What causes pancreatitis?

What Causes 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, and trauma. 1, 2

Primary Etiologies

Gallstone Disease (45-60% of cases)

• Gallstones, particularly those 5 mm or smaller, represent the most common cause of acute pancreatitis. 1, 2, 3
• Gallstone migration obstructs the pancreatic duct, triggering inflammation and premature enzyme activation. 1
• Do not accept a diagnosis of "idiopathic" pancreatitis without obtaining at least two good-quality ultrasound examinations, as initial ultrasound may miss stones. 4, 1
• When ultrasound is negative but clinical suspicion remains high, MRCP has 97.98% sensitivity and 84.4% specificity for detecting bile duct stones. 1
• Endoscopic ultrasound may detect microlithiasis in the gallbladder or common bile duct in recurrent cases where standard imaging is negative. 4, 1

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

• Alcohol is the second most common cause overall and the dominant factor in chronic pancreatitis. 1, 2
• High alcohol intake is particularly associated with chronic pancreatitis in Europe and varies by geographic region. 2
• Abstinence from alcohol is essential for patients with alcoholic pancreatitis to prevent recurrence. 2

Secondary Causes

Hypertriglyceridemia (4-10% of cases)

• Hypertriglyceridemia is the third most common cause and carries a worse prognosis than other etiologies. 1, 5
• Serum triglyceride levels over 11.3 mmol/L (approximately 1000 mg/dL) indicate hypertriglyceridemia as the etiology. 1
• Free fatty acids released by pancreatic lipase sequester calcium intravascularly, contributing to cellular injury and systemic hypocalcemia. 1

Medication-Induced Pancreatitis

• Azathioprine and 6-mercaptopurine cause pancreatitis in approximately 4% of treated IBD patients, typically within the first 3-4 weeks of treatment, and the reaction is dose-independent. 1, 5
• Patients carrying the HLA-DQA102:01-HLA-DRB107:01 haplotype are more prone to thiopurine-induced pancreatitis. 1
• 5-ASA (mesalazine) has a much lower risk than thiopurines but can still cause pancreatitis. 1, 5
• Valproic acid can cause life-threatening pancreatitis in both children and adults, occurring shortly after initial use or after several years of treatment. 6

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. 1

Anatomical Abnormalities

• Pancreas divisum and other pancreatic duct abnormalities obstruct normal pancreatic drainage. 1, 2
• Pancreatic duct changes (main duct obstruction, severe irregularity, dilatation) are found in 8% of Crohn's disease and 16% of ulcerative colitis patients. 1

Autoimmune Pancreatitis

• Autoimmune processes can trigger pancreatitis, particularly in patients with inflammatory bowel disease. 1, 2

Infections

• Viral infections (mumps, Coxsackie B4) can occasionally trigger pancreatitis. 4, 1
• Helicobacter pylori infection increases relative risk (RR 1.5, attributable fraction 4-25%). 1

Trauma and Post-Procedural

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

Genetic Factors

• Germline mutations in BRCA2, p16, ATM, STK11, PRSS1/PRSS2, SPINK1, PALB2, and DNA mismatch repair genes increase pancreatic disease risk. 1
• Hereditary or tropical pancreatitis are additional etiologies. 2

Critical Clinical Pearls

• No more than 20-25% of cases should be labeled as idiopathic; approximately 10-25% remain unexplained after thorough workup. 4, 1
• In patients older than 50 years presenting with first acute pancreatitis, the presence of a tumor (benign or malignant) must be specifically ruled out using CT-scan, MRI, and endoscopic ultrasound. 7
• The risk of gallstones is increased in Crohn's disease but not ulcerative colitis. 1
• Rising obesity rates may be contributing to increasing frequency of acute pancreatitis by increasing the likelihood of gallstone pancreatitis. 8