Chapter 74: Pancreatitis

• The most common etiologies of pancreatitis are trauma, systemic disease, structural anomalies of the pancreatic-biliary system, drugs, infections, and idiopathic causes.

• The most common symptoms are abdominal pain, nausea, and irritability.

• Amylase and lipase levels are low at birth and slowly increase over several months.

• The mainstay of treatment is to provide supportive care through fluid resuscitation, pain control, and nutritional support.

• Ranson criteria, Glasgow score, and pediatric acute pancreatitis severity (PAPS) scoring system show limited ability to predict severity in children with acute pancreatitis.

• Approximately 25% of children with acute pancreatitis develop a complication, but less than 6% of children develop multiorgan dysfunction.

• The mortality rate reported in children with pancreatitis varies between 4% and 10%.

• Hypercalcemia, hypertriglyceridemia, structural abnormalities, and genetic mutations can cause recurrent pancreatitis.

• Chronic pancreatitis often presents as acute pancreatitis followed by recurring abdominal pain.

Pancreatitis is defined as inflammation within the parenchyma of the pancreas. This is a reversible process characterized by the presence of acute inflammatory cells, interstitial edema, and varying degrees of necrosis, apoptosis, and hemorrhage within the pancreas.¹

Pancreatitis is a disease process with multiple possible causes (Table 74-1). The most common etiologies are trauma, systemic disease, structural anomalies of the pancreatic-biliary system, drugs, infections, and idiopathic causes.^2–4

Trauma

The most common cause of pancreatitis in children is blunt trauma, which accounts for 10% to 40% of cases.^2–5 Motor vehicle crashes, sports injuries, accidental falls, and child abuse account for the majority of cases. However, it should be noted that in trauma patients, the amylase levels might be elevated due to intestinal perforation.

Systemic Diseases

The systemic diseases most commonly associated with pancreatitis are sepsis, shock, hemolytic-uremic syndrome, and systemic lupus erythematous.^2,3 In children younger than 3 years of age, pancreatitis was often associated with one of these systemic diseases.^5,6

Structural/Biliary Diseases

Structural defects such as pancreas divisum (dorsal and ventral pancreatic ducts fail to fuse) is found in 5% to 10% of the population, thus it is unclear if this also causes pancreatitis. Gallstones or sludge found in bile duct can lead to pancreatitis.^2,3,5,7

Medications

Several medications have been linked to pancreatitis.^2–5,8,9 The most common medications are valproic acid, asparaginase, azathioprine, prednisone, and 6-mercaptopurine. No clear mechanism has been delineated for the development of medication-induced pancreatitis. Most of the drugs are implicated due to the cause-and-effect relation observed between drugs and pancreatitis.

Infections

Infectious causes are seen in approximately 10% of patients.^2–5 Infectious causes associated with pancreatitis include mumps virus,² hepatitis A virus,¹⁰ rotavirus,¹¹ hepatitis E virus,¹² and varicella.¹³ Other infections include adenovirus, coxsackie virus, mycoplasma pneumonia, and moraxella catarrhalis.²

Metabolic

Metabolic causes are rare and occur in approximately 1% to 5% of patients.^2,3,5 These include diabetic ketoacidosis, hypertriglyceridemia, and hypercalcemia.

Hereditary

Hereditary causes are seen in about 2% to 8% of patients.^2–5,14,15 Mutations are most commonly found in the cationic trypsinogen gene (PRSS1), the pancreatic secretory trypsin inhibitor gene (SPINK1), and the cystic fibrosis transmembrane conductance regulator gene (CFTR).^9,13,14 A recent review by Whitcomb provides details on the loss of protective mechanisms due to genetic defects.¹⁵ It remains to be determined to what extent genetic factors are involved in the pathogenesis of idiopathic acute pancreatitis.

Idiopathic

Patients with idiopathic pancreatitis ranged from 13% to 34%.^2–5 However, it is likely that some of these patients may have had unidentified infections, drugs, toxins, or trauma-related etiologies.

The pathophysiology of acute pancreatitis remains obscure. Acinar cell injury can occur from drugs, metabolic disorders, and infection. Premature activation of trypsinogen to trypsin in the pancreas can occur from obstruction of ductal flow (structural) or failure in feedback control (hereditary). This results in an aggressive immune and inflammatory response leading to a common pathway.^2,15

Pancreatitis is diagnosed by clinical presentation, laboratory, and imaging tests. Children should meet at least two of the following three parameters to qualify as having acute pancreatitis: abdominal pain, elevated amylase/lipase usually greater than three times the upper limit of normal, or confirmatory findings on cross-sectional abdominal imaging such as ultrasound, computed tomography (CT) scan, or magnetic resonance imaging (MRI).^2,3

Symptoms

In pediatric studies of acute pancreatitis, 80% to 95% of patients present with abdominal pain.^2–5 The most common location of pain is the epigastric region (62%–89% of cases). However, occasionally pain can be diffuse, located in the lower abdomen and sometimes radiates to the back. In young children, irritability and fever are often nonspecific presenting complaints.^16,17 The second most common symptom is nausea or vomiting, and is reported in 40% to 80% of patients.² Other symptoms can include fever and jaundice.

Physical Findings

Physical examination can be quite variable.³ The child is often still but becomes uncomfortable with movement. Tachycardia, fever, diffuse abdominal tenderness, quiet bowel sounds can be present. Other findings include dyspnea and epigastric mass (pseudocyst formation). Rarely, there may be signs of hemorrhagic pancreatitis with bluish flanks (Grey-Turner sign) or a bluish area surrounding the umbilicus (Cullen sign).⁵

Labs

Elevations in serum amylase and lipase are the most common biochemical determinants of pancreatitis. In pediatric studies, the sensitivity of the amylase test in diagnosing pancreatitis has ranged from 50% to 90%.^2,5 In particular, serum amylase elevations can arise from nonpancreatic sources such as the salivary gland and intestine or result from reduced renal clearance. In addition, newborn levels of total amylase and pancreatic isoamylase are very low. Total amylase levels reach normal adult values by 8 to 18 months of age and pancreatic isoamylase levels reach adult values by 10 to 15 years of age.³

Lipase levels are also low at birth and slowly increase by 12 months of life.³ Lipase levels can be increased in intestinal diseases as well. In pancreatitis, lipase remains elevated longer than amylase levels. Neither amylase nor lipase correlates with pancreatitis severity. Therefore, it is recommended that both amylase and lipase be obtained in children suspected of pancreatitis. The elevation of amylase and lipase in children has a sensitivity of 94%.¹⁸ Serum cationic trypsinogen, and trypsinogen activation peptide are currently being investigated as possible marker of pancreatitis.^2,19

White blood cell count (WBC) and hematocrit are often elevated due to hemoconcentration and volume depletion. Hypocalcemia and hyperglycemia can be seen in acute pancreatitis.

Imaging

Imaging modalities can confirm the diagnosis of pancreatitis, help to identify the cause, and assess for complications. Ultrasound is often recommended as the initial imaging test. An enlarged, edematous pancreas or decreased pancreatic echogenicity suggests pancreatitis but the sensitivity is only 33% to 67%.^2,5,20 However, it can also evaluate for possible gallstones, fluid collections, abnormalities in pancreaticobiliary drainage system and can look for other causes of an acute abdomen (e.g., appendicitis, intussusception, volvulus).²⁰

CT with contrast is helpful in evaluating the severity of pancreatitis but due to radiation exposure, it is only recommended for complicated cases or if the diagnosis is unclear.^21,22 MRI is noninvasive, radiation free but the data is still limited in children with pancreatitis.²³ Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) are becoming more utilized and experience with these modalities is increasing.^24,25

Estimating Severity

In adults, clinical scales such as Ranson criteria and Glasgow score are used to measure the severity and prognosis of acute pancreatitis after 48 hours. Unfortunately, these have shown to have low sensitivity and negative predictive value in children.²⁶ A PAPS scoring system was created to predict severity and major complications with acute pancreatitis but this also showed limited ability to predict severity in children.^26,27 However, statistical regression analysis suggests that admission WBC count, calcium levels, and BUN levels are important factors in evaluating the severity of pancreatitis and should be considered for future scoring systems.²⁶

The mainstay of treatment is to provide supportive care through fluid resuscitation, pain control, and nutritional support. Appropriate antibiotic therapy is indicated for underlying infection and is debated for patients with pancreatic necrosis. However, prophylactic antibiotic use is typically not recommended in children with pancreatitis.²⁸

IV Fluids

Adequate intravenous fluid resuscitation is an important supportive measure in the management of acute pancreatitis. Although early and aggressive fluid resuscitation is recommended, the optimal rate, type, and volume of fluid is not clearly defined even in adults.²⁹ Fluid administration is aimed at replacing third spacing while maintaining good urine output.

Nutrition

Nutrition has emerged as an important treatment modality in pancreatitis. Several large randomized controlled and meta-analysis suggests enteral feeding reduces complications of acute pancreatitis in adults but there is very limited data in children.^2,3,30 Despite the lack of data in pediatric patients, most authors recommend jejunal feeding with high protein and low-fat formula be started 1 to 2 days after developing severe pancreatitis.^2,5 Total parenteral nutrition (TPN) is generally not recommended unless a patient proves intolerant to enteral feeding.

Approximately 25% of children with acute pancreatitis develop a complication but less than 6% of children develop multiorgan dysfunction.² Early complications include shock, acute respiratory distress syndrome, pneumonia, pulmonary effusion, or renal failure. Late complications develop several days to weeks after the initial acute presentation. These complications include pancreatic necrosis and pseudocyst formation. Pseudocysts are rare in children and usually occur in trauma patients and often resolve spontaneously.

The mortality rate reported in children with pancreatitis varies between 4% and 10%.^2,4,26 The higher end of the range may be inaccurate as severe pancreatitis is most commonly associated with trauma and systemic disease. These patients often die due to their underlying disease rather than a complication of pancreatitis.^2,31

Approximately 10% of children with acute pancreatitis develop recurrent episodes.^3,28 Hypercalcemia, hypertriglyceridemia, and structural abnormalities should be considered in all acute pancreatitis cases. If any of these causes are found, they should be treated to prevent the development of recurrent pancreatitis.³² In addition, genetic causes should also be considered as mutational analysis for PRSS1, SPINK1, and CFTR are now commercially available.

Chronic pancreatitis is a progressive, irreversible, inflammatory disease of the pancreas. Fibrosis and infiltration of chronic inflammatory cells can lead to exocrine or endocrine failure or both.⁵ This often presents as acute pancreatitis followed by recurring abdominal pain. Although the etiologies are similar to acute pancreatitis, obstructive and genetic causes are the most common causes of chronic pancreatitis. This is often associated with malabsorption, weight loss, growth failure, and development of diabetes mellitus. Initial laboratory testing includes: complete blood count, electrolytes, liver function tests, amylase, and lipase. Further workup can include stool-fat testing, genetic testing, and pancreatic function testing. Imaging tests can help to confirm the diagnosis. These include abdominal x-rays, transabdominal ultrasound, CT scan, magnetic resonance cholangiopancreatography (MRCP), ERCP, and EUS. Data on treatment in pediatric patients is limited and is often aimed at treating chronic unremitting pain. If needed, endoscopic interventions and surgery can provide adequate drainage of pancreatic ducts.³³