Pancreatitis

The frequency of pancreatitis (i.e., inflammation of the pancreas) in children and adolescents has been increasing over the past 10 to 15 years. There are several common causes of pancreatitis, including blunt abdominal trauma; infections such as enterovirus, Epstein-Barr virus, hepatitis A, rubella, Coxsackie virus B, cytomegalovirus, HIV, and influenza; congenital anomalies of the pancreas; choledochal cysts; and choledocholithiasis. Medications, including azathioprine, 6-mercaptopurine, glucocorticoids, valproate, and L-asparaginase, can cause pancreatitis. Pancreatitis can also be the result of systemic diseases and metabolic abnormalities, including CF, diabetic ketoacidosis, hypercalcemia, hyperlipidemia, and hemolytic-uremic syndrome.

Pancreatitis occurs when intracellular trypsinogen and other digestive enzymes are activated, leading to damage of the pancreatic acinar cells. This damage leads to pancreatic edema (Figure 114-2), a local inflammatory response, and the initiation of autodigestion of the pancreas. These pancreatic secretions may form a collection that becomes walled off by granulation tissue to form a pseudocyst.

Figure 114-2 Pancreatitis.

Chronic pancreatitis occurs with recurrent episodes of acute pancreatitis, leading to chronic inflammation as well as end-stage fibrosis (see Figure 114-2). The most common causes of chronic pancreatitis in children are CF, hereditary pancreatitis including mutations in the SPINK1, CFTR, and PRSS1 genes, and idiopathic causes.

Cystic Fibrosis

Pancreatic insufficiency in patients with CF is caused by dysfunction of the CFTR gene (Figure 114-3). This leads to impaired transport of sodium and chloride and subsequent obstruction of the pancreatic ducts with viscous exocrine fluid. These patients have diminished secretion of amylase, lipase, colipase, and phospholipases, as well as a decreased concentration of bicarbonate in their pancreatic secretions.

Figure 114-3 Pancreatic disease in cystic fibrosis.

Congenital and Inherited Anomalies

Congenital anomalies of the pancreas arise during fetal development. The pancreas forms from fusion of dorsal and ventral buds, which develop from the embryonic foregut. The ventral process rotates at about the eighth week of gestation and settles posterior and inferior to the dorsal portion of the pancreas. Pancreas divisum is the most common pancreatic anomaly and occurs when the dorsal and ventral portions fail to fuse. Annular pancreas occurs when the ventral bud fails to rotate with the duodenum and instead surrounds it (Figure 114-4).

Figure 114-4 Annular pancreas.

Pancreatic disease may present as part of an inherited syndrome. This category includes CF and hereditary pancreatitis (see above). In addition, Schwachman-Diamond syndrome is caused by mutations in SDS and is characterized by short stature, variable neutropenia, and PI. The latter often improves as patients grow older. Finally, the spectrum of abnormalities seen in Johanson-Blizzard syndrome includes progressive PI.

Pancreatitis

Pancreatitis in children most commonly presents with nausea, vomiting, and epigastric abdominal pain that may radiate to the back. Additional symptoms include fever, tachycardia, hypotension, and jaundice. Physical examination findings include abdominal distention, hypoactive bowel sounds, and epigastric tenderness, rebound, or guarding. Patients with a pseudocyst may present with abdominal distention and a palpable and tender epigastric mass. Acute hemorrhagic pancreatitis is a rare entity in children and is life threatening when it occurs. These patients may present in shock and have physical examination findings that include a bluish discoloration of the flanks (Grey Turner’s sign) or periumbilical area (Cullen’s sign).

Cystic Fibrosis

Pancreatic insufficiency in patients with CF becomes more common with increasing age, with only about 60% of neonates affected as compared with 80% to 90% of older children. These children generally present with symptoms of fat malabsorption and malnutrition and have decreased serum levels of pancreatic digestive enzymes, but elevated levels of salivary and brush border amylase.

Congenital and Inherited Anomalies

Congenital anomalies of the pancreas are often asymptomatic and are typically found incidentally on imaging or at autopsy. Pancreas divisum is the most common pancreatic congenital anomaly. This condition can lead to pancreatitis in a subset of patients and therefore should be on the differential diagnosis for patients with pancreatitis of unknown etiology. Annular pancreas is the second most common congenital anomaly of the pancreas and can cause duodenal obstruction in some patients. This obstruction can present with a range of symptoms depending on the degree of obstruction; the range includes feeding difficulty, vomiting, and abdominal distension in a newborn with severe obstruction to postprandial fullness, nausea, and weight loss in an older child with a lower grade obstruction.

The differential diagnosis of pancreatitis includes disorders of the stomach, intestines, gallbladder, kidneys, lungs, and liver (Box 114-1).

Pancreatitis

A thorough history is important to distinguish pancreatitis from other causes of acute abdominal pain. It is important to determine the onset and the character of the pain, as well as any other associated symptoms. A complete list of current medications is important to obtain because many medications may cause pancreatitis, including nonsteroidal antiinflammatory drugs, corticosteroids, antibiotics (sulfonamides, tetracyclines), diuretics (thiazides, furosemide), azathioprine, and mercaptopurine, to name a few. The laboratory evaluation should include amylase and lipase levels, which may be elevated more than three times the upper limit of normal but can be unreliable because they may be elevated for reasons other than pancreatitis (Table 114-1). An ultrasound may reveal an enlarged pancreas with an alteration in echogenicity and can also identify the presence of a pseudocyst. Other findings on ultrasound may include gallstones or biliary sludge in the case of gallstone pancreatitis, pancreatic calcifications, choledochal cysts, dilated pancreatic ducts, or dilated common or hepatic bile ducts. Magnetic resonance cholangiopancreatography can be helpful in further identifying ductal abnormalities. In patients with recurrent or chronic pancreatitis, genetic testing for SPINK1, CF, and cationic trypsinogen (PRSS1) can be helpful. Additionally, an elevated triglyceride level may indicate hyperlipidemia as a cause of recurrent pancreatitis.

Table 114-1 Causes of Elevated Amylase and Lipase Levels