A Practical Approach To Chronic Diarrhea: Allergy, Pathology or Nothing Rick Schreiber MD FRCP(Can) Clinical Professor of Pediatrics Faculty of Medicine University of British Columbia Director BC Pediatric Liver Transplant Program Division of Pediatric Gastroenterology, Hepatology and Nutrition BC Children’s Hospital Vancouver BC Canada North Pacific Pediatric Society Aug 2013 Objectives • Understand the physiologic mechanisms of diarrhea • Provide a practical evaluation of pediatric chronic diarrhea highlighting the important elements in the history, physical exam and laboratory testing • Be familiar with the leading causes of chronic diarrhea with and without failure to thrive • Appreciate the approach to therapies for chronic diarrhea in children North Pacific Pediatric Society Aug 2013 Pediatric Diarrheal Disease Globally: • 2-4 million childhood deaths per year because of diarrheal illness • 50% due to chronic diarrhea • 3 episodes chronic diarrhea/yr in kids 6 months to 3 years old • Major economic burden especially in developing nations North Pacific Pediatric Society Aug 2013 Daily fluid intake and endogenous secretions are efficiently absorbed by the GI tract Oral fluid intake 2000 Salivary glands 1500 Endogenous Secretions 7000 Stomach 2500 Bile 500 Pancreas 1500 Small Intestine 1000 9000 -7300 -1500 200 Total presented to small Intestine Absorbed from Small bowel Absorbed from Colon Stool % absorbed: 8800 : 98% 9000 North Pacific Pediatric Society Aug 2013 VOLUME OF FLUID IN THE HUMAN INTESTINE: Comparison of Infants to Adults WATER FLOW (ml/kg/24hrs) INFANTS ADULTS Entering Duodenum Entering Colon 285 60 120 25 Stool 5-10 1-3 North Pacific Pediatric Society Aug 2013 DIARRHEA: Physiologic Classification • OSMOTIC Fecal Osmolarity (290 mosm/kg) -2(Na+K) >50 An “Osmotic” gap Worse with eating • SECRETORY Fecal Osmolarity (290 Osm/kg) -2(Na +K) <50 A stool rich in electrolytes; stool [Na] almost same as serum [Na] Persists despite fasting North Pacific Pediatric Society Aug 2013 Diarrhea: Clinical Classification • Acute: Self limited mostly infectious: Rotavirus Other viruses Bacterial Parasitic • Chronic: Diarrheal illness lasting >2 weeks North Pacific Pediatric Society Aug 2013 PEDIATRIC CHRONIC DIARRHEA: A Careful History is Key • AGE OF ONSET • STOOL CHARACTERISTICS: Watery/Steatorrhea/Blood • STOOL PATTERN: Frequency/Night time Large water volume Small bowel Small water volume Colon Colitis: bloody, tenesmus, urgency • DIETARY RECORD • PLOT GROWTH PARAMETERS: ? Failure to thrive • OTHER: Travel, Contacts, Medication, Psychosocial North Pacific Pediatric Society Aug 2013 CHRONIC DIARRHEA: The Physical Exam • Assess for dehydration and malnutrition • Make sure to plot growth parameters on a graph • Obtain previous weights/heights for comparison • Look for signs of Edema •Usually exam is unremarkable but look for clues: North Pacific Pediatric Society Aug 2013 CHRONIC DIARRHEA RECOMMENDED INITIAL LABORATORY INVESTIGATIONS • Stools for C&S, C diff, O&P, WBCs • CBC • CRP/ESR • Albumin • IgA/TTG • U/A, urine C&S Especially in younger aged children North Pacific Pediatric Society Aug 2013 CLINICAL APPROACH TO PEDIATRIC CHRONIC DIARRHEA ? IS THE PATIENT DEHYDRATED yes ORAL REHYDRATING SOLUTION WE HAVE THE SOLUTION…… SO WHAT’S THE PROBLEM North Pacific Pediatric Society Aug 2013 COMPOSITION OF SOME ORS AND OTHER CLEAR FLUIDS Solution WHO Rehydralyte Infalyte Lytren Pedialyte Na 90 75 50 50 45 Cola 2 Ginger Ale 3 Apple Juice 3 Chicken Broth 250 Tea 0 Gatorade 20 K 20 20 20 25 20 Cl 80 65 40 45 35 Base 10 10 10 10 10 0.1 2 15 1 2 4 28 30 0 8 250 0 0 0 0 North 3Pacific Pediatric Society Aug 2013 Glucose Osm 111 (D2.0) 310 140 (2.5) 305 111 (2.0) 270 111 (2.0) 290 111 (2.0) 270 730 500 690 0 0 310(D5.6) 750 540 730 450 5 300 CLINICAL APPROACH TO PEDIATRIC CHRONIC DIARRHEA yes ? IS THE PATIENT DEHYDRATED ORAL REHYDRATING SOLUTION INITIAL INVESTIGATIONS ? IS THERE FAILURE TO THRIVE no 1. 2. 3. 4. 5. 6. 7. 8. Intestinal Parasite: Giardia, Crypto C. Difficile Excluded Celiac by initial lab UTI Toddler’s Diarrhea Lactose Intolerance Constipation with overflow incontinence Irritable Bowel Syndrome: Diarrheal type North Pacific Pediatric Society Aug 2013 CHRONIC DIARRHEA WITHOUT FAILURE TO THRIVE TODDLER’S DIARRHEA Non Specific Diarrhea of Childhood • 6-39 months • Onset usually post infectious gastro • Watery non-bloody diarrhea with vegetable matter • Normal Growth • Negative exam and initial laboratory investigations are normal TREATMENT This is most often iatrogenic: BRAT diet is old school Normalize the diet: Milk is ok in 90% of cases Starches like rice/pasta are best Increase fat content Eliminate sugar/juice North Pacific Pediatric Society Aug 2013 CHRONIC DIARRHEA WITHOUT FAILURE TO THRIVE Lactase Deficiency Primary Secondary Congenital lactase deficiency: Very rare Any enteropathy: disrupts Intestinal Brush border Post viral gastro: only in 10% of cases Primary Hypolactasia : Onset after age 5 /6; usually in adolescence Common in Asians, Aboriginal, Native Indian, Middle Eastern North Pacific Pediatric Society Aug 2013 HYDROGEN BREATH TEST North Pacific Pediatric Society Aug 2013 Irritable Bowel Syndrome with Diarrhea • A diagnosis in older children and adolescents • Rome III: Abdominal pain (3 days/month in past 3 months) and altered bowel habit • No “red flags” based on history, physical exam or initial lab studies Fecal Calprotectin and Endoscopic Diagnosis Medications with Efficacy in IBS-D Loperamide Amitriptyline Rifaximin Gabapentin ? Probiotics Trinkley KE: J Clin Pharm Ther 2011 Chen CC, Walker A Nat Med J India 2011 Licata A J Clin Gastro 2012 North Pacific Pediatric Society Aug 2013 CLINICAL APPROACH TO PEDIATRIC CHRONIC DIARRHEA ORAL REHYDRATING SOLUTION ? IS THE PATIENT DEHYDRATED BASIC INVESTIGATIONS ? IS THERE FAILURE TO THRIVE yes MALABSORPTION 1. 2. 3. 4. 5. 6. 7. 8. Intestinal Parasite: Giardia, Crypto C. Difficile Celiac UTI Lactose Intolerance Toddlers Diarrhea Constipation with overflow incontinence Irritable Bowel Syndrome: Diarrheal type North Pacific Pediatric Society Aug 2013 CHRONIC DIARRHEA WITH FAILURE TO THRIVE INTRALUMINAL MUCOSAL SECRETORY Stool rich in electrolytes Diarrhea persists when NPO Rare Infectious toxins: Cholera, other Neuroblastoma Other secreting tumours: VIP Carcinoid ZE syndrome Mastocytosis These patients should be referred to GI specialist North Pacific Pediatric Society Aug 2013 CHRONIC DIARRHEA WITH FAILURE TO THRIVE INTRALUMINAL MUCOSAL SECRETORY Fat or CHO Malabsorption Pancreatic Insufficiency: Must exclude CF as this is most common Cholestatic Liver Disease with bile salt deficiency CHO Enzyme deficiencies Laxative Abuse North Pacific Pediatric Society Aug 2013 CHRONIC DIARRHEA WITH FAILURE TO THRIVE INTRALUMINAL 2nd line investigations Pancreatic Insufficiency Cystic Fibrosis Schwachman Diamond Cholestasis Tests of Liver function Fat Soluble vitamin levels CHO ENZYME DEFICIENCIES LACTASE SUCRASE/ISOMALTASE SORBITOL MAGNESIUM LAXATIVE ABUSE Sweat Test Fecal Elastin 72 hr stool for fat study Fat Soluble vitamins AN OSMOTIC diarrhea: Stool osmotic gap >125 Stool pH <5 Stool Mg 45-100mmol/L Stool SO4 or PO4 >10mmol/L North Pacific Pediatric Society Aug 2013 CHRONIC DIARRHEA WITH FAILURE TO THRIVE INTRALUMINAL MUCOSAL Celiac Disease SECRETORY Most common causes in infancy Food Protein Allergy Post infectious enteritis/Intractable diarrhea of infancy IBD: Most common cause by end of first decade and adolescence Immunodeficiency disorders Eosinophilic gastroenteritis Acrodermatitis Enteropathica Other North Pacific Pediatric Society Aug 2013 COW’S MILK - SOY PROTEIN ALLERGY • A diagnosis in neonates and young infants: Does not have onset in childhood • Has a variety of clinical GI presentations: - Necrotizing enterocolitis in term newborns - Allergic colitis of neonate/young infant: bloody stool without other symptoms. - Eosinophilic enteropathy: Profuse Vomiting, Chronic diarrhea, FTT, Pallor, Edema • Look for Anemia/Hypoalbuminemia; Eosinophilia not a sensitive or specific test • Usually mediated by Non IgE mechanisms: IgE levels may or may not be elevated • The clinical presentation will influence need for referral endoscopy and biopsy • Dietary trial is individualized and depends on presentation North Pacific Pediatric Society Aug 2013 CHRONIC DIARRHEA WITH FAILURE TO THRIVE MUCOSAL OFTEN NEEDS REFERRAL TO GI FOR EVALUATION AND MANAGEMENT Celiac Allergic enteropathy Post infectious/ Intractable diarrhea of infancy IBD OTHER Refer for: Endoscopy/biopsy (rapid triage) Keep on regular diet Markedly FTT Refer for: Significant anemia Advanced Nutritional Support Edema with hypoproteinemia Endoscopy/Biopsy Not responsive to basic Other management formula shift Elevated TTG > 3x normal High risk patients r/o infection Immunoglobulins Refer for: Advanced Nutritional Support Endoscopy/Biopsy Other management Most common cause in older age groups Refer for: r/o infection Endoscopy/colonoscopy (rapid CBC ,ESR, CRP, Albumin, LFTs triage) Management Earlier age onset more concern North Pacific Pediatric Society Aug 2013 Unusual and rare problem Refer for Diagnostics/management Pediatric Chronic Diarrhea Summary • Chronic diarrhea is a complex syndrome with many different etiologic categories. • A careful approach thinking about age at onset, stool characteristics, diet and whether FTT is present or not is key. • Along with basic laboratory studies most of the diagnostic possibilities can be sorted out. • Gastroenterology referral is usually reserved for those with FTT or where laboratory abnormalities suggest the need for further diagnostic tests or more advanced management. North Pacific Pediatric Society Aug 2013