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

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 enzyme activation. 1
• Initial ultrasound may miss gallstones; at least two good-quality ultrasound examinations should be performed before labeling a case as idiopathic, as a repeat ultrasound remains the most sensitive test after one negative study. 4, 1
• MRCP has 97.98% sensitivity and 84.4% specificity for choledocholithiasis when ultrasound is negative but clinical suspicion remains high. 1
• Endoscopic ultrasound may detect microlithiasis in the gallbladder or common bile duct in recurrent cases with no identified cause. 4, 1

Alcohol Consumption (20-25% of acute cases)

• Alcohol is the second most common cause overall and the dominant etiological factor in chronic pancreatitis, accounting for 60-70% of chronic cases. 1, 2
• Excess alcohol consumption is the most common cause of chronic pancreatitis in Europe. 1
• Abstinence from alcohol is essential for patients with alcoholic pancreatitis. 2

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 indicate hypertriglyceridemia as the etiology. 1
• Free fatty acids released by pancreatic lipase sequester calcium intravascularly, contributing to cellular injury and systemic hypocalcemia. 1

Secondary and Less Common Causes

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. 1, 5, 2
• 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, with cases occurring shortly after initial use or after several years of treatment. 6
• Abdominal pain, nausea, vomiting, and/or anorexia can be symptoms of drug-induced pancreatitis that require prompt medical evaluation and discontinuation of the offending agent. 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. 4, 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 pancreatitis has been described in IBD patients and represents a distinct etiology. 1, 2

Infections

• Viral infections (mumps, Coxsackie B4, and others) 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-operative acute pancreatitis represents a high-risk subset with worse outcomes. 1
• Post-ERCP pancreatitis is a recognized complication. 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 Approach

Idiopathic Pancreatitis

• No more than 20-25% of cases should be labeled as idiopathic; approximately 10-25% remain unexplained after thorough workup. 4, 1
• The diagnosis of idiopathic pancreatitis should not be accepted in the absence of a vigorous search for gallstones. 4
• In recurrent idiopathic cases, endoscopic ultrasound is as accurate and safer than ERCP for detecting common bile duct stones. 4
• Bile sampling may be the only way to identify patients with recurrent acute pancreatitis due to microlithiasis. 4

Special Populations

• In IBD patients, the most common causes by decreasing frequency are drugs (mostly thiopurines), gallstones, alcohol, and ERCP. 1
• 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). 1
• In patients older than 50 years 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