What are the common causes of acute pancreatitis?

Common Causes of Acute Pancreatitis

Gallstones are the leading cause of acute pancreatitis, accounting for approximately 45-60% of cases, followed by alcohol abuse (20-25%), hypertriglyceridemia (4-10%), and drug-induced causes, with the goal of identifying a definitive etiology in at least 75-80% of patients. 1, 2, 3, 4

Primary Etiologies (Ranked by Frequency)

1. Gallstone Disease (45-60% of cases)

• Gallstones represent the single most common cause of acute pancreatitis, with higher prevalence in women, patients over 50 years, and those with obesity. 2, 4, 5
• In elderly men ≥80 years, gallstone-related pancreatitis rises to 24-35% at age 90 and reaches up to 80% among institutionalized elders. 2
• Early elevation of aminotransferases (AST/ALT) or bilirubin strongly suggests a biliary etiology and should prompt immediate ultrasound evaluation. 1, 2

2. Alcohol Abuse (20-25% of cases)

• Alcohol is the second most common cause, requiring consumption of >80 g/day for >5 years to establish alcoholic pancreatitis as the etiology. 1, 2, 6
• Critical pitfall: One-quarter of heavy drinkers presenting with pancreatitis actually have other explainable causes (especially occult gallstones), so systematic evaluation is mandatory even in known alcoholics. 6
• Alcoholic pancreatitis tends to produce higher rates of pancreatic necrosis compared to gallstone pancreatitis, though overall outcomes are similar. 7

3. Hypertriglyceridemia (4-10% of cases)

• Hypertriglyceridemia is the third most common cause, with serum triglyceride levels >11.3 mmol/L (>1000 mg/dL) indicating this as the causative etiology. 2, 3
• This etiology carries a worse prognosis than gallstone or alcohol-related pancreatitis due to intravascular calcium sequestration through free fatty acid-albumin complexes. 2, 3

4. Drug-Induced Pancreatitis

• Thiopurines (azathioprine, 6-mercaptopurine) precipitate acute pancreatitis in approximately 4% of IBD patients, typically within the first 3-4 weeks of treatment, independent of dose. 2, 3
• 5-ASA agents (mesalazine) carry a markedly lower risk than thiopurines but remain a recognized cause. 2, 3
• A comprehensive medication history (prescription and non-prescription) is essential in all cases. 1, 2

5. Post-ERCP Pancreatitis

• Endoscopic retrograde cholangiopancreatography is a well-recognized iatrogenic cause, with risk amplified when therapeutic maneuvers such as sphincterotomy are performed. 2

6. Hypercalcemia

• Fasting calcium concentrations must be determined in all patients, especially when gallstones and alcohol have been excluded. 1, 2
• Hypercalcemia should be investigated as a potential cause, particularly in idiopathic cases. 2

7. Other Specific Causes

• Autoimmune (IgG4-related) pancreatitis occurs in IBD patients and those with primary sclerosing cholangitis. 2
• Direct extension of transmural inflammation from duodenal Crohn's disease can cause pancreatitis. 2
• Pancreatic malignancy must be excluded in patients >40 years with unexplained pancreatitis using contrast-enhanced CT or EUS. 1, 2
• Trauma, viral infections, and concomitant autoimmune diseases should be explored in the initial history. 1, 2

8. Idiopathic Pancreatitis (Should be <20-25% of cases)

• No more than 20-25% of cases should remain classified as "idiopathic" after thorough investigation. 2, 4
• The diagnosis of idiopathic pancreatitis should not be accepted without at least two high-quality ultrasound examinations to exclude occult gallstones or microlithiasis. 2
• In recurrent idiopathic cases, endoscopic ultrasound (EUS) may detect microlithiasis in the gallbladder or common bile duct that was missed on transabdominal ultrasound. 2

Systematic Diagnostic Approach to Identify Etiology

Initial History (Target Specific Risk Factors)

• Biliary symptoms: Previous gallstone episodes, right upper quadrant pain, jaundice. 1, 2
• Alcohol quantification: Exact daily intake in grams, duration of heavy use (>80 g/day for >5 years required for diagnosis). 1, 2, 6
• Medication review: All prescription drugs (especially thiopurines, 5-ASA), over-the-counter medications, and supplements. 1, 2
• Metabolic history: Prior hypertriglyceridemia, hypercalcemia, or family history of lipid disorders. 1, 2
• Family history: Pancreatic disease suggesting genetic predisposition. 1, 2
• Autoimmune conditions: IBD, primary sclerosing cholangitis, other autoimmune diseases. 2
• Recent procedures: ERCP, abdominal surgery, or trauma. 2

Mandatory Initial Laboratory Tests

• Serum lipase or amylase (≥3× upper limit of normal supports diagnosis). 1, 2, 4
• Liver function tests (AST, ALT, alkaline phosphatase, bilirubin): Early elevation suggests biliary etiology. 1, 2
• Fasting triglyceride level: Levels >11.3 mmol/L confirm hypertriglyceridemia as cause. 1, 2
• Serum calcium: Hypercalcemia must be excluded, especially in idiopathic cases. 1, 2

First-Line Imaging

• Abdominal ultrasound should be performed immediately at admission to detect gallstones or choledocholithiasis. 1, 2, 4
• If the initial ultrasound is inadequate or negative but clinical suspicion for gallstones remains, repeat ultrasound after recovery is mandatory. 1, 2

Advanced Imaging for Specific Indications

• Endoscopic ultrasound (EUS) is the preferred test for detecting microlithiasis in recurrent idiopathic pancreatitis and can screen for cholelithiasis/choledocholithiasis with high accuracy. 1, 2
• MRCP has 97.98% sensitivity and 84.4% specificity for choledocholithiasis when ultrasound is nondiagnostic but clinical suspicion remains high. 2
• Contrast-enhanced CT should be performed in patients >40 years with unexplained pancreatitis to exclude pancreatic malignancy. 1, 2

Critical Pitfalls to Avoid

• Do not accept "idiopathic" diagnosis prematurely: Failure to perform at least two high-quality ultrasounds leads to missed gallstone disease in up to 25% of cases. 2
• Do not assume alcohol is the cause in heavy drinkers: Systematic evaluation reveals other explainable causes in 29% of patients who consume alcohol above the threshold. 6
• Do not skip triglyceride measurement: If not obtained at admission, fasting levels must be measured after recovery when normal intake resumes. 1, 2
• Do not overlook medication-induced causes: A comprehensive drug history (including over-the-counter and supplements) is essential, as drug-induced pancreatitis is frequently missed. 1, 2
• Do not delay cholecystectomy in mild gallstone pancreatitis: If gallstones are not removed, recurrence rates reach 14% at 6 weeks, 19% at 12 weeks, and 29% at 1 year. 2