CHAPTER 10: Gastroenterology

GASTROESOPHAGEAL REFLUX DISEASE

Gastroesophageal reflux (GER) is a physiologic process of stomach contents regurgitating into the esophagus. Gastroesophageal reflux disease (GERD) occurs when GER is accompanied by disturbing symptoms or complications such as esophagitis, respiratory disease, failure to thrive, and/or neurobehavioral manifestations.

EPIDEMIOLOGY

• In infants, most GER is physiologic and benign

• Functional GER occurs in more than half of all infants

• Most common esophageal disorder

PATHOPHYSIOLOGY

• Transient lower esophageal sphincter (LES) relaxation allows gastric contents to flow retrograde up the esophagus

• Decreased gastric compliance in infants compared to adults

CLINICAL MANIFESTATIONS

• Functional/Simple GER: Silent oral regurgitation, effortless spitting, or forceful vomiting; symptoms peak at 1–4 months and resolve by 12–18 months of age; usually benign

• Complicated GER (GERD): Significant complications develop in about 10% of untreated children

  • ✓ Esophagitis: Crying, irritability, food aversion, heartburn, epigastric or chest pain, odynophagia, hematemesis, anemia, and/or guaiac-positive stools

  • ✓ Respiratory: Laryngospasm, bronchospasm, microaspiration pneumonia

  • ✓ Failure to thrive

  • ✓ Neurobehavioral manifestations: Sandifer syndrome (opisthotonic posturing, head tilting, seizure-like activity); arching; excessive irritability

DIAGNOSTICS

• With uncomplicated GER, no diagnostic tests are warranted. In infants or children with complicated GER, consider:

  • ✓ Upper Gastrointestinal (GI) Series: Defines anatomy; useful to exclude malrotation, pyloric stenosis, webs, atresias, or other anatomic causes; not diagnostic for reflux

  • ✓ Scintigraphy or “Milk Scan”: Detects delayed gastric emptying and/or pulmonary aspiration; not diagnostic for reflux

  • ✓ pH Probe: Gold standard to quantify acid reflux; helps establish causal relationship between reflux and other symptoms

  • ✓ Impedance Probe: Measures movement of air, fluid, and solids in the esophagus through electrical impedance (resistance). Can detect presence of nonacid contents and can be combined with pH probe monitoring. Particularly useful in correlating symptoms with reflux events in patient on acid suppression therapy or in postprandial period when stomach contents likely to be nonacid

  • ✓ Upper Endoscopy: Allows direct visualization of the mucosa and the pathologic diagnosis of mucosal disease related to reflux; basal cell hyperplasia, papillary elongation, and an inflammatory cellular infiltrate seen in esophagitis

MANAGEMENT

• Conservative Therapy: Appropriate as a component of treatment for all GER, and may be sole therapy for uncomplicated GER. These measures may mitigate GER symptoms in about 20% of affected infants

  • ✓ Thicken formula with rice cereal (½–1 tablespoon per ounce)

  • ✓ Hold upright during and after feeds

  • ✓ Sleep with head elevated 30 degrees

    • ■ While prone positioning may mitigate GER symptoms, the association of sudden infant death syndrome (SIDS) with prone positioning of young infants precludes a recommendation of prone positioning as a routine strategy

  • ✓ Formula changes: Allergy to cow’s milk or soy-based formulas is uncommon and unlikely to present with emesis as the sole symptom. Therefore, formula changes are generally not warranted. If cow’s milk protein intolerance is suspected, one may switch to a protein hydrolysate or elemental formula for a 2-week period while observing for symptom improvement

• Medical Therapy:

  • ✓ Antacid magnesium hydroxide/aluminum hydroxide preparations (e.g., Maalox, Mylanta): 0.5 mL/kg/dose (maximum 15 mL) three times daily 10 minutes before feedings; separate from other medications by 1 hour

  • ✓ Acid suppression (H2 receptor antagonists (H2RAs) [i.e., ranitidine, famotidine] and proton pump inhibitors (PPI) [i.e., omeprazole, lansoprazole, esomeprazole]) does not prevent GER but helps prevent complications. H2RAs are generally first-line therapy in infants and children <12–18 months. PPI therapy in infants is less effective at reducing symptoms than in older children based on available controlled clinical trials. Therefore, PPIs are only considered potential first-line therapy in children >18 months of age

  • ✓ Prokinetics: Include metoclopramide, erythromycin, bethanechol, domperidone, and cisapride. Metoclopramide and low-dose erythromycin (3–5 mg/kg/dose) are available in the United States, but are not currently recommended for treatment of GERD based on insufficient evidence and potential for side effects. Domperidone and cisapride are available only through a clinical trial

• Post-pyloric feedings via feeding tube (naso-jejunal or gastro-jejunal), especially in setting of aspiration events

• Surgical Therapy:

  • ✓ Fundoplication: Indicated for severe complicated GERD with failure of maximal medical therapy; may result in other long-term complications such as gas-bloat syndrome, chronic retching, and dumping syndrome (a cluster of symptoms resulting from rapid transit of food or formula from stomach into small intestine, including abdominal pain, nausea, vomiting, diarrhea, dizziness, flushing, fatigue, and palpitations. Symptoms are result of stretching of the intestinal wall and release of hormones leading to alterations in blood pressure and serum glucose levels.)

    • ▪ Fundoplication—Surgical procedure that involves wrapping the gastric fundus around the lower esophagus. Many forms of this surgery exist based on the degree the stomach is wrapped. Efficacy in part is related to increased baseline tone of the LES and decreased transient LES relaxations

      • ▷ Increased fundoplication failure rate has been observed in early infancy and children with neurological impairment or status post esophageal atresia repair

      • ▷ Hospitalization for adverse respiratory events decreases after fundoplication surgery in children <4 years, however, no significant decrease in older children

PEPTIC ULCER DISEASE

Histologic inflammation and ulceration of the mucosa of the stomach and/or duodenum.

EPIDEMIOLOGY

• During childhood typically occurs after 8 years of age

• Accounts for 15% of abdominal pain seen in specialty practice

ETIOLOGY

• Primary peptic ulcer disease (PUD) (typically gastritis and duodenal ulcers) tends to have a chronic relapsing and remitting course. It may be Helicobacter pylori-associated, non-H. pylori-associated, or idiopathic

• Secondary PUD (typically gastric ulcers) tends to be acute and, with therapy, recovery is usually complete. Etiologies include physiologic stress, illness, burns, sepsis, shock, head injury, trauma (e.g., retching, nasogastric tube), drugs (e.g., NSAIDs, alcohol, valproate, chemotherapy, KCl), allergic or eosinophilic gastritis, infectious, iron overdose, diabetes mellitus, Crohn’s disease, Zollinger–Ellison syndrome, hyperparathyroidism, cystic fibrosis, vascular insufficiency (sickle cell disease, Henoch–Schönlein purpura), radiation gastropathy

PATHOPHYSIOLOGY

• Imbalance between cytotoxic factors (acid, pepsin, aspirin/NSAIDs, bile acids, H. pylori infection) and cytoprotective factors (mucous layer, local bicarbonate secretion, mucosal blood flow)

• Role of H. pylori: Gram-negative rod; causes chronic active gastritis and duodenal ulcers; spread by human to human transmission; H. pylori infection is often acquired during childhood but uncommonly leads to PUD

CLINICAL MANIFESTATIONS

• Abdominal pain: Often epigastric but may not be localized in children; may be postprandial and nocturnal

• Anorexia, weight loss, early satiety, nausea, recurrent vomiting, upper GI bleeding, anemia

• On physical exam, may note oral ulcers (e.g., Crohn’s disease), wheezing (may imply GERD), abdominal tenderness

• Perform rectal exam to look for perianal disease (e.g., Crohn’s disease) and occult blood in stool

DIAGNOSTICS

• Endoscopy: Biopsies of the upper intestinal tract is the gold standard for diagnosis

  Numerous noninvasive tests are available with variable sensitivities and specificities. Current guidelines recommend a tissue biopsy to confirm a new diagnosis, rather than relying on a noninvasive test alone. Blood antibody tests for H. pylori are NOT recommended in pediatric patients due to low sensitivity and specificity

• Stool Antigen Test: Useful to diagnose H. pylori in conjunction with endoscopic biopsy and to test for eradication of infection (4–8 weeks after treatment completion). Some tests have sensitivity >95% for detection of H. pylori before and after treatment. Highest yield noninvasive test available

• Urea Breath Test: Useful for the initial diagnosis of H. pylori when combined with endoscopic biopsy and to test for eradication after therapy. Has limited availability compared with stool antigen testing

MANAGEMENT

Acid Suppression

• Use alone for non-H. pylori PUD or in conjunction with antibiotics for H. pylori-associated PUD

• H2 receptor antagonist: Ranitidine, famotidine

• PPI: Omeprazole, esomeprazole, lansoprazole

  • IV pantoprazole 1 mg/kg/day up to 40 mg/day for inpatient treatment

H. pylori Therapy

• Treatment options: Treatment regimens 1–3 are given 7–14 days duration determined by response to therapy, medication side effects, and costs of therapy

  1. PPI + amoxicillin + clarithromycin

  2. PPI + amoxicillin + metronidazole

  3. Bismuth salts + amoxicillin + metronidazole

  4. PPI + amoxicillin for 5 days then PPI + clarithromycin + metronidazole for 5 days

     • ▪ A noninvasive test (stool antigen or urease breath test) to monitor eradication of the organism is recommended 4–8 weeks after completion of therapy

ALPHA-1 ANTITRYPSIN DEFICIENCY

An autosomal recessive disorder associated with chronic liver disease and premature pulmonary emphysema that is caused by a deficiency of the serine protease inhibitor, alpha-1 antitrypsin (Alph1-AT).

EPIDEMIOLOGY

• Most common inherited cause of liver disease in children

• Affects 1 in 2000 live births of white children in the United States

PATHOPHYSIOLOGY

• Alph1-AT is predominantly produced in hepatocytes, released into the bloodstream, and functions in the lung to inhibit cleavage of connective tissue proteins

• When Alph1-AT is genetically mutated, it cannot be released from hepatocytes and becomes hepatotoxic

• Absence of Alph1-AT or abnormal function allows uninhibited cleavage of connective tissue by elastase leading to lung injury

CLINICAL MANIFESTATIONS

• May present at any age from infancy to adulthood

• Variable presentation: Some allele variants cause both liver and lung disease, while others cause only lung disease

• Liver disease (neonate to adult): Prolonged conjugated hyperbilirubinemia in neonate, small for gestational age, acholic stools, elevated transaminases, severe bleeding episode (vitamin K deficiency from liver disease), severe liver failure, hepatomegaly, portal hypertension, varices, chronic hepatitis, cirrhosis, hepatocellular carcinoma

• Lung disease (adult): Emphysema

• On physical exam: Jaundice, hepatomegaly, splenomegaly, ascites, excoriations from pruritus

DIAGNOSTICS

• Serum Alph1-AT Level: Normal is 150–350 mg/dL; may be misleading because it is an acute phase reactant and could be falsely elevated in a pro-inflammatory state. Further, a normal serum level does not equate to normal protein function

• Pi Typing (Pi = protease inhibitor): Defines alleles present, which indicates a normal (MM genotype) or mutant (ZZ genotype) Alph1-AT protein. Other genotypes exist, leading to variable phenotypes

• Liver Biopsy: Necessity for diagnosis is controversial

MANAGEMENT

• Supportive care for liver dysfunction

• Counsel against cigarette smoking

• Protein replacement therapy (recombinant or purified): Only for established emphysema; does not help liver disease

• Surgical options include: Orthotopic liver transplantation, portocaval or splenorenal shunt, lung transplantation

AUTOIMMUNE HEPATITIS

A chronic inflammatory liver disease of unknown etiology characterized by hypergammaglobulinemia, autoantibodies, histological findings of a portal area focused mononuclear infiltrate and interface hepatitis between the portal tract and the lobule, and clinical response to immunosuppressive therapy. There are two primary types of autoimmune hepatitis (AIH):

• Type I: Antinuclear antibody (ANA), anti-smooth muscle antibody (anti-SMA), and anti-F actin-positive

• Type II: Liver-kidney-microsomal (LKM) antibody-positive; more common in pediatrics

• Soluble liver antigen (SLA)-antibody positivity can be found in either type and is associated with more aggressive disease

EPIDEMIOLOGY

• Relatively uncommon; may present at any age

• Female predominance (4:1)

• About 20% of patients have at least one other autoimmune disorder: Associations observed with autoimmune thyroiditis, nephrotic syndrome, type I diabetes mellitus, behcet disease, vitiligo, inflammatory bowel disease (IBD), and Addison’s disease

PATHOPHYSIOLOGY

• Likely autoimmune process in genetically susceptible persons

• Associated with certain HLA haplotypes (A1, B8, DR3, DR4)

• May overlap with autoimmune sclerosing cholangitis

CLINICAL MANIFESTATIONS

• Extremely variable from asymptomatic to liver failure; may be acute or insidious and progressive

• An acute viral hepatitis syndrome is the most common presentation, characterized by fatigue, malaise, nausea, anorexia, upper abdominal discomfort, arthralgia, myalgia, oligomenorrhea, skin rashes, mild pruritus, jaundice, dark urine, pale stools

• Physical exam should evaluate for signs of chronic liver disease: Jaundice, cutaneous stigmata of liver disease, ascites, hepatomegaly, splenomegaly, rash, altered mental status

DIAGNOSTICS

• ALT, AST levels are increased. Alkaline phosphatase (ALP) and GGT levels are normal or increased

• PT, albumin: To check liver synthetic function

• Gamma-globulin levels (high IgG, normal IgA)

• ANA; anti-SMA; anti-F actin, LKM-1; perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA); rarely patients with AIH are negative for traditional antibodies (seronegative autoimmune hepatitis). The initial diagnostic evaluation should at least include ANA, anti-SMA, and LKM-1 antibodies

  • ✓ When evaluating patient for elevated aminotransferases (ALT/AST), in addition to testing for the above antibodies, additional initial evaluations to consider include antibody titers for infection (hepatitis A, B, C, EBV) and celiac disease (anti-transglutaminase Ab IgA, anti-endomysial Ab IgA), and creatine kinase (CK) to rule out muscle inflammation as source of enzyme elevation

• Liver biopsy: Required to confirm diagnosis and rule out other causes of chronic hepatitis. “Interface hepatitis” is the hallmark of AIH on biopsy. (Treatment may be initiated without a biopsy in the setting of acute liver failure and coagulopathy when risks of biopsy outweigh benefits)

  • ✓ The overall diagnosis is based on clinical, laboratory, and histologic findings. A scoring system for diagnosis likelihood is provided in the AASLD practice guidelines on the diagnosis and management of autoimmune hepatitis

MANAGEMENT

• Prednisone 2 mg/kg/day, maximum 60 mg/day; gradually decrease dose over 6–8 weeks to the minimal dose required to maintain normal ALT/AST

• Azathioprine (0.5 mg/kg/day, maximum 2 mg/kg/day): Add if steroid alone not showing improvement

• Initial relapse after achieving remission is often treated by returning to the initial prednisone dose with addition of azathioprine for long-term maintenance therapy

• Discontinuation of therapy is considered in a subset of patients who have been treated for more than 3 years, have normal ALT/AST for 2 consecutive years, and demonstrate histological remission on liver biopsy; discontinuation of therapy just before or during puberty may be associated with higher rates of relapse; many patients require lifelong immunosuppressive therapy

• Liver transplantation for initial presentation with severe liver failure or progressive disease unresponsive to medical therapy

BILIARY ATRESIA

A disease of unknown etiology in which there is progressive destruction of the extra-hepatic biliary tree with variable involvement of the intrahepatic biliary system.

EPIDEMIOLOGY

• Incidence: 1 in 10,000–20,000

• Slight female predominance

• 10–25% of cases associated with other congenital anomalies (see Clinical Manifestations)

PATHOPHYSIOLOGY

• Natural history is complete obliteration of bile ducts leading to biliary cirrhosis and liver failure

• Most cases affect the entire extrahepatic biliary tree

• 10% of cases affect only the distal biliary tree

• Untreated extrahepatic disease: Life expectancy is 11 months

CLINICAL MANIFESTATIONS

• Usually normal at birth

• Conjugated hyperbilirubinemia most commonly presents around 2–6 weeks of age. Approximately 10–35% will be jaundiced at birth, with the bile ductular injury occurring in the prenatal period

• Associated anomalies: Polysplenia, abdominal heterotaxy, intestinal malrotation, cardiovascular malformations, and anomalies of hepatic arteries/portal vein

• On physical exam: Jaundice/greenish hue to skin, hepatomegaly, splenomegaly, dark urine, acholic stools, ascites, edema

DIAGNOSTICS

• Bilirubin (total, conjugated, and unconjugated): Conjugated fraction greater than 2 mg/dL or greater than 15% of total bilirubin

• ALT/AST (two to three times normal); GGT/ALP (markedly elevated); PT/PTT (elevated); albumin (low due to liver synthetic dysfunction)

• Thrombocytopenia/neutropenia: If there is hypersplenism

• Ultrasound: May not be diagnostic but important to rule out choledochal cyst and to detect polysplenia, heterotaxy. Absence of the gallbladder raises suspicion for biliary atresia

• DISIDA scan (diisopropyl iminodiacetic acid labeled with 99m-technetium): Normally after injection, this lipid-soluble, albumin-bound substance is depicted in the liver and followed by excretion into the small bowel. In biliary atresia, there is normal uptake by liver but excretion occurs into the urinary tract due to an absent/obstructed biliary tree

• Liver biopsy: Typically shows bile duct proliferation with cholestasis and fibrosis, but very early may not be diagnostic

• Surgical cholangiography: Necessary if biopsy not diagnostic and clinical suspicion remains high

MANAGEMENT

Portoenterostomy (Kasai Procedure)

• Anastomosis of intrahepatic biliary tract directly to bowel at the portal plate

• 80% eventually require liver transplantation even if done early

• 70–80% success of palliation if done before 60 days of age; only 20–30% success if done after 90 days of age

• High morbidity and mortality

• Complications include cholangitis, portal hypertension/varices, malnutrition/fat-soluble vitamin deficiency

Liver Transplantation

• Indicated for extrahepatic biliary atresia when diagnosis is delayed past time window for Kasai

• Indicated after Kasai if: Hepatic insufficiency, portal hypertension with recurrent variceal bleeding, irreversible failure to thrive, recurrent cholangitis, persistent cholestasis, hepatopulmonary syndrome

GALLBLADDER DISEASE

DEFINITIONS

• Cholelithiasis: Gallstones

• Choledocholithiasis: Stones in common bile duct (CBD)

• Cholecystitis: Infected or inflamed gallbladder

• Calculous Cholecystitis: Infected or inflamed gallbladder that contains stones

• Acalculous Cholecystitis: Infected or inflamed gallbladder that does not contain stones

EPIDEMIOLOGY

• Cholelithiasis and cholecystitis are uncommon in children and are often secondary to a predisposing condition

• More than 50% of cholecystitis in children is acalculous

• Biliary symptoms develop in only 20% of patients with gallstones

ETIOLOGY

• Conditions that predispose to cholelithiasis in children: Prematurity, congenital anomaly of biliary tract, hemolytic disorders (e.g., sickle cell disease), ileal resection or disease, obesity, pregnancy, cystic fibrosis, chronic furosemide use, total parenteral nutrition (TPN), long-term ceftriaxone

PATHOPHYSIOLOGY

Cholelithiasis

• Due to alteration in relative proportions of bile components

• Cholesterol gallstones due to bile supersaturated with cholesterol

• Pigment gallstones: Black pigment stones due to bile supersaturated with unconjugated bilirubin that forms complexes with free ionized calcium. Brown pigment stones involve biliary stasis and bacterial infection

Choledocholithiasis

• Primary: Stones formed in CBD

• Secondary: Stone migrates from gallbladder and lodges in CBD

• Causes obstructive cholestasis; may lead to pancreatitis, cholangitis

Cholecystitis

• Calculous: Obstruction of cystic duct by stone leads to acute inflammatory response of gallbladder mucosa; secondary bacterial infection may occur

• Acalculous: Biliary stasis (e.g., post-surgery, TPN, infectious illness) causes acute symptoms whereas functional disorders (e.g., biliary dyskinesia) cause chronic symptoms

CLINICAL MANIFESTATIONS

• Cholelithiasis: 80% asymptomatic; biliary colic with right upper quadrant (RUQ) pain

• Choledocholithiasis: Biliary colic, obstructive jaundice, cholangitis, pancreatitis

• Calculous Cholecystitis: Acute presentation involves abdominal pain (RUQ or diffuse), low-grade fever, nausea, vomiting, anorexia. Chronic presentation often includes history of biliary colic or history of acute cholecystitis episode that resolved. Symptoms may be minimal

• Acalculous Cholecystitis: Acute presentation similar to acute calculous cholecystitis. Chronic presentation involves recurrent biliary type pain

• May be ill-appearing with abdominal tenderness, rebound, guarding, palpable gallbladder, jaundice, splenomegaly

• Murphy’s sign: On palpation of RUQ, pain worsens with inspiration, which leads to cessation of breath

DIAGNOSTICS

• Bilirubin, aminotransferases, alkaline phosphatase: May be elevated or normal

• Leukocytosis: Variable

• Amylase/lipase: May be elevated

• Abdominal x-ray: May show calcified stones

• Ultrasound: Best to detect cholelithiasis, choledocholithiasis, and acute cholecystitis

• DISIDA scan: No filling of gallbladder in acute cholecystitis; delayed filling in chronic cholecystitis (delayed ejection fraction with cholecystokinin [CCK] or pain with CCK stimulation suggests either chronic cholecystitis or biliary dyskinesia)

• MRCP: MRI of the biliary duct system. Improved resolution compared to ultrasound and may identify stones or other anomalies of the ducts missed on previous ultrasound

• ERCP: More invasive cholangiogram, advantage of being diagnostic and therapeutic for CBD obstruction due to stones

MANAGEMENT

Cholelithiasis

• Observation in asymptomatic patients

Choledocholithiasis

• ERCP with or without sphincterotomy and biliary stent

• Elective cholecystectomy

• Surgical correction of anatomic abnormality of biliary tree, such as choledochal cyst

Acute Cholecystitis

• Rehydration, analgesia, antibiotics, observation (usually resolves spontaneously in 2–3 days)

• Typical antibiotic regimens: Ampicillin-sulbactam; ampicillin-sulbactam plus gentamycin; third-generation cephalosporin plus metronidazole; ticarcillin-clavulanate; piperacillin-tazobactam; imipenem (if life-threatening)

• Elective cholecystectomy after resolution of acute illness (early or up to 2–3 months later) in uncomplicated cases

• Emergent cholecystectomy is indicated if complicated by necrosis, perforation, or empyema

Chronic Cholecystitis

• Cholecystectomy for chronic calculous cholecystitis (in general)

• For biliary dyskinesia, cholecystectomy has variable results, with many children continuing to experience pain symptoms in the postoperative period

GLYCOGEN STORAGE DISEASE

A family of inherited disorders affecting glycogen metabolism. Glycogen is a highly branched polymer of glucose and is stored in liver and muscle. The glycogen found in these disorders is abnormal in quantity, quality, or both.

• Conversion of glycogen into pyruvate occurs in two parts: Glycogenolysis from glycogen to glucose-6-phosphate and glycolysis from glucose-6-phosphate to pyruvate

• Some enzyme defects are localized in liver, others in muscles; a few are generalized

EPIDEMIOLOGY

• Frequency (all forms) about 1/20,000 live births

• Autosomal recessive inheritance

• Types I, II, III, and IX most commonly present in early childhood; type V (McArdle disease) most common in adults

ETIOLOGY

• More than 12 types; can be classified by organ involvement and clinical manifestations into liver and muscle glycogenoses (Table 10-1)

• Hepatic Glycogen Storage Disease: Type I (von Gierke disease), type III, type IV, type VI, type IX, glycogen synthetase deficiency, and glucose transporter-2 defect; typically cause hepatomegaly and fasting hypoglycemia; types III and IV are also associated with hepatic cirrhosis

• Muscle Glycogen Storage Disease: Divided into two groups: progressive skeletal muscle weakness, cardiomyopathy or both (type II); muscle pain, exercise intolerance, myoglobinuria and fatigue (types V, VII)

DIAGNOSTICS

• Hepatic glycogen storage disease: Enzyme defects can only be detected in tissue acquired on a liver biopsy but preliminary screening can be performed with an oral glucose tolerance test or a glucagon test

• Muscle glycogen storage disease: Exercise test (semi-ischemic forearm test, bicycle ergometer test, or treadmill test) used to demonstrate the failure of venous lactate and pyruvate to rise and the production of uric acid, inosine, hypoxanthine, and ammonia to increase excessively; if exercise test is abnormal, myopathy should be verified by enzyme assay

MANAGEMENT

• Prevention of hypoglycemia while avoiding storage of even more glycogen in the liver and muscle

• Hepatic Glycogen Storage Disease:

  • ✓ Nasogastric tube feedings at night; frequent feedings every 2–3 hours during the day using a lactose-free and sucrose-free formula

  • ✓ Uncooked cornstarch (1.75–2.5 g/kg) mixed in water, soy formula or soy milk is given every 4 hours in infants and every 6 hours in older children

  • ✓ Restrict intake of fructose and galactose

  • ✓ Supplementation with calcium and multivitamins

  • ✓ Allopurinol is used to lower the concentration of uric acid

  • ✓ Liver transplantation has been successful

• Muscle Glycogen Storage Disease: Muscle function may be influenced by diet (protein may compensate for increased muscle catabolism); glucose use depends on underlying condition

WILSON DISEASE

Autosomal recessive disease of copper metabolism that involves defective biliary copper excretion, which leads to abnormal copper accumulation in the liver, central nervous system (CNS), eyes, and kidneys.

EPIDEMIOLOGY

• Prevalence: 1:30,000

PATHOPHYSIOLOGY

• Wilson disease gene on chromosome 13 encodes a transmembrane copper-transporting ATPase protein (ATPase 7B). Mutations result in an abnormal transporter protein, which prevents normal export of copper from hepatocytes

• Copper accumulates first in the liver and then spills over to other tissue

CLINICAL MANIFESTATIONS

• Frequently presents in childhood but rarely before age 5 years

• Classic triad: Hepatic disease, neurologic disease, Kayser–Fleischer rings (brown-yellow ring around the corneo–scleral junction resulting from copper deposits)

• In children, hepatic effects precede neurologic effects and typically present in the second decade of life

• Liver: Acute hepatitis, chronic active hepatitis, cirrhosis, fulminant hepatic failure

• CNS: Basal ganglia involvement leads to dystonia, incoordination, tremor, fine motor skill difficulty, rigidity, dysarthria, and gait disturbances. Psychiatric manifestations include depression, aggressive behaviors, impulsivity, compulsivity, poor school performance, psychosis

• Ophthalmologic: Kayser–Fleischer rings, sunflower cataracts (cataract related to copper deposits described as brown-green deposits in anterior and posterior lens capsule)

• Other: Hemolytic anemia, proximal renal tubular dysfunction, bone demineralization, osteoporosis, pathologic fractures, cardiac dysrhythmias, cholelithiasis

DIAGNOSTICS

• Laboratory Tests: Ceruloplasmin level less than 20 mg/dL; serum copper low or high; 24-hour urine copper greater than 100 μg/day; CBC (hemolysis); LFTs (hepatitis, cholestasis)

• Liver Biopsy: Gold standard; quantitation of hepatic copper, typical findings of steatosis, inflammation, +/− fibrosis

• Head CT: Ventricular dilatation, brain atrophy, basal ganglia abnormalities

• Head MRI: More sensitive than CT for specific changes

MANAGEMENT

• D-Penicillamine (20 mg/kg/day divided four times a day, maximum 1 g/day; start with reduced dose): Copper chelator used as initial treatment in hepatic disease. Give 1 hour before or 2 hours after meals. Supplement with vitamin B₆

• Trientine: A copper chelator and alternative to D-penicillamine. Typical dose in range of 20 mg/kg/day in 2–3 divided doses rounded to nearest 250 mg dose

• Zinc: Antagonist of copper absorption used as adjunctive therapy or alternative maintenance therapy after chelation. Typical dose is 150 mg/day in larger children and adults, and 75 mg/day in smaller children. Daily dose is divided two to three times per day

• Ammonium Tetrathiomolybdate: Still experimental

• Diet: Restrict dietary sources of copper: animal liver and kidney, shellfish, chocolate, dried beans, peas, unprocessed wheat

• Liver Transplantation: For severe disease with fulminant hepatic failure or worsening disease unresponsive to medical therapy

• Screening of asymptomatic relatives of patients with Wilson disease

CELIAC DISEASE

An autoimmune disorder of the small intestine characterized by a permanent intolerance to wheat gluten that results in mucosal damage and malabsorption.

EPIDEMIOLOGY

• Prevalence: 1 in 300 worldwide

• More common in persons of European descent

• Associated with juvenile-onset diabetes mellitus, selective IgA deficiency, dermatitis herpetiformis, autoimmune thyroid disease, Down syndrome, Turner syndrome, and Williams syndrome

• Increased prevalence in children with first-degree relatives with celiac disease

• Increased risk of small bowel lymphoma

PATHOPHYSIOLOGY

• Gut exposure to grain proteins in wheat, rye, barley, and oats results in an autoimmune reaction that is toxic to enterocytes and leads to a flattened mucosal lining and impaired small intestinal absorptive capacity

CLINICAL MANIFESTATIONS

• Symptoms are variable and can present at any age

• Classically presents around age 1–3 years, but this is changing as more children are identified by increased screening practices

• Diarrhea, foul-smelling bulky greasy stools, abdominal distention and pain

• Poor growth, anorexia, malaise, muscle wasting, irritability, unexplained iron deficiency anemia

• Symptoms can be subtle with only mild diarrhea or recurrent abdominal pain or constipation complaints

• Physical exam: Weight loss, short stature, edema, abdominal distention, rectal prolapse, muscle wasting, dental erosion, angular stomatitis, aphthous lesions, osteopenia, rickets

DIAGNOSTICS

• Antibody Tests: Anti-gliadin antibody (IgA and IgG; moderate sensitivity, low specificity), anti-endomysial IgA (sensitivity = 90–95%, specificity = 98–100%; false-negative results more common in children younger than 2 years of age), anti-tissue transglutaminase antibody (IgA anti-tTG; sensitivity = 92–98%, specificity = 96–100%)

• Antibody tests are good for initial screen but endoscopy required for definitive diagnosis

• Anti-gliadin antibodies are not used for standard screening, except in the young child less than 2 years old. Deamidated anti-gliadin antibody is more sensitive and specific than previous standard test

• May present with elevated hepatic transaminases

• Endoscopy: Small bowel biopsies on a gluten-containing diet help make diagnosis; increased epithelial lymphocytes, villous atrophy, crypt hyperplasia, infiltration of lamina propria with inflammatory cells are features consistent with celiac disease; resolution of abnormalities on gluten-free diet confirms diagnosis

MANAGEMENT

• Permanent gluten-free diet leads to full clinical and histologic remission; gluten-free means no wheat, rye, barley, or oats; corn and rice are permitted

• Dietary counseling and careful attention to ALL food and medicinal products that may contain traces of gluten

• Multivitamin/fat-soluble vitamins

• Medical therapy for iron deficiency and rickets if present

• Very close follow-up of growth parameters and symptoms

• Periodic monitoring of dietary compliance with antibody profile; antibodies usually undetectable within 3–6 months after initiation of appropriate diet

• Screening of all immediate family members is indicated

CONSTIPATION

A symptom of abnormal defecation characterized by infrequent stooling, incomplete evacuation of the rectum, passage of large painful stools, involuntary soiling, or the inability to pass stool.

EPIDEMIOLOGY

• Occurs in more than 10% of all children

• Majority of constipation in older children is functional

• Encopresis occurs in 1–2% of all children

ETIOLOGY

• Anatomic: Hirschsprung disease, imperforate anus, anal stenosis, malpositioned anus, ileal atresia, meconium ileus, colonic stricture, abdominal mass, hydrometrocolpos

• Physiologic: Hypothyroidism, celiac disease, lumbosacral spinal cord defect, infant botulism, muscular diseases, cystic fibrosis, diabetes, lead poisoning, post-viral “ileus,” prune-belly syndrome, ascariasis, medications, excessive cow’s milk ingestion, inadequate fluid intake, malnutrition, anorexia nervosa, functional constipation

PATHOPHYSIOLOGY

• Functional Constipation: Cycle typically begins with voluntary withholding of stool. Stool returns from anal canal to rectum. Sensation of urge to defecate is decreased. Stool bolus becomes larger and harder, which perpetuates more withholding. Over time, rectal vault distends and normal sensation diminishes

• Retentive Encopresis: Involuntary soiling of liquid stool around solid stool, which results from chronic constipation

• Grunting Baby Syndrome: An infant with grunting, straining, and turning red while passing a soft stool has immature coordination of the stooling process and not true constipation

CLINICAL MANIFESTATIONS

• Signs of possible anatomic abnormalities: Blood in stool, failure to thrive, emesis, abdominal distention

• Signs of functional constipation: Retentive posturing; infrequent passage of large, hard bowel movements; involuntary soiling

• Complaints of abdominal pain

• Stool consistency may be hard, soft, or even diarrheal

• Stool frequency can be daily or infrequent

• On physical exam, note abdominal tenderness/distention, palpable stool on abdominal palpation, anal wink, anal tone, stool in rectal vault, width of rectal vault, neurologic and back exams

DIAGNOSTICS

• Consider laboratories depending on suspected cause

Abdominal x-ray

• 1-view abdominal x-ray: Most useful to diagnose fecal impaction in the rectum. Limited use in correlating colonic stool burden with degree of constipation

• Radiopaque Sitz Marker study: Child swallows 24 radiopaque markers in one sitting and x-ray obtained 5 days later. Location of markers aids in determining type of constipation. May be done to assess a current bowel regimen or following a bowel clean-out to assess GI transit without stool burden

  • ✓ Slow transit: Markers distributed throughout the colon

  • ✓ Outlet dysfunction: Numerous markers clustered in rectosigmoid

  • ✓ Functional: Less than 3 markers remaining on x-ray

• Unprepped Contrast Enema/Rectal Biopsy: To evaluate for Hirschsprung disease

• L-spine MRI: Suspected spinal cord abnormality

MANAGEMENT

• Treat underlying medical disorders

• Surgical correction of anatomic defects

• Treatment of functional constipation may take months to years

  • ✓ Bowel clean-out: Enemas, suppositories, lubricants, hyperosmolar agents

  • ✓ Maintenance: Dietary fiber and fluids, hyperosmolar agents

  • ✓ Toilet sitting: Twice-daily stooling attempts

  • ✓ Diary/journal: Positive reinforcement

  • ✓ Educate patient and parents. Frequent follow-up is critical to success

• Medications used to treat constipation:

  • ✓ Enema: Mineral oil (rectally); sodium biphosphate (Fleets); or saline; all in children ≥2 years of age. Larger volume enemas such as polyethylene glycol enemas to relieve rectal fecal impaction may be necessary

  • ✓ Suppositories: Glycerin, bisacodyl

  • ✓ Lubricants: Mineral oil (orally)

  • ✓ Osmotic laxatives: Polyethylene glycol (PEG) 3350 (Miralax), lactulose, PEG with electrolytes (Go-Lytely)

  • ✓ Stimulant laxatives: Senna, bisacodyl, magnesium citrate, magnesium hydroxide

  • ✓ Fiber/bulk forming agents: Benefiber, Citrucel, Metamucil, Maltsupex

• Typical clean-out regimen:

  • ✓ Enemas to clean out rectal vault

  • ✓ Hyperosmotic and/or stimulant therapy: May require nasogastric tube for administration. Continue until clear effluent. Monitoring serum electrolytes appropriate when using larger volumes

GASTROINTESTINAL BLEEDING

Loss of blood via the GI tract:

• Hematemesis: Bloody emesis due to active bleeding proximal to the ligament of Treitz

• Hematochezia: Bright red or maroon stool due to active bleeding in the colon or brisk bleeding from a more proximal site

• Melena: Dark, tarry stool due to bleeding proximal to the ileocecal valve

DIFFERENTIAL DIAGNOSIS

• Upper intestinal bleeding

  • ✓ Infant: Swallowed maternal blood, esophagitis, gastric ulcer

  • ✓ Older child: Esophagitis, Mallory–Weiss tear, esophageal varices, foreign body with mucosal erosion, duplication cyst, Dieulafoy lesion, gastritis, gastric ulcer, vascular malformation, duodenitis, hemobilia, swallowed blood from oral/nasal pharynx, pulmonary bleeding (hemoptysis)

• Lower intestinal bleeding

  • ✓ Infant: Anal fissure, swallowed maternal blood, milk protein allergic colitis, infectious enterocolitis, vascular malformation, necrotizing enterocolitis, Hirschsprung disease with enterocolitis, Meckel diverticulum (>2 months), intussusception, intestinal duplication

  • ✓ Older child: Anal fissure, perianal strep cellulitis, solitary rectal ulcer, infectious enterocolitis/Clostridium difficile colitis, intussusception, IBD, vascular malformations, Meckel diverticulum, polyp, intestinal duplication, Henoch–Schönlein purpura, hemolytic uremic syndrome, hemorrhoids, rectal trauma, sexual abuse

CLINICAL MANIFESTATIONS

• Variable presentation from hemodynamically stable to shock

• Note prior use of NSAIDs, steroids, indomethacin, antibiotics

• Note history of trauma, liver disease, umbilical vein catheterization (history of umbilical vein catheterization is associated with portal vein thrombosis and development of portal hypertension predisposing to esophageal varices)

• May present with vomiting, retching, casual regurgitation of bloody fluid, abdominal pain, anorexia, fever, weight loss, sepsis, asphyxia, recent surgery, mental status changes

• Inspect mouth, nares, pharynx for trauma

• Abdomen: Hepatomegaly, splenomegaly, prominent abdominal vessels, right lower quadrant mass or tenderness

• Rectal: Blood, erythema, fissure, fistula, skin tag, polyp, hemorrhoid, rectal prolapse

• Stool: Blood or mucous within or surrounding stool

• Extremities: Capillary refill, digital clubbing, palmar erythema, purpura, or petechiae

• Skin: Pallor, jaundice, facial petechiae, pigmented freckles on lips/buccal mucosa, excoriations, hemangiomas, other vascular appearing lesions

• For breastfeeding infant, inspect mother’s nipple (dry, cracked, bleeding nipples suggest swallowed maternal blood)

DIAGNOSTICS

• Stool guaiac: False-positive results may be due to rare meat, horseradish, turnips, iron, tomatoes, fresh red cherries; false negatives may be due to vitamin C, outdated card or developing solution, storage of stool greater than 4 days

• Nasogastric lavage: Use normal saline at room temperature; absent blood does not exclude an upper GI source; present blood does not identify the exact origin

• Laboratory studies: CBC, PT/PTT, LFTs, electrolytes, type and screen

• Stool bacterial culture and stool C. difficile toxins

• Abdominal x-ray: Free air, toxic megacolon, pneumatosis, small bowel dilation

• Air or gastrograffin contrast enema: For suspected intussusception

• Meckel diverticulum scan

• Upper GI series: Structural abnormality, tumor, polyp, signs of IBD

• CT/MR angiography studies useful in both slower and brisk bleeding to localize lesion. CTA with oral contrast (CT Enterography) is most sensitive test if patient can tolerate oral contrast

• Tagged Red Blood Cell bleeding scan and Angiography reserved for brisk bleeding without clear localization on imaging studies

• Endoscopy or colonoscopy: Direct visual inspection, biopsy, culture

• Wireless video capsule endoscopy: For small bowel obscure GI bleeding

MANAGEMENT

• Initial Management of all GI Bleeding: Identify and treat shock with IV access, isotonic fluids, oxygen, blood products

• Non-Variceal Upper GI Bleed: Acid reduction (ranitidine, pantoprazole); discontinue NSAIDs; endoscopic hemostasis therapy if bleed persists (bipolar electrocoagulation, heater probe, clips, injection therapy)

• Variceal Upper GI Bleed:

  • ✓ Fluid resuscitation; transfuse red cells to maintain hemoglobin near 10 g/dL; transfuse platelets to greater than 50,000/mm³; FFP to correct coagulopathy

  • ✓ Octreotide (bolus 1–2 μg/kg over 2–5 minutes, then 1–2 μg/kg/h infusion): Reduces splanchnic arterial blood flow to decrease portal pressure

  • ✓ Endoscopic band ligation, sclerotherapy

  • ✓ Emergent surgical therapy for unresponsive severe bleeding: Portosystemic shunt, trans-jugular intrahepatic portal shunt (TIPS), Blakemore–Sengstaaken tube occlusive balloon therapy, liver transplantation

• Lower GI Bleed in an Infant:

  • ✓ Surgical evaluation for suspected intussusception, necrotizing enterocolitis, toxic megacolon, Hirschsprung disease

  • ✓ If otherwise healthy and has blood-streaked mucus in stool without evidence of fissure, send stool culture and consider changing to elemental formula for presumptive milk-protein allergy

  • ✓ Flexible sigmoidoscopy for persistent bloody stools despite elemental formula and negative stool culture

  • ✓ Anal fissures heal without intervention

• Lower GI Bleed in an Older Child:

  • ✓ Treat according to underlying cause if known

  • ✓ Treat constipation if present

  • ✓ Flexible sigmoidoscopy or colonoscopy for recurrent or persistent bleeding to detect colitis, polyps, IBD

  • ✓ Polyp removal by electrocautery

  • ✓ Meckel scan if no source identified by endoscopy

  • ✓ Surgical evaluation if severe bleed of unidentified source

INFLAMMATORY BOWEL DISEASE

An idiopathic chronic disease of the GI tract resulting in inflammation, tissue destruction, diarrhea, protein-losing enteropathy, GI bleeding, abdominal pain, and many extraintestinal manifestations. IBD is broadly divided into Crohn’s disease, ulcerative colitis (UC), and indeterminate colitis (IC).

EPIDEMIOLOGY

• Family history predisposes to IBD

• 20–30% of new IBD presents in persons younger than 20 years of age

• 4% of pediatric IBD presents in children younger than 5 years of age

• More common in developed countries

ETIOLOGY

• Interaction between environmental, gut microbiota, immunologic and genetic factors

• Dysregulation of mucosal immune system driven by normal intestinal flora

PATHOPHYSIOLOGY

• Crohn’s Disease:

  • ✓ May involve any segment of the GI tract, mouth to anus

  • ✓ Commonly involves small intestine and terminal ileum

  • ✓ Transmural disease with thickened nodular bowel, non-caseating granulomas, strictures, fistulas, abscesses, adhesions

  • ✓ Skip lesions, discontinuous disease

  • ✓ Perianal disease (15%)

  • ✓ Malabsorption of iron, zinc, folate, and vitamin B₁₂

  • ✓ Bacterial overgrowth

  • ✓ Carcinoma (increased risk over general population)

• Ulcerative Colitis:

  • ✓ Limited to the colon; starts in rectum and ascends continuously

    • Nonspecific gastritis and/or duodenitis common

  • ✓ Diffuse mucosal involvement/submucosal sparing

  • ✓ Crypt abscesses; toxic megacolon (<5%)

  • ✓ Carcinoma (significant increased risk over general population)

• Indeterminate Colitis:

  • ✓ Term used when macroscopic disease is localized to colon but cannot be definitively said to be UC or CD

CLINICAL MANIFESTATIONS

Intestinal Manifestations:

• Crohn’s disease: Abdominal pain, diarrhea, rectal bleeding, aphthous oral lesions, perianal fissures/tags/fistulas, abdominal abscesses, anorexia, weight loss, linear growth deceleration

• Ulcerative colitis: Bloody mucoid diarrhea, lower abdominal pain/tenderness, urgency to defecate, nausea/vomiting associated with defecation

Extraintestinal Manifestations:

Occur in approximately 30% of patients with IBD, more typically after IBD diagnosis is made. A minority will manifest extraintestinal symptoms prior to intestinal-related symptoms.

• Systemic: Fever, malaise, anorexia, weight loss, growth delay/linear growth deceleration, delayed puberty

• Skin: Erythema nodosum, pyoderma gangrenosum, perianal disease

• Joints: Arthritis, arthralgia, clubbing, ankylosing spondylitis, sacro-ileitis

• Eyes: Uveitis, episcleritis, keratitis, retinal vasculitis

• Biliary: Sclerosing cholangitis (UC > crohn’s disease), chronic active hepatitis, fatty liver, cholelithiasis

• Bone: Osteopenia

• Renal: Stones, hydronephrosis, enterovesical fistula

• Vascular: Thrombophlebitis, vasculitis

• Heme: Anemia (iron, vitamin B₁₂, folate deficiency, hemolysis, marrow suppression from medications, anemia of chronic disease), thrombocytosis, neutropenia

• Oncologic: Lymphoma, acute myelogenous leukemia, colon cancer

DIAGNOSTICS

• Complete blood count (low hemoglobin, low mean corpuscular volume, high platelets), ESR (high), C-reactive protein (high), albumin (low), alkaline phosphatase (low), iron studies, folate, vitamin B₁₂ levels, electrolytes, calcium, magnesium, phosphorus

• Unique IBD-related antibody serologies are sometimes used to aid the differentiation of crohn’s disease and UC when unclear. ASCA (anti-Saccharomyces cerevisiae antibody) and ANCA are most well described, although other antibodies are now available. These antibodies are generally not used as screening tests to evaluate for IBD

• Stool guaiac: Positive

• Stool for culture, C. difficile toxins A and B, ova and parasites, cryptosporidium and Giardia

• Fecal calprotectin is highly sensitive and specific for GI tract inflammation, especially colitis. Highly valuable in distinguishing between IBD and irritable bowel syndrome (IBS)

  • ✓ When a combination of the above tests raise suspicion for IBD, the gold standard test to rule out the disease is endoscopy and colonoscopy. A radiology study (see below) may be chosen before endoscopy/colonoscopy depending on presenting symptoms (concern for obstruction, abscess, perforation)

Radiology

There is no one perfect imaging study to evaluate the small bowel in patients with IBD. Each study has its benefits and limitations. The optimal initial study depends on the patient and his/her symptoms and course of illness.

• Upper GI with small bowel follow-through: Useful to evaluate for strictures. False-negatives common for superficial mucosal disease

• Abdominal CT: Useful to assess for complications of crohn’s disease such as intra-abdominal abscess or phlegmon

• MR Enterography: MRI of bowel with IV and oral contrast. No ionizing radiation. Useful to assess transmural disease

• MRI Pelvis: Frequently used to assess perianal disease and fistulae

• Wireless video capsule endoscopy: Useful to assess the mucosal surface, unable to assess disease beyond bowel lumen. Risk of capsule retention at site of narrowing/stricture. A test capsule is available for those considered at higher risk

• Bone Age: Assess for delayed bone maturation

• DXA Scan: Assesses bone mineral density, which may be low in chronic inflammatory diseases such as IBD. Normal range: Z score +2 to −2. Below Z − 2, patients may be at risk for fracture

Endoscopy

• Gold standard for diagnosis

• Mucosa may appear erythematous, edematous, friable, ulcerated

• Loss of normal vascular pattern

• Well-established diagnostic histology criteria—Chronic inflammation, crypt abscesses, architectural mucosal abnormalities, etc

MANAGEMENT

Medical

Choice of therapy for a given patient depends on many factors including disease phenotype, location of disease, severity of symptoms, growth status, age of patient, and among other factors. “Bottom up” (salicylates, steroids, antibiotics), “top down” (biologics, immunomodulators), or use of enteral therapy at time of newly diagnosed IBD may be appropriate depending on the above factors.

• Salicylates: Sulfasalazine, mesalamine (Pentasa, Delzicol), balsalazide (Colazal), rowasa (enemas), canasa (suppositories)

• Antibiotics: Metronidazole, ciprofloxacin, rifaximin, oral vancomycin

  • ✓ Antibiotics are indicated in setting of penetrating (fistulizing) luminal or perianal disease and comorbid C. difficile infection

  • ✓ Use in active luminal crohn’s disease and UC as adjunctive therapy is patient-specific. Metronidazole and ciprofloxacin have each been shown to improve symptoms in some studies while lack significant benefit in others

• Steroids: Prednisone, methylprednisone, budesonide (ileal release with less systemic absorption), budesonide MMX (Multimatrix system technology; colonic release with less systemic absorption) hydrocortisone enema

• Immunomodulators: To reduce steroid dependency or as adjunct to infliximab

  • ✓ 6-mercaptopurine, azathioprine, methotrexate, cyclosporine, tacrolimus

• Biologic agents: Moderate to severe crohn’s disease or UC, fibrostenotic or fistulizing crohn’s disease, steroid refractory UC, other indications

  • ✓ Infliximab (Remicade), adalimumab (Humira), certolizumab pegol (Cimzia)

  • ✓ Obtain PPD/CXR to rule out latent TB infection before initiation

  • ✓ Make sure vaccination series completed

• Enteral nutritional therapy: Nutritional-based therapy for crohn’s disease, typically with delivery of semi-elemental formula via NG tube. May modulate gut microbiota to favor anti-inflammatory response. Given as 80–100% of daily caloric intake to induce remission of disease

• In acute severe UC, use of the PUCAI (pediatric UC activity index) scoring system of symptoms can guide clinical judgment regarding response to therapy and need to escalate therapy. The scoring includes abdominal pain, rectal bleeding, stool consistency, number of stools per day, nocturnal bowel movements, and activity level

  • ✓ Management of an acute IBD flare that requires hospitalization often includes reevaluation of disease severity and location, with objective determination of symptoms through accurate documentation of pain pattern and stool consistency and frequency

    • ▪ Medication adherence should be inquired

    • ▪ If disease has worsen from previous baseline, escalation or change of therapy is strongly considered

• Discharge criteria following acute flare include improvement of presenting symptoms (e.g., tolerating oral intake without severe pain, minimal gross blood in stool and maintaining stable hemoglobin level, fewer diarrheal stools, gaining weight if admitted with weight loss, resolution of emesis, resolution of obstruction)

Surgical

• Indicated in uncontrolled bleeding, bowel perforation, bowel obstruction, intractable disease, and intractable perianal disease

• Crohn’s disease: Local resection (such as ileocecectomy), ostomy diversion, fistula management

  • ✓ Incision and drainage of perirectal abscesses +/− drain placement

  • ✓ Seton: A suture is placed through the fistulous tract forming a loop, to allow for continuous draining and healing from lumen to skin. Without seton, fistulous tracts tend to heal at the skin side first, and pus may be trapped creating an abscess

• UC: Total colectomy with ileo-anal anastomosis for medically refractory disease

MECKEL’S DIVERTICULUM

A true diverticulum that results from incomplete closure of the omphalomesenteric or vitelline duct. It may contain gastric or other mucosa, and occurs along the ileum usually within 100 cm of the ileocecal valve.

EPIDEMIOLOGY

• 2% of the population

• Has been associated with cleft palate, bicornuate uterus, and annular pancreas

PATHOPHYSIOLOGY

• Persistence of vitelline duct; contains all three intestinal layers

• May contain ectopic tissue: Gastric (50%), pancreatic (5%), other

• Bleeding occurs when acid secreted by ectopic gastric mucosa causes adjacent ileal ulceration or erodes into the vitelline artery

CLINICAL MANIFESTATIONS

• Asymptomatic: 95% of cases

• Painless lower intestinal bleeding: Most common symptom accounting for 50% of symptomatic presentations, generally in patients 2 months–2 years

• Other manifestations: Intestinal obstruction, intussusception, volvulus, herniation through mesenteric defect, severe right lower quadrant abdominal pain (Meckel’s diverticulitis), umbilical cysts/sinuses, palpable abdominal mass

DIAGNOSTICS

• Technetium-99m pertechnetate scintigraphic study. Test has high specificity (95–100%) but lower sensitivity (50–92%). Use of H2 receptor antagonist (ranitidine) prior to test may increase yield with a sensitivity of 62.5% with conventional study, and sensitivity of 87.5% when pretreated with ranitidine

• Tagged red blood cell scan if active bleed

• Upper GI with small bowel follow through

• Wireless video capsule endoscopy may identify isolated ileal ulcer

• Barium enema (if intussusception suspected)

• Occasionally discovered as incidental finding at laparoscopy

MANAGEMENT

• Medically resuscitate the patient with a lower GI bleed

• Symptomatic Meckel’s diverticulum should be surgically resected

• Meckel’s diverticulum found incidentally during surgery performed for another reason should be resected if there is are palpable heterotopic mucosa or mass, fibrous bands to umbilicus, or surrounding inflammation

PANCREATITIS

DEFINITIONS

Acute Pancreatitis: An acute inflammatory process of the pancreas characterized by two of the following three characteristics: acute abdominal pain, elevated pancreatic enzymes at least 3× upper limit of normal, and radiologic evidence of pancreatic inflammation.

Acute Recurrent Pancreatitis: At least two episodes of acute pancreatitis with resolution of pain and pancreatic enzymes between episodes.

Chronic Pancreatitis: A condition of recurring or persisting abdominal pain, pancreatic inflammation, and progressive destruction of the pancreas that often leads to pancreatic insufficiency or failure.

EPIDEMIOLOGY

• All ages; male = female

• Heritable forms of pancreatitis are the most common forms of chronic pancreatitis in children (cationic trypsinogen, SPINK1, CFTR gene mutations)

ETIOLOGY

Acute Pancreatitis

• Systemic Disease: Infections; inflammatory/vascular (Henoch–Schönlein purpura, hemolytic-uremic syndrome, Kawasaki, IBD, collagen vascular); sepsis/shock; transplantation

• Mechanical/Structural: Trauma (blunt injury, child abuse, post-ERCP); anatomic (annular pancreas, pancreas divisum, choledochal cyst, stricture); obstruction (stones, tumor)

• Metabolic/Toxic: Hyperlipidemia, hypercalcemia, cystic fibrosis, severe malnutrition, refeeding, renal disease, organic acidemia, drugs/toxins

• Idiopathic: Up to 25% of cases

• Chronic Pancreatitis

• Obstructive: Congenital anomaly (choledochal cyst), ductal fibrosis or stricture, tumor, pseudocyst, sphincter of Oddi dysfunction, trauma, idiopathic fibrosing pancreatitis, autoimmune pancreatitis, sclerosing cholangitis

• Calcific: Heritable pancreatitis (cationic trypsinogen deficiency, SPINK1 and CFTR mutations), hypercalcemia, hyperlipidemia, juvenile tropical pancreatitis

• Idiopathic: (30%)

PATHOPHYSIOLOGY

• Acute Pancreatitis: Inappropriate activation of enzymes within pancreatic parenchyma leads to inflammation and tissue destruction resulting in necrosis of peripancreatic fat, interstitial edema, and cytokine release

  • ✓ Complications include hypocalcemia, hyperglycemia, GI hemorrhage, severe necrosis, pseudocyst rupture, abscess, acute tubular necrosis, gastritis, duodenitis, and pleural effusion

• Chronic Pancreatitis: Fibrotic parenchymal disease resulting from obstructive or calcific processes; exact mechanisms unknown

  • ✓ Complications include pancreatic exocrine and endocrine insufficiency or failure

• Hereditary Pancreatitis (cationic trypsinogen deficiency): Autosomal dominant form of calcific chronic pancreatitis due to mutations of cationic trypsinogen, resulting in recurrent bouts of acute pancreatitis

• Autoimmune Pancreatitis: Associated with increased IgG levels (particularly IgG4), presence of autoantibodies, diffuse enlargement of pancreas, narrowing of main pancreatic duct, and lymphocytic infiltration of the pancreas with fibrotic changes

CLINICAL MANIFESTATIONS

• Acute Pancreatitis: Severe abdominal pain of acute onset; +/− epigastric location; nausea, vomiting, anorexia. Clinical course is highly variable

  • ✓ Most commonly is a self-limited process resolving over a period of 5–8 days on average in previously healthy children

  • ✓ A minority may develop a systemic inflammatory response syndrome (SIRS) with hypotension, renal failure, pulmonary edema or pleural effusions, hemorrhage, and shock

• Chronic Pancreatitis: Recurring or persistent abdominal pain or painless; some patients have recurrent episodes of acute pancreatitis; pain diminishes as pancreas burns out (may take 10–20 years);

  • ✓ Other manifestations include pancreatic exocrine or endocrine insufficiency (end-stage), steatorrhea, excessive appetite, growth failure, obstructive jaundice

DIAGNOSTICS

• Amylase: Level increases early; lasts 3–5 days

• Lipase: More specific than amylase; typically elevated longer

• In chronic pancreatitis, enzyme levels may not be increased

• C-reactive protein: Peaks at 36–48 hours

• Markers of severe disease: Hyperglycemia, hypocalcemia, hypoxemia, hypoproteinemia, high BUN, high white blood cells, low hematocrit

• Abdominal x-ray: To exclude other causes of abdominal pain

• Chest x-ray: Evaluate for pleural effusion

• Ultrasound: Pancreatic inflammation, calcification, ductular dilatation, stones, pseudocyst

• CT: Only needed when ultrasound is technically unsatisfactory (sensitivity >90% if necrosis involves >30% of pancreas). Consider CT-guided fine-needle aspiration if diagnosis of necrosis/infection uncertain

MANAGEMENT

• Supportive care, bed rest

• Nothing by mouth and nasogastric decompression if vomiting

• Fluid and electrolyte replacement. May need aggressive fluid resuscitation, requiring 1.5–2× maintenance intravenous fluids in early phases of disease

• Early nutrition with jejunal enteral feeds. Some evidence suggests early nasogastric feedings may be appropriate, but this remains an area of active research

• TPN reserved for patients who cannot safely tolerate enteral feedings

• Monitor acid/base status, electrolytes, renal function

• Analgesia: Ibuprofen, tramadol, narcotics

• Adjuncts in chronic pancreatic pain: Amitriptyline, nortriptyline, neurontin

• Antibiotics: For severe systemic illness or pancreatic necrosis (imipenem, ticarcillin-clavulanate, piperacillin-tazobactam, or ciprofloxacin + metronidazole)

• Repeat ultrasound or an alternative imaging study may be useful for patients not improving as expected to evaluate for pseudocyst, abscess, necrosis, or hemorrhage

• Attempt to identify underlying cause to help prevent recurrence

• ERCP to relieve stones or strictures

• Surgical management of complications such as symptomatic pseudocyst, abscess, necrosis, hemorrhage. Surgical correction of structural lesions is performed after acute illness resolves

• Once symptoms resolve and able to tolerate oral feedings, maintain on low-fat diet until complete recovery or indefinitely in chronic cases; consider pancreatic enzymes