David Suskind MD Associate Professor of Pediatrics Division of Gastroenterology Hepatology and Nutrition University of Washington Seattle Childrens Hospital Disclosure Statement I do not have any financial interest arrangement or affiliation with medicalpharmaceuticalequipment companie ID: 934829
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Slide1
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
Slide2Disclosure Statement
I do not have any financial interest, arrangement or affiliation with medical/pharmaceutical/equipment companies
Slide3Objectives
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
Slide4Epidemiology - 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
Slide5What’s in a name?
Slide6All roads lead to Rome
Rome III abdominal pain-related FGIDs
Functional dyspepsia
Irritable bowel syndrome
Abdominal migraine
Childhood functional abdominal pain
Slide7Diagnostic 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
Slide8Diagnostic 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
Slide9Diagnostic 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
Slide10Diagnostic 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
Slide11“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.”’
Slide12“It’s all in your head”
Slide13“It’s all in your head
”
Slide14Slide15Pathophysiology
Slide16Visceral 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-HT
3
“Wind-up” / central sensitization phenomenon
Slide17Early 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
Pediatr
Gastroenterol
Nutr
2011;52:166-9
Slide18Motility
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
Gastroenterol
2001;96:1499-506.
Prolonged colonic transit time in those with IBS and constipation
Agrawal
et al.
Am J
Gastroenterol
2009;104:998-2004.
Slide19Altered Gastrointestinal Flora
Qualitative and quantit
a
tive 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
Slide20Altered 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
Slide21Psychological Factors
Slide22Psychological Factors
Relationships
Pain Mastery
+
+
-
-
Walker et all.
Pain
2006;122:43-52.
Slide23Parenting Techniques
Aim: to assess the impact of parent attention versus distraction on symptom complaints
Walker et al.
Pain
2006;122:43-52.
Slide24Parenting 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.
Slide25Study 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
Slide26Pathophysiology - 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
Slide27Natural History
Slide28Natural 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
Pediatr
Gastroenterol
Nutr
2011;52:162-5.
Slide29Making 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
Slide30Alarm 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
Slide31Appropriate 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
.
Clin
Pediatr
2011;(
epub
ahead of print).
Slide32Treatment
Pharmacotherapy
Probiotics
Psychological
Cognitive Behavioral Therapy
Hypnotherapy
Biofeedback
Complementary and Alternative
Acupuncture
Slide33Pharmacotherapy
“Primum non nocere”
Slide34Peppermint 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
Pediatr
2001;138:125-8.
Slide35Antibiotics
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.
Slide36Rifaximin
Slide37Probiotics
RCT of
Lactobacillus GG
(LGG) vs placebo in children with FAP or IBS
N = 144 (9 primary care sites and 1 referral center)
LGG (3x10
9
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.
Slide38Lactobacillus GG
Slide39Amitriptyline
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.
Slide40Slide41Cognitive 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
Gastroenterol
2010;105:946-956.
Slide42CBT - 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
)
Levy et al.
Am J Gastroenterol
2010;105:946-956.
Slide43Hypnotherapy
Vlieker et al.
Gastroenterology
2007;133:1430-1436.
Slide44Hypnotherapy - Study design
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.
Slide45Study 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.
Slide46Figure 2.
Changes in pain intensity scores during and after treatment
Vlieger
et al.
Gastroenterology
2007;133:1430-1436.
Slide47Figure 3.
Changes in pain frequency scores during and after treatment
Vlieger
et al.
Gastroenterology
2007;133:1430-1436.
Slide48Vlieker 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.
Slide49Biofeedback
Excellent evidence for chronic headaches
Data lacking for abdominal pain, but seems to work!
Slide50Complementary Medicine
Acupuncture
Slide51Complementary Medicine
Acupuncture
Magge and Lembo
. Gastroenterol Clin N Am
2011;40:245-253.
Slide52Treatment - Conclusions
Peppermint oil may have some role
Emerging data for efficacy of probiotics
Psychological based treatment, particularly cognitive behavioral therapy and gut directed hypnotherapy are the most effective, evidence-based treatments
Slide53Summary
Almost all chronic abdominal pain in children is functional
Concept should be introduced to families early
It’s not just “in your head!”
Cognitive behavioral therapy and hypnotherapy are the most evidence-based therapies
Key to effective treatment is the patient-physician relationship