CHRONIC ABDOMINAL PAIN IN CHILDREN David Suskind M

CHRONIC 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

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 Apley’s Rule Intensity and character Aggravating or alleviating factors Associated signs and symptoms • • • Bowel habits Vomiting Gassiness Weight loss Dietary habits Psychosocial stressors • Diagnosis / Family history

“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 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 The four-step treatment plan Step 1 : 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 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 Step 1: The cleanout phase 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

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 • H 2 Breath Test • bacteria in the bowel digest lactose • generating hydrogen (H 2) → detection of H 2 in the exhaled air • Biopsy for lactase deficiency • Removal of lactose from diet

Celiac disease • Immune-mediated enteropathy caused by a permanent sensitivity to gluten in genetically susceptible individuals • Healthy population: 1: 133 • 1 st degree relatives: 1: 18 to 1: 22 • 2 nd degree relatives: 1: 24 to 1: 39 • Symptomatic and asymptomatic individuals • including subjects affected by: • Type 1 diabetes • Williams/Downs/Turner syndrome • Selective Ig. A deficiency 28

The Celiac Iceberg Symptomatic Celiac Disease Manifest mucosal lesion Silent Celiac Disease Latent Celiac Disease Normal Mucosa Genetic susceptibility: - DQ 2, DQ 8 Positive serology 29

Celiac: Epidemiological Study in USA Population screened 13145 Healthy Individuals 4126 Risk Groups 9019 Symptomatic subjects 3236 Positive 31 Negative 4095 Prevalence 1: 133 Positive 81 Negative 3155 1 st degree relatives 4508 Positive 205 Prevalence 1: 40 Negative 4303 Prevalence 1: 22 2 nd degree relatives 1275 Positive 33 Negative 1242 Prevalence 1: 39 Projected number of celiacs in the U. S. A. : 2, 115, 954 Actual number of known celiacs in the U. S. A. : 40, 000 For each known celiac there are 53 undiagnosed patients. A. Fasano et al. , Arch Int Med 2003; 163: 286 -292. 30

Celiac Disease Prevalence Data Geographic Area Prevalence 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 *based on classical, clinical presentation Fasano & Catassi, Gastroenterology 2001; 120: 636‑ 651. 31

1 2 b 2 2 a 8 8 Cytokines (IL 2, IL 15) Tk P AGA, EMA, at. TG 6 b 6 a B 3 7 TTG 4 APC T 5 Submucosa 32

Gastrointestinal Manifestations 6 -24 months Older Children and Adults • Chronic or recurrent diarrhea • Abdominal distension • Anorexia • Failure to thrive or weight loss • Vomiting • Constipation • Irritability • • • Dermatitis Herpetiformis Dental enamel hypoplasia Osteopenia/Osteoporosis Short Stature Delayed Puberty Iron-deficient anemia Resistant to oral Fe Hepatitis Arthritis 33

Typical Celiac Disease 34

Asymptomatic Celiac • 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 36

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 37

Celiac Diagnosis 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 38

Serologic. Testing 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 39

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 40

Serological Test Comparison AGA-Ig. G AGA-Ig. A EMA (Ig. A) TTG (Ig. A) Sensitivity % Specificity % 69 – 85 75 – 90 85 – 98 90 – 98 73 – 90 82 – 95 97 – 100 94 – 97 Farrell RJ, and Kelly CP. Am J Gastroenterol 2001; 96: 3237 -46. 41

Histological Features Normal 0 Infiltrative 1 Hyperplastic 2 Partial atrophy 3 a Subtotal atrophy 3 b Total atrophy 3 c 43 Horvath K. Recent Advances in Pediatrics, 2002.

Treatment • Only treatment for celiac disease is a gluten-free diet (GFD) • Strict, lifelong diet • Avoid: • Wheat • Spelt • Rye • Barley 44

Gastroesophageal Reflux Disease GERD Gastroesophageal reflux; reflux of the stomach and duodenal contents into the esophagus Any condition noted clinically or histologically that results from GER Regurgitation - Gastric contents pass the lower and upper esophageal sphincter Vomiting - Ejection of gastric contents through the mouth.

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 p. H probe monitoring Impedance monitoring Upper endoscopy and biopsy Nuclear scintigraphy study

Hiatal hernia diaphragm stomach

Diagnostic test • Esophageal p. H 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 p. H < 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, placebocontrolled trial assessing the efficacy and safety of proton pump inhibitor lansoprazole in infants with symptoms of gastroesophageal reflux disease Lansoprazole doubleblind (≤ 4 weeks, n = 81) Placebo double-blind (≤ 4 weeks, n =81) P value Primary efficacy: Responder rate, n (%) 44 (54%) NS Discontinued due to non efficacy, n (%) 28 (35%) 29 (36%) NS Cry, % of feeds/week -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 Orenstein SR, et al J Pediatr 2009 April; 154(4): 514 -520

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 IGERQ-R scores Orenstein, et al. J Pediatr 2008 Mar; 152(3): 310 -4 Maternal Child Health J 2012 Aug; 16(6): 1319 -31 • “Milk protein allergy” • Dietary elimination in mother diet / hypoallergenic formula trial

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

(An H 2 Receptor H 2 Ranitidine Receptor Antagonist Mechanism Antagonist) Mechanism of Action K+ H+

® (An PREVACID (lansoprazole) Mechanism of Ranitidine H 2 Receptor Proton Pump Inhibitor Antagonist) Mechanism of Action K+ H+

Rebound Acid Hypersecretion Temporal changes in the proportion of subjects with heartburn, acid regurgitation or dyspepsia. Christina R. , Gastroenterology 2009, 137(1) : 80 – 87.

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 • Non-invasive tests • Serum and whole blood antibody • Saliva antibody • Urine antibody • Stool antigen • Urea breath testing • Invasive tests requiring endoscopy • Biopsies and histology • Rapid urease testing • Bacterial culture • Polymerase chain reaction of bacterial DNA

Indications for treatment of H. pylori Treatment indicated? Diagnosis No No evidence of infection No Gastritis caused by H. pylori, no symptoms No Yes Gastritis caused by H. pylori, nonulcer dyspepsia Gastritis caused by H. pylori, gastric Yes ulcer Gastritis caused by H. pylori, Yes duodenal ulcer Gastritis caused by H. pylori, Yes MALT lymphoma

H. pylori treatment: 14 -day regimen • Omeprazole or Lansoprazole. • Clarithromycin 30 mg/kg/day. • Amoxicillin 60 mg/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