pediatric gi: chronic abdominal pain evaluation and ... gi: chronic abdominal pain evaluation and...

·:{iC0Fp'16ACOFP 53rd Annual Convention & Scientific Seminars

Pediatric GI: Chronic Abdominal Pain Evaluation and Treatment

Paul Ufberg, DO, MBA

ACOFP FULL DISCLOSURE FOR CME ACTIVITIES

Please check where applicable and sign below. Provide additional pages as necessary.

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_______________________________

DISCLOSURE OF FINANCIAL RELATIONSHIPS WITHIN 12 MONTHS OF DATE OF THIS FORM

X A. Neither I nor any member of my immediate family has a financial relationship or interest with any proprietary entity producing

health care goods or services.

B. I have, or an immediate family member has, a financial relationship or interest with a proprietary entity producing health caregoods or services. Please check the relationship(s) that applies.

Research Grants Stock/Bond Holdings (excluding mutual funds)

Speakers’ Bureaus* Employment

Ownership Partnership

Consultant for Fee Others, please list:

Please indicate the name(s) of the organization(s) with which you have a financial relationship or interest, and the specific clinical area(s) that correspond to the relationship(s). If more than four relationships, please list on separate piece of paper:

Organization With Which Relationship Exists Clinical Area Involved

1. 1.

2. 2.

3. 3.

4. 4.

*If you checked “Speakers’ Bureaus” in item B, please continue:

• Did you participate in company-provided speaker training related to your proposed Topic? Yes: No:

• Did you travel to participate in this training? Yes: No:

• Did the company provide you with slides of the presentation in which you were trained as a speaker? Yes: No:

• Did the company pay the travel/lodging/other expenses? Yes: No:

• Did you receive an honorarium or consulting fee for participating in this training? Yes: No:

• Have you received any other type of compensation from the company? Please specify: Yes: No: • When serving as faculty for ACOFP, will you use slides provided by a proprietary entity for your presentation

and/or lecture handout materials? Yes: No:

• Will your Topic1 involve information or data obtained from commercial speaker training? Yes: No:

DISCLOSURE OF UNLABELED/INVESTIGATIONAL USES OF PRODUCTS

__X_A. The content of my material(s)/presentation(s) in this CME activity will not include discussion of unapproved or investigational uses of products or devices.

______B. The content of my material(s)/presentation in this CME activity will include discussion of unapproved or investigational uses of products or devices as indicated below:

I have read the ACOFP policy on full disclosure. If I have indicated a financial relationship or interest, I understand that this

information will be reviewed to determine whether a conflict of interest may exist, and I may be asked to provide additional

information. I understand that failure or refusal to disclose, false disclosure, or inability to resolve conflicts will require

the ACOFP to identify a replacement.

Signature: Date:

Paul Ufberg, DO, MBA

Please email this form to [email protected] as soon as possible

Deadline: Friday, January 15, 2016

mailto:[email protected]

3/17/2016

1

Abominable Pain

Paul J. Ufberg DO, MBA

Children’s Hospital of Philadelphia

ACOFP 53rd Annual Convention

April 6-9, 2016

San Juan, Puerto Rico

© 2016 by Paul J. Ufberg DO, MBA

1

Pediatric Abdominal Pain

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.

3/17/2016

2

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 costs6

3/17/2016

3

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

3/17/2016

4

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

3/17/2016

5

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 three14

A Practical Approach to

Abdominal Pain

15

3/17/2016

6

Clinical Approach to

Abdominal Pain

• History

– Questions directed at the

patient

• Developmentally

appropriate

• Friendly vs Silly

– Minimize parental

influence

– One finger, one spot

method

– Observe

• Focus on:

– Quality

– Intensity

• 0-10

• Smiley faces (Wong

– Duration

– Timing

– Sleep cycle

– Eating

– Temporal correlation

16

More History

• Medications – before

or after the pain

– Prescriptions

– Over the counter

– Supplements

• Allergy

– Medication

– Environmental

• Past History

• Family 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 Exam18

3/17/2016

7

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 use20

The Red Flags

• Nocturnal Symptoms

• Involuntary weight loss

• Deceleration of linear growth

• Delayed puberty

• Perianal disease

• Dysphagia ***

21

3/17/2016

8

Differential Diagnosis

• Multitude of

causes

• Distinguish in

broad terms

– Well

– Sick

• Published list from

1976

22Dodge, 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

3/17/2016

9

25

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

Serological Test Comparison

Farrell RJ, and Kelly CP. Am J Gastroenterol 2001;96:3237-46.

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

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

3/17/2016

10

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 symptoms29

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 disorders30

3/17/2016

11

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

3/17/2016

12

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 incontinence35

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

3/17/2016

13

Criteria for FAP• FAP – Functional

Abdominal Pain

• Must include all 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

• FAPS - Functional

Abdominal Pain Syndrome

• Must include childhood

functional abdominal pain at

least 25% of the time and 1

or more of the following:

– 1. Some loss of daily

functioning

– 2. Additional somatic

symptoms such as

headache, limb pain, or

difficulty sleeping

37•At least once per week for at least 2 months before diagnosis

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

39AAP subcommittee and NASPHGAN committee on Chronic Abdominal Pain, Technical Report J Pediatr Gastroenterol Nutr, Vol. 40, No. 3, 249-61 March 2005

3/17/2016

14

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


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


What Causes FAP?

42

3/17/2016

15

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 pain43

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

45Trimble 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

3/17/2016

16

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

46Shulman, 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




3/17/2016

17


• 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

3/17/2016

18

A Positive Approach

52

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 +

Meds

50 no “I do not know if

pills will help”42%

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 work53

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

3/17/2016

19

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

55Saha, A Preliminary Study of Melatonin in Irritable Bowel Syndrome, J of Clinic Gastro Volume 41(1), January 2007, pp 29-32

Melatonin

Melatonin (9) Placebo (9)

Before After Before After

Overall IBS

Score300 170 240 200

Improvement 45% 16.66%

Overall Extra-

Colonic Score235 95 180 155

Improvement 49.16% 13.88%

56Saha, A Preliminary Study of Melatonin in Irritable Bowel Syndrome, J of Clinic Gastro Volume 41(1), January 2007, pp 29-32

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

3/17/2016

20

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


3/17/2016

21

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

61Sanders, 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 symptoms62

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

63Webb AN. Hypnotherapy for treatment of irritable bowel syndrome. Cochrane Database of Systematic Reviews. :CD005110, 200

3/17/2016

22

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

66

Emergency

Room

Testing,

Radiology

PMD

CBC, X ray

US

Enema X ?

Sub Specialist

TTG, IgA

BMP, LFT

Scope, VCUG,

Surgery

3/17/2016

23

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 solutions68

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

3/17/2016

24

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 community-

based 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

pediatric gi: chronic abdominal pain evaluation and ... gi: chronic abdominal pain evaluation and...

Documents