CHRONIC ABDOMINAL PAIN IN CHILDREN

David Suskind M.D.Associate Professor of PediatricsDivision of Gastroenterology Hepatology and NutritionUniversity of WashingtonSeattle Children’s Hospital

Talk outline

• General over view of chronic abdominal pain• Disease specific entities

• Constipation• Lactose• Fructose intolerance• Celiac• GERD• H. pylori

• General work-up

Primary Causes of Chronic Abdominal pain

• Constipation • Lactose intolerance• Fructose intolerance• Functional abdominal

pain• Celiac• Food allergies

eosinophilic esophagitis

• Acid related disorders: Gastroesophageal reflux disease gastritis and ulcers

• Infections: Mononucleosis, intestinal parasites, H. pylori bacterial infection

• inflammatory bowel disease: ulcerative colitis and Crohn’s disease

A Physicians Aspiration

• ‘Our goal is to diagnose and treat our patients’

• Unfortunately we only have a handful of minutes to do so

• So we triage our patients based upon our knowledge, our experience and the medical literature

The History

• Timeframe and time of day• Location• Intensity and character• Aggravating or alleviating factors• Associated signs and symptoms

• Bowel habits• Vomiting • Gassiness• Weight loss• Dietary habits• Psychosocial stressors

• Diagnosis / Family history

Apley’s Rule

“Red Flags” in Chronic Abdominal Pain

• Weight loss or growth deceleration

• Vomiting

• Pain awakens patient

• Radiation pain

• Recurrent oral ulcerations

• Rectal bleeding

• Constitutional symptoms• Rash• Arthralgia• Temperature

• Pain well localized away from umbilicus

• Positive family history of celiac, H. pylori or inflammatory bowel disease, pancreatitis

Physical exam

• Rectal exam

Constipation: Recognition

TABLE 1. Normal frequency of bowel movements

Age Bowel movements

per weeka Bowel movements

per dayb

0-3 months Breast-fed 5-40 2.9 Formula-fed 5-28 2.0 6-12 months 5-28 1.8 1-3 years 4-21 1.4 More than 3 years 3-14 1.0

Adapted from Fontana M. Bianch C, Cataldo F, et al. Bowel frequency in healthy children. Acta Paediatr Scand 1987; 78:682-4. aApproximately mean ± 2 SD. bMean.

• 3% of general pediatric outpatient visits and 25% of pediatric gastroenterology

Archives of disease, child 1983; 58:257 – 61.

Variable Symptoms

Constipation Treatment

• After two-month period - 37% remained constipated • Specific fixed dose of laxative

• parents did not realize that they needed to adjust the dose

• failure to mention behavioral interventions and dietary interventions

• Treatment success corresponded to how aggressively treated

• colonic evacuation followed by daily laxative therapy

Borowitz, SM, et al treatment of childhood constipation by primary care physicians: efficacy and predictors of outcome, Pediatrics 2005 April;115 (4):873-7.

The treatment plan

Step1 : Cleanout phase: emptying the colon

Step 2: Maintenance phase: keeping the colon empty

Step 3: Changing the behaviors and habits that increase the problem

Step 4: Recognizing and treating relapses early

The four-step treatment plan

The treatment plan

• Cleanout phase is to empty the old stool out of the colon. • Floppy colon can’t move firm stool

• Maintenance is to keep stools soft to let colon empty itself easily. • Exercise itself back into shape• Can take a year or more to shrink

The treatment plan – cleanout

Get old stool emptied out of the colon.

• Polyethylene Glycol

• Each cleanout lasts 2 days

• Usually needs to be repeated.

• May cause cramping as the stool moves through the colon

• Stay near a bathroom during the cleanout

Step 1: The cleanout phase

The treatment plan – cleanout

Cleanout, cont.

• Results during the first cleanout will vary from a slightly noticeable increase to 4 to 6 large volume stools a day.

• Cleanout should be repeated every 2 weeks until stools are daily, very soft and pain is gone.

• Symptoms will improve over time, not always immediately.

The treatment plan – clean out

AND• Stimulant laxatives

• Increase the strength of the colon’s contractions and help move stool out.

• Examples: Senna, Little Tummy’s Laxative or

bisacodyl (Dulcolax)

The treatment plan – maintenance

Step 2: Maintenance phase

• Continue giving the stool softener once every day at the maintenance dose

• Adjust maintenance to assure soft stool

• 1-3 soft mashed-potato-consistency stools per day.

• Wait 3 days between dose changes

• Continue treatment for 4 to 6 months

• Even if things seem much better

• Improves colonic tone

Treatment plan – changing behaviors

Step 3: Changing old behaviors and habits

• Constipation gets worse with certain habits• Waiting too long to go

• Not drinking enough liquid

• Too much dairy

• Not eating enough fiber

• Eating too many constipating

foods like bananas and cheese

Treatment plan – changing behaviors

New behaviors to adopt

Have your child:

Drink enough liquid throughout the day so their urine stays clear or pale yellow.

Treatment plan – changing behaviors

Get enough fiber every day

• General rule:

Your child’s age plus 5 = grams of fiber per day.

Teens over 15 years old need 20-30 grams per day, just like adults.

Treatment plan – changing behaviors

Get enough fiber every day

• fruits and vegetables, legumes

and whole grains

• Eat most grains as whole

grains

• Include 5 servings of fruit or vegetables every day.

(Serving size: 1 serving = 1/4-1/2 cup brown rice, ½ c or 5 broccoli flowers, 1 handful raisins)

Treatment plan – changing behaviors

Know how to read food labels for fiber

Treatment plan – changing behaviors

Regular, relaxed toilet time.

• After meals, sit on the toilet for about 5 minutes.

• Use a foot stool so their feet don’t dangle when sitting.

• Reward your child for cooperation in sitting on toilet. They don’t need to stool to be rewarded.

• Star charts and point systems

• Make it fun and avoid getting into arguments.

• Continue this at least 2 times a day, consistently for at least the next year.

Treatment plan – respond to relapses

Step 4: Recognize and respond to relapses quickly

• The children with the least frequent relapses are the ones who make the needed diet and behavior changes.

• Restart stool softeners at the first sign of a relapse.

• Cleanout whenever needed, as often as every 2 weeks.

Lactose intolerance

• Symptoms caused by maldigestion of lactose

• Lactose is the carbohydrate (sugar) of milk

• Lactase splits lactose in the intestine

Disaccharidase Activities in Children: Normal Values and Comparison Based on Symptoms and Histologic Changes Gupta, Sandeep K.; Chong, Sonny K. F.; Fitzgerald, Joseph F. Journal of Pediatric Gastroenterology & Nutrition 28(3), March 1999, pp 246-251

Diagnostic tests

• H2 Breath Test• bacteria in the bowel digest lactose• generating hydrogen (H2) →

detection of H2 in the exhaled air• Biopsy for lactase deficiency• Removal of lactose from diet

28

Celiac disease• Immune-mediated enteropathy caused by a permanent sensitivity to gluten in genetically susceptible individuals

• Healthy population: 1:133

• 1st degree relatives: 1:18 to 1:22

• 2nd degree relatives: 1:24 to 1:39

• Symptomatic and asymptomatic individuals• including subjects affected by:

•Type 1 diabetes

•Williams/Downs/Turner syndrome

•Selective IgA deficiency

29

The Celiac Iceberg

SymptomaticCeliac Disease

Silent Celiac Disease

Latent Celiac Disease

Genetic susceptibility: - DQ2, DQ8 Positive serology

Manifest mucosal lesion

Normal Mucosa

30

Celiac: Epidemiological Study in USA

Prevalence1:39

Prevalence1:22

Population screened13145

Positive31

Negative4095

Positive81

Negative3155

Positive205

Negative4303

Positive33

Negative1242

Prevalence1:40

Symptomatic subjects3236

1st degree relatives4508

2nd degree relatives1275

Healthy Individuals4126

Risk Groups9019

Prevalence1:133

Projected number of celiacs in the U.S.A.: 2,115,954Actual number of known celiacs in the U.S.A.: 40,000For each known celiac there are 53 undiagnosed patients.

A. Fasano et al., Arch Int Med 2003;163:286-292.

31

Celiac Disease Prevalence Data

Geographic AreaPrevalence on clinical

diagnosis*Prevalence on screening

data

Brasil ? 1:400

Denmark 1:10,000 1:500

Finland 1:1,000 1:130

Germany 1:2,300 1:500

Italy 1:1,000 1:184

Netherlands 1:4,500 1:198

Norway 1:675 1:250

Sahara ? 1:70

Slovenia ? 1:550

Sweden 1:330 1:190

United Kingdom 1:300 1:112

USA 1:10,000 1:133

Worldwide (average) 1:3,345 1:266

Fasano & Catassi, Gastroenterology 2001; 120:636‑651.

*based on classical, clinical presentation

32

5

Submucosa

T

BAGA, EMA,atTG

Cytokines (IL2, IL15)Tk

P

TTG3

47

APC

21

6b

6a

8

2a

2b

8

33

Gastrointestinal Manifestations

6-24 months• Chronic or recurrent

diarrhea• Abdominal distension• Anorexia• Failure to thrive or weight

loss• Vomiting• Constipation• Irritability

Older Children and Adults• Dermatitis Herpetiformis• Dental enamel hypoplasia• Osteopenia/Osteoporosis• Short Stature• Delayed Puberty• Iron-deficient anemia • Resistant to oral Fe• Hepatitis• Arthritis

34

Typical Celiac Disease

36

• Silent - No or minimal symptoms• Damaged mucosa and positive serology • Asymptomatic individuals from groups at risk such:

• First degree relatives• Down syndrome patients• Type 1 diabetes patients

• Latent - No symptoms, normal mucosa• May show positive serology.• Identified by following in time asymptomatic individuals

previously identified at screening from groups at risk

Asymptomatic Celiac

37

Major Complications of Celiac Disease

• Short stature• Dermatitis

herpetiformis• Dental enamel

hypoplasia• Recurrent stomatitis• Fertility problems

• Osteoporosis • Gluten ataxia and

other neurological disturbances

• Refractory celiac disease and related disorders

• Intestinal lymphoma

38

Diagnostic principles• Confirm diagnosis before treating

• Diagnosis of Celiac Disease mandates a strict gluten-free diet for life

• following the diet is not easy• QOL implications

• Failure to treat has potential long term adverse health consequences

• increased morbidity and mortality

Celiac Diagnosis

39

SerologicTesting for Celiac

Role of serological tests:

• Identify symptomatic individuals who need a biopsy

• Screening of asymptomatic “at risk” individuals

• Supportive evidence for the diagnosis

• Monitoring dietary compliance

40

Serological Tests for Celiac

• Antigliadin antibodies (AGA)

• Antiendomysial antibodies (EMA)

• Anti tissue transglutaminase antibodies (TTG)

– first generation (guinea pig protein)

–second generation (human recombinant)

• HLA typing

41

Serological Test Comparison

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

Sensitivity % Specificity %

AGA-IgG 69 – 85 73 – 90AGA-IgA 75 – 90 82 – 95

EMA (IgA) 85 – 98 97 – 100

TTG (IgA) 90 – 98 94 – 97

43

Histological Features

Normal 0 Infiltrative 1 Hyperplastic 2

Partial atrophy 3a Subtotal atrophy 3b Total atrophy 3c

Horvath K. Recent Advances in Pediatrics, 2002.

44

Treatment

• Only treatment for celiac disease is a gluten-free diet (GFD)• Strict, lifelong diet• Avoid:

• Wheat• Spelt• Rye• Barley

Gastroesophageal Reflux Disease

Regurgitation - Gastric contents pass the lower and upper esophageal sphincter

Vomiting - Ejection of gastric contents through the mouth.

GER Gastroesophageal reflux; reflux of the stomach and duodenal contents into the esophagus

GERD Any condition noted clinically or histologically that results from GER

Pathophysiology

• Lower Esophageal Sphincter (LES)

• Cardioesophageal angle of His

• Size Matters

Pathophysiology cont.

• Intragastric pressure • gastric compliance• meal size/volume relation• gastric emptying• body position

Diagnostic tests

• Upper GI x-ray • Rules out structural causes of reflux

• congenital and acquired • webs, rings, slings, strictures, or malrotation

• DOES NOT DIAGNOSE REFLUX

Diagnostic tests

• Upper GI contrast study• Esophageal pH probe monitoring• Impedance monitoring• Upper endoscopy and biopsy• Nuclear scintigraphy study

Hiatal herniadiaphragm

stomach

Diagnostic test

• Esophageal pH monitoring• regarded as the “gold standard” ( 24 Hr)• Performed more often as inpatients.• Placement determined by regression equations. And

check with x-ray • Scored based on population criteria • Age dependent

Ph Probe Criteria

• Number of reflux episodes in 24º• Longest reflux episode• Reflux index- % time the esophageal pH < 4• Symptom correlation

Diagnostic test

• Scintigraphy - Usually with technetium.• Image is less sharp than barium• Monitor reflux up to 1-1.5 Hr. after a meal, or even

overnight• Aspiration and gastric emptying.• Radiation several fold less than barium.• Sensitivity: 60%-93%

Diagnostic test

• Endoscopy and biopsy• Differentiate reflux from other GI disease with

similar symptoms.• Erythema, erosions and ulcerations, to strictures

and Barrett’s esophagus, allergic esophagitis and H. pylori.

Management of Pediatric GERD

• Antireflux measures and pharmacotherapy, should be used in a stepwise and progressive manner

• Begin with conservative measures

Multicenter, double-blind, randomized, placebo-controlled trial assessing the efficacy and safety of proton pump inhibitor lansoprazole in infants with

symptoms of gastroesophageal reflux disease

Orenstein SR, et al J Pediatr 2009 April; 154(4):514-520

Lansoprazole double-blind (≤4 weeks, n = 81)

Placebo double-blind (≤4 weeks, n =81)

P value

Primary efficacy: Responder rate, n (%)

44 (54%) 44 (54%) NS

Discontinued due to non efficacy, n (%)

28 (35%) 29 (36%) NS

Cry, % of feeds/week -20 -20 NS

Regurgitate, % of feeds/week

−14 −11 NS

Feed refusal, % of days/week

−14 −10 NS

Arching back, % of days/week

−20 −18 NS

Physician: Improved at week 4

44 (55%) 40 (49%) NS

Efficacy of conservative therapy

• Feeding modifications, positioning, and tobacco smoke avoidance

• Infant Gastroesophageal Reflux Questionnaire-Revised (I-GERQ-R; n = 40)

• 78% of infants improved with 24% having normal I-GERQ-R scores

• “Milk protein allergy”• Dietary elimination in

mother diet / hypoallergenic formula trial

Orenstein, et al. J Pediatr 2008 Mar; 152(3):310-4Maternal Child Health J 2012 Aug; 16(6):1319-31

Nonpharmacologic management

• Diet changes• Infants: thickened feeds• Children: limiting caffeinated foods, spicy foods, acidic

foods and fatty foods

• Positioning• Left-side positioning and head elevation during sleep.

• Lifestyle changes• Fast prior to bedtime• Avoid large meals/tight fitting cloth• Avoid alcohol and smoking

Ranitidine (An H2 Receptor Antagonist) Mechanism of Action

K+ H+

H2 Receptor Antagonist Mechanism of Action

PREVACID® (lansoprazole) Mechanism of Action

K+ H+

Ranitidine (An H2 Receptor Antagonist) Mechanism of Action

Proton Pump Inhibitor Mechanism of Action

Temporal changes in the proportion of subjects with heartburn, acid regurgitation or dyspepsia.

Christina R., Gastroenterology 2009, 137(1) :80 – 87.

Rebound Acid Hypersecretion

So what do you do?

• Make sure of diagnosis• Emphasize diet and exercise• If trialing acid suppression, do short course• Explain down side of medications

Helicobacter Pylori

• Infects >50% of the world’s human population• Incidence in industrialized countries is ~0.5% of

the population/year• Incidence in developing countries is 3-10%/year• In North America, the prevalence among Asian-

Americans, African-Americans and Hispanics are similar to those of residents of developing countries.

Risk factors

• residence in a developing country• poor socioeconomic conditions• family overcrowding• possibly an ethnic or genetic predisposition

When to suspect H. pylori infection

• Upper gastrointestinal hemorrhage• Severe epigastric abdominal pain• Protracted vomiting

But not in classic recurrent abdominal pain syndrome.

Who not to test?

• Recurrent abdominal pain• 6 studies performed in N Am, Europe, and Australia

• 2715 children evaluated by EGD, serology, or UBT

• 5-17% of children with abdominal pain infected• 5-29% of children without abdominal pain also

infected• Treating did not affect symptoms of chronic

abdominal pain

• Asymptomatic w/ increased risk• Family history alone

Diagnosis

• Invasive tests requiring endoscopy• Biopsies and

histology• Rapid urease testing• Bacterial culture• Polymerase chain

reaction of bacterial DNA

• Non-invasive tests• Serum and whole

blood antibody• Saliva antibody• Urine antibody• Stool antigen• Urea breath testing

Indications for treatment of H. pyloriTreatment indicated?

NoNo

No Yes

Yes

Yes

Yes

DiagnosisNo evidence of infectionGastritis caused by H. pylori, no symptomsGastritis caused by H. pylori, non-ulcer dyspepsiaGastritis caused by H. pylori, gastric ulcerGastritis caused by H. pylori, duodenal ulcerGastritis caused by H. pylori, MALT lymphoma

H. pylori treatment:14-day regimen

• Omeprazole or Lansoprazole.

• Clarithromycin 30mg/kg/day.

• Amoxicillin 60mg/kg/day.

How to treat?

Summary

• Think Constipation, Lactose/fructose intolerance, Functional abdominal pain

• Always do a rectal• Don’t hesitate to screen for Celiac disease• Hesitate to screen for H. pylori for Chronic

abdominal pain• And beware of chronic acid suppression