What are the causes of pancreatitis?

Causes of Pancreatitis

Gallstones are the leading cause of acute pancreatitis, accounting for 45-60% of cases, followed by alcohol abuse at 20-25%, with the remaining cases due to hypertriglyceridemia, medications, anatomical abnormalities, autoimmune processes, hypercalcemia, infections, trauma, and idiopathic causes. 1, 2

Primary Causes (Account for 80-85% of Cases)

Gallstones (45-60% of cases)

• Gallstone migration obstructs the pancreatic duct, triggering inflammation and enzyme activation. 1
• The risk of gallstones is increased in Crohn's disease but not ulcerative colitis. 3
• Initial ultrasound may miss gallstones; at least two good-quality ultrasound examinations should be performed before labeling a case as idiopathic. 1, 2
• MRCP has 97.98% sensitivity and 84.4% specificity for choledocholithiasis when ultrasound is negative but clinical suspicion remains high. 2

Alcohol Abuse (20-25% of acute cases, 60-70% of chronic cases)

• Alcohol is the second most common cause overall and the dominant etiological factor in chronic pancreatitis. 1, 2
• The incidence is increasing among younger populations due to rising alcohol consumption. 1
• Excess alcohol consumption is the most common cause of chronic pancreatitis in Europe. 3

Secondary Causes (Account for 10-15% of Cases)

Hypertriglyceridemia (4-10% of cases)

• This is the third most common cause and carries a worse prognosis than other etiologies. 4
• Serum triglyceride levels over 11.3 mmol/L indicate hypertriglyceridemia as the etiology. 2
• Free fatty acids released by pancreatic lipase sequester calcium intravascularly, contributing to cellular injury and systemic hypocalcemia. 2

Drug-Induced Pancreatitis

• Azathioprine/6-mercaptopurine causes pancreatitis in approximately 4% of treated IBD patients, typically within the first 3-4 weeks of treatment, and is dose-independent. 3, 4
• Patients carrying the HLA-DQA102:01-HLA-DRB107:01 haplotype are more prone to thiopurine-induced pancreatitis. 3
• 5-ASA (mesalazine) has a much lower risk than thiopurines but can still cause pancreatitis. 3, 4
• Other medications include valproic acid and various other agents. 1

Hypercalcemia

• Elevated calcium activates pancreatic enzymes prematurely, leading to autodigestion and inflammation. 1
• Fasting calcium concentrations must be determined in all patients with acute pancreatitis, especially when gallstones and alcohol have been excluded. 2

Anatomical Abnormalities

• Pancreas divisum and other pancreatic duct abnormalities obstruct normal pancreatic drainage. 1
• Pancreatic duct changes (main duct obstruction, severe irregularity, dilatation) are found in 8% of Crohn's disease and 16% of ulcerative colitis patients. 3

Autoimmune Pancreatitis

• This is an immune-mediated form that may be associated with IgG4-related disease. 1
• Autoimmune pancreatitis has been described in IBD patients. 3

Post-Procedural Causes

• Post-ERCP pancreatitis is a recognized complication. 3
• Trauma or surgery, particularly after abdominal or cardiac procedures, can cause direct pancreatic injury. 1
• Post-operative acute pancreatitis represents a high-risk subset with worse outcomes. 1

Infectious Causes

• Viral infections can occasionally trigger pancreatitis. 1
• Helicobacter pylori infection increases relative risk (RR 1.5, attributable fraction 4-25%). 3

Chronic Pancreatitis-Specific Causes

Environmental Factors

• Alcohol abuse (OR 3.1 for ≥5 drinks/day) and smoking (OR 4.59 for >35 pack-years) are the dominant environmental risk factors. 5
• Smoking, obesity, and dietary factors (butter, saturated fat, red meat, processed foods) contribute to pancreatic cancer risk, which can present as pancreatitis. 3

Genetic Factors

• Between 28-80% of chronic pancreatitis cases are classified as "idiopathic," with up to 50% having mutations in SPINK1 or CFTR genes. 5
• Approximately 1% have hereditary pancreatitis associated with PRSS1 gene mutations. 5
• Germline mutations in BRCA2, p16, ATM, STK11, PRSS1/PRSS2, SPINK1, PALB2, and DNA mismatch repair genes increase pancreatic disease risk. 3

Critical Clinical Pearls

Idiopathic Pancreatitis

• No more than 20-25% of cases should be labeled as idiopathic; approximately 10-25% remain unexplained after thorough workup. 1
• Endoscopic ultrasound may detect microlithiasis in the gallbladder or common bile duct in recurrent cases with no identified cause. 2

Age-Specific Considerations

• In patients over 50 years with first acute pancreatitis, pancreatic tumors (benign or malignant) must be specifically ruled out using CT-scan, MRI, and endoscopic ultrasound. 6

IBD-Specific Forms

• Two IBD-specific forms exist: one related to shared pathogenic pathways (autoimmune, idiopathic, granulomatous, PSC-associated) and one due to IBD management or associated diseases (biliary, drug-induced, duodenal Crohn's disease, post-procedural). 3
• In IBD patients, the most common causes by decreasing frequency are drugs (mostly thiopurines), gallstones, alcohol, and ERCP. 3