Overview
Chronic pancreatitis describes chronic, irreversible, inflammation and/or fibrosis of the pancreas that affects both the endocrine and exocrine functions of the pancreas. Chronic pancreatitis usually begins as recurrent episodes of acute pancreatitis leading to fibrosis of pancreatic tissue and calcification of the pancreatic duct and its branches.
Pathophysiology
The exocrine functions of the pancreas involve releasing pancreatic enzymes that hydrolyse molecules such as carbohydrates, fats, and proteins in the duodenum. The endocrine functions of the pancreas include the release of hormones regulating blood sugar levels (insulin and glucagon).
Hence, if exocrine function is affected, patients have pancreatic exocrine insufficiency, characterised by malabsorption, steatorrhoea, and weight loss due to damage to acinar cells.
If endocrine function is affected, patients have pancreatic endocrine insufficiency leading to a deficiency of insulin and other hormones leading to non-diabetic hyperglycaemia and pancreatogenic diabetes mellitus (type 3c diabetes) due to damage of the islets of Langerhans.
Pancreatic insufficiency results when more than 90% of the pancreas is damaged.
Causes and Risk Factors
Cause
Some causes include:
- Alcohol is the most common cause (up to 80%):
- However, <10% of people who are dependent on alcohol develop chronic pancreatitis
- This suggests the involvement of other factors such as genetics, anatomical variations, and environmental factors
- Up to 20% of the other causes are idiopathic
Risk factors
Risk factors for acute pancreatitis:
- Smoking
- Hypertriglyceridaemia
- Hyperglycaemia
- Autoimmune – either autoimmune pancreatitis or in association with another disorder (e.g. inflammatory bowel disease)
- Genetic causes – more likely in people <35 years old with pancreatitis
- Some drugs – thiazides, azathioprine, oestrogens, sodium valproate, tetracyclines, DPP-4 inhibitors
- Pancreatic duct obstruction – gallstones, pancreatic strictures, pancreatic cancers, masses
- Recurrent acute pancreatitis:
- Some studies suggest around 10% of people develop chronic pancreatitis after the first episode of acute pancreatitis, and this increases up to 36% after recurrent acute pancreatitis
Epidemiology
- The prevalence of chronic pancreatitis in the UK is around 3/100,000
- The median age of diagnosis is 51-58 years in chronic pancreatitis
- Chronic pancreatitis is more common in men
Presentation
Overview
Features of pancreatitis include:
- Dull epigastric pain that may radiate to the back and is worse ~30 minutes after a meal
- Some people may find the pain is eased by leaning forwards
- Pain may be present in up to 20% of people
- Nausea and vomiting
- Steatorrhoea – seen in around 20% at diagnosis
- Hyperglycaemia and pancreatogenic diabetes mellitus (type 3c diabetes)
- Seen in most patients after around 25 years of symptoms
- Osteoporosis
- Diarrhoea, bloating, abdominal cramps
- Weight loss and malabsorption
Investigations
Overview
The first-line investigations for chronic pancreatitis usually involve imaging tests, either alone or in combination. A CT or MRI pancreas is usually the first-line test for chronic pancreatitis.
They may show pancreatic calcifications (pathognomonic for chronic pancreatitis), ductal dilation, and enlargement of the pancreatic glands.
Other imaging tests may involve:
- Endoscopic ultrasonography
- Secretin-enhanced magnetic resonance cholangiopancreatography (s-MRCP)
Other tests
Other investigations may be performed if imaging is inconclusive or to assess the function of the pancreas:
- Liver function tests (LFTs):
- May be abnormal if there is coexisting hepatobiliary disease
- Serum HbA1c:
- To assess for hyperglycaemia or pancreatogenic diabetes mellitus (type 3c diabetes)
- Faecal elastase:
- Assesses the exocrine function of the pancreas
- If low, this suggests pancreatic exocrine insufficiency
- Pancreatic elastase is released by the pancreas and breaks down collagen. It does not normally get degraded while passing through the gut, therefore, reduced amounts suggest the pancreas cannot secrete enough
Serum amylase is not routinely tested in chronic pancreatitis and is not diagnostic.
Referral and Management
Referral
If in primary care:
- Routinely refer to secondary care if chronic pancreatitis is suspected to confirm the diagnosis and initiate management
- Urgently admit to hospital if acute pancreatitis is suspected
- Urgently refer to secondary care if a serious complication of pancreatitis is suspected, depending on clinical judgement
Management
The principles of management involve treating pain and malabsorption, correcting nutritional deficiencies, and treating complications of chronic pancreatitis. This is coordinated by a multidisciplinary team. Some key elements of management may include:
- Pancreatic enzyme supplements – for malabsorption
- Pain relief – often requires opiates, but should start with simple analgesia first
- Manage complications:
- Type 3c diabetes – assess every 6 months for consideration of insulin therapy
- Pancreatic duct obstruction – surgery may be required
- Pseudocysts – endoscopic ultrasound-guided drainage if symptomatic (e.g. pain, vomiting, weight loss)
Monitoring and Patient Advice
Monitoring
Diabetes and osteoporosis should be screened for:
- Check HbA1c every 6 months to assess for type 3c diabetes mellitus:
- If a diagnosis is confirmed, refer to secondary care for diagnosis and management (treated with insulin)
- Offer a dual-energy X-ray absorptiometry (DEXA) scan for bone density every 2 years
Patient advice
Advice for chronic pancreatitis may include:
- Support with alcohol consumption and possible dependency
- Support with smoking cessation
- Management hypercalcaemia
- Hypertriglyceridaemia
Complications
- Malabsorption – seen in around 20% at diagnosis, usually seen in later stages
- May lead to deficiencies in fat-soluble vitamins (A, D, E, and K), water-soluble vitamins (B12 and folic acid), iron, zinc, selenium, and magnesium
- Maldigestion of fats and proteins
- Pancreatogenic diabetes (type 3c diabetes mellitus):
- This is different to type 1 and 2 diabetes mellitus
- Seen in most patients around 25 years after symptoms start
- Osteopenia, osteoporosis, and increased fracture risk:
- Due to malabsorption
- Pancreatic cancer – having chronic pancreatitis increases the risk up to 13 times
- Chronic abdominal pain
- Pseudocysts – more common in alcohol-related chronic pancreatitis:
- May rupture, bleed, become infected, or compress surrounding structures (e.g. biliary/gastric/duodenal obstruction)
- Pseudoaneurysm – may haemorrhage
- Splenic/portal vein thrombosis – may lead to gastric/oesophageal varices
Prognosis
- The natural history of chronic pancreatitis is as follows:
- First 5 years: episodic acute pancreatitis, pain, hospitalisations, and surgeries
- 5-10 years: biliary duct structures, pseudocysts, pancreatic calcifications and progressive pancreatic insufficiencies
- >10 years: progressive pancreatic endocrine and exocrine insufficiency
- Overall survival is 70% at 10 years and 45% at 20 years
- Alcohol-related pancreatitis and older people have a worse prognosis
