What are the common causes of acute pancreatitis?

Causes of Acute Pancreatitis

Gallstones are the leading cause of acute pancreatitis, accounting for 45-60% of cases, followed by alcohol (20-25%), with hypertriglyceridemia, drugs, post-ERCP, and other etiologies comprising the remainder. 1, 2

Primary Etiologies (Ranked by Frequency)

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

• Gallstones represent approximately half of all acute pancreatitis cases, making biliary obstruction the most common etiology 1, 2, 3
• Mechanism involves stone impaction at the distal common bile-pancreatic duct, causing pancreatic duct obstruction, increased pressure, and active trypsin reflux 4
• Microlithiasis (small gallstones) should be considered even when initial ultrasound is negative 5
• In elderly men ≥80 years, gallstone-related pancreatitis prevalence rises to 24-35% at age 90 and up to 80% in institutionalized elders 3

2. Alcohol (20-25% of cases)

• Alcohol abuse is the second most common cause, requiring consumption >80 g/day for >5 years to establish alcoholic pancreatitis as the etiology 1, 2, 6
• Important caveat: Among heavy drinkers presenting with pancreatitis, approximately 29% actually have other explainable causes (particularly gallstones), meaning alcohol may be over-diagnosed without systematic evaluation 6

3. Hypertriglyceridemia (4-10% of cases)

• Third most common cause, but carries a worse prognosis than other etiological factors 1
• Serum triglyceride levels >11.3 mmol/L indicate hypertriglyceridemia as the causative etiology 3
• Mechanism involves free fatty acids released by pancreatic lipase that sequester calcium intravascularly, contributing to cellular injury and systemic hypocalcemia 3

4. Drug-Induced Pancreatitis

Thiopurines (Azathioprine and 6-Mercaptopurine):

• Occur in approximately 4% of treated IBD patients 7, 1
• Dose-independent reaction, typically within first 3-4 weeks of treatment 7
• Risk is higher in Crohn's disease patients 7
• Patients carrying HLA-DQA102:01-HLA-DRB107:01 haplotype are more prone to develop thiopurine-induced pancreatitis 7

5-ASA Compounds (Mesalazine):

• Much lower risk than thiopurines 7, 1

Other medications should be reviewed in the history, as various drugs can trigger pancreatitis 7

5. Post-ERCP Pancreatitis

• Recognized complication of endoscopic retrograde cholangiopancreatography 7, 2
• Risk increases with therapeutic interventions like sphincterotomy 7

6. Other Specific Causes

Duodenal Crohn's Disease:

• Direct extension of transmural inflammation can cause pancreatitis 7

Hypercalcemia:

• Fasting calcium concentrations must be determined in all patients, especially when gallstones and alcohol are excluded 3
• Hypercalcemia should be investigated as a potential cause, particularly in idiopathic cases 3

Autoimmune/IgG4-Related Pancreatitis:

• Described in IBD patients, represents shared pathogenic pathways 7

Primary Sclerosing Cholangitis (PSC):

• Associated with both biliary pancreatitis and autoimmune forms 7

Pancreatic Malignancy:

• Must be excluded in patients >40-50 years with first episode of unexplained pancreatitis using CT scan, MRI, or endoscopic ultrasound 3, 5
• Particularly important in elderly patients given increasing incidence of malignancy with age 3

Diagnostic Approach to Establish Etiology

The etiology should be established in at least 75-80% of patients; no more than 20-25% should remain "idiopathic." 7, 3

Initial Evaluation (All Patients):

• Detailed history focusing on: previous gallstone symptoms, alcohol intake (quantify amount and duration), medication review (especially thiopurines, 5-ASA), family history of pancreatitis, and viral exposures 7, 3
• Laboratory tests: Liver function tests (early elevation of aminotransferases or bilirubin suggests biliary etiology), serum lipase or amylase, fasting lipid panel, and serum calcium 7, 3
• Right upper quadrant ultrasound to identify gallstones 7, 3

When Initial Workup is Negative:

• Repeat ultrasound examination if initial study is negative, as gallstones may be missed on first imaging 3
• MRCP has sensitivity of 97.98% and specificity of 84.4% for choledocholithiasis when ultrasound is nondiagnostic but clinical suspicion remains high 3
• Endoscopic ultrasound (EUS) may detect microlithiasis in gallbladder or common bile duct in recurrent cases with no identified cause 3
• Contrast-enhanced CT scan in patients >40 years to rule out pancreatic tumors 3, 5

Common Pitfalls to Avoid:

• Do not accept "idiopathic" diagnosis without vigorous search for gallstones, including at least two good quality ultrasound examinations 3
• Do not attribute pancreatitis to alcohol without confirming consumption >80 g/day for >5 years, as one-quarter of heavy drinkers have other explainable etiologies 6
• In elderly patients (≥80 years), recognize atypical presentations: absent or minimal abdominal pain occurs in 5-12% of cases, fever >38°C in only 6.4-10%, and Murphy's sign has sensitivity of only ~48% 3

IBD-Specific Considerations

Two distinct forms exist in IBD patients: 7

1. Autoimmune/shared pathogenic pathways: Autoimmune pancreatitis, idiopathic pancreatitis, granulomatous pancreatitis, and PSC-associated pancreatitis 7

2. Management-related or associated disease: Biliary pancreatitis, drug-induced (thiopurines, 5-ASA), pancreatitis secondary to duodenal Crohn's disease, and post-ERCP/post-enteroscopy pancreatitis 7

Most common causes in IBD by decreasing frequency: drugs (mostly thiopurines), gallstones, alcohol, and ERCP 7