The Journal of Pediatrics
Volume 156, Issue 1 , Pages 5-7, January 2010

Rectal Perceptual Hypersensitivity: A Biomarker for Pediatric Irritable Bowel Syndrome

  • Paul E. Hyman, MD

      Affiliations

    • Corresponding Author InformationReprint requests: Paul E Hyman, MD, Professor of Pediatrics, Louisiana State University, Chief, Pediatric Gastroenterology, Children's Hospital, 200 Henry Clay Avenue, New Orleans, LA 90118.
    • ,
  • Javier Monagas, MD

Children's Hospital, New Orleans, Louisiana

Article Outline

IBS, Irritable bowel syndrome, RAP, Recurrent abdominal pain

 

See related article, p 60

In this issue of The Journal, Halac et al1 present prospective data showing that children with chronic or recurrent abdominal pain (RAP) who meet symptom-based criteria for irritable bowel syndrome (IBS) or functional abdominal pain develop discomfort at lower rectal distension pressures compared with age-matched children with organic diseases (Table). Perceptual responses were not influenced by psychological symptoms and did not correlate with pain intensity or other gastrointestinal symptoms. Halac et al conclude that results of testing with a barostat, a computer-driven air pump that simultaneously reports volume and pressure within a plastic balloon placed in a hollow organ, such as the rectum, can discriminate between functional and organic abdominal pain. Children later diagnosed with IBS had hypersensitivity, “an exaggerated perception to peripheral events, such as controlled visceral distension, compared with control subjects.”1 Moreover, rectal hypersensitivity, an abnormality in pain physiology that may not be evident in healthy children2, 3 or in children with organic disease,1 is a biomarker for IBS. A biomarker is defined as a characteristic that is objectively measured and evaluated as an indicator of a normal biological process, pathogenic process, or pharmacologic response to a therapeutic intervention.4

Table. Rome III diagnostic criteria for IBS in children and adolescents2
Must include both:
1. Abdominal discomfort or pain associated with 2 or more of the following at least 25% of the time:
a. Improvement with defecation
b. Onset associated with a change in stool frequency
c. Onset associated with a change in stool form (appearance)
2. No evidence of an inflammatory, anatomic, metabolic, or neoplastic process that explains symptoms. Criteria fulfilled at least once per week for at least 2 months._____

Abdominal pain is an everyday office complaint for pediatricians, and for decades (from the 1950s through the 1990s), the term “recurrent abdominal pain” was used to include all children with symptoms who did not have an easily discovered “organic disease.” In the 1990s, some clinicians recognized that more than half of children with chronic abdominal pain had real symptoms but no physical abnormality or test result to explain what was wrong. As each test or procedure returned normal results, some patients, parents, and clinicians became concerned that something was being missed. Children were suffering and needed treatment, but there was no infection, bleeding, anatomic abnormality, or thought or eating disorder to treat.

In the early 1990s, a few gastroenterology “thought leaders” came together because of their common belief that the central nervous system and the enteric nervous system interact in important ways. They attempted to define symptom-based diagnostic criteria for common (eg, IBS, affecting 15% to 20% of the US population) and uncommon (eg, chronic intestinal pseudo-obstruction) conditions lacking a reliable diagnostic biomarker. Later in the decade, they invited pediatric gastroenterologists to define symptom-based criteria for pediatric functional gastrointestinal disorders. When the Pediatric Rome Working Team (named for the site of the meeting) discussed chronic abdominal pain, Hyams argued successfully that Apley's criteria for RAP do not define a diagnosis, but only allow a convenient grouping. The Pediatric Rome Working Team chose the adult abdominal pain categories to replace RAP based on 3 factors. First, there was consensus that we all evaluated and treated children with abdominal pain who met adult diagnostic criteria for functional dyspepsia, functional abdominal pain, or IBS. Second, we thought that dividing RAP into groups with similar symptoms would facilitate the identification of differences among groups, such as defecation disorder and pain for IBS and upper abdominal discomfort related to meals for functional dyspepsia. Finally, we attempted to harmonize our criteria with adult criteria. A questionnaire was developed to determine the validity of the Rome criteria.5 Some 80% of children presenting to pediatric gastroenterology clinics for bellyaches met symptom-based criteria for 1 or more functional gastrointestinal disorders.6 Many children who did not meet the Rome criteria would have done so had they been symptomatic for 3 months or longer. In the next iteration, Rome III, the Pediatric Working Team reduced the time for diagnosis to 2 months, justifying this change by recognizing that many concerned parents sought medical attention more quickly for their children than for themselves.7 The Working Team believed that shortening the symptom duration would not decrease the specificity of the diagnostic criteria.

Since the publication of the Pediatric Rome II Criteria in 1999, there has been an increase in peer-reviewed publications focused on functional gastrointestinal disorders, along with a concomitant increase in the number of new investigators in the emerging field of pediatric neurogastroenterology. This new research has included epidemiologic studies,8, 9 treatment trials,10, 11 and explorations of disease pathophysiology, including attempts to identify biomarkers for IBS.1, 2, 3 Shulman et al12 reported increased gut mucosal permeability and inflammation in children with IBS. Barostat testing is one of several methods used to identify perceptual hypersensitivity. In adults, barostat testing has shown that 20% to 94% of subjects with IBS are hypersensitive to distension.13 Two studies in children found rectal hypersensitivity in 70% and 100% of patients.2, 3 Both studies used healthy control groups. In contrast, the present study used children with organic causes of abdominal pain as controls, but found similar results.

Will every clinic need a barostat? Not as long as symptom-based criteria are the gold standard for diagnosis. But parents and children sometimes respond to a symptom-based diagnosis by accusing the practitioner of believing that the pain is “all in their head.” In those patients, a barostat test showing visceral hypersensitivity will demonstrate that the pain is not “all in their head,” and that separating the body from the brain is not a useful concept in IBS. Although the barostat procedure is cumbersome and invasive, it appears to be more accurate (sensitivity, 94%; specificity, 77%; overall accuracy, 82% in the Halac et al study) than the new serologic test for IBS (sensitivity, 50%; specificity, 88%; overall accuracy, 70%).14 However, health care providers should not dismiss patients with symptoms even in the absence of a biomarker and good scientific understanding. Initial patient interactions regarding IBS should include a discussion of perceptual hypersensitivity and an explanation of the important findings of Halac et al.1

How many children diagnosed with IBS develop organic disease later in life? There are no studies in children addressing this important question; however, follow-up data in adult patients who met Rome criteria for IBS show that IBS persisted in many patients. Furthermore, patients who met symptom-based criteria for IBS followed for a decade or more did not develop any abdominal conditions that could have been mistaken for IBS. The IBS symptom-based diagnosis seems to be specific and durable.15

In contrast to the flurry of research directed at validating functional gastrointestinal disorders in general and IBS in particular, practicing clinicians have not adopted the functional gastrointestinal disorders. Shurman et al16 surveyed members of the North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition and concluded that even though nearly all knew of the Rome criteria, fewer than half used these criteria in practice.

There is now ample evidence indicating that IBS occurs in children as well as adults. Pediatric practitioners have the option of diagnosing IBS and other functional disorders by symptom-based criteria in the absence of signs or symptoms indicative of organic disease, such as blood in stool, fever, and unexplained weight loss. There are compelling reasons for primary care clinicians to use the Rome criteria to make common diagnoses without referring patients to a gastroenterologist. First, making a symptom-based diagnosis of IBS during the first patient visit saves time and worry. If the primary care physician recognizes a child with IBS and communicates to the child and family that IBS is a treatable condition not associated with serious consequences, than education and guidance may assuage the family's concerns. Second, a primary care evaluation for abdominal pain symptoms costs only one-third of a gastroenterologist's evaluation.17 Third, the gastroenterologist's evaluation to rule out organic disease often includes costly tests. In some families, each negative test result stimulates fear that their child has some mysterious disease that is evading identification. They may seek multiple second opinions, increasing stress in the child and family until disability ensues. The degree of disability in a child with IBS correlates with the intensity of comorbid emotional distress in the child and family.18

Every parent wants answers to 4 questions when they visit the doctor:

1.What is wrong with my child? Answer: It is IBS.

2.Is IBS dangerous? Answer: It is not dangerous, but it may be bothersome.

3.Will it go away? Answer: It may come and go.

4.What can we do about it? Answer: If symptoms are not too bothersome, then education and reassurance may be all that is needed. We have pills that have been proven to help. Some prefer cognitive behavioral therapy or hypnosis. If the child is out of school or afraid to leave home, we might choose all 3 approaches: education, medicine, and a mental health treatment known to be effective for IBS.

It is incredibly satisfying to the clinician, the family, and the patient when the clinician makes a symptom-based diagnosis on the first visit. Time is our diagnostic ally; new symptoms are a reason for reevaluation.

Back to Article Outline

 

We thank Drs Tom and Carol Garvey, Lin Chang, Robin English, and Andrea Hauser for their critical review of the manuscript.

Back to Article Outline

References 

  1. Halac U, Noble A, Faure C. Rectal sensory threshold for pain is a diagnostic marker of irritable bowel syndrome and functional abdominal pain in children. J Pediatr. 2009;156:60–65
  2. Van Ginkle R, Voskuijl WP, Benninga MA, Taminiau JA, Boeckstaens GE. Alterations in rectal sensitivity and motility in childhood irritable bowel syndrome. Gastroenterology. 2001;120:31–38
  3. Di Lorenzo C, Youssef NN, Sigurdsson L, Scharff L, Griffiths J, Wald A. Visceral hyperalgesia in children with functional abdominal pain. J Pediatr. 2001;139:838–843
  4. Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69:89–95
  5. Caplan A, Walker LS, 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
  6. Walker LS, Lipani TA, Greene JW, Caines K, Stutts J, Polk DB, et al. Recurrent abdominal pain: symptom subtypes based on the Rome II criteria for pediatric functional gastrointestinal disorders. J Pediatr Gastroenterol Nutr. 2004;38:187–191
  7. Rasquin A, Di Lorenzo C, Forbes D, Guiraldes E, Hyams JS, Staiano A, et al. Childhood functional gastrointestinal disorders: child/adolescent. Gastroenterology. 2006;130:1527–1537
  8. Hyams JS, Treem WR, Justinich CJ, Davis P, Shoup M, Burke G. Characterization of symptoms in children with recurrent abdominal pain: resemblance to irritable bowel syndrome. J Pediatr Gstroenterol Nutr. 1995;20:209–214
  9. Hyman PE, Oller M, Cocjin J. Infant dyschezia. Clin Pediatr. 2009;48:438–439
  10. Bahar RJ, Collins BS, Steinmetz B, Ament ME. Double-blind, placebo-controlled trial of amitriptyline for the treatment of irritable bowel syndrome in adolescents. J Pediatr. 2008;152:685–689
  11. Saps M, Youssef N, Miranda A, Nurko S, Hyman P, Cocjin J, et al. Multicenter, randomized placebo-controlled trial of amitriptyline in children with functional gastrointestinal disorders. Gastroenterology, in press.
  12. Shulman RJ, Eakin MN, Czyzewski DI, Jarrett M, Ou CN. Increased gastrointestinal permeability and gut inflammation in children with functional abdominal pain and irritable bowel syndrome. J Pediatr. 2008;153:594–596
  13. Camilleri M, Chang L. Challenges to the therapeutic pipeline for irritable bowel syndrome: endpoints and regulatory hurdles. Gastroenterology. 2008;136:1877–1891
  14. Lembo AJ, Neri B, Tolley J, Barken D, Carroll S, Pan H. Use of serum biomarkers in a diagnostic test for irritable bowel syndrome. Aliment Pharmacol Ther. 2009;29:834–842
  15. Adeniji OA, Barnett CB, Di Palma JA. Durability of the diagnosis of irritable bowel syndrome based on clinical criteria. Dig Dis Sci. 2004;49:572–574
  16. Shurman JV, Hunter HL, Friesen CA. Conceptualization and treatment of functional gastrointestinal disorders in pediatric gastroenterology practice. J Pediatr Gastroenterol Nutr, in press.
  17. Lane MM, Weidler EM, Czyzewski DI, Shulman RJ. Pain symptoms and stooling patterns do not drive diagnostic costs for children with functional abdominal pain and irritable bowel syndrome in primary or tertiary care. Pediatrics. 2009;123:758–764
  18. Hyman PE, Bursch B, Sood M, Schwankovsky L, Cocjin J, Zeltzer LK. Visceral pain-associated disability syndrome: a descriptive analysis. J Pediatr Gastroenterol Nutr. 2002;35:663–668

PII: S0022-3476(09)00769-0

doi:10.1016/j.jpeds.2009.07.064

Refers to article:

  • Rectal Sensory Threshold for Pain is a Diagnostic Marker of Irritable Bowel Syndrome and Functional Abdominal Pain in Children , 05 October 2009

    Ugur Halac, Angela Noble, Christophe Faure
    The Journal of Pediatrics January 2010 (Vol. 156, Issue 1, Pages 60-65.e1)

The Journal of Pediatrics
Volume 156, Issue 1 , Pages 5-7, January 2010

Article Tools