Abdominal Pain

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ACOFP 53rd Annual Convention & Scientific Seminars
Pediatric GI: Chronic Abdominal
Pain Evaluation and Treatment
Paul Ufberg, DO, MBA
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Name of CME Activity: ACOFP 53rd Annual Convention and Scientific Seminars
Dates and Location of CME Activity: April 6-9, 2016, The San Juan Puerto Rico Convention Center
Your presentation Thursday, April 7, 2016 from 8:00am-9:00am: Pediatric GI: Chronic Abdominal Pain Evaluation
and Treatment
Name of Faculty/Moderator: ___Paul J. Ufberg DO, MBA_______________________________
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Paul Ufberg, DO, MBA
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Deadline: Friday, January 15, 2016
3/17/2016
Abominable Pain
Pediatric Abdominal Pain
Paul J. Ufberg DO, MBA
Children’s Hospital of Philadelphia
ACOFP 53rd Annual Convention
April 6-9, 2016
San Juan, Puerto Rico
1
© 2016 by Paul J. Ufberg DO, MBA
Disclosures
• No conflicts
• No disclosures
2
Recurrent Abdominal Pain
• Apley defined recurrent abdominal pain
– At least one episode of pain per month
– 3 consecutive months
– Pain interferes with normal activities
• Survey of 1000 kids found that 10.8% fit
criteria for recurrent abdominal pain
• Girls > Boys (1.3:1)
• In 1958
3
Apley J, Naish N. Recurrent abdominal pains: a field survey of 1,000 school children. Arch Dis Child 1958;33:165-70.
1
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Abdominal Pain - Prevalence
• Focused study of adolescents – 7th to 10th graders
• Goal:
– Determine the prevalence of abdominal pain
– Relationship of pain to anxiety and depression
• N = 507 students
– GI Symptom Questionnaire, Anxiety and Depression
Inventory
• 75 % of all students had some abdominal pain
• 13-17 % had weekly abdominal pain
4
Hyams JS, et al. Abdominal pain and irritable bowel syndrome in adolescents: a community-based study J Pediatr 1996; 129:220
5
Problem Defined
• 2-4% of outpatient pediatric visits
• 20% of middle and high school students are affected
by functional gastrointestinal disorders
• 50% miss school at least one day
• Significant school loss (6 days or more)
– 5% of middle school students
– 4% of high school students
• 8% of all students saw a physician in the last year for
abdominal pain
• Family effects
• $25 billion in direct and indirect costs
6
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Abdominal Pain - Physiology
7
Neurophysiology of
Abdominal Pain
• Neuroreceptors AKA Nociceptors
• Located thought the abdominal viscera
and supporting structures
• Respond to noxious stimuli
• Different types of pain
8
Embryology
• Most abdominal viscera begin as midline
structures and have bilateral, symmetric
innervation
• Location of abdominal pain is determined by the
level at which the afferent nerves from
abdominal viscera enter the spinal cord
• Visceral Vs. Somatic pain
9
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Foregut
• Innervated by nerves entering at T5 to T9
• Abdominal structures derived from the foregut
–
–
–
–
–
–
Distal esophagus
Stomach
Duodenum
Liver
Biliary tree
Pancreas
• Pain is perceived midline from the xiphoid
process to the umbilicus
10
Midgut
• Innervated by nerves entering at T8 to L1
• Structures from the midgut
–
–
–
–
Majority of small intestine
Appendix
Ascending colon
Proximal two thirds of transverse colon
• Pain is perceived periumbilically
11
Hindgut
• Innervated by nerves entering at T11 to L1
• Structures from the hindgut
– Distal one third of transverse colon
– Descending colon
– Recto sigmoid
• Pain is perceived between the umbilicus and
pubic symphysis
12
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Referred Pain
• Localized pain in an area
remote from the
abdominal pathology
• Referred pain is
associated with skin
hyperalgesia over the
cutaneous dermatone
supplied by the same
neural segment as the
injured organ
13
Summary
• Visceral pain is often accompanied by
constitutional symptoms (nausea, vomiting, etc)
and is poorly localized pain
• Parietal pain is intense, well localized, and
aggravated by movement
• Referred pain occurs in a recognizable pattern
away from the site of pathology
• Abdominal pain
–
–
–
–
Visceral pain
Somatic pain
Referred pain
Combination of all three
14
A Practical Approach to
Abdominal Pain
15
5
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Clinical Approach to
Abdominal Pain
• History
• Focus on:
– Questions directed at the
patient
– Quality
– Intensity
• Developmentally
appropriate
• Friendly vs Silly
• 0-10
• Smiley faces (Wong
–
–
–
–
–
– Minimize parental
influence
– One finger, one spot
method
– Observe
Duration
Timing
Sleep cycle
Eating
Temporal correlation
16
More History
• Medications – before
or after the pain
• Family History
–
–
–
–
–
– Prescriptions
– Over the counter
– Supplements
• Allergy
– Medication
– Environmental
• Past History
Recent illnesses
Migraines
IBD
IBS
Celiac
• Social History
– School
– Home Life
– Stressors
• Changes
17
Physical Examination
• Growth Parameters – prior to seeing patient
– Be prepared to verify with family
• Begin immediately
– Facial expression
– Body movement and position
– Family interaction
• Full examination
– Focused on Abdomen
– Rectal Exam
18
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What Do We Make Of It?
19
The Red Flags
• Patient <5 years old
• Constitutional Symptoms:
–
–
–
–
Fever
Weight loss
Joint pain
Oral Ulcers
• Persistent vomiting
– Bilious
– Bloody
• Gastrointestinal blood loss
• Family history (IBD, celiac disease, etc)
• Chronic medication use
20
The Red Flags
•
•
•
•
•
Nocturnal Symptoms
Involuntary weight loss
Deceleration of linear growth
Delayed puberty
Perianal disease
• Dysphagia ***
21
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Differential Diagnosis
• Multitude of
causes
• Distinguish in
broad terms
– Well
– Sick
• Published list from
1976
22
Dodge, Recurrent Abdominal Pain in Childhood, British Medical Journal 1976, 385-387
Laboratory and Imaging
• Labs should be
individualized
• Lab screening should
include
–
–
–
–
–
–
–
CBC
UA
CMP
ESR and CRP
Celiac panel
Stool Studies
UPT/HCG
• Abdominal US (?)
– Prospective study of
93 children with
recurrent abdominal
pain
• 3 had anatomic
abnormalities
• None accounted for the
abdominal pain
23
Van de Meer, Diagnostic value of ultrasound in children with recurrent abdominal pain. Pediatr Radiol, 20, 7. 501-503
Celiac Disease
• A word on celiac…
• Multiple tests available
• Results can be confusing
• Body of knowledge is growing rapidly
24
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Celiac Disease
Requirements for Diagnosis
• Small bowel biopsy on a gluten
containing diet
– Villous atrophy
– Crypt hyperplasia
– Abnormal surface epithelium
• Clinical remission on a gluten-free diet
25
Serological Test Comparison
Sensitivity % Specificity %
AGA IgG
69 – 85
73-90
AGA IgA
75-90
82-95
EMA IgA
85-98
97-100
TTG IgA
96-100
91-100
Farrell RJ, and Kelly CP. Am J Gastroenterol 2001;96:3237-46.
26
Serologic Testing
• Anti-gliadin antibodies (AGA)
– LOW sensitivity/specificity NOT RECOMMENDED*
• Tissue Transglutaminase (tTG)/ Anti-endomysial
antibodies
– Requires IgA level to assure reliability
– Good sensitivity and specificity
• tTG IgA and Total IgA should be sent
– IgA deficient, can send tTG IgG or proceed
with intestinal biopsy
27
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Testing and Abdominal Pain
Normal Physical Exam
+
Normal Screening Labs
_________________________
Rule out organic disease in 95% of
Recurrent Abdominal Pain Cases
28
Types of Abdominal Pain
• Organic abdominal pain - pain that is
explained on the basis of a structural or
biochemical abnormality
• Functional abdominal pain - episodic or
continuous abdominal pain without
evidence of inflammatory, anatomic,
metabolic or neoplastic process that
explains the symptoms
29
Functional Abdominal Pain
• The Rome Foundation
–
–
–
–
–
Classify and diagnose functional GI disorders (FGID)
Legitimize and update knowledge
Create scientific data
Education
Treatment
• Clinicians and scientists from around the world
• Goal to improve the lives of people with
functional GI disorders
30
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Paradigm Shift
• Reductionist Model
– 300 years old
– One etiology for disease
– Separation of mind and body
• Mind was the seat of the soul
• Biopsychosocial Model
– 30 years ago
– Connection of mind and body
• Dysregulation can produce illness
31
Biopsychosocial Model
32
Rome III Criteria
• Rome III Launched May 2006
– Updated from 1999
• Current set of diagnostic criteria for FGID
– Symptom based diagnosis
– Domains based on age
• Adult (A-F)
• Neonate/Toddler (G)
• Adolescent (H)
– Overlap does exist
33
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G. Functional disorders:
neonates and toddlers
•
•
•
•
•
•
•
G1. Infant regurgitation
G2. Infant rumination syndrome
G3. Cyclic vomiting syndrome
G4. Infant colic
G5. Functional diarrhea
G6. Infant dyschezia
G7. Functional constipation
34
H. Functional disorders: children
and adolescents
• H1. Vomiting and aerophagia
– H1a. Adolescent rumination syndrome
– H1b. Cyclic vomiting syndrome
– H1c. Aerophagia
• H2. Abdominal pain–related FGIDs
–
–
–
–
H2a. Functional dyspepsia
H2b. Irritable bowel syndrome
H2c. Abdominal migraine
H2d. Childhood functional abdominal pain
• H2d1. Childhood functional abdominal pain syndrome
• H3. Constipation and incontinence
– H3a. Functional constipation
– H3b. Nonretentive fecal incontinence
35
Criteria for IBS
• Must include all of the following:
– 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 stool frequency
• Onset associated with a change in stool form
– 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
36
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Criteria for FAP
• FAP – Functional
Abdominal Pain
• FAPS - Functional
Abdominal Pain Syndrome
• Must include all of the
following:
• Must include childhood
functional abdominal pain at
least 25% of the time and 1
or more of the following:
– 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
– 1. Some loss of daily
functioning
– 2. Additional somatic
symptoms such as
headache, limb pain, or
difficulty sleeping
•At least once per week for at least 2 months before diagnosis
37
What Contributes to FAP?
38
Stressors
• Life stress events
– Small amount of evidence
– Recent negative life events is NOT useful in
distinguishing functional abdominal pain and
abdominal pain of other causes
• Daily Stressors
– Limited evidence
– Associated with the occurrence of pain episodes
– Higher levels of negative life events are associated
with increased likelihood of symptom persistence
• No evidence on stress influence on severity,
course or treatment response
39
AAP subcommittee and NASPHGAN committee on Chronic Abdominal Pain, Technical Report J Pediatr Gastroenterol Nutr, Vol. 40, No. 3, 249-61 March 2005
13
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Emotional and Behavior Problems
• Anxiety and depression
– Increased frequency in patients with recurrent
abdominal pain
– NOT useful in distinguishing FAP from other causes
• Conduct disorders
– Patients do NOT have increased prevalence
• Future symptoms and outcome
– Increased risk of later emotional symptoms
– Long term - no data on emotional/behavioral
symptoms and disease severity, course or treatment
response
40
AAP subcommittee and NASPHGAN committee on Chronic Abdominal Pain, Technical Report J Pediatr Gastroenterol Nutr, Vol. 40, No. 3, 249-61 March 2005
Family Functioning
• Family History
– Parents with recurrent abdominal pain have more
children with anxiety, depression and somatization
• Family Dynamics
– Families with recurrent abdominal pain do NOT differ
from control groups or families with acute illness in
broad areas of family functioning
• Family cohesion, conflict and marital satisfaction
41
AAP subcommittee and NASPHGAN committee on Chronic Abdominal Pain, Technical Report J Pediatr Gastroenterol Nutr, Vol. 40, No. 3, 249-61 March 2005
What Causes FAP?
42
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Motility
• FAP initially considered a motility disorder
• Patients with FAP
– More frequent migrating motor complexes
– Slower propagation velocity
– High pressure duodenal contractions associated with
pain
• Subsequent research found no specific diagnostic
pattern of motility disturbances
• Increased contractility is not universally present
• Hypercontractile episodes not related to pain
43
Hypersensitivity
• Recurrent abdominal pain may be related to
alteration in the pain axis
– Amplification of incoming sensory information
– Increased responsiveness to physiologic and
noxious stimuli
– Failure of down-regulation
• Visceral Hypersensitivity
44
Sensitivity
• N = 22 patients with IBS or
Dyspepsia vs Controls
• Balloon distention
– Esophagus
– Rectum
• Perception
• Desire to defecate
• Urgency
• IBS
– Lower rectal and esophageal
sensory thresholds
• Functional Dyspepsia
– Similar to IBS
45
Trimble Heightened visceral sensation in functional gastrointestinal disease is not site-specific. Evidence for a generalized disorder of gut sensitivity. Dig Dis Sci
(1995) 40:1607–13
15
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Permeability and Inflammation
• Population
– 7 to 10 years old
– Compared IBS/FAP to controls
• Diary of stool pattern and pain for 2 weeks
• GI permeability test
– Solution of sucrose, lactulose, mannitol, sucralose
– Collected urine
– Measure ratios to determine permeability
• Gut inflammation
– Measure stool calprotectin concentrations
• Calcium binding protein in neutrophils, monocytes, and
macrophages that resists degradation in the GI tract and is
excreted in feces
46
Shulman, Increased Gastrointestinal Permeability and Gut Inflammation in Children with Functional Abdominal Pain and Irritable Bowel Syndrome, Jour of Ped, Jun 6 08
Permeability and Inflammation
47
Shulman, Increased Gastrointestinal Permeability and Gut Inflammation in Children with Functional Abdominal Pain and Irritable Bowel Syndrome, Jour of Ped, Jun 6 08
Permeability and Inflammation
48
Shulman, Increased Gastrointestinal Permeability and Gut Inflammation in Children with Functional Abdominal Pain and Irritable Bowel Syndrome, Jour of Ped, Jun 6 08
16
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Permeability and Inflammation
• FAP/IBS may have increased permeability
in the proximal GI tract and colon
– Adult studies showed small intestine
permeability
• Suggest that children with FAP/IBS also
have increased inflammation
• Increased fecal calprotectin concentration
was related to pain symptoms
49
Now What?
50
Treatment - Explanation
• Explain the diagnosis in a way the patient and
their family can understand
– May use headache as an example
– Hypersensitivity can be described in the same way skin
is more sensitive after a burn
• Involve the family
– Address their concerns
– Common problem – affects up to 20% of school age
children
• Set consistent limits
• Make recommendations consistent with patient
interests
51
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A Positive Approach
Approach
N
Definitive
Diagnosis
Physician
Attitude
%
Improved
Positive
50
yes
“You will be
better soon”
64%
Positive +
Meds
50
yes
“Pills will help”
64%
Negative
50
no
“I do not know
what you have”
36%
Negative + 50
Meds
no
“I do not know if
pills will help”
42%
52
The Medications
• Available Drugs
–
–
–
–
Levsin - Anticholinergic
Bentyl - Anticholinergic
Periactin - Serotonin and Histamine antagonist
Zelnorm - partial 5-HT4 receptor agonist
• Similar to Serotonin
• On March 30, 2007, Novartis suspended its U.S. marketing
and sales at the request of FDA, because a safety analysis
found a higher chance of heart attack, stroke, and unstable
angina (heart/chest pain) in patients treated with Zelnorm
compared with treatment with placebo
– Elavil – Tricyclic Antidepressant
• Neuromodulatory and anticholinergic effect
• May take up to 10 weeks to work
53
Serotonin
• Neurotransmitter present in high concentrations in
the enterochromaffin cells of the GI tract
• Alterations in mucosal serotonin signaling have
been explored as a mechanism of IBS
• 5-HT3
– Zofran
• 5HT4
– Zelnorm
• SSRIs may be useful
54
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Melatonin
• Melatonin is involved in the regulation of gut motility and
sensation
• Placebo controlled study
– N = 18 adults with IBS
• 9 Melatonin 3mg at bed time
• 9 Placebo
– 8 week study
• Assessments every 2 weeks
• Follow up at 16,24, 48 weeks
• Overall IBS Score
• Extracolonic IBS Score
• Quality of Life
Saha, A Preliminary Study of Melatonin in Irritable Bowel Syndrome, J of Clinic Gastro Volume 41(1), January 2007, pp 29-32
55
Melatonin
Melatonin (9)
Overall IBS
Score
After
Before
After
300
170
240
200
Improvement
Overall ExtraColonic Score
Improvement
Placebo (9)
Before
45%
235
95
16.66%
180
49.16%
155
13.88%
Saha, A Preliminary Study of Melatonin in Irritable Bowel Syndrome, J of Clinic Gastro Volume 41(1), January 2007, pp 29-32
56
Melatonin
• Melatonin significantly decreased the
individual and overall IBS symptoms scores
• Post-treatment overall extra-colonic IBS
score was significantly lower in the
melatonin group compared to pretreatment
and placebo group
57
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Peppermint Oil
• May provide benefit in children with IBS
– Causes intestinal relaxation by decreasing calcium
influx in smooth muscles
• 42 children with IBS in randomized double blind
control trial
58
Kline, Enteric-coated, pH-dependent peppermint oil capsules for the treatment of irritable bowel syndrome in children, J Pediatr 2001;138:125-8
Investigational Drugs
59
Saad, Recent developments in the therapy of irritable bowel syndrome, Expert Opin. Investig. Drugs (2008) 17(2)
Alternatives Treatments
• Lactose Free Diet
– Inconclusive evidence
• Fiber Supplementation
– Inconclusive evidence
• Surgery
– No evidence of the possible beneficial role of
surgery in the evaluation or management of
the child with recurrent abdominal pain
60
AAP subcommittee and NASPHGAN committee on Chronic Abdominal Pain, Technical Report J Pediatr Gastroenterol Nutr, Vol. 40, No. 3, 249-61 March 2005
20
3/17/2016
Alternative Therapies
• Cognitive-Behavioral Therapy
– Teaching coping skills to patient and family
•
•
•
•
Higher rate of complete elimination of pain
Lower levels of relapse at 6 and 12 months
Lower level of interference with activities
Higher level of satisfaction with care
61
Sanders, Cognitive-behavioral treatment of recurrent nonspecific abdominal pain in children: an analysis of generalization, maintenance, and side effects, J Consult
Clin Psychol. 1994 Apr;62(2):306-14
Alternative Therapy
• Relaxation Techniques
– Yoga, Meditation, Progressive Muscle Relaxation
• Randomized study of yoga and IBS
– 25 adolescents, age 11 to 18 years with IBS
• 1 hour instructional session + daily home practice
• Waiting list
– After 4 weeks the waiting list was trained with yoga
– Questionnaires at 0, 4 and 8 weeks
• Yoga group had less functional disability, less
anxiety and lower scores for IBS symptoms
62
Kuttner, A randomized trial of yoga for adolescents with irritable bowel syndrome Pain Res Manag. 2006 Winter;11(4):217-23
Alternative Therapy
• Hypnotherapy & IBS: Cochrane Review
– Some evidence that suggests that
hypnotherapy might be effective in treating
IBS symptoms including abdominal pain
– Hypnotherapy was well tolerated and no
serious side effects were reported in the
studies
– Currently insufficient evidence
– Long term efficacy unclear
Webb AN. Hypnotherapy for treatment of irritable bowel syndrome. Cochrane Database of Systematic Reviews. :CD005110, 200
63
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Alternative Therapy - Barriers
• Willingness/motivation of both patient and
parents
• Explanation of referral in terms of the
diagnosis
• Local availability
• Insurance coverage or financial resources
64
Now What?
65
Abdominal Pain Flow Chart
Emergency
Room
PMD
BMP, LFT
CBC, X ray
US
Enema X ?
TTG, IgA
Testing,
Radiology
Scope, VCUG,
Surgery
Sub Specialist
66
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Diagnostic Roller Coaster
67
Prognosis and Prevention
• 35-50% of children were admitted to the
hospital for abdominal pain had resolution
• 25% will have pain into adulthood
• Prevention and reassurances are key
– Advise against excessive anxiety for minor
illnesses
– Stress the importance of supportiveness for
child and family
– Working together to find solutions
68
Conclusion
• Thorough history and physical
exam
• Use thoughtful diagnostic tests
• Positive messages to patients
are helpful
• Establish a therapeutic
relationship with the family
• Consider medical and
alternative therapies
• Many new drugs and therapies
are being considered
69
23
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References
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Apley J, Naish N. Recurrent abdominal pains: a field survey of 1,000 school children. Arch Dis
Child 1958;33:165-70
Hyams JS, et al. Abdominal pain and irritable bowel syndrome in adolescents: a communitybased study J Pediatr 1996; 129:220
Dodge, Recurrent Abdominal Pain in Childhood, British Medical Journal 1976, , 385-387
Van de Meer, Diagnostic value of ultrasound in children with recurrent abdominal pain. Pediatr
Radiol, 20, 7 501-503
AAP subcommittee and NASPHGAN committee on Chronic Abdominal Pain, Technical Report J
Pediatr Gastroenterol Nutr, Vol. 40, No. 3, 249-61 March 2005
AAP subcommittee and NASPHGAN committee on Chronic Abdominal Pain, Clinical Report J
Pediatr Gastroenterol Nutr, Vol. 40, No. 3, 245-48 March 2005
Trimble Heightened visceral sensation in functional gastrointestinal disease is not site-specific.
Evidence for a generalized disorder of gut sensitivity. Dig Dis Sci (1995) 40:1607–13
Shulman, Increased Gastrointestinal Permeability and Gut Inflammation in Children with Functional
Abdominal Pain and Irritable Bowel Syndrome, Jour of Ped, Jun 6 08
Saha, A Preliminary Study of Melatonin in Irritable Bowel Syndrome, J of Clinic Gastro Volume
41(1), January 2007, pp 29-32
Kline, Enteric-coated, pH-dependent peppermint oil capsules for the treatment of irritable bowel
syndrome in children, J Pediatr 2001;138:125-8
Saad, Recent developments in the therapy of irritable bowel syndrome, Expert Opin Investig
Drugs, 17, 2, 117-130
Sanders, Cognitive-behavioral treatment of recurrent nonspecific abdominal pain in children: an
analysis of generalization, maintenance, and side effects, J Consult Clin Psychol. 1994
Apr;62(2):306-14
Kuttner, A randomized trial of yoga for adolescents with irritable bowel syndrome Pain Res
Manag. 2006 Winter;11(4):217-23
Webb AN. Hypnotherapy for treatment of irritable bowel syndrome. Cochrane Database of
Systematic Reviews. :CD005110, 200
Romecriteria.org
70
24