Hereditary Pancreatitis

Hereditary pancreatitis is an autosomal dominant condition with early onset recurrent acute pancreatitis progressing to chronic pancreatitis, in patients with pathogenic variants affecting trypsin regulation.

• Cationic trypsinogen gene PRSS1 mutations (R122H, N29I; gain of function with 80% penetrance) are the classic cause, and PRSS1 copy number variants.
• Other genes: SPINK1, CTRC, CFTR, CPA1, CEL (increase susceptibility, more often complex inheritance).
• Onset in childhood (median 10 years) with recurrent attacks; chronic pancreatitis by early adulthood.
• Pancreatic cancer risk is raised 50 fold, cumulative risk 40% by age 70 (higher with smoking and diabetes).
• Complications: pain, exocrine insufficiency, pancreatogenic diabetes (type 3c), pseudocysts, ductal stones and strictures.

• Recurrent episodes of severe epigastric pain with vomiting beginning in childhood, often triggered by minor stressors.
• Family history across generations.
• Chronic pain, steatorrhoea, weight loss, diabetes.
• Smoking and alcohol accelerate disease.

• Clinical suspicion: two or more family members across two generations, or unexplained pancreatitis before age 25.
• Genetic testing: PRSS1 sequencing and copy number analysis, with SPINK1, CFTR, CTRC panel after counselling.
• Imaging: MRCP/secretin MRCP, EUS and CT: ductal changes, calcifications, strictures, stones.
• Fecal elastase (below 200 micrograms/g), HbA1c, fat soluble vitamins.
• Exclude gallstones, hypertriglyceridaemia, hypercalcaemia, autoimmune pancreatitis, anatomic variants.
• Cancer surveillance: MRI/MRCP or EUS annually starting at age 40 (or 20 years after onset) in those with PRSS1 mutations; CA 19-9 adjunct.

• Strict avoidance of alcohol and smoking (smoking increases cancer risk 2 to 3 fold).
• Acute attacks: aggressive IV hydration with lactated Ringer solution (250 to 500 mL/h for first 12 to 24 hours as tolerated), multimodal analgesia (paracetamol 1 g, opioids as needed), early oral feeding, antiemetics.
• Chronic pain: stepwise analgesia, pancreatic enzymes (lipase 40,000 to 50,000 units with meals), pregabalin 75 to 300 mg twice daily, antioxidants (limited evidence), celiac plexus block, endoscopic therapy for stones and strictures (ERCP with stenting, lithotripsy).
• Exocrine insufficiency: pancreatic enzyme replacement therapy (500 to 2,500 units lipase/kg/meal, maximum 10,000 units/kg/day), fat soluble vitamin replacement, PPI.
• Diabetes: insulin therapy, careful hypoglycaemia avoidance.
• Surgery (Frey, Beger or lateral pancreaticojejunostomy; total pancreatectomy with islet autotransplantation (TPIAT) for refractory pain, best in children and early disease).
• Cancer surveillance, with referral for specialist centre follow up; genetic counselling for relatives (testing of children is debated).
• Bone health and vaccination.