Key Facts

Chronic pancreatitis is characterised by progressive, irreversible inflammatory changes leading to fibrosis and loss of exocrine and endocrine function. Pain management and nutritional support are central to care.

Epidemiology

Prevalence approximately 50 per 100,000 in the UK. Incidence 5-12 per 100,000 per year. Male predominance (3:1) — related to higher alcohol consumption. Mean age at diagnosis 35-55 years.

Aetiology

TIGAR-O classification:

• Toxic-metabolic: alcohol (~70% in UK), smoking (independent risk factor, doubles risk), hypercalcaemia, hypertriglyceridaemia
• Idiopathic: ~20% (early-onset <35 years and late-onset >55 years)
• Genetic: PRSS1 (hereditary pancreatitis — AD, high penetrance), SPINK1, CFTR mutations
• Autoimmune: type 1 (IgG4-related, associated with sclerosing cholangitis, sialoadenitis) and type 2 (duct-centric, associated with IBD)
• Recurrent acute pancreatitis: sentinel acute pancreatitis event (SAPE) hypothesis
• Obstructive: pancreas divisum, ampullary stenosis, pancreatic duct tumour

Pathophysiology

Repeated episodes of pancreatic inflammation (recurrent acute pancreatitis or subclinical injury from alcohol/oxidative stress) trigger a fibrotic response. Pancreatic stellate cells are activated, producing excessive collagen and extracellular matrix → progressive fibrosis → duct stricture → ductal hypertension → pain. Loss of acinar cells causes exocrine insufficiency (steatorrhoea occurs when >90% of function lost). Loss of islets causes endocrine insufficiency (type 3c diabetes — brittle, with glucagon deficiency → hypoglycaemia risk).

Pain

• Chronic epigastric pain radiating to the back
• Constant or episodic; worsened by eating and alcohol
• May "burn out" in late disease (fibrosis replaces functional tissue)
• Often requires opioid analgesia → risk of dependence

Exocrine Insufficiency

• Steatorrhoea: pale, bulky, offensive stools that are difficult to flush
• Weight loss, malnutrition
• Fat-soluble vitamin deficiency (A, D, E, K)

Endocrine Insufficiency

• Type 3c (pancreatogenic) diabetes mellitus: typically develops after years of chronic pancreatitis; both insulin and glucagon deficiency → brittle diabetes with hypoglycaemia risk

Red Flags

• New/worsening jaundice (bile duct stricture, pancreatic cancer)
• Rapid weight loss (pancreatic cancer)
• New diabetes in chronic pancreatitis (pancreatic cancer risk)
• GI bleeding (splenic vein thrombosis → gastric varices)
• Palpable abdominal mass (pseudocyst)

Bedside

• Faecal elastase-1: <200 μg/g = exocrine insufficiency; <100 = severe; simple stool test
• HbA1c/fasting glucose: diabetes screening

Bloods

• LFTs: raised ALP/bilirubin if bile duct stricture
• Amylase/lipase: may be normal in chronic pancreatitis (burnt-out pancreas)
• HbA1c, fasting glucose: diabetes
• Fat-soluble vitamins (A, D, E): deficiency assessment
• Nutritional markers: albumin, prealbumin, magnesium, zinc
• IgG4: if autoimmune pancreatitis suspected
• CA19-9: if malignancy suspected (limited specificity)
• Genetic testing: PRSS1, SPINK1, CFTR if hereditary/early-onset

Imaging

• CT abdomen: pancreatic calcifications (pathognomonic), duct dilatation, parenchymal atrophy, pseudocysts
• MRCP/secretin-MRCP: pancreatic and biliary duct assessment — sensitivity for early disease
• EUS: most sensitive test for early chronic pancreatitis — Rosemont criteria (parenchymal and ductal features)
• AXR: may show pancreatic calcifications

Special Tests

• 72-hour faecal fat collection: >7 g/day confirms fat malabsorption (gold standard but impractical — faecal elastase preferred)
• DEXA scan: osteoporosis screening (vitamin D/calcium malabsorption)

Non-pharmacological

• Alcohol abstinence: most important — slows progression, reduces pain
• Smoking cessation: independent risk factor for progression
• Dietary: small frequent meals, low-fat diet, avoid large fatty meals; dietitian involvement essential
• Nutritional supplementation: fat-soluble vitamins, calcium, vitamin D
• Psychosocial support: addiction services, pain management teams, psychological support

Pharmacological

• PERT (pancreatic enzyme replacement therapy): CREON — 50,000 units lipase with main meals, 25,000 with snacks; adjust dose to stool output; take with food
  • Add PPI (omeprazole 20 mg OD) if suboptimal response (acid degrades enzymes)
• Pain management:
  • Step 1: paracetamol 1 g QDS ± low-dose NSAID (if renal function allows)
  • Step 2: weak opioid (codeine, tramadol)
  • Step 3: strong opioid (morphine, oxycodone — use with caution, addiction risk)
  • Adjuvants: pregabalin 75-300 mg BD, amitriptyline 10-50 mg ON, duloxetine 60 mg OD
  • Antioxidant therapy: some evidence for selenium, vitamin C, vitamin E combination
• Diabetes management: insulin (often required); metformin if mild; beware hypoglycaemia (glucagon deficiency)

Surgical/Interventional

• ERCP: pancreatic duct stenting, stone extraction, stricture dilatation
• ESWL (extracorporeal shockwave lithotripsy): for large pancreatic duct stones before ERCP
• EUS-guided coeliac plexus block: pain management (temporary effect — 3-6 months)
• Surgery for pain:
  • Frey procedure (lateral pancreaticojejunostomy + limited head excision): large duct disease
  • Beger procedure: duodenum-preserving pancreatic head resection
  • Total pancreatectomy with islet autotransplantation (TPIAT): selected centres, refractory pain
• Pseudocyst drainage: EUS-guided, endoscopic, or surgical if symptomatic/complicated

Referral Criteria

• Hepato-pancreatico-biliary (HPB) team referral for all
• Pain management service for refractory pain
• Diabetes team for pancreatogenic diabetes
• Genetics referral if hereditary pancreatitis suspected
• Addiction/alcohol services

Chronic pancreatitis is a progressive condition. Alcohol cessation slows but does not halt progression. Pain may improve in late-stage disease ("burn-out"). Exocrine insufficiency develops in ~60% over 10 years. Type 3c diabetes develops in ~30-50%. Pancreatic cancer risk is 5-10% lifetime (~15-fold increased risk). Mortality is increased: 10-year survival ~70% (primarily from comorbidities — cardiovascular, liver disease in alcohol-related). Quality of life is significantly impaired by chronic pain.

TIGAR-O Classification

PERT (CREON) Dosing Guide