Pediatric Chronic Abdominal Pain

1. Pediatric Chronic Abdominal Pain John F. Pohl MD Professor of Pediatrics Primary Children’s Medical Center University of Utah Salt Lake City, Utah

2. Disclosure: INSPPIRE to Study Acute Recurrent and Chronic Pancreatitis in Children, NIH R21 Grant, NIDDK

3. Learning Objectives • Understand the physiology and differential diagnosis of chronic abdominal pain in children. • Understand the testing (laboratory, radiographic, endoscopic) available for the treatment of chronic abdominal pain in children. • Understand the treatment options for chronic abdominal pain, including treatment for recurrent abdominal pain of childhood and irritable bowel syndrome.

4. Somatic Complaints in Our Practice • IBS • Chronic pelvic pain • Interstitial cystitis • Fibromyalgia • Certain headache presentations 38-60% of visits to the primary care office practice! Kroenke, et al. Am J Med (1989): Only 16% of 1000 general medical outpatients had an organic cause to somatic complaints.

5. Somatic Complaints in Our Practice • Just because no organic source for a complaint is found, this does not rule out neurobiological alterations. • Regardless, many of us feel this way: “A patient has irritable bowel syndrome if your stomach hurts after you leave the patient’s room…”

6. How Common in Pediatric Abdominal Pain? • Survey of 500 adolescents in a community clinic. • 13-17% experienced weekly abdominal pain • 20% of these cases severe enough to affect daily activities. • Need to consider medical, social, cultural, familial, and emotional factors during evaluation. Thiessen. Recurrent abdominal pain. PIR, 2002; Vol. 23: pp. 39-45.

7. IBS -- History • First described by Cummings in 1849 (London Med Gazette). • Various terms used: Spastic colon, nervous colon, irritable colon, “colitis” • Defined by the Rome criteria: • 12week (or more) history in a 12month period of time of abdominal pain that cannot be explained by structural / biochemical abnormalities. • Pain is relieved with defecation. • Pain is associated with BM frequency change. • Pain is associated with BM form change. Need 2 of 3 features.

8. Separate like nuts Sausage shaped but lumpy Like a sausage but with cracks Like a snake, smooth and soft Soft blobs with clear cut edges Fluffy with ragged edges This is the only scale validated for determining diarrhea in a toilet (6 or 7)

9. In children, the presentation of IBS can appear differently AND all functional abdominal pain may not be IBS!

10. Diagnosis • History and physical examination are the cornerstone to establishing a clear diagnosis!!! • Can take at least 1 hour to completely work-up childhood abdominal pain. • Therefore, many children are sent to the pediatric gastroenterolgist due to PCP time restraints. • BUT most causes can be determined by the primary care provider.

11. Diagnosis Most referrals to the pediatric gastroenterologist: • Symptomatic for 12 months or less. • Multiple diagnostic tests (laboratory and radiographic) have already been performed by PCP. • Large number of negative tests reinforces parental / patient anxiety as to cause of abdominal pain (Glass-half full vs. Glass-half empty).

12. Pathophysiology of IBS…Potential Pathway Hypothesis: Psychosocial factor? Motility Disturbance? • Neurotransmitter imbalance • Infection • Inflammation Visceral Hypersensitivity? Horwitz and Fisher, NEJM (2001)

13. Pathophysiology of IBS…Potential Pathway Psychosocial factor? Motility Disturbance? • Neurotransmitter imbalance • Infection • Inflammation CNS defect? MRI / PET changes at thalamus and anterior cingulate cortex Visceral Hypersensitivity? Rectal balloon distention of IBS patients Horwitz and Fisher, NEJM (2001)

14. CNS Defect Mechanism? Ascending Aminergic System EMOTIONAL MOTOR SYSTEM Autonomic Neuroendocrine Pain Modulation

15. Bowel Motility Alteration? • Bowel motility is altered with stress. • May increase / decrease colon contraction. • Fasting (anorexia?)  loss of MMC complexes in IBS patients. • Increased contraction after high-fat meal in IBS patients.

16. ARM

17. ARM Internal sphincter External sphincter

18. ARM

19. ARM

20. Visceral Hypersensitivity? • Balloon distention of rectum  IBS patients experience pain with smaller balloon volumes compared to controls. • WHY? Two ideas: • Are the pain receptors in this region “primed” by infection, lumen contents, etc? • Are there inherent pain modulation differences in nociceptor regions in these patients (i.e., genetic predisposition)?

21. Visceral Hypersensitivity? Faure and Wieckowska. J Peds (2007): Looked at children with IBS, FAP, Functional dyspepsia, and no symptoms. Noted significantly decreased threshold for pain sensation with polyvinyl bag.

22. Visceral Hypersensitivity? No difference P<0.002 compared to controls

23. Psychosocial factors • Stress affects bowel motility. • Patients with IBS  higher rate of psychiatric disease. • Childhood history of abuse  ↑ severity of IBS symptoms. • Noxious stimuli after birth (gastric suctioning)? Anand KJS, Runeson B, Jacobson B. “Gastric Suction at Birth Associated with Long-Term Risk for Functional Intestinal Disorders in Later Life.” The Journal of Pediatrics, 2004; Vol. 144, pp. 449-454.

24. Neurotransmitter Imbalance? • 95% of body serotonin in the GI tract. • Serotonin enhances intestinal secretion, peristalsis (nausea, vomiting, abdominal pain, etc.). • Other transmitters involved? Acetylcholine Substance P Nitric oxide Vasoactive intestinal peptide etc…

25. Anxiety and Sensorimotor Function • Geeraerts, et al. (Gastroenterology 2005): • Took 14 patients and placed them in an anxious emotional state (anxious face + 10-minute audiotape of stressful event). • Evaluated gastric sensitivity and accommodation. Gerrarets, et al. “Influence of Experimentally Induced Anxiety on Gastric Sensorimotor Function in Humans.” Gastro 2005; 129: 1437-1444.

26. Anxiety and Sensorimotor Function During anxiety induction: • Gastric compliance was decreased compared to controls. • Balloon volume to cause gastric discomfort decreased compared to controls. • Suggests a psychological component for pain. Gerrarets, et al. “Influence of Experimentally Induced Anxiety on Gastric Sensorimotor Function in Humans.” Gastro 2005; 129: 1437-1444.

27. Infection / Inflammation? • Inflammatory mediators  ↑ intestinal motility • ?infectious enteritis  ↑ risk of developing IBS • Increased risk of IBS in patients with IBD (Crohn’s, Ulcerative colitis).

28. Infection / Inflammation? Mearin ,et al. Gastroenterology 2005; 129: 98-104. • Shigella enteritidis outbreak occurred in Catalonia, Spain (1243 persons). • Prospective evaluation of IBS symptoms in these people over time. • Followed for one year (controls vs. infected patients): • Dyspepsia incidence ↑’d in affected patients. • IBS (diarrhea-type) ↑’d in affected patients. • Is this an immune response? • Also, patients who were treated with antibiotics had a higher rate of post-infectious IBS… The reason for this is unknown. • Genetic tendency? • ↑ IL-1 (pro-inflammatory)? •  IL-10 (antiinflammatory)?

29. Infection / Inflammation? Do pediatric patients with IBS have specificmicrobiomes? Ruminococcus-like microbe seen in pediatric patients using metagenomicPhyloChip DNA hybridization Saulnier, et al. Gastroenterology 2011 Do antibiotics work for IBS (diarrhea type) Example: Rifaximin Krause, et al. NEJM 2011

30. 1. Rule out the “Red Flags” of the History 2. Rule out the “Red Flags” of the Physical Exam Diagnosis of IBS Thiessen, Peds in Review, 2002

31. Red Flags during the History • Pain LOCALIZES away from the umbilicus. • Pain associated with bowel habit changes. • Pain with nighttime wakening. • Repetitive emesis (esp. bloody / bilious) • Constitutional symptoms: fever, weight loss • Emesis with unusual headaches (occipital) Thiessen, Peds in Review, 2002

32. Where is the Pain? • RUQ • Epigastric • LUQ • RLQ • Peri-umbilical • LLQ • Suprapubic . 1 2 3 5 4 6 7

33. Where is the Pain? • RUQ – gallstones, liver disease • Epigastric – ulcer, pancreatitis • LUQ – renal (UPJ obstruction) • RLQ – appendicitis, infectious enteritis • Periumbilical – RAP • LLQ – constipation, colitis, proctitis • Suprapubic – UTI

34. Red Flags during the P.E. • Loss of weight / decreased height velocity • Organomegaly / abdominal mass • Localized abdominal tenderness away from umbilicus. • Peri-rectal changes • Joint swelling or tenderness • Unusual rash • Pale mucosa / conjunctivae Thiessen, Peds in Review, 2002

35. Laboratory tests: CBC, ESR Liver panel, GGT Amylase, lipase UA, urine culture -HCG T4 / TSH Anti-endomysial Antibody Tissue transglutaminase Antibody (celiac testing) Radiographic tests: Abdominal flat plate Abdominal US Abdominal CT UGI ± SBFT Pertinent Tests

36. Laboratory tests: CBC, ESR Liver panel, GGT Amylase, lipase UA, urine culture -HCG T4 / TSH Anti-endomysial Ab Tissue transglutaminase Ab Radiographic tests: Abdominal flat plate Abdominal US Abdominal CT UGI ± SBFT Pertinent Tests ENDOSCOPY WITH BIOPSY?

37. What other functional abdominal pain disorders exist in children? +

38. Functional Pain (“irritable bowel syndrome”) Keep in Mind: • In 90-95% of children, no cause for abdominal pain is ever found (functional pain). • Is the pain RAP or IBS? RAP IBS

39. Functional Pain (“irritable bowel syndrome”) • Is this RAP? • Recurrent abdominal pain (RAP) • Apley (1958) had 1st description. • Defined as 3 episodes of pain that interfere with activity in a period ≧ 3 months. • Incidence: 10-15% of children • Slightly increased prevalence in girls.

40. Functional Pain (“irritable bowel syndrome”) • Study of 1000 school children: • RAP: Boys = girls until 9 years of age. • After 9 years of age, girls > boys (1.5 : 1) • RAP rare before age 5.

41. RAP • No organic cause • Usually peri-umbilical • Self-limited • Rarely related to meals • Rarely awakens child from sleep. • “Organicity of pain is inversely proportional to the number of school absences.”

42. Irritable Bowel Syndrome (IBS) • RAP may develop into IBS. • Some children develop IBS without RAP. • Criteria for IBS: • Abd. pain relieved with defecation. • ↑d stooling at onset of pain. • Alteration of stool form at time of pain • Passage of mucus • Associated bloating / abdominal distention • No pathological cause (pain fiber dysfunction?) But can see constipation or a “mixed type.”

43. Functional Pain (“irritable bowel syndrome”) Organic disease (10-15%) PAIN Psychological Stressors (family, home) Inherent stress of child (controversial) “Functional” pain (no clear cause)

44. Imaging in IBS

45. Constipation

46. Malrotation

47. Small Bowel Follow Through Ileal stricture

48. Abdominal CT Ileocecal Thickening

49. Peri-Rectal Abscess

50. Irritable Bowel Syndrome