Am J Gastroenterol - Benton Franklin County Medical Society

Report
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
What’s in a name?
Chronic
Recurrent
Abdominal
Pain
CRAP
Recurrent
Abdominal
Pain
RAP
CAP
Chronic
Abdominal
Pain
FAP
Functional
Abdominal
Pain
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)
1. Abdominal discomfort or pain associated with 2 or more
of the following at least 25% of the time:
a) Improved with defecation
b) Onset associated with a change in frequency of
stool
c) Onset associated with a change in form
(appearance) of stool
2. 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
1.
Paroxysmal episodes of intense, acute periumbilical pain that lasts
for 1 hour or more
2. Intervening periods of usual health lasting weeks to months
3. The pain interferes with normal activities
4. The pain is associated with 2 or more of the following:
a. Anorexia
b. Nausea
c. Headache
d. Photophobia
d. Pallor
5. 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
1. Episodic or continuous abdominal pain
2. Insufficient criteria for other FGIDs
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
“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.”’
“It’s all in your head”
“It’s all in your head”
Psychological
Biological
Social
Pathophysiology
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 Pediatr Gastroenterol Nutr 2011;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 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.
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
Psychological Factors
Psychological Factors
+
+
Pain Mastery
-
Engaged
Copers
Dependent
Copers
Self-reliant
copers
Avoidant
copers
Relationships
-
Walker et all. Pain 2006;122:43-52.
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
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 Pediatr Gastroenterol Nutr 2011;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;40:24961.
• Negative EGD does not reassure /improve outcome
• Bonilla et al. Clin Pediatr 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 Pediatr 2001;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.
Rifaximin
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.
Lactobacillus GG
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 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)
Levy et al. Am J Gastroenterol 2010;105:946-956.
Hypnotherapy
Vlieker et al. Gastroenterology
2007;133:1430-1436.
Hypnotherapy - 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
• 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
• Provided with CD and
encouraged to practice
self-hypnosis
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
Vlieger et al. Gastroenterology 2007;133:1430-1436.
Table 2. Percentage of Patients in Clinical Remission
After therapy
No effect
Improved
Clinical remission
At 6 mo follow-up
At 1 yr follow-up
SMT group
(n = 25) (n = 27)
HT group SMT group HT group SMT group HT group
(n = 24) (n = 27) (n = 24)
(n = 27)
56%
32%
12%
66%
17%
17%
15%
26%
59%
7%
22%
71%
46%
29%
25%
4%
11%
85%
P < .001 between the treatment groups at all end points.
Vlieker et al. Gastroenterology 2007;133:1430-1436.
Biofeedback
• Excellent evidence for chronic headaches
• Data lacking for abdominal pain, but seems to
work!
Complementary Medicine
• Acupuncture
Complementary Medicine
• Acupuncture
Magge and Lembo. Gastroenterol Clin N Am 2011;40:245-253.
Treatment - 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, evidencebased treatments
Summary
• 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 patientphysician relationship

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