Definition

Etiology (TIGAR-O)

• Toxic-metabolic: Alcohol is the most common cause in adults (about 60-70%). Smoking is an independent and synergistic risk factor. Other causes are hypercalcemia, hypertriglyceridemia and chronic kidney disease.
• Idiopathic: This includes early-onset and late-onset forms and tropical pancreatitis.
• Genetic: Mutations in PRSS1 (hereditary pancreatitis), SPINK1, CFTR and CTRC.
• Autoimmune: IgG4-related (type 1) and type 2 disease.
• Recurrent or severe acute pancreatitis: Necrosis and scarring after attacks.
• Obstructive: Pancreas divisum (controversial), strictures, tumors, sphincter of Oddi dysfunction.

Pathophysiology

Clinical features

• Pain: Epigastric pain radiating to the back. It is often worse after meals and can be constant or episodic. Over time it may "burn out," though this is less common than once thought.
• Exocrine insufficiency: Steatorrhea, weight loss and fat-soluble vitamin deficiency (A, D, E, K). Steatorrhea appears only after lipase output falls below about 10% of normal.
• Endocrine insufficiency: Pancreatogenic (type 3c) diabetes, which develops late. It is brittle, with a risk of hypoglycemia because glucagon is also lost.
• Complications:
  • Pseudocyst
  • Bile duct stricture, causing jaundice
  • Duodenal obstruction
  • Splenic vein thrombosis, leading to left-sided portal hypertension and gastric varices
  • Pancreatic ascites or pleural effusion
  • Pancreatic cancer (risk increased roughly 10-fold or more, especially in hereditary pancreatitis)
  • Opioid dependence, malnutrition and osteoporosis

Diagnosis

• Imaging is the mainstay.
  • CT shows calcifications, a dilated duct and atrophy. Calcification is nearly pathognomonic.
  • MRI/MRCP, ideally with secretin stimulation, shows ductal changes.
  • Endoscopic ultrasound (EUS) is the most sensitive for early disease, using Rosemont criteria.
  • Plain abdominal film may show calcifications.
  • ERCP is now used mainly for therapy.
• Function tests:
  • Fecal elastase-1 is a good screen. A value below 200 mcg/g suggests insufficiency, and below 100 mcg/g indicates severe insufficiency.
  • A 72-hour fecal fat test is also available.
  • Direct secretin tests are rarely done.
  • Serum amylase and lipase are often normal or only mildly raised in advanced disease.
• Other tests:
  • Fasting glucose and HbA1c.
  • Serum IgG4 and autoantibodies if autoimmune pancreatitis is suspected.
  • Genetic testing in young patients or those with a family history.
  • Always exclude pancreatic cancer with a mass or stricture.

Management

• Stop alcohol and smoking completely.
• Give small, frequent, low-fat meals. Do not restrict fat strictly unless it is poorly tolerated.
• Supplement fat-soluble vitamins, and check bone density.

• Start with analgesics in a stepwise manner: paracetamol, NSAIDs, then tramadol.
• Neuropathic agents such as gabapentin, pregabalin or tricyclic antidepressants can be added.
• Avoid long-term opioids where possible.
• Pancreatic enzymes can be tried for pain, though evidence is mixed.
• Antioxidants have limited evidence.
• Celiac plexus block gives short-lived relief.

• Sphincterotomy, stone removal (with or without ESWL), and ductal stenting.
• Stenting is also used for biliary strictures and dominant ductal strictures.

• Indications are refractory pain, complications, or suspected malignancy.
• Drainage procedures include the Puestow (lateral pancreaticojejunostomy), best for a dilated duct.
• Resection procedures include Whipple, Beger and Frey for head disease, and distal pancreatectomy for tail disease.
• Total pancreatectomy with islet autotransplantation is an option for selected patients, especially hereditary pancreatitis.
• The ESCAPE trial found that early surgery can be better than a step-up endoscopic approach for pain.

• Give pancreatic enzyme replacement (PERT) with meals and snacks.
• A typical dose is 40,000-50,000 lipase units per main meal and half that per snack. Adjust to symptoms and weight.
• Add a PPI if the response is poor.

• Insulin is usually needed. Metformin may be used early.
• Be careful with hypoglycemia.

• Treat symptomatic pseudocysts by endoscopic drainage.
• Stent or operate on biliary strictures.
• Manage varices or splenic vein thrombosis as needed.

Follow-up

• Imaging
• Pain management
• Surgical options
• Autoimmune pancreatitis