What are the common causes of pancreatitis?

Common Causes of Pancreatitis

The most common causes of pancreatitis in decreasing order of frequency are drugs (particularly thiopurines), gallstones, alcohol, and endoscopic retrograde cholangiopancreatography (ERCP). 1

Acute Pancreatitis Causes

Most Common Causes

• Gallstones: Leading cause of acute pancreatitis in the general population 1, 2
• Alcohol abuse: Second most common cause, particularly with chronic consumption 1, 2
• Medications: Particularly:
  • Thiopurines (azathioprine, 6-mercaptopurine): Occurs in approximately 4% of treated IBD patients 1
  • 5-ASA compounds: Lower risk than thiopurines 1
  • Valproic acid: Can cause life-threatening pancreatitis, sometimes with rapid progression from initial symptoms to death 3

Other Important Causes

• Post-ERCP pancreatitis: Procedural complication 1
• Hypertriglyceridemia: Particularly with levels >1000 mg/dL
• Hypercalcemia: Disrupts calcium homeostasis in pancreatic cells
• Trauma: Direct injury to the pancreas
• Autoimmune pancreatitis: IgG4-related disease described in IBD patients 1
• Pancreatic duct obstruction: From tumors, strictures, or anatomic variants
• Pancreas divisum: Congenital anatomic variant 1
• Hereditary/genetic causes: Associated with specific gene mutations 4
• Idiopathic: Approximately 15-35% of chronic pancreatitis cases have no apparent underlying cause 1

Inflammatory Bowel Disease-Specific Forms

Two IBD-specific forms of acute pancreatitis exist 1:

1. Related to shared pathogenic pathways:

   • Autoimmune pancreatitis
   • Idiopathic pancreatitis
   • Granulomatous pancreatitis
   • Pancreatitis associated with primary sclerosing cholangitis (PSC)

2. Related to IBD management or associated diseases:

   • Biliary pancreatitis
   • Drug-induced pancreatitis (especially thiopurines)
   • Pancreatitis secondary to duodenal Crohn's Disease
   • Post-ERCP or post-enteroscopy pancreatitis

Chronic Pancreatitis Causes

• Alcohol: Etiological factor in 60-70% of chronic pancreatitis patients 1
• Pancreatic duct obstruction: Can lead to chronic inflammation
• Pancreas divisum: Congenital anatomic variant
• Hereditary pancreatitis: Associated with 50-70-fold increased risk of pancreatic cancer 5
• Tropical pancreatitis: Geographic variant
• Idiopathic: 15-35% of patients have no apparent underlying disease 1

Risk Factors for Pancreatic Cancer

While not direct causes of pancreatitis, these factors are associated with increased risk of pancreatic cancer:

• Cigarette smoking: Accounts for 25-30% of pancreatic cancer cases 5
• Chronic pancreatitis: Associated with 5-15-fold increased risk 5
• Hereditary pancreatitis: Associated with 50-70-fold increased risk 5
• Diabetes mellitus: Relative risk 1.4-2.2 5
• Obesity: Relative risk 1.2-1.5 5

Clinical Pearls and Pitfalls

• Diagnostic challenge: Abdominal pain due to pancreatitis can be difficult to differentiate from pain caused by active IBD 1
• Asymptomatic elevation: An asymptomatic elevated lipase is found in 7% of IBD patients 1
• Drug-induced pancreatitis: Azathioprine/6-mercaptopurine-induced pancreatitis is dose-independent and typically occurs within 3-4 weeks of treatment initiation 1
• Genetic predisposition: Patients who carry the HLA-DQA102:01-HLA-DRB107:01 haplotype are more prone to develop pancreatitis after thiopurine administration 1
• First episode in older patients: In patients older than 50 years with first acute pancreatitis, the presence of a tumor (benign or malignant) should be specifically ruled out 2
• Idiopathic cases: The diagnosis of idiopathic pancreatitis should not be accepted without a vigorous search for gallstones, including at least two good quality ultrasound examinations 1

When evaluating a patient with suspected pancreatitis, always consider the most common etiologies first (gallstones, alcohol, medications), but maintain vigilance for less common causes, particularly in recurrent or idiopathic cases.