Pediatric Pancreatitis

Educational Gaps The incidence of acute pancreatitis has increased in pediatric patients over the past two decades, approaching the incidence in adults. Clinicians should know : approaches to pancreatic rest and fluid management have changed, as have long-time teachings on the use of opiods and the institution of nutrition.

Objectives should be able to: Differentiate between acute and chronic pancreatitis. Know how to diagnose acute pancreatitis. List common causes for acute, recurrent, and chronic pancreatitis Explain the utility of clinical symptoms, biochemical testing, and radiographic imaging Understand the management

Introduction An inflammatory condition of the pancreas Acute pancreatitis is a reversible process, whereas chronic pancreatitis (CP) is irreversible Differences between pancreatitis in children and adults, particularly in presentation, etiology, prognosis, and nature of acute recurrent pancreatitis (ARP). 

Acute Pancreatitis in Pediatrics

Epidemiology occurs in all age groups, even in infants. 3.6~13.2/10W, approaches to adults (greater awareness)

Pathophysiology Acinar cell injury 1. initiate the premature intracellular activation of trypsinogen to trypsin. Trypsin, in turn, activates other digestive proenzymes. The activated digestive enzymes then mediate acinar cell injury. 2. an aberrant unfolded protein response and the resultant endoplasmic reticulum stress may initiate apoptotic pathways and inflammatory signals.

Gallstone pancreatitis is a more common cause than previously believed.

>20% of reported cases Multifactorial: Sepsis Shock Hemolytic uremic syndrome(++) Systemic lupus erythematosus Virus like mumps virus

L-asparaginase Valproic acid Azathioprine Mercaptopurine Mesalamine May disrupt acinar cell metabolism

not as high as previously thought Unintentional blunt trauma Child abuse

Metabolite: treatment can prevent recurrent episodes. Disorders that cause hypercalcemia, hypertriglyceridemia, and inborn errors Genetic: discuss later

Type 1: may elevated IgG4, diffuse or segmental enlargement of the pancreas, strictures of the pancreatic duct. Type 2: more common in children , association with inflammatory bowel disease and other autoimmune diseases →respond to corticosteroid therapy.

Choledochal cysts Pancreas divisum( 15%), related to SPINK-1 or CFTR gene Annular pancreas

Pancreas divisum 胰腺分裂

Diagnosis ≥ two of three criteria: (1) Abdominal pain (2) Serum amylase or lipase > 3 times than the upper limit of normal (3) Imaging findings compatible with acute pancreatitis. Mild: >90%, limited to the pancreas and the peripancreatic fat Severe: pancreatic necrosis, involvement of other organs, cardiovascular collapse, infection, or fluid collections. (1) abdominal pain suggestive of or compatible with acute pancreatitis (ie, abdominal pain of acute onset, especially in the epigastric region)

ABDOMINAL PAIN 80% to 95% in pediatric patients who have acute pancreatitis. Epigastric: 62% to 89% Diffusely: 12% ~ 20% Radiating to the back: 1.6%~5.6% Nonverbal or encephalopathy-> irritability

Amylase and lipase Rise time- Amylase: 2~12 hours Lipase: 4 ~ 8 hours May just one elevate Other elevation cause

Management Pancreatic rest Fluid support: 1.5 times maintenance IVF in first 24 hours Nutrition: priming since 24~48hrs if mild( Regular meal. No low fat. 10% pain. Continue even elevated enzyme. TPN for prolonged ileus, pancreatic fistulae, or complicating abdominal compartment syndrome)

Management Antiemetics and analgesia: opioid( morphine) Treat reversible cause( antibiotic is not routine) Monitoring for complications.

Complications Pancreatic fluid collections are the most common

Pseudocyst

Outcomes better than in adults and are not correlated with initial amylase and lipase levels. no existing scoring systems like APACHE (Acute Physiology and Chronic Health Evaluation) or the Ranson system used pediatrics.

Acute Recurrent Pancreatitis( ARP)

Definition ≥2 episodes of acute pancreatitis per year, or >3 episodes over a lifetime, in a patient without CP or a pancreatic pseudocyst 10% to 35% of patients will have recurrence

Etiology

Genetic mutation PRSS-1: cationic trypsinogen Several mutations in the PRSS-1 gene that encodes cationic trypsinogen cause hereditary pancreatitis. Autosomal dominant with an 80% penetrance. The lifetime risk of pancreatic cancer is 40% or greater in these patients.

Genetic mutation SPINK-1: serine protease inhibitor Kazal type 1 Produced in acinar cells and acts as a defense for premature trypsinogen activation. But most people who have these mutations, even when homozygous, do not develop pancreatitis. Thought to be related to decreased ability to inactivate trypsin. But toxicity from misfolded protein, remain possible

Genetic mutation CFTR: cystic fibrosis transmembrane conductance regulator Disease modifiers Lack other clinical features of cystic fibrosis or have mild disease in other organs and are pancreatic-sufficient at presentation, although some will develop pancreatic insufficiency over time. the effect of many changes in the gene sequence on protein function is unknown.

Genetic mutation CTRC: chymotrypsin C gene Encodes for the digestive enzyme chymotrypsin C Disease modifiers. Can inactivate trypsin in vitro

Duplication cysts- duodenum or stomach Secondary to pancreaticobiliary obstruction Difficult to detect

Management Genetic screening for PRSS-1 and SPINK-1 mutations Sweat test-> indeterminate or low positive zone-> gene sequencing for CFTR MRCP: anatomy Pancreas divisum-> ERCP: sphincterotomy and stenting of the minor papilla Endoscopy for mass lesion which obstruct the ampulla Autoimmune pancreatitis: if MRCP suspect- IgG4 Systemic inflammatory disease, especially for Crohn disease Ultrasonography or CT scan- to identify duplication cysts

Chronic Pancreatitis

Definition and epidemiology A process leading to irreversible destruction of the pancreatic parenchyma and ducts and loss of exocrine function. Classic cystic fibrosis is the most common cause in children Incidence and prevalence in childhood are not known.

Etiology and pathophysiology Causes of CP are the same as those of ARP Results from the sequelae of long-standing destructive inflammation Fibrosis

Diagnosis Clinical and based on a combination of symptoms, imaging studies, and functional insufficiency Diagnosis often is delayed With advanced disease, amylase and lipase levels will not be elevated, even in the presence of disabling pain.

Clinical features Pain: mild to intense, usually epigastric, constant or intermittent, deep and penetrating, radiation to the back, episodic. - obstruction of pancreatic ducts by fibrosis or stone - inflammation of the parenchyma - perineural inflammation - pain imprinting in the peripheral or central nervous system

Clinical features Malabsorption: weight loss, fatty stools, or diarrhea Jaundice from extrahepatic biliary obstruction caused by pancreatic fibrosis or a pseudocyst Upper gastrointestinal hemorrhage from venous thrombosis Diabetes

Pancreatic function testing Identify pancreatic insufficiency: - Duodenal intubation with secretin-cholecystokinin stimulation: standard for diagnostic testing - Pancreatic secretions collected at upper endoscopy: underestimates - Fecal elastase: poor sensitivity trypsin output <50 U/kg/h as the reference standard Elastase, a kind of proteinase, Elastase breaks down elastin, an elastic fibre that, together with collagen, determines the mechanical properties of connective tissue.

Management Pain : acetaminophen; narcotics/ nerve ablation/ surgery Pancreatic enzyme supplement Endoscopic treatment for ductal strictures or pancreatic duct stones Surgical intervention: partial resection; Total pancreatectomy with islet cell auto-transplant Diabetes: insulin only medical center west of the Mississippi UCSF harvesting functioning islets from the patient's own diseased pancreas and then infusing them into the portal vein, where they migrate to the liver.

Complications The pain may vacillate in intensity and frequency, but it will not resolve with time Diabetes may take 2 or 3 decades to become clinically significant In hereditary pancreatitis, pancreatic cancer appears first in the fourth decade (incidence of 0.5%)

Summary Increasing prevalence in pediatrics Different etiologic: gallstone; trauma; genetic; idiopathic Diagnosis: symptom, lab, image Feeding: early, non-low fat Chronic-> irreversible