What are the causes of pancreatitis in children?

Etiology of Pancreatitis in Children

The most common causes of pancreatitis in children include genetic mutations (particularly PRSS1, SPINK1, and CFTR genes), medications (especially valproic acid), biliary disease, and systemic conditions like cystic fibrosis, with genetic factors being present in nearly 50% of cases previously classified as idiopathic. 1, 2

Genetic Causes

• Hereditary pancreatitis is a significant cause of acute, acute recurrent, and chronic pancreatitis in the pediatric population, with genetic mutations identified in more than 50% of children with chronic pancreatitis 1
• PRSS1 gene mutations (cationic trypsinogen) are strongly associated with hereditary pancreatitis, even in children without a family history of pancreatitis 3
• SPINK1 gene mutations (serine protease inhibitor Kazal type 1) are found in approximately 27% of children with recurrent pancreatitis 2
• CFTR gene mutations (cystic fibrosis transmembrane conductance regulator) are identified in about 48% of children with recurrent pancreatitis 2
• Combined mutations (such as CFTR with either SPINK1 or PRSS1) significantly increase the risk of developing chronic pancreatitis 2
• Genetic testing should be considered in children with recurrent or chronic pancreatitis, as studies show almost 50% of idiopathic chronic and acute recurrent pancreatitis cases have genetic predisposition 4

Medication-Induced Pancreatitis

• Medications are associated with approximately 25.6% of pediatric pancreatitis cases 5
• Valproic acid is the most commonly implicated medication, particularly in children younger than 11 years 5
• Corticosteroids are another common medication associated with pancreatitis in children 5
• Drug-induced pancreatitis is often more severe, with longer hospital stays and greater need for nutritional support compared to non-drug-associated cases 5
• Life-threatening pancreatitis has been reported with valproic acid use, with some cases progressing rapidly from initial symptoms to death 6

Systemic Diseases

• Cystic fibrosis (CF) is an important cause of pancreatitis in children, with a birth prevalence of approximately 1/3,700 in the United States 7
• In CF, patients with pancreatic sufficiency (about 10-20% of CF patients) are at risk for developing pancreatitis as they age 7
• Inflammatory bowel disease, particularly Crohn's disease, is associated with pancreatitis in children 7, 5
• Hypertriglyceridemia can cause pancreatitis, especially when triglyceride levels exceed 700-1000 mg/dL 7

Anatomical and Other Causes

• Pancreatic duct abnormalities, including obstruction, irregularity, or dilatation, can lead to pancreatitis 7
• Pancreas divisum is an anatomical variant that predisposes to pancreatitis 7
• Biliary tract disease, including gallstones, is an important cause of pancreatitis in children 7
• Hypercalcemia can contribute to the development of pancreatitis 7
• Autoimmune pancreatitis, though less common in children, should be considered in the differential diagnosis 7

Clinical Implications and Management Considerations

• Children with genetic mutations are at higher risk for progression from acute to chronic pancreatitis 4
• Patients with hereditary pancreatitis have an increased risk of developing diabetes mellitus, exocrine pancreatic insufficiency, and pancreatic adenocarcinoma later in life 1
• Management requires a multidisciplinary approach with avoidance of triggers, surveillance of associated conditions, treatment of pancreatic insufficiency, and appropriate interventions for complications 1
• In children with drug-associated pancreatitis, approximately one-third have an additional pancreatitis etiology, highlighting the importance of comprehensive evaluation 5
• Common comorbidities in children with drug-associated pancreatitis include seizure disorders, acute lymphocytic leukemia, and Crohn's disease 5

Diagnostic Approach

• Genetic testing should be considered in children with recurrent or unexplained pancreatitis, especially when there is a family history 3
• Screening for cystic fibrosis should be performed in children with unexplained pancreatitis 7
• Evaluation for metabolic disorders (hyperlipidemia, hypercalcemia) is important in the workup 7
• Imaging studies to identify anatomical abnormalities are essential in the diagnostic approach 7