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Functional abdominal pain in children. David Suskind M.D. Associate Professor of Pediatrics Division of Gastroenterology Hepatology and Nutrition University of Washington Seattle Children’s Hospital. Disclosure Statement.
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Functional abdominal pain in children David Suskind M.D. Associate Professor of Pediatrics Division of Gastroenterology Hepatology and Nutrition University of Washington Seattle Children’s Hospital
Disclosure Statement • I do not have any financial interest, arrangement or affiliation with medical/pharmaceutical/equipment companies
Objectives • Understand the definition and classification of pain predominant functional gastrointestinal disorders • Synthesize various factors involved in their pathophysiology • Apply the pathophysiology principles in understanding evidence based treatments
Epidemiology - Functional GI Disorders • Vast majority of ALL childhood abdominal pain is functional • 2-4% of all general pediatric visits • >50% of consultations in pediatric GI • Frequently misdiagnosed • Significant morbidity • Quality of life substantially poorer than in those suffering from asthma or migraine
All roads lead to Rome • Rome III abdominal pain-related FGIDs • Functional dyspepsia • Irritable bowel syndrome • Abdominal migraine • Childhood functional abdominal pain
Diagnostic Criteria for Functional Dyspepsia 1. Persistent or recurrent pain or discomfort centered in the upper abdomen (above the umbilicus) 2. Not relieved by defecation or associated with the onset of a change in stool frequency or stool form (i.e., not IBS) 3. No evidence of an inflammatory, anatomic, metabolic, or neoplastic process that explains the subject’s symptoms * Criteria fulfilled at least once per week for at least 2 months before diagnosis
Diagnostic Criteria for Irritable Bowel Syndrome (IBS) • Abdominal discomfort or pain associated with 2 or more of the following at least 25% of the time: • Improved with defecation • Onset associated with a change in frequency of stool • Onset associated with a change in form (appearance) of stool • No evidence of an inflammatory, anatomic, metabolic, or neoplastic process that explains the subject’s symptoms * Criteria fulfilled at least once per week for at least 2 months before diagnosis
Diagnostic Criteria for Abdominal Migraine • Paroxysmal episodes of intense, acute periumbilical pain that lasts for 1 hour or more • Intervening periods of usual health lasting weeks to months • The pain interferes with normal activities • The pain is associated with 2 or more of the following: • Anorexia b. Nausea c. Headache d. Photophobia d. Pallor • No evidence of an inflammatory, anatomic, metabolic, or neoplastic process that explains the subject’s symptoms * Criteria fulfilled at least once per week for at least 2 months before diagnosis
Diagnostic Criteria for Childhood Functional Abdominal Pain • Episodic or continuous abdominal pain • Insufficient criteria for other FGIDs • No evidence of an inflammatory, anatomic, metabolic, or neoplastic process that explains the subject’s symptoms * Criteria fulfilled at least once per week for at least 2 months before diagnosis
“A Prescription for Abdominal Pain: Due Diligence” By Perri Klass, M.D. 11/22/2010 ‘The stomachache people look with some envy at the headache people. “For some reason people respect headaches,” said Dr. Carlo Di Lorenzo, a leading pediatric gastroenterologist and professor of clinical pediatrics at Ohio State. “I’ve never seen a parent or a pediatrician tell a child complaining of a headache, ‘You don’t have a headache – it’s not real.’ Bellyache is just as real as headache.”’
Visceral Hypersensitivity • Distention and excessively strong contractions are primary causes of digestive tract pain • Detected by mechanoreceptors • Hypersensitivity found in substantial subset of patients with IBS/FGID • Balloon inflation during sigmoidoscopy and endoscopy • Modulated by 5-HT3 • “Wind-up” / central sensitization phenomenon
Early Life Events and Visceral Hypersensitivity • Pain sensing neuronal circuits are formed during the neonatal period • Adverse events early in life may “prime” a child for chronic abdominal pain • Trauma/surgery? • Stress? • Cow’s milk allergy? Saps et al. J PediatrGastroenterolNutr2011;52:166-9
Motility • Strong contractions during power propulsion underlie sensation of cramping abdominal pain • Power propulsion occurs more frequently and with stronger force in those with IBS with diarrhea • Chey et al. Am J Gastroenterol2001;96:1499-506. • Prolonged colonic transit time in those with IBS and constipation • Agrawal et al. Am J Gastroenterol2009;104:998-2004.
Altered Gastrointestinal Flora • Qualitative and quantitative changes in gut flora have been described in IBS patients • Lower level of Lactobacillus spp. in IBS-diarrhea • Higher rates of small bowel bacterial overgrowth • Patients who received antibiotics in the previous months are 3 times more likely to develop functional symptoms
Altered Gastrointestinal Flora • Post-infectious IBS • 36% of children with bacterial gastroenteritis met criteria for FGID 6 months later (vs 11% of controls) • Changes in flora may alter visceral perception and motility • Saps et al. J Peds 2008;152:812-816
Walker et all. Pain 2006;122:43-52. Psychological Factors Pain Mastery - + + Relationships -
Parenting Techniques • Aim: to assess the impact of parent attention versus distraction on symptom complaints • Walker et al. Pain 2006;122:43-52.
Parenting Techniques • Aim: to assess the impact of parent attention versus distraction on symptom complaints • Included children with and without FAP • Water load provocation to induce pain • Parents randomly assigned/trained to: attention, distraction, or no instruction • Self-reported GI symptoms recorded before and after parent interaction • Parents’ and children’s perceptions of their interaction were assessed • Walker et al. Pain 2006;122:43-52.
Study Results • Symptom complaints by both FAP and well children: • Nearly doubled in the ‘Attention’ group • Reduced by half in the ‘Distraction’ group • Children in the ‘Distraction’ group rated parents as making them feel much better than ‘Attention’ group • Parents rated distraction as having greater potential negative impact on their children than attention Walker et al. Pain 2006;122:43-52
Pathophysiology - Review • Biopsychosocial model • Visceral hypersensitivity • Central sensitization / “Wind-up” phenomenon • Possible effect from early life events • Motility disturbance • Altered gastrointestinal flora • Psychologic factors, including coping strategies • Parenting techniques
Natural History • Children with RAP seen by a subspecialist more likely to have anxiety, depression, and migraine headaches as adults • Campo et al. Pediatrics 2001:108:e1 • 35% of children with FAP (N=188) had persistent FGID at follow-up 4-15 years later • Prevalence of non-GI somatic complaints associated with persistent functional disease • Dengler-Crish et al. .J PediatrGastroenterolNutr2011;52:162-5.
Making the diagnosis • History • Children with FAP are more likely to have headache, joint pain, anorexia, nausea, excessive gas, and altered bowel habits • Yet none of these symptoms can distinguish functional from “organic” abdominal pain
Alarm Symptoms • Involuntary weight loss or growth failure • Dysphagia • Frequent vomiting • Chronic, severe diarrhea • Nocturnal symptoms, especially BM’s • Persistent RUQ or RLQ pain • Rectal bleeding without constipation
Appropriate work-up • Predictive value of blood tests not well studied • No evidence that ultrasound of abdomen/pelvis has significant yield • EGD NOT indicated without alarm symptoms • Subcommittee on Chronic Abdominal Pain. Pediatrics 2005;40:249-61. • Negative EGD does not reassure /improve outcome • Bonilla et al. ClinPediatr 2011;(epub ahead of print).
Treatment • Pharmacotherapy • Probiotics • Psychological • Cognitive Behavioral Therapy • Hypnotherapy • Biofeedback • Complementary and Alternative • Acupuncture
Pharmacotherapy • “Primum non nocere”
Peppermint Oil • RDBPCT of 42 children with IBS • Enteric coated peppermint oil capsules vs placebo • After 2 weeks, 75% of peppermint oil group had decreased severity of pain vs 19% with placebo • Limitations • Short study • Entry criteria not well described • Kline et al. J Pediatr2001;138:125-8.
Antibiotics • Rifaximin • 2 DBPCTs randomized 1260 patients to rifaximin (550 mg TID) or placebo x 2 weeks • Primary endpoint = proportion with self-reported relief for at least 2 of the 4 weeks immediately post treatment • 40% relief with rifaximin vs 31% with placebo (p<0.001) • Effect “persisted” at 12-week follow-up • Pimentel et al. NEJM 2011;364:22-32.
Probiotics • RCT of Lactobacillus GG (LGG) vs placebo in children with FAP or IBS • N = 144 (9 primary care sites and 1 referral center) • LGG (3x109 BID) vs placebo for 8 weeks • 8-week follow-up phase • LGG but not placebo significantly reduces the frequency (p<0.01) and severity (p<0.01) of abdominal pain by end of treatment • Effects persisted at 8-week follow-up • Francavilla et al. Pediatrics 2010;126:e1445-52.
Amitriptyline • Children with FAP, IBS, or functional dyspepsia randomized to 4 weeks placebo or amitriptyline • 10 mg/d, weight <35 kg; 20 mg/day, weight >35 kg • Pain, psychological traits, and daily activities assessed before and after intervention • Primary outcome = self assessment of pain relief and sense of improvement • Saps et al. Gastroenterology 2009;137:1261-9.
Cognitive Behavioral Therapy • 200 children/parents with FAP randomized to : • 3 session intervention of CBT: relaxation training; modifying response to illness/wellness; altering dysfunctional thoughts about symptoms • 3 session education intervention controlled for time and intervention • Children and parents assessed pre-treatment and serially up to 6 months post-treatment • Outcome measures: child and parents reports of pain levels, function, and adjustment • Levy et al. Am J Gastroenterol2010;105:946-956.
Levy et al. Am J Gastroenterol 2010;105:946-956. CBT - Results • CBT group with greater baseline to follow-up decrease in pain and GI symptoms (p<0.01) • CBT parents with greater decreases in solicitous responses to child’s symptoms (p<0.0001)
Vlieker et al. Gastroenterology 2007;133:1430-1436. Hypnotherapy
Gut directed hypnotherapy (HT) Single experienced provider 6 sessions of 50 minutes over a 3-month period Specific protocol, adapted to child’s developmental age Control of gut functions General relaxation Ego strengthening suggestions Provided with CD and encouraged to practice self-hypnosis Standard medical therapy (SMT) Education Dietary advice and added fiber “Pain medications” or PPIs, if necessary 6 therapy sessions to explore stressful factors and/or triggers Vlieger et al. Gastroenterology 2007;133:1430-1436. Hypnotherapy - Study design
Vlieger et al. Gastroenterology 2007;133:1430-1436. Study Design - Outcomes • Pain intensity and frequency measured serially up to 12 months after therapy • Remission: >80% decrease in pain intensity and frequency scores
Vlieger et al. Gastroenterology 2007;133:1430-1436. Figure 2. Changes in pain intensity scores during and after treatment
Vlieger et al. Gastroenterology 2007;133:1430-1436. Figure 3. Changes in pain frequency scores during and after treatment
Vlieker et al. Gastroenterology 2007;133:1430-1436. Table 2. Percentage of Patients in Clinical Remission After therapy At 6 mo follow-up At 1 yr follow-up SMT group HT group SMT group HT group SMT group HT group (n = 25) (n = 27) (n = 24) (n = 27) (n = 24) (n = 27) No effect 56% 15% 66% 7% 46% 4% Improved 32% 26% 17% 22% 29% 11% Clinical remission 12% 59% 17% 71% 25% 85% P < .001 between the treatment groups at all end points.
Biofeedback • Excellent evidence for chronic headaches • Data lacking for abdominal pain, but seems to work!
Complementary Medicine • Acupuncture