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CHRONIC ABDOMINAL PAIN IN CHILDRENDavid Suskind M.D.Associate Professor of PediatricsDivision of Gastroenterology Hepatology and NutritionUniversity of WashingtonSeattle Childrens Hospital1Talk outlineGeneral over view of chronic abdominal painDisease specific entitiesConstipationLactoseFructose intoleranceCeliacGERDH. pyloriGeneral work-upPrimary Causes of Chronic Abdominal painConstipationLactose intoleranceFructose intoleranceFunctional abdominal painCeliacFood allergies eosinophilic esophagitisAcid related disorders: Gastroesophageal reflux disease gastritis and ulcers Infections: Mononucleosis, intestinal parasites, H. pylori bacterial infectioninflammatory bowel disease: ulcerative colitis and Crohns disease

A Physicians AspirationOur goal is to diagnose and treat our patientsUnfortunately we only have a handful of minutes to do soSo we triage our patients based upon our knowledge, our experience and the medical literatureSo what do we need to know, We need to know what causes abdominal pain and then we need to know how to differentiate the different diagnosis4The HistoryTimeframe and time of dayLocationIntensity and characterAggravating or alleviating factorsAssociated signs and symptomsBowel habitsVomiting GassinessWeight lossDietary habitsPsychosocial stressorsDiagnosis / Family history

Apleys Rule5The history can be the most cumbersome but is also the most important part of differentiating abdominal pain. We can get the answer to almost any patients problem within 5 minutes of discussion through history.Red Flags in Chronic Abdominal PainWeight loss or growth decelerationVomitingPain awakens patientRadiation painRecurrent oral ulcerationsRectal bleedingConstitutional symptomsRashArthralgiaTemperaturePain well localized away from umbilicus Positive family history of celiac, H. pylori or inflammatory bowel disease, pancreatitis

6Physical examRectal exam

Constipation: Recognition

3% of general pediatric outpatient visits and 25% of pediatric gastroenterologyArchives of disease, child 1983; 58:257 61.8Key point of this slide ismost young kids have (and should have) at least one good poop per day, up to 20 a week.Variable Symptoms

Constipation TreatmentAfter two-month period - 37% remained constipated Specific fixed dose of laxativeparents did not realize that they needed to adjust the dosefailure to mention behavioral interventions and dietary interventionsTreatment 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.

10The treatment planStep1 : Cleanout phase: emptying the colonStep 2: Maintenance phase: keeping the colon emptyStep 3: Changing the behaviors and habits that increase the problemStep 4: Recognizing and treating relapses earlyThe four-step treatment planThe treatment planCleanout phase is to empty the old stool out of the colon. Floppy colon cant move firm stool

Maintenance is to keep stools soft to let colon empty itself easily. Exercise itself back into shapeCan take a year or more to shrinkThe treatment plan cleanoutGet old stool emptied out of the colon. Polyethylene Glycol Each cleanout lasts 2 daysUsually needs to be repeated.May cause cramping as the stool moves through the colonStay near a bathroom during the cleanout Step 1: The cleanout phase13All the old stool has to be emptied out of the colon before it can start working better.Often the cleanout process needs to be repeated a number of times.It may cause cramping as the stool moves through the colon.Plan to stay near a bathroom during the cleanout.We will give specific dosing information to your PCP

The treatment plan cleanoutCleanout, 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 outANDStimulant laxatives Increase the strength of the colons contractions and help move stool out.Examples: Senna, Little Tummys Laxative or bisacodyl (Dulcolax)

15Stool softeners (i.e. polyethelene glycol, lactulose) in large doses will begin to soften the stool and make it easier to passStimulant laxatives (i.e. senna or bisacodyl) will increase the strength of the colons contractions and help move stool outResults during the first cleanout will vary from a slightly noticeable increase to 4-6 large volume stools.Cleanout should be repeated every 2 weeks until stools are daily, very soft and pain is gone.Symptoms will improve over time, not necessarily immediately.Stool softeners (i.e. polyethelene glycol, lactulose) in large doses will begin to soften the stool and make it easier to passStimulant laxatives (i.e. senna or bisacodyl) will increase the strength of the colons contractions and help move stool outResults during the first cleanout will vary from a slightly noticeable increase to 4-6 large volume stools.Cleanout should be repeated every 2 weeks until stools are daily, very soft and pain is gone.Symptoms will improve over time, not necessarily immediately.

The treatment plan maintenanceStep 2: Maintenance phaseContinue giving the stool softener once every day at the maintenance doseAdjust maintenance to assure soft stool1-3 soft mashed-potato-consistency stools per day.Wait 3 days between dose changesContinue treatment for 4 to 6 monthsEven if things seem much betterImproves colonic tone

Treatment plan changing behaviorsStep 3: Changing old behaviors and habits Constipation gets worse with certain habits Waiting too long to goNot drinking enough liquidToo much dairyNot eating enough fiberEating too many constipating foods like bananas and cheese

Treatment plan changing behaviorsNew behaviors to adopt Have your child:Drink enough liquid throughout the day so their urine stays clear or pale yellow.

18If your child takes a multivitamin, their urine may not ever reach clear color.Treatment plan changing behaviorsGet enough fiber every dayGeneral rule:

Your childs 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 behaviorsGet enough fiber every dayfruits and vegetables, legumes and whole grainsEat most grains as whole grainsInclude 5 servings of fruit or vegetables every day.(Serving size: 1 serving = 1/4-1/2 cup brown rice, c or 5 broccoli flowers, 1 handful raisins)Treatment plan changing behaviorsKnow how to read food labels for fiber

Treatment plan changing behaviorsRegular, relaxed toilet time.

After meals, sit on the toilet for about 5 minutes. Use a foot stool so their feet dont dangle when sitting.Reward your child for cooperation in sitting on toilet. They dont need to stool to be rewarded. Star charts and point systemsMake it fun and avoid getting into arguments.Continue this at least 2 times a day, consistently for at least the next year.

The body is not telling themwhen to go we need to help them. This helps retrain the body.

22Treatment plan respond to relapsesStep 4: Recognize and respond to relapses quicklyThe 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.

23Could you add a slide about Examples of early signs of relapse.Lactose intoleranceSymptoms caused by maldigestion of lactoseLactose is the carbohydrate (sugar) of milkLactase 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 testsH2 Breath Testbacteria in the bowel digest lactosegenerating hydrogen (H2) detection of H2 in the exhaled airBiopsy for lactase deficiencyRemoval of lactose from diet28Celiac disease Immune-mediated enteropathy caused by a permanent sensitivity to gluten in genetically susceptible individuals Healthy population: 1:1331st degree relatives: 1:18 to 1:222nd degree relatives: 1:24 to 1:39 Symptomatic and asymptomatic individuals including subjects affected by:Type 1 diabetesWilliams/Downs/Turner syndrome Selective IgA deficiency29The Celiac Iceberg

SymptomaticCeliac DiseaseSilent Celiac DiseaseLatent Celiac Disease Genetic susceptibility: - DQ2, DQ8 Positive serologyManifest mucosal lesionNormal Mucosa30Celiac: Epidemiological Study in USAPrevalence1:39Prevalence1:22Population screened13145Positive31Negative4095Positive81Negative3155Positive205Negative4303Positive33Negative1242Prevalence1:40Symptomatic subjects32361st degree relatives45082nd degree relatives1275Healthy Individuals4126Risk Groups9019Prevalence1:133Projected 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;163:286-292.31Celiac Disease Prevalence DataGeographic AreaPrevalence on clinical diagnosis*Prevalence on screening dataBrasil?1:400Denmark1:10,0001:500Finland1:1,0001:130Germany1:2,3001:500Italy1:1,0001:184Netherlands1:4,5001:198Norway1:6751:250Sahara?1:70Slovenia?1:550Sweden1:3301:190United Kingdom1:3001:112USA1:10,0001:133Worldwide (average)1:3,3451:266Fasano & Catassi, Gastroenterology 2001; 120:636651.*based on classical, clinical presentation32

5SubmucosaTBAGA, EMA,atTGCytokines (IL2, IL15)Tk

PTTG347APC216b6a82a2b832Proposed role of aberrant intestinal permeability in celiac disease pathogenesis. Gliadin peptides (both non-toxic [triangles] and toxic [squares) are present in the intestinal lumen (1) and cross the intestinal barrier either transcellularly (2a) or paracellularly (2b) in subjects with dysregulation of the zonulin system. Gliadin is deamidated by TTG (3) with subsequent conformational changes that allow the gliadin peptide to bind to HLA receptors present on the surface of APC (4). In turn, these peptides are presented to T lymphocytes (5). In genetically susceptible individuals, an aberrant immune response (both umoral [6a] and cell-mediated [6b]), together with the production of cytokines (7) leads to the autoimmune process mainly targeting the intestinal mucosa with subsequent histological damage typical of celiac disease (8).

Gastrointestinal Manifestations6-24 monthsChronic or recurrent diarrheaAbdominal distensionAnorexiaFailure to thrive or weight lossVomitingConstipationIrritabilityOlder Children and AdultsDermatitis HerpetiformisDental enamel hypoplasiaOsteopenia/OsteoporosisShort StatureDelayed PubertyIron-deficient anemia Resistant to oral FeHepatitisArthritis

333334Typical Celiac Disease

3536Silent - No or minimal symptomsDamaged mucosa and positive serology Asymptomatic individuals from groups at risk such:First degree relativesDown syndrome patientsType 1 diabetes patientsLatent - No symptoms, normal mucosaMay show positive serology.Identified by following in time asymptomatic individuals previously identified at screening from groups at risk

Asymptomatic Celiac37Major Complications of Celiac DiseaseShort statureDermatitis herpetiformisDental enamel hypoplasiaRecurrent stomatitisFertility problems

Osteoporosis Gluten ataxia and other neurological disturbancesRefractory celiac disease and related disordersIntestinal lymphoma

38Diagnostic principlesConfirm diagnosis before treatingDiagnosis of Celiac Disease mandates a strict gluten-free diet for lifefollowing the diet is not easyQOL implicationsFailure to treat has potential long term adverse health consequencesincreased morbidity and mortalityCeliac Diagnosis

38A diagnosis of celiac disease means the individual must stay on a strict gluten free diet for life. Following such a diet strictly is not always easy as there are many hidden sources of "gluten". A gluten free diet may also involve added cost to the individual and impact their quality of life. Therefore it is essential that the physician first confirm the diagnosis before recommending life long adherence to the diet. On the other hand it is equally important to not miss the diagnosis of celiac disease. Failure to treat an individual with celiac disease carries potential adverse long term health consequences involving both increased morbidity and mortality.

39SerologicTesting for CeliacRole of serological tests:Identify symptomatic individuals who need a biopsyScreening of asymptomatic at risk individualsSupportive evidence for the diagnosisMonitoring dietary compliance39Serological tests for celiac disease have a number of potential uses.First, they may be used to identify symptomatic individuals who require an intestinal biopsy to diagnose celiac disease. This is particularly useful in those with non specific gastrointestinal complaints or with non gastrointestinal symptoms of celiac disease. Second, the tests are helpful for screening asymptomatic individuals who belong to a group considered at increased risk for celiac disease. Those with positive tests should be referred for a biopsy.Third, positive tests prior to treatment, that become negative on treatment, in an individual with characteristic changes on small intestinal biopsy are strong supportive evidence for the diagnosis of celiac disease.Fourth, tests that revert from positive to negative may provide indirect evidence that the individual is adhering to the diet. Alternatively, tests that become positive again after having become negative suggest the individual is again ingesting gluten containing products.

40Serological Tests for CeliacAntigliadin antibodies (AGA)Antiendomysial antibodies (EMA)Anti tissue transglutaminase antibodies (TTG) first generation (guinea pig protein)second generation (human recombinant)HLA typing40Commercially available tests for celiac disease include the antigliadin, anti endomysial and anti tissue-transglutaminase tests. Tissue transglutaminase has been identified as the auto-antigen in celiac disease against which endomysial antibodies are directed. Initial transglutaminase tests used guinea pig protein as the antigen. Cloning of the gene for human transglutaminase has allowed for tests using human recombinant protein. In addition to antibody tests, some commercial laboratories are offering tests to identify the HLA DQ2 and DQ8 genotypes that are known to be strongly associated with celiac disease.

41Serological Test ComparisonFarrell RJ, and Kelly CP. Am J Gastroenterol 2001;96:3237-46.Sensitivity %Specificity %

AGA-IgG69 8573 90AGA-IgA75 9082 95EMA (IgA)85 98 97 100TTG (IgA)90 9894 9741This slide summarizes the sensitivities and specificities for the various antibody tests.

4243Histological Features

Normal 0Infiltrative 1Hyperplastic 2Partial atrophy 3aSubtotal atrophy 3bTotal atrophy 3cHorvath K. Recent Advances in Pediatrics, 2002.43This slide illustrates the various histolopathological findings that occur in celiac disease.

44TreatmentOnly treatment for celiac disease is a gluten-free diet (GFD)Strict, lifelong dietAvoid:WheatSpeltRyeBarley

Gastroesophageal Reflux DiseaseRegurgitation - Gastric contents pass the lower and upper esophageal sphincterVomiting - Ejection of gastric contents through the mouth. GERGastroesophageal reflux; reflux of the stomach and duodenal contents into the esophagus GERDAny condition noted clinically or histologically that results from GERPathophysiologyLower Esophageal Sphincter (LES) Cardioesophageal angle of His Size Matters

Pathophysiology cont.Intragastric pressure gastric compliancemeal size/volume relationgastric emptyingbody positionDiagnostic testsUpper GI x-ray Rules out structural causes of refluxcongenital and acquired webs, rings, slings, strictures, or malrotation DOES NOT DIAGNOSE REFLUXDiagnostic testsUpper GI contrast studyEsophageal pH probe monitoringImpedance monitoringUpper endoscopy and biopsyNuclear scintigraphy study

Hiatal herniadiaphragmstomachDiagnostic testEsophageal pH monitoringregarded 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 CriteriaNumber of reflux episodes in 24Longest reflux episodeReflux index- % time the esophageal pH < 4Symptom correlationDiagnostic testScintigraphy - Usually with technetium.Image is less sharp than bariumMonitor reflux up to 1-1.5 Hr. after a meal, or even overnightAspiration and gastric emptying.Radiation several fold less than barium.Sensitivity: 60%-93%Diagnostic testEndoscopy and biopsyDifferentiate reflux from other GI disease with similar symptoms.Erythema, erosions and ulcerations, to strictures and Barretts esophagus, allergic esophagitis and H. pylori.Management of Pediatric GERDAntireflux measures and pharmacotherapy, should be used in a stepwise and progressive mannerBegin with conservative measuresMulticenter, 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):514-520Lansoprazole double-blind (4 weeks, n = 81)Placebo double-blind (4 weeks, n =81)P valuePrimary efficacy: Responder rate, n (%)44 (54%)44 (54%)NS

Discontinued due to non efficacy, n (%)28 (35%)29 (36%)NS

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

Regurgitate, % of feeds/week1411NS

Feed refusal, % of days/week1410NS

Arching back, % of days/week2018NS

Physician: Improved at week 444 (55%)40 (49%)NS

Efficacy of conservative therapy Feeding modifications, positioning, and tobacco smoke avoidanceInfant Gastroesophageal Reflux Questionnaire-Revised (I-GERQ-R; n = 40) 78% of infants improved with 24% having normal I-GERQ-R scores

Milk protein allergyDietary 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):1319-31Nonpharmacologic managementDiet changesInfants: thickened feedsChildren: limiting caffeinated foods, spicy foods, acidic foods and fatty foodsPositioningLeft-side positioning and head elevation during sleep.Lifestyle changesFast prior to bedtimeAvoid large meals/tight fitting clothAvoid alcohol and smokingRanitidine (An H2 Receptor Antagonist) Mechanism of Action

K+H+

H2 Receptor Antagonist Mechanism of Action 59PREVACID (lansoprazole) Mechanism of Action

K+H+

Ranitidine (An H2 Receptor Antagonist) Mechanism of ActionProton Pump Inhibitor Mechanism of Action 60

Temporal changes in the proportion of subjects with heartburn, acid regurgitation or dyspepsia.Christina R., Gastroenterology 2009, 137(1) :80 87.Rebound Acid HypersecretionProton-Pump Inhibitor Therapy Induces Acid-Related Symptoms in Healthy Volunteers After Withdrawal of Therapy

61So what do you do?Make sure of diagnosisEmphasize diet and exerciseIf trialing acid suppression, do short courseExplain down side of medicationsHelicobacter PyloriInfects >50% of the worlds human populationIncidence in industrialized countries is ~0.5% of the population/yearIncidence in developing countries is 3-10%/yearIn North America, the prevalence among Asian-Americans, African-Americans and Hispanics are similar to those of residents of developing countries.Risk factorsresidence in a developing countrypoor socioeconomic conditionsfamily overcrowdingpossibly an ethnic or genetic predispositionWhen to suspect H. pylori infectionUpper gastrointestinal hemorrhageSevere epigastric abdominal painProtracted vomitingBut not in classic recurrent abdominal pain syndrome.65Who not to test?Recurrent abdominal pain6 studies performed in N Am, Europe, and Australia2715 children evaluated by EGD, serology, or UBT5-17% of children with abdominal pain infected5-29% of children without abdominal pain also infectedTreating did not affect symptoms of chronic abdominal painAsymptomatic w/ increased riskFamily history aloneDiagnosisInvasive tests requiring endoscopyBiopsies and histologyRapid urease testingBacterial culturePolymerase chain reaction of bacterial DNANon-invasive testsSerum and whole blood antibodySaliva antibodyUrine antibodyStool antigenUrea breath testingIndications for treatment of H. pyloriTreatment indicated?NoNo

No Yes

Yes

Yes

YesDiagnosisNo 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 lymphoma68H. pylori treatment:14-day regimenOmeprazole or Lansoprazole.

Clarithromycin 30mg/kg/day.

Amoxicillin 60mg/kg/day.69How to treat?

SummaryThink Constipation, Lactose/fructose intolerance, Functional abdominal painAlways do a rectalDont hesitate to screen for Celiac diseaseHesitate to screen for H. pylori for Chronic abdominal painAnd beware of chronic acid suppression

Dynamic with Animation73TABLE 1. Normal frequency of bowel movements

AgeBowel movements per weekaBowel movements per dayb

0-3 months

Breast-fed5-402.9

Formula-fed5-282.0

6-12 months5-281.8

1-3 years4-211.4

More than 3 years3-141.0

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.