Causes of Chronic Pancreatitis
The dominant cause of chronic pancreatitis in Western countries is excess alcohol consumption, followed by idiopathic cases (approximately 20%), genetic factors, anatomical abnormalities, and metabolic disorders. 1
Primary Etiological Factors
- Alcohol consumption: Responsible for 60-70% of chronic pancreatitis cases in Western countries, with risk increasing with higher intake 2
- Cigarette smoking: Significant independent risk factor that may account for 25-30% of cases and increases risk of developing chronic pancreatitis 1
- Idiopathic: Approximately 20% of cases have no identifiable cause despite thorough evaluation 1
- Genetic factors: Several genetic mutations are associated with chronic pancreatitis 1, 3
- PRSS1 gene mutations (hereditary pancreatitis)
- SPINK1 gene mutations
- CFTR gene mutations
- Up to 10% of patients have an inherited component without familial pancreatic cancer
Anatomical and Structural Causes
- Pancreatic obstruction: Ductal stones, strictures, or anatomical abnormalities 1, 2
- Pancreas divisum: Congenital anatomical variant that predisposes to pancreatitis 4
- Pancreatic duct abnormalities: Including obstruction, irregularity, or dilatation 4, 2
Metabolic and Systemic Causes
- Hypercalcemia: Disrupts normal pancreatic secretion and can lead to chronic inflammation 1, 4
- Hypertriglyceridemia: Particularly when levels exceed 700-1000 mg/dL 4, 2
- Cystic fibrosis: Important cause of pancreatitis, especially in children 4
- Autoimmune pancreatitis: Characterized by specific immunological features 4, 2
Other Associated Conditions
- Chronic pancreatitis and diabetes: Type 3c (pancreatogenic) diabetes may develop as pancreatic islet cells are destroyed 1
- Inflammatory bowel disease: Particularly Crohn's disease, associated with increased risk 4
- Tropical pancreatitis: Occurs in tropical/subtropical countries, typically in younger, undernourished patients with early diabetes development 1
Clinical Manifestations and Complications
- Exocrine pancreatic insufficiency (PEI): Occurs when lipase secretion drops to <10% of normal 1
- Symptoms include fatty diarrhea, bloating, abdominal cramping, flatulence
- Requires pancreatic enzyme replacement therapy (PERT)
- Endocrine insufficiency: Type 3c diabetes develops as islet cells are destroyed 1
- Structural changes: Progressive atrophy of pancreatic tissue, fibrosis, ductal dilation and stricturing, calcification 1, 3
- Increased cancer risk: Chronic pancreatitis increases risk of pancreatic cancer, particularly with hereditary pancreatitis (50-70 fold increased risk) 1
Special Considerations
- Hereditary pancreatitis: Associated with 50-70-fold increased risk of pancreatic cancer and a cumulative lifetime risk of 40% by age 75 1
- Patients with familial pancreatic cancer: Approximately 17-19% may have disease-causing BRCA2 mutations 1
- Smoking cessation: Critical for all patients with chronic pancreatitis as smoking accelerates disease progression 2, 5
Diagnostic Approach
- Imaging: Contrast-enhanced CT is the radiographic test of choice, with ductal calcifications being pathognomonic 5, 6
- Advanced imaging: Endoscopic ultrasonography and magnetic resonance cholangiopancreatography provide diagnostic results similar to ERCP 7, 6
- Functional testing: Measurement of fecal elastase-1 to assess exocrine function 1
Management Principles
- Lifestyle modifications: Cessation of alcohol and tobacco use is essential 2, 6
- Pain management: NSAIDs and weak opioids such as tramadol are first-line 5
- Pancreatic enzyme supplementation: For exocrine insufficiency 1, 5
- Interventional procedures: Endoscopic or surgical drainage for ductal obstruction 5, 6