insufficient evidence to evaluate the predictive value of blood investigations for organic pathology, even in the presence of alarm signals.6Devanarayana NM, Rajindrajith S, De Silva HJ. Indian Pediatrics 2009; 46: 389-9.  

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Management

The clinician’s first task is to rule out the wide range of organic disorders that may present with recurrent abdominal pain. The recommendation for treating children with non-organic RAP includes support and empathy for the family. Thus, the mainstay of treatment is reassurance, that no serious disease is present, with an emphasis on rehabilitation. The guidelines outlined by Rappaport and Leichtner in 1993 are still valid in the management of these children (Box 2).6Devanarayana NM, Rajindrajith S, De Silva HJ. Indian Pediatrics 2009; 46: 389-9.  

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If a specific cause for abdominal pain is discovered during the evaluation, the physician should discuss specific management of conditions.

Therapeutic Options

Dietary management

  1. Dietary restrictions
  2. Food allergy and intolerance is common in small children. Careful history-taking usually identify those with food allergies or intolerances. Lactose intolerance has long been implicated as a possible factor in IBS, especially for patients with predominant symptoms of diarrhoea. Brush border lactase activity peaks at around 3 years of age then gradually decreases with age. A diagnosis of lactase deficiency is unlikely in younger children, but can be considered for older children and adolescents.

    Malabsorption of other carbohydrates, such as fructose, has also been implicated in the pathogenesis of chronic abdominal pain. Persistence of fructose in the GI tract, especially in the form of high-fructose corn syrup, is postulated to cause an osmotic diarrhoea, as well as serve as a substrate for fermentation by colonic bacteria, resulting in the production of gas. Restricting such diet helps in the symptomatic management of stomach pain in children.10Chiou E, Nurko S. Expert Rev Gastroenterol Hepatol. 2010 June ; 4(3): 293-304.  

  3. Use of dietary fiber
  4. Many physicians routinely recommend the use of bulking agents or dietary fiber to produce more regular bowel movements and to decrease abdominal pain associated with FAP or IBS. The benefit of dietary fiber in the treatment of RAP and IBS in children is unclear and should be weighed against the low but potential risk of increased pain and bloating, which has been reported in some adult studies of IBS patients given bran fiber. On the other hand, an empiric trial of psyllium husk fiber may be considered, especially if there are associated symptoms of constipation.10Chiou E, Nurko S. Expert Rev Gastroenterol Hepatol. 2010 June ; 4(3): 293-304.  

  5. Probiotics

Commensal bacteria of the GI tract are believed to play an important role in homeostasis. Alterations to such children with RAP have been implicated in dysmotility, visceral hypersensitivity, abnormal colonic fermentation and immunologic activation. Probiotics commonly contain Lactobacillus, bifidobacteria or other living microorganisms thought to be healthy for the host organism when ingested in sufficiently large amounts.

Overall, there is no conclusive evidence that dietary carbohydrate restriction, fiber supplementation or probiotic supplementation is effective in the management of FAP and IBS. Further studies are needed to evaluate the role of dietary interventions; until then, these options may be considered on a case-by-case basis after careful discussion with the patient and family.10Chiou E, Nurko S. Expert Rev Gastroenterol Hepatol. 2010 June ; 4(3): 293-304.  

Cognitive-behavioral therapy & other psychosocial interventions

Acceptance of the biopsychosocial model of FGIDs has provided the basis for the use of psychosocial interventions, including parental education, family therapy, cognitive-behavioral techniques, relaxation, distraction, hypnotherapy, guided imagery and biofeedback. Many of these strategies aim not only to have direct effects on somatic symptoms, but also promote the child's ability to self-manage symptoms. The American Academy of Pediatrics subcommittee on chronic abdominal pain suggested that Cognitive-behavioral therapy (CBT) may be useful in 11 "improving pain and disability outcome in the short term". In retrospective studies of children with RAP, FAP and IBS, psychosomatic approaches to management resulted in decreased abdominal pain in 70-89% of children.10Chiou E, Nurko S. Expert Rev Gastroenterol Hepatol. 2010 June ; 4(3): 293-304.  

Pharmacological therapy

Various drug treatment approaches for the different types of abdominal pain-related FGIDs exist, based on emerging understanding of the interactions between the CNS, enteric nervous system and GI tract, also known as the 'brain–gut axis'. A significant degree of abdominal pain in functional disorders is believed to be associated with abnormal perception of visceral sensations or alterations in motility. Targets for modulation have included smooth muscle cells of the GI tract, peripheral neurotransmitter receptors for various stimuli, interneurons of the spinal cord that transmit information bidirectionally and cortical areas responsible for the perception of pain. Medications initially indicated for the treatment of depression, anxiety and seizures have also been adopted for the management of FGIDs because of their effects on both the CNS and peripheral nervous system.10Chiou E, Nurko S. Expert Rev Gastroenterol Hepatol. 2010 June ; 4(3): 293-304.  

These drug treatments include: prokinetics and antisecretory agents for functional dyspepsia; pizotifen, propranolol, cyproheptadine or sumatriptan for abdominal migraine; and antispasmodic and antidiarrhoeal regimen for irritable bowel syndrome. Antidepressants have been shown to be effective in some studies of adults with functional gastrointestinal disorders. As a result young patients with similar complaints are sometimes treated with antidepressants.12Kaminski A, Kamper A, Thaler K, et al. Cochrane Database of Systematic Reviews 2011, Issue 7.  

Antidepressants

Antidepressants are among the most studied pharmacologic agents for FGIDs. They are suggested to act by the reduction of pain perception, improvement of mood and sleep patterns, as well as modulation of the GI tract, often through anticholinergic effects.

A review of adult studies found that antidepressants, such as tricyclic antidepressants (TCAs) and selective serotonin-reuptake inhibitors (SSRIs), were beneficial for the treatment of FGIDs. Tricyclic antidepressants primarily act through noradrenergic and serotonergic pathways but also have antimuscarinic and antihistaminic properties. Although their anticholinergic effects on the GI tract in terms of slowing transit can be beneficial for patients with IBS characterised by diarrhoea, but may worsen constipation. Additional side effects include the potential for inducing cardiac arrhythmias, so evaluation for prolonged QT syndrome with a baseline ECG is recommended by the American Heart Association.

Selective serotonin-reuptake inhibitors act by blocking uptake of 5-hydroxytryptamine, increasing its concentration at presynaptic nerve endings. In addition to its CNS effects on mood and anxiety, SSRIs may also be beneficial for gastrointestinal complaints, since serotonin is an important neurotransmitter in the GI tract and greater than 80% of the body's stores are located in enterochromaffin cells of the gut. The exact role of serotonin in the GI tract has not been fully elucidated, but it has been implicated in the modulation of colonic motility and visceral pain in the gut.10Chiou E, Nurko S. Expert Rev Gastroenterol Hepatol. 2010 June ; 4(3): 293-304.  

Antispasmodics

It is presumed that in FGIDs a dysregulation within enteric and the central nervous systems results in alternations in sensation and motility and probably causes intolerance to gastric distension. Along with this presumption, antispasmodics which modulate the smooth-muscle contraction have been investigated as treatments for FGIDs. Antimuscarinic/anticholinergic drugs, smooth-muscle relaxants, and selective calcium channel blockers are subtypes of antispasmodic agents.4Pourmoghaddas Z, Saneian H, Roohafza H, Gholamrezaei A. BioMed Research International. 2014, pp:1-6.   Antispasmodic medications may be helpful for FAP and IBS through their effects on decreasing smooth muscle spasms in the GI tract that may produce symptoms such as pain.

However, conventional use of anti-cholinergic analgesics is discouraged in patients with abdominal pain for fear of interfering with accurate evaluation and diagnosis as they often mask the physical symptoms of 'acute abdomen' making it difficult to achieve a rapid diagnosis and accurate management in emergency situations.13Leung AKC. Am Fam Physician 2003;67:2321-6.   Also, sedation, constipation, dryness of mouth and other bothersome side-effect caused by anticholinergic anti-spasmodic agents may interfere with diagnostic evaluation and can be a hindrance for their long-term use.14Jones JD, Ramakrishnan K. The Internet Journal of Emergency Medicine 2005;2(2).  

Drotaverine: Safe antispasmodic for abdominal pain relief

Drotaverine is highly potent and safe spasmolytic agent, suited for oral administration and is capable of relieving or preventing smooth muscle spasm of various organs. It does not interfere with the diagnosis of abdominal pain and is free of side effects, so can be used in children for the management of acute and recurrent abdominal pain, particularly long-term.15Blasko G. JAMA India; 4(12).  

Drotaverine is a benzyl isoquinoline derivative and is an analogue of papaverine. Being a selective inhibitor of phosphodiesterase isoenzyme IV, it possess a powerful spasmolytic action on smooth muscle cells and has been found useful in spastic and motility disorders of the smooth muscle. This inhibition of enzyme increases the intracellular level of cyclic adenosine monophosphate, which further causes relaxation of smooth muscle that suppress the pain associated with spasm caused by smooth muscle contraction. This drug helps in prolonging the pain-relief and does not mask the symptoms of "acute abdomen";a feature making it unique in the group, and may have relevant application in practice.

It is quickly absorbed orally (nearly 100%) and has a short onset of action (5-12min). It is free of the side-effects associated with anticholinergic anti-spasmodics such as dicyclomine etc, and doesn't affect gut motility, thus can be given safely for long-term. Moreover, it does not have any morphine or dextropropoxyphene like effect, and thus, does not result in addiction. Drotaverine could be given in cases without finalized diagnosis. Several benefits of drotaverine have been mentioned in Table 5. A survey (reported in 2010) of all paediatric uses of medicinal products in Europe showed that drotaverine is used commonly in pre-school and school children.16Available at: http://www.ema.europa.eu/docs/en_GB/document_ library/Report/2011/01/WC500101006.pdf   In children, dosage of oral drotaverine is dependent on their age group; such as: for 1-6 years: 40-120 mg of drotaverine should be given in 2-3 divided doses or ½ tab (40 mg) tid; and for 6-12 years: 80-200 mg in 2-3 divided doses (max. upto 5 times) or 1 tab (40 mg)tid.

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Conclusion

Children and adolescents with chronic or recurrent abdominal pain pose unique challenges to their families and paediatric healthcare professionals. Because RAP is a real problem that can seriously interfere with a child's life, it is important to find effective treatments. Restricted diet, psychotherapy and medications-the combined approach may help in fastest recovery. Medications such as antispasmodics, acid reducers and antidepressants are commonly prescribed for children with RAP. The choice should be followed up until the symptom resolves.

References

  1. Campo JV. Functional Recurrent Abdominal Pain in Children and Adolescents.International Foundation for Functional Gastrointestinal Disorders (IFFGD).
  2. Plunkett A, Beattie RM. J R Soc Med 2005; 98:101-6.
  3. Bremner AR, Sandhu BK. Indian Pediatr 2009;46: 375-9.
  4. Pourmoghaddas Z, Saneian H, Roohafza H, Gholamrezaei A. BioMed Research International. 2014, pp:1-6.
  5. Banez GA. Recurrent abdominal pain in children and adolescents: classification, epidemiology, and etiology/conceptual models from UNC.
  6. Devanarayana NM, Rajindrajith S, De Silva HJ. Indian Pediatrics 2009; 46: 389-9.
  7. Available at: http://contemporarypediatrics.modernmedicine.com/contemporary-pediatrics/news/modernmedicine/modern-medicine-news/ managing-chronic-abdominal-pain-chi?page=full
  8. El-Matary W, Spray C, Sandhu B. Eur J Pediatr 2004;163:584-8
  9. Chronic Abdominal Pain in Children: A Clinical Report. JPGN 40:245-8, 2005
  10. Chiou E, Nurko S. Expert Rev Gastroenterol Hepatol. 2010 June ; 4(3): 293-304.
  11. Chronic abdominal pain in children. Pediatrics 2005;115(3):812-5.
  12. Kaminski A, Kamper A, Thaler K, et al. Cochrane Database of Systematic Reviews 2011, Issue 7.
  13. Leung AKC. Am Fam Physician 2003;67:2321-6.
  14. Jones JD, Ramakrishnan K. The Internet Journal of Emergency Medicine 2005;2(2).
  15. Blasko G. JAMA India; 4(12).
  16. Available at: http://www.ema.europa.eu/docs/en_GB/document_ library/Report/2011/01/WC500101006.pdf
Dr. Pravin Rathi

M.D, D.N.B, D.M. (Gastroenterology)
Consultant Gastroenterologist: Bombay Hospital & Institute of Medical Sciences, Mumbai.
Prof and Head Department of Gastroenterology,
T. N. Medical College & B. Y. L. Nair. Ch. Hospital,
A. Nair Road, Mumbai.

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