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Chapter 12 Gastroenterology Rebecca F. Rabin, MD, MHS See additional content on Expert Consult I. WEBSITESAmerican Academy of Pediatrics: www.aap.orgNorth American Society for Pediatric Gastroenterology, Hepatology, and Nutrition: www.naspghan.orgAmerican College of Gastroenterology: www.acg.gi.org II. GASTROINTESTINAL EMERGENCIESA. Gastrointestinal Bleeding1. Presentation—Blood loss from the gastrointestinal (GI) tract occurs in four ways: Hematemesis, hematochezia, melena, and occult bleeding2. Differential diagnosis of GI bleeding: Table 12-1.3. Initial evaluation and managementa. Assess airway, breathing, circulation, and hemodynamic stabilityb. Perform physical examination, looking for evidence of bleedingc. Verify bleeding with rectal examination, testing of stool or emesis for 12 occult blood, and/or gastric lavage. If possible, differentiate between upper vs. lower GI bleeding and assess for ongoing bleedingd. Obtain baseline laboratory tests. Complete blood count (CBC), prothrombin time/partial thromboplastin time (PT/PTT), blood type and cross-match, reticulocyte count, blood smear, blood urea nitrogen/ creatinine, electrolytes, and a panel to assess for disseminated intravascular coagulation (D-dimer, ﬁbrinogen)e. Begin initial ﬂuid resuscitation with normal saline or lactated Ringer’s solution. Consider transfusion if there is continued bleeding, symptomatic anemia, and/or a hematocrit level <20%. Initiate intravenous acid suppression therapy, preferably with a proton pump inhibitor (PPI)f. Further evaluation and therapy based on assessment and site of bleeding: (1) + Gastric lavage: Consider esophagogastroduodenoscopy (EGD). Treatment may include H2 blocker, PPI (use nasogastric tube with caution if esophageal varices are suspected) (2) + Stool hemoccult: Abdominal ﬁlm, upper GI study (± small bowel follow-through), air-contrast barium enema, colonoscopy, Meckel scan, tagged red cell scan. If signs/symptoms of infection exist, 293
294 Part II Diagnostic and Therapeutic Information TABLE 12-1DIFFERENTIAL DIAGNOSIS OF GI BLEEDINGAge Upper GI Tract Lower GI Tract Newborns (0–30 days) Swallowed maternal blood Necrotizing enterocolitis Gastritis Malrotation with midgut volvulus Anal ﬁssure Hirschsprung disease Infant (30 days–1 year) Gastritis Anal ﬁssure Esophagitis Allergic proctocolitis Peptic ulcer disease Intussusception Meckel’s diverticulum Lymphonodular hyperplasia Intestinal duplication Infectious colitis Preschool (1–5 years) Gastritis Juvenile polyps Esophagitis Lymphonodular hyperplasia Peptic ulcer disease Meckel’s diverticulum Esophageal varices Hemolytic-uremic syndrome Epistaxis Henoch-Schönlein purpura Infectious colitis Anal ﬁssure School age and Esophageal varices Inﬂammatory bowel disease adolescent Peptic ulcer disease Infectious colitis Epistaxis Juvenile polyps Gastritis Anal ﬁssure HemorrhoidsModiﬁed from Pearl R: The approach to common abdominal diagnoses in infants and children. Part II. Pediatr Clin North Am 1998;45:1287–1326. consider stool culture, stool ova & parasites, Clostridium difﬁcile toxinB. Acute Abdomen11. Deﬁnition: Severe abdominal pain (localized or generalized).2 May require emergency surgical evaluation/intervention2. Differential diagnosis:a. GI source: Appendicitis, pancreatitis, intussusception, malrotation with volvulus, inﬂammatory bowel disease, gastritis, bowel obstruction, mesenteric lymphadenitis, irritable bowel syndrome, abscess, hepatitis, perforated ulcer, Meckel diverticulitis, cholecystitis, choledocholithiasis, constipation, gastroenteritisb. Renal source: Urinary tract infection, pyelonephritis, nephrolithiasisc. Gynecologic source: Ectopic pregnancy, ovarian cyst/torsion, pelvic inﬂammatory diseased. Oncologic source: Wilms tumor, neuroblastoma, rhabdomyosarcoma, lymphomae. Other sources: Henoch-Schönlein purpura, pneumonia, sickle cell anemia, diabetic ketoacidosis, juvenile rheumatoid arthritis
Chapter 12 Gastroenterology 2953. Evaluation:a. History: Course and characterization of pain, diarrhea, melena, hematochezia, fever, last oral intake, menstrual history, vaginal discharge/bleeding, urinary symptoms, and respiratory symptoms. Assess past GI history, travel history, and dietb. Physical examination: Vital signs, toxicity, rashes, arthritis, jaundice. Abdominal tenderness on palpation, rebound/guarding, rigidity, masses, change in bowel sounds. Rectal exam with stool hemoccult test. Pelvic exam (discharge, masses, adnexal/cervical motion tenderness)c. Radiologic studies: First obtain plain abdominal radiographs to assess for obstruction, constipation, free air, gallstones, and kidney stones. Consider chest radiograph to evaluate for pneumonia, abdominal/pelvic ultrasonography, abdominal spiral computed tomography with contrast (include rectal contrast for appendicitis evaluation), other contrast studies, and endoscopyd. Laboratory studies: Electrolytes, chemistry panel, CBC, liver and kidney function tests, coagulation studies, blood type and screen/cross-match, urinalysis, amylase, lipase, gonorrhea/chlamydia cultures (or polymerase chain reaction probes), beta-human chorionic gonadotropin (β-hCG), erythrocyte sedimentation rate (ESR), C-reactive protein4. Management:a. Immediate: Patient should be placed on nothing by mouth (NPO) status. Begin rehydration. Consider nasogastric decompression, serial abdominal examinations, surgical/gynecologic/GI evaluation as indicated, pain control, and antibiotics as indicated 12b. Deﬁnitive: Surgical or endoscopic exploration as warranted III. CONDITIONS OF THE GI TRACT (ESOPHAGUS/STOMACH/BOWEL)A. VomitingSee Table 12-2 for evaluation of vomiting.B. Diarrhea31. Deﬁnition: Usual stool output is 10 g/kg/day in children and 100 g/day in adults. Stool loss of >10 g/kg/day in infants and young children or >200 g/day in older children or adults is considered diarrhea.4 Diarrhea is characterized by passage of loose or watery stools. The volume of ﬂuid lost through stools can vary from 10 mL/kg/day (approximately normal) to >200 mL/kg/day. Acute diarrhea is >3 loose or watery stools per day. Chronic diarrhea is diarrhea lasting more than 14 days2. Diagnosis/evaluation: History to assess acute vs. chronic, travel, recent antibiotic use, immune status. Consider laboratory evaluation: electrolytes, CBC, stool hemoccult, urine culture (young, febrile children), stool culture (febrile, ± bloody stools), stool tests for leukocytes, C. difﬁcile toxin, ova and parasites, viral antigens (e.g., rotavirus)
296 Part II Diagnostic and Therapeutic Information TABLE 12-2EVALUATION OF VOMITINGType Typically bilious Etiology: Obstruction, intussusception, malrotation ± volvulus, pancreatitis, intestinal dysmotility, peritoneal adhesions, incarcerated inguinal hernia, intestinal atresia/stenosis, superior mesenteric artery syndrome Evaluation: Review feeding and medication history; NG/OG tube for decompression if GI obstruction is suspected; if bilious and/or hematemesis, consider surgical consultation, BMP, CBC, ± UA, β-hCG, pancreatic enzymes, plain abdominal ﬁlm with upright or cross-table lateral views to rule out obstruction, free air; abdominal ultrasound if pyloric stenosis is suspected; upper GI series to rule out pyloric stenosis, obstruction, anomalies and evaluate GI motility, neurologic evaluation and imaging Typically nonbilious Etiology: Overfeeding, GERD, milk-protein sensitivity, infection (GU, respiratory, GI), peptic disease, drugs, electrolyte imbalance, eating disorders, necrotizing enterocolitis, metabolic abnormality, pyloric stenosis, CNS lesion, esophageal/gastric atresia/stenosis, Hirschsprung disease, annular pancreas, web, pregnancy Evaluation: Consider feeding modiﬁcations ± medications if GERD is suspected; avoid antiemetics unless a speciﬁc benign etiology is identiﬁed Either bilious or nonbilious Etiology: Ileus, appendicitisBMP, Basic metabolic panel; CBC, complete blood count; CNS, central nervous system; GERD, gastroesophageal reﬂux disease; GI, gastrointestinal; GU, genitourinary; hCG, human chorionic gonadotropin; NG/OG, nasogastric/orogastric; UA, urinalysis.Modiﬁed from Saavedra J: Gastroenterology. In Seidel H et al (eds): Primary care of the newborn, 4th ed. St. Louis, Mosby, 2006; and Sondheimer JM: Vomiting. In Walker WA et al (eds): Pediatric gastrointestinal disease, 3rd ed. New York, BC Decker, 2000.3. Etiology: Infectious or malabsorptive with osmotic or secretory mechanisma. Osmotic diarrhea: Water is drawn into intestinal lumen by maldigested nutrients (e.g., celiac or pancreatic disease, lactose) or other osmotic compounds. Stool volume depends on diet and decreases with fasting (stool osmolar gap ≥100 mOsm/kg)b. Secretory diarrhea: Water accompanies secreted or unabsorbed electrolytes into the intestinal lumen (e.g., excessive secretion of chloride ions caused by cholera toxin). Stool volume is increased and does not vary with diet (stool osmolar gap <100 mOsm/kg)c. Stool osmolar gap = Stool Osm − (2 × (stool [Na]mEq/L + stool [K] mEq/L)). Stool Osm is infrequently measured: standard value is 290 mOsm/kg54. Managementa. Oral rehydration therapy (ORT): Mainstay of initial management regardless of etiology. Parenteral hydration is indicated in severe dehydration, hemodynamic instability, or failure of ORT. See Chapter
Chapter 12 Gastroenterology 297 11 for oral rehydration solutions and for calculation of deﬁcit and maintenance ﬂuid requirementsb. Diet: Continue breastfeeding. Restart regular diet once patient is rehydrated, unless found to be the source of the diarrhea (e.g., gluten in Celiac Disease (CD), lactose in lactose intolerance)c. Other: Nonspeciﬁc antidiarrheal agents (e.g., adsorbents such as kaolin-pectin), antimotility agents (e.g., loperamide), antisecretory drugs, and toxin binders (e.g., cholestyramine) have limited data regarding efﬁcacy. If infectious, antimicrobial therapy may be indicated. If malabsorptive (e.g., celiac disease, inﬂammatory bowel disease), therapy should be tailored to disease process (e.g., gluten- free diet, steroids)d. Probiotics: Evidence supporting the use of probiotics (live microorganisms in fermented foods that promote optimal health by establishing an improved balance in intestinal microﬂora) is limited but efﬁcacy has been demonstrated in the following circumstances: antibiotic-associated diarrhea, mild to moderate acute diarrhea, C. difﬁcile diarrhea (severe recurrent disease only), and prevention of atopic dermatitis. Probiotics are not regulated by the Food and Drug Administration; thus, there is no oversight of quality control (including potency)6C. Constipation and Encopresis7Normal stooling patterns by age: Infants 0–3 months: 2–3 bowelmovements (BMs)/day, 6–12 months: 1.8/day, 1–3 years: 1.4/day,>3 years: 1/day 121. Deﬁnitions:a. Constipation: Delay or difﬁculty in defecation for 2 or more weeks. Functional causes of constipation are most common. (See Table EC 12-A on Expert Consult for differential diagnosis)b. Encopresis: Leakage of stool around impaction occurring in chronic constipation with loss of sensation in a distended rectal vault2. Diagnosis/evaluation:a. History: Timing of ﬁrst meconium stool, family’s deﬁnition of constipation, duration of condition and age of onset, toilet training experience, frequency/consistency/size of stools, pain or bleeding with defecation, presence of abdominal pain, soiling of underwear, stool withholding behavior, change in appetite, abdominal distension, anorexia, nausea, vomiting, weight loss, or poor weight gain, allergies, dietary history, medications, developmental history, psychosocial history, peer interactions, possibility of abuse, toilet habits at school, family history (constipation, thyroid disorders, cystic ﬁbrosis)b. Physical Exam: External perineum and perianal exam, digital anorectal exam (perianal sensation, anal tone, rectal size, presence of anal wink, amount/consistency/location of stool within the rectum). Stool occult blood test for all infants with constipation, any child with abdominal
298 Part II Diagnostic and Therapeutic Information pain, failure to thrive, intermittent diarrhea, or family history of colon cancer or colonic polyps. Fecal impaction may be diagnosed with physical exam (hard mass within abdomen), digital exam (dilated rectal vault ﬁlled with stool), and/or abdominal radiography3. Treatment of functional constipation:a. Disimpaction (2–5 days) (1) Oral/nasogastric approach: Polyethylene glycol electrolyte solutions are effective for initial disimpaction. May also use magnesium hydroxide, magnesium citrate, lactulose, sorbitol, senna, or bisacodyl laxatives (avoid magnesium-containing products in infants due to potential toxicity, beware of overdose in children) (2) Rectal approach: Saline or mineral oil enemas. Avoid soap suds, tap water, and magnesium enemas due to potential toxicity. Avoid enemas in infants, may use glycerin suppositories. Avoid phosphate-containing products due to risk of acute phosphate nephropathy (reported with use of oral sodium phosphate products)b. Maintenance therapy (usually 3–12 months): Goal is to prevent recurrence (1) Dietary changes: Increase intake of ﬂuids and absorbable and nonabsorbable carbohydrates to soften stools. A balanced diet that includes whole grains, fruits, and vegetables is recommended. Data are too weak to support a deﬁnitive recommendation for ﬁber supplementation in the treatment of constipation in children (2) Behavioral modiﬁcations: Regular toilet habits, positive reinforcement, and proper toilet positioning (stable seating, feet ﬁrmly planted, knees and hips at 90-degree angle). Referral to mental health for help with motivational or behavioral concerns (3) Medications: Polyethylene glycol (osmotic laxatives), lactulose, magnesium hydroxide, or sorbitol is recommended. Avoid prolonged use of stimulant laxatives. Discontinue therapy gradually only after return of regular bowel movements with good evacuation4. Special considerations in infants <1 year of age: Increased intake of ﬂuids, particularly of juices containing sorbitol, such as prune, pear, and apple juices, is recommended within the context of a healthy diet. Barley malt extract, corn syrup, lactulose, or sorbitol can be used as stool softeners. Glycerin suppositories may be useful. Avoid mineral oil, stimulant laxatives, and phosphate enemasD. Inﬂammatory Bowel Disease (IBD)8,91. Classiﬁcation/types:a. Crohn’s disease: Transmural inﬂammatory process affecting any segment of the GI tract from mouth to anus in discontinuous fashion. Clinical presentation is variable and frequently non-speciﬁc. Abdominal pain in majority of cases, minority of children with “classical triad” of abdominal pain, weight loss, and diarrhea. Other symptoms include
Chapter 12 Gastroenterology 299 lethargy, anorexia, fever, nausea, vomiting, growth retardation, malnutrition, delayed puberty, psychiatric symptoms, arthropathy, and erythema nodosum9b. Ulcerative colitis (UC): Chronic relapsing inﬂammatory disease of the colon and rectum. Symptoms (present for at least 2 weeks) include gross or occult rectal bleeding, diarrhea, abdominal pain with or around time of defecation. Exclusion of enteric pathogens (e.g., Salmonella, Shigella, Yersinia, Campylobacter, Escherichia coli 0157:H7, C. difﬁcile) is necessary.10 Weight loss, anorexia, lethargy are less common than in Crohn’s disease2. Evaluation:a. Complete history and physical exam including family history, exposure to infectious agents or antibiotic treatment, assessment of hydration and nutritional status, signs of peritoneal inﬂammation, signs of systemic chronic disease. Stomatitis, perianal skin tags, ﬁssures, ﬁstulas are suggestive of Crohn’s Disease. Presence of fever, orthostasis, tachycardia, abdominal tenderness, distension, or masses suggests moderate to severe disease and need for hospitalizationb. Laboratory assessment: CBC, ESR, CRP, serum urea and creatinine, serum albumin, liver function tests. IBD is associated with decreased hemoglobin and albumin, rise in platelet count, ESR, CRP (although children with UC may have normal hemoglobin, platelets, and ESR). Anti-neutrophil cytoplasmic antibodies (ANCA) may be elevated in UC. Diagnostic endoscopy is typically used to make diagnosis3. Management:a. First-line therapy: Corticosteroids, 5-aminosalicylates, antibiotics 12b. Second-line: Immunosuppression includes azathioprine, methotrexate Crohn’s, cyclosporine, tacrolimus and anti-tumor necrosis factor (TNF) monoclonal antibodiesc. Surgical intervention is indicated only after medical management has failed in both Crohn’s and UC. In Crohn’s, surgery is indicated for localized disease (strictures), abscess, or disease refractory to medical managementE. Gastrointestinal Reﬂux Disease111. Deﬁnitions: Gastroesophageal reﬂux (GER) is passage of gastric contents into the esophagus, and gastroesophageal reﬂux disease (GERD) is deﬁned as symptoms or complications of GER2. Evaluation/diagnosis:a. History and physical examination: Usually sufﬁcient to reliably diagnose GER, identify complications, and initiate managementb. Esophageal pH monitoring: Valid and reliable method of measuring acid reﬂuxc. Esophageal impedance monitoring: Combine with esophageal pH monitoring to detect both acid as well as nonacid reﬂux with greater sensitivity than pH monitoring alone12
300 Part II Diagnostic and Therapeutic Informationd. Upper GI series: Neither sensitive nor speciﬁc for GER but may be useful for the evaluation of anatomic abnormalities3. Management:a. Diet: Milk protein sensitivity is one cause of unexplained crying and vomiting in formula-fed infants; evidence supports 2–4 week trial of extensively hydrolyzed protein formula. Milk-thickening agents decrease visible regurgitation but do not decrease GER. No evidence to support routine elimination of speciﬁc foods to treat GERD in older childrenb. Lifestyle: Prone or left-side sleeping position, elevation of head of bed may improve GER symptoms in adolescents. Infants up to 12 months should continue to sleep supine—sudden infant death syndrome (SIDS) risk far outweighs beneﬁt of prone or lateral sleeping in GERD. (May consider prone positioning for infants while awake and monitored). Obesity and large meal volume are associated with increased GER in adultsc. Acid-suppressant therapy: Both PPIs and histamine-2 receptor antagonists (H2RAs) are effective in relieving symptoms and promoting mucosal healing. PPIs are superior to H2RAs. The smallest effective dose should be utilized for acid suppressiond. Prokinetic therapy: Potential side effects of each currently available prokinetic agent outweigh the potential beneﬁts. There is insufﬁcient evidence to support the routine use of metoclopramide, erythromycin, bethanechol, or domperidone for GERDF. Eosinophilic Esophagitis (EE)131. Deﬁnition: Symptoms of esophageal dysfunction with ≥15 eosinophils/ high-power ﬁeld (hpf) on peripheral blood smear, and absence of pathologic GERD as evidenced by lack of responsiveness to high-dose PPI or normal pH monitoring of distal esophagus2. Presentation: Dysphagia, food impaction, chest pain, food refusal or intolerance, GER symptoms, emesis, abdominal pain, failure to thrive. High rate of atopy in children with EE3. Diagnosis: Endoscopy and esophageal biopsy, allergic evaluation for other atopic conditions4. Management: Dietary therapy (elemental formula or removal of speciﬁc foods identiﬁed by skin prick or atopy patch testing), PPI therapy (as co-treatment), may consider systemic steroids for emergencies (e.g., dysphagia leading to dehydration, weight loss), topical steroids for less severe symptoms (6–8 week course of Fluticasone or Budesonide metered dose inhaler (MDI) administered orally without spacer). There are limited data on the use of steroids in EE—recommendation based on expert opinion and current literature5. Differential diagnosis of esophageal eosinophilia: GERD, EE, eosinophilic gastroenteritis, Crohn’s disease, connective tissue disease, hypereosinophilic syndrome, infection, drug hypersensitivity
Chapter 12 Gastroenterology 301G. Celiac Disease141. Deﬁnition: An immune-mediated enteropathy caused by a permanent sensitivity to gluten of the GI tract in genetically susceptible individuals. Increased occurrence in children with type 1 diabetes mellitus, autoimmune thyroiditis, Down syndrome, Turner syndrome, Williams syndrome, selective IgA deﬁciency, and in ﬁrst-degree relatives of those with celiac disease2. Presentation: Diarrhea, vomiting, abdominal pain, constipation, abdominal distension, failure to thrive. Non-GI symptoms include dermatitis herpetiformis, dental enamel hypoplasia of permanent teeth, osteoporosis, short stature, delayed puberty, and iron-deﬁcient anemia resistant to oral iron3. Diagnosis: Measure IgA antibody to human recombinant tissue transglutaminase (TTG) and serum IgA (high prevalence of IgA deﬁciency in celiac disease). Endomysial antibody is subject to interpretation error and adds cost. If there is known selective IgA deﬁciency and symptoms are suggestive of celiac disease, testing with TTG IgG is recommended. Conﬁrmation requires an intestinal biopsy in all cases with ﬁndings of villous atrophy as a characteristic histopathologic feature4. Management: Lifetime gluten-free diet IV. CONDITIONS OF THE LIVERA. Liver Function Studies: (See Table 12-3)1. Synthetic function: Albumin, prealbumin, PT, activated PTT, 12 cholesterol. Elevated NH3 is evidence of decreased ability to detoxify ammonia2. Liver cell injury: Elevation of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase3. Cholestasis: Increased bilirubin, urobilinogen, γ-glutamyltransferase, alkaline phosphatase, 5′-nucleotidase, serum bile acidsB. Acute Liver Failure (ALF)151. Deﬁnition: Biochemical evidence of liver injury with no history of known chronic liver disease, presence of coagulopathy not corrected by vitamin K administration, and international normalized ratio (INR) >1.5 if the patient has encephalopathy or >2.0 if the patient does not have encephalopathy. Causes of ALF vary in reversibility (with treatment or withdrawal of offending agent) and in age of presentation2. Etiologies: (incidence varies by age):a. Infection: Herpes virus, hepatitis A, hepatitis B, adenovirus, cytomegalovirus, Epstein-Barr virus, enterovirus, indeterminateb. Vascular: Budd-Chiari syndrome, portal vein thrombosis, veno- occlusive disease, ischemic hepatitisc. Immune dysregulation: Natural killer (NK) cell dysfunction (hemophagocytic lymphohistiocytosis), autoimmune
302 TABLE 12-3EVALUATION OF LIVER FUNCTION TESTSEnzyme Source Increased Decreased Comments AST/ALT Liver Hepatocellular injury Vitamin B6 deﬁciency ALT more speciﬁc than AST for liver Heart Rhabdomyolysis Uremia AST >ALT in hemolysis Skeletal muscle Muscular dystrophy AST/ALT >2 in 90% of alcohol disorders in adults Pancreas Hemolysis RBCs Liver cancer Kidney Alkaline phosphatase Liver Hepatocellular injury Low phosphate Highest in cholestatic conditions Osteoblasts Bone growth, disease, trauma Wilson disease Must be differentiated from bone source Small intestine Pregnancy Zinc deﬁciency Kidney Familial Hypothyroidism Placenta Pernicious anemia GGT Bile ducts Cholestasis Estrogen therapy Not found in bone Renal tubules Newborn period Artiﬁcially low in Increased in 90% primary liver disease Pancreas Induced by drugs hyperbilirubinemia Biliary obstruction Part II Diagnostic and Therapeutic Information Small intestine Intrahepatic cholestasis Brain Induced by alcohol Speciﬁc for hepatobiliary disease in nonpregnant patient
Enzyme Source Increased Decreased Comments 5′-NT Liver cell membrane Cholestasis Speciﬁc for hepatobiliary disease in nonpregnant patient Intestine Brain Heart Pancreas NH3 Bowel Hepatic disease secondary to Converted to urea in liver Bacteria urea cycle dysfunction Protein metabolism Hemodialysis Valproic acid therapy Urea cycle enzyme deﬁciency Organic acidemia and carnitine deﬁciencyAST/ALT, Aspartate aminotransferase/alanine aminotransterase; 5′-NT, 5′-nucleotidase; GGT, γ-glutamyl transpeptidase; RBCs, red blood cells. Chapter 12 Gastroenterology 303 12
304 Part II Diagnostic and Therapeutic Informationd. Inherited/metabolic: Wilson’s disease, mitochondrial, tyrosinemia, galactosemia, fatty acid oxidation defect, iron storage diseasee. Drugs/toxins: Acetaminophen, anticonvulsantsf. Other: Unknown, cancer/leukemia3. Presentation: Prodrome of malaise, nausea, emesis, and anorexia; jaundice and encephalopathy (hyperammonemia, cerebral edema) may be delayed by hours to weeks; glucose instability with hypoglycemia, coagulopathy4. Evaluation:a. Clinical: Neurologic status, signs of chronic liver disease, other chronic diseaseb. Laboratory: Electrolytes, BUN, creatinine, blood glucose, calcium, magnesium, phosphorous, blood gas, CBC with peripheral smear, reticulocyte count, liver function/production (albumin, aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase), INR, PT, PTT, ammonia, factors V, VII (depleted ﬁrst in ALF), VIII, ﬁbrinogen. Urine toxicology screen, serum acetaminophen level. Consider viral studiesNOTE: See Table 12-4 for interpretation of serologic markers of Hepatitis B.c. Imaging: Abdominal ultrasound with Doppler ﬂows, head computed tomography (CT) scan to exclude hemorrhage/edema, chest radiographd. Studies to explore causation: Viral studies, immune function, metabolic studies, tissue biopsiesC. Hyperbilirubinemia16,17Bilirubin is the product of hemoglobin metabolism. There are two forms:direct (conjugated) and indirect (unconjugated). Hyperbilirubinemiais usually the result of increased hemoglobin load, reduced hepaticuptake, reduced hepatic conjugation, or decreased excretion. Directhyperbilirubinemia is deﬁned as direct bilirubin >20% of total or direct TABLE 12-4INTERPRETATION OF THE SEROLOGIC MARKERS OF HEPATITIS BIN COMMON SITUATIONS Serologic MarkerHBsAg Total HBcAb IgM HBcAb HBsAb Interpretation − − − − No prior infection, not immune − − − + Immune after hepatitis B vaccination (if concentration ≥10 mlU/mL or passive immunization from HBIG administration) − + − + Immune after recovery from HBV infection + + + − Acute HBV infection + + − − Chronic HBV infectionHBsAg, Hepatitis B surface antigen; HBcAb, antibody to hepatitis B core antigen; HBsAb, antibody to hepatitis B surface antigen; HBIG, hepatitis B immune globulin.From Davis AR, Rosenthal P: Hepatitis B in children. Pediatr Rev 2008;29;111–120.
Chapter 12 Gastroenterology 305 TABLE 12-5DIFFERENTIAL DIAGNOSIS OF HYPERBILIRUBINEMIAINDIRECT HYPERBILIRUBINEMIA Transient neonatal Breast milk jaundice, physiologic jaundice jaundice Polycythemia, reabsorption of extravascular blood Hemolytic disorders Autoimmune disease, blood group incompatibility, hemoglobinopathies, microangiopathies, red cell enzyme deﬁciencies, red cell membrane disorders Enterohepatic Cystic ﬁbrosis, Hirschsprung disease, ileal atresia, pyloric stenosis recirculation Disorders of bilirubin Acidosis, Crigler-Najjar syndrome, Gilbert syndrome, hypothyroidism, metabolism hypoxia Miscellaneous Dehydration, drugs, hypoalbuminemia, sepsisDIRECT HYPERBILIRUBINEMIA Biliary obstruction Biliary atresia, choledochal cyst, ﬁbrosing pancreatitis, gallstones or biliary sludge, inspissated bile syndrome, neoplasm, primary sclerosing cholangitis Infection Cholangitis, cytomegalovirus, Epstein-Barr virus, herpes simplex virus, histoplasmosis, HIV, leptospirosis, liver abscess, sepsis, syphilis, toxocariasis, toxoplasmosis, tuberculosis, urinary tract infection, varicella-zoster virus, viral hepatitis Genetic/metabolic α1-Antitrypsin deﬁciency, Alagille syndrome, Caroli disease, cystic disorders ﬁbrosis, Dubin-Johnson syndrome, galactokinase deﬁciency, galactosemia, glycogen storage disease, hereditary fructose intolerance, hypothyroidism, Niemann-Pick disease, rotor syndrome, tyrosinemia, Wilson disease Chromosomal Trisomy 18, trisomy 21, Turner syndrome abnormalities 12 Drugs Acetaminophen, aspirin, erythromycin, ethanol, iron, isoniazid, methotrexate, oxacillin, rifampin, steroids, sulfonamides, tetracycline, vitamin A Miscellaneous Neonatal hepatitis syndrome, parenteral alimentation, Reye syndromebilirubin >2 mg/dL. See Table 12-5 for differential diagnosis ofhyperbilirubinemia. Refer to Chapter 18 for evaluation and treatment ofneonatal hyperbilirubinemia V. PANCREATITIS18,19Inﬂammatory disease of the pancreas; falls into two major categories,acute and chronic.A. Acute Pancreatitis1. Presentation: Sudden onset of abdominal pain associated with rise of pancreatic digestive enzymes in serum or urine with or without radiographic changes in the pancreas. It is a reversible process. Most common etiologies: trauma, multisystem disease, drugs, infections, idiopathic, and congenital anomalies. See Table 12-6 for conditions associated with acute pancreatitis
306 Part II Diagnostic and Therapeutic Information TABLE 12-6CONDITIONS ASSOCIATED WITH ACUTE PANCREATITISSYSTEMIC DISEASES Infections Coxsackie, CMV, cryptosporidium, EBV, hepatitis, inﬂuenza A or B, leptospirosis, mycoplasma, mumps, rubella, typhoid fever, varicella Inﬂammatory and Collagen vascular diseases, hemolytic uremic syndrome, vasculitic disorders Henoch-Schönlein purpura, inﬂammatory bowel disease, Kawasaki disease Sepsis/peritonitis/shock TransplantationIDIOPATHIC (UP TO 25% OF CASES)MECHANICAL STRUCTURAL Trauma Blunt trauma, child abuse, ERCP Perforation Anomalies Annular pancreas, choledochal cyst, pancreatic divisum, stenosis, other Obstruction Parasites, stones, tumorsMETABOLIC AND TOXIC FACTORS Cystic ﬁbrosis Diabetes mellitus Drugs/toxins Salicylates, cytotoxic drugs (L-asparaginase), corticosteroids, chlorothiazides, furosemide, oral contraceptives (estrogen), tetracyclines, sulfonamides, valproic acid, azathioprine, 6-mercaptopurine Hypercalcemia Hyperlipidemia Hypothermia Malnutrition Organic acidemia Renal diseaseCMV, Cytomegalovirus; EBV, Epstein-Barr virus; ERCP, endoscopic retrograde cholangiopancreatography.Modiﬁed from Robertson MA: Pancreatitis. In Walker WA et al (eds): Pediatric gastrointestinal disease, 3rd ed. New York, BC Decker, 2000, pp. 1321–1344; and Werlin SL: Pancreatitis. In McMillan, JA et al (eds.), Oski’s pediatrics. Philadelphia, PA, Lippincott Williams & Wilkins, 2006, pp. 2010–2012.2. Diagnosis/evaluation:a. Clinical signs/symptoms: Abdominal pain (sudden or gradual, most commonly epigastric), anorexia, nausea, vomiting, tachycardia, fever, hypotension, guarding/rebound tenderness/decreased bowel sounds, sonographic or radiologic evidence of pancreatic inﬂammation. Gray-Turner and Cullen’s sign are rare in childrenb. Laboratory ﬁndings: (1) Elevated lipase and amylase: ≥3 times above normal limit (but no correlation with disease severity); lipase is more sensitive and speciﬁc for acute pancreatitis but normalizes more slowly so it may be preferable to follow amylase after establishment of diagnosis8 (2) Additional ﬁndings: Leukocytosis, hyperglycemia, glucosuria, hypocalcemia, hyperbilirubinemia
Chapter 12 Gastroenterology 307 TABLE 12-7PROPOSED ETIOLOGIES OF CHRONIC PANCREATITIS IN CHILDHOOD Calciﬁc Cystic ﬁbrosis, hereditary pancreatitis (e.g. PRSS1 and SPINK1 mutations), hypercalcemia, hyperlipidemia, idiopathic, juvenile tropical pancreatitis Obstructive (noncalciﬁc) Congenital anomalies, idiopathic ﬁbrosing pancreatitis, renal disease, sclerosing cholangitis, sphincter of Oddi dysfunction, trauma3. Management:a. Pancreatic rest: Nasogastric decompression, analgesia, IV ﬂuid hydration, and oral intake restriction. Enteral feeding via naso-jejunal tube may be used for nutrition. (In adults, enteral nutrition is associated with lower incidence of infection, surgical intervention and shorter hospital stay. There is minimal pediatric evidence available)b. Antibiotics are reserved for only the most severe casesB. Chronic Pancreatitis1. Deﬁnition: A progressive, inﬂammatory process causing irreversible changes in the architecture and function of the pancreas. Common complications include chronic abdominal pain, loss of exocrine function (malabsorption, malnutrition) and/or endocrine function (diabetes mellitus). Two major morphologic forms: Calciﬁc and obstructive. See Table 12-72. Management: (for acute exacerbations) Same as management of acute 12 pancreatitis; See Section V.A.3C. Miscellaneous Tests (for Descriptions, See Expert Consult, Chapter 12)REFERENCES 1. Moir CR. Abdominal pain in infants and children. Mayo Clin Proc. 1996;71(10): 984–989. 2. World Health Organization. ICD-10, 2007, World Health Organization, Available online. http://www.who.int/classiﬁcations/icd/en/. 3. King CK, Glass R, Bresee JS, et al. Managing acute gastroenteritis among children: oral rehydration, maintenance, and nutritional therapy. MMWR Recomm Rep. 2003;52:1–16. 4. Vanderhoof JA. Chronic diarrhea. Pediatr Rev. 1998;19(12):418. 5. Thomas PD, Forbes A, Green J, et al. Guidelines for the investigation of chronic diarrhoea, 2nd ed. Gut. 2003;52(suppl 5):v1–15. 6. Clinical Practice Guideline. Clinical efﬁcacy of probiotics: review of the evidence with focus on children. NASPGHAN Nutrition Committee Report. J Pediatr Gastroenterol Nutr. 2006:43:550–557. 7. Constipation Guideline Committee of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. Evaluation and treatment of constipation in infants and children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2006;43:e1–e13.
308 Part II Diagnostic and Therapeutic Information 8. McMillan JA, Feigin RD, DeAngelis CD. Oski’s pediatrics, 4th ed. 2006, pp. 1926, 1954, Philadelphia, PA: Lippincott Williams & Wilkins; 2011. 9. Beattie RM, Croft NM, Fell JM, et al. Inﬂammatory bowel disease. Arch Dis Child. 2006;91:426–432.10. Clinical Report: Differentiating ulcerative colitis from Crohn disease in children and young adults: report of a working group of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the Crohn’s and Colitis Foundation of America. J Pediatr Gastroenterol Nutr. 2007;44:653–674.11. Vandenplas Y, Rudolph CD, Di Lorenzo C, et al. Pediatric gastroesophageal reﬂux clinical practice guidelines: joint recommendations of the North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr. 2009;49:498–547.12. Hirano I, Richter JE; Practice Parameters Committee of the American College of Gastroenterology. ACG practice guidelines: esophageal reﬂux testing. Am J Gastroenterol. 2007;102:668–685.13. Furuta GT, Liacouras CA, Collins MH, et al. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology. 2007;133:1342–1363.14. Hill ID, Dirks MH, Liptak GS, et al. Guideline for the diagnosis and treatment of celiac disease in children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2005;40:1–19.15. Bucuvalas J, Yazigi N, Squires RH Jr. Acute liver failure in children. Clin Liver Dis. 2006;10:149–168.16. Harb R, Thomas DW. Conjugated hyperbilirubinemia: screening and treatment in older infants and children. Pediatr Rev. 2007;28:83–91.17. Moyer V, Freese DK, Whitington PF, et al. Guideline for the evaluation of cholestatic jaundice in infants: Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2004;39:115–128.18. Lowe ME. Pancreatitis in childhood. Curr Gastroenterol Rep. 2004;6:240–246.19. Nydegger A, Couper RTL. Childhood pancreatitis. J Gastroenterol Hepatol. 2006;21(3):499–509.