Chronic Pancreatitis

Chronic pancreatitis is a chronic fibro-inflammatory disease of the pancreas, with progressive and irreversible damage to the pancreatic parenchyma.

The incidence of chronic pancreatitis is quoted between 2-10 new cases per 100,000 people per year in several European and North American studies. It has a prevalence of approximately 13 cases per 100,000, with a male to female ratio of 4:1, and an average age of onset of 40 yrs.

In this article, we shall look at the causes, clinical features and management of chronic pancreatitis.


Aetiology

The causes of chronic pancreatitis include:

  • Chronic alcohol abuse (60%)
  • Idiopathic (30%)
  • Metabolic
    • Hyperlipidaemia
    • Hypercalcaemia
  • Fig 1 - The pancreatic duct. Obstruction of the duct, by stricture or neoplasm, can result in chronic pancreatitis.

    Fig 1 – The pancreatic duct. Obstruction of the duct, by stricture or neoplasm, can result in chronic pancreatitis.

    Infection

    • Viral (HIV, mumps, coxsackie)
    • Bacterial (Echinococcus)
  • Hereditary
    • Cystic fibrosis
  • Autoimmune
    • Autoimmune pancreatitis (AIP)
    • SLE
  • Obstruction (of pancreatic duct)
    • Stricture formation
    • Neoplasm
  • Congenital
    • Pancreas divisum
    • Annular pancreas

Pathophysiology of Chronic Pancreatitis

Chronic pancreatitis can occur in large duct or small duct form:

  • Large duct disease – there is dilatation and dysfunction of the large pancreatic ducts, therefore visible on most diagnostic imaging. The pancreatic fluid changes composition and facilitates the deposition of precursors to calcium carbonate stones and causes diffuse pancreatic calcification. This subtype is more commonly found in males.
  • Small duct disease – usually associated with normal imaging and no pancreatic calcification, making it difficult to diagnose. It is predominantly found in females.

Risk Factors

The greatest risk factor for chronic pancreatitis is excess alcohol consumption; 5-10% of people with alcohol dependence will develop chronic pancreatitis.

Whilst smoking has recently emerged as a risk factor for chronic pancreatitis, it also increases the risk of pancreatic malignancy.


Clinical Features

The major symptom in chronic pancreatitis is chronic pain, which may be complicated by recurring attacks of acute pancreatitis. The pain is typically felt in the epigastrium and radiating to the back, partially eased by the patient leaning forward. It is often associated with nausea and vomiting.

Patients can also present with symptoms secondary to endocrine dysfunction (such as diabetes) or exocrine dysfunction (such as steatorrhoea or malabsorption).

Physical examination at the time of an acute attack may be fairly unremarkable and demonstrate only a patient in pain with epigastric tenderness on palpation. Severe attacks can lead to a SIRS response with tachycardia, hypotension and oliguria, with abdominal examination revealing more widespread tenderness with guarding.

Occasionally, a fullness or mass can be felt in the epigastrium, which suggests the presence of a pseudocyst or inflammatory mass. Patients with exocrine dysfunction may show signs relating to malabsorption.


Differential Diagnosis

Important differentials to consider with this presentation includes acute cholecystitis, peptic ulcer disease, acute hepatitis, or Sphincter of Oddi dysfunction.


Investigations

Laboratory Investigations

Routine bloods, as per investigation of any acute abdomen, are required. Specifically for acute pancreatitis, it is important to consider:

  • BM – raised glucose, secondary to reduce endocrine function.
  • Serum calcium – hypercalcaemia.
  • LFTs – may be abnormal, especially if there is hepatic aetiology.

It is important to note that serum amylase and lipase levels are rarely significantly raised in established disease. Moreover, markers of nutrition such as magnesium, haemoglobin, and albumin may be low, but are not diagnostic.

A relatively sensitive test for chronic pancreatitis is a faecal elastase level, which will be abnormally low in the majority of patients.

Imaging

There are four main types of imaging that are typically considered:

  • Abdominal USS – typically the first line imaging in suspected chronic pancreatitis.
  • CT scan – may be performed following ultrasound if required, demonstrating pancreatic calcification or pseudocyst formation.
    • These patients are often frequent attenders, and consideration should be taken regarding their number of CT scans they receive.
  • Magnetic resonance cholangiopancreatography (MRCP) – will identify the presence of biliary obstruction and assess the pancreatic duct. A normal appearance of the pancreas on imaging does not however exclude chronic pancreatitis.
  • Endoscopic retrograde cholangiopancreatography (ERCP) – is a more accurate way of eliciting the anatomy of the pancreatic duct and also has the advantage of being combined with intervention, e.g. dilatation for any strictures present.

MRCP or ERCP can be combined with administration of intravenous secretin, causing the pancreas to produce a bicarbonate rich fluid. This may reveal a pancreatic duct stricture which may not otherwise have been evident – and is therefore more accurate than standard MRCP/ERCP for detecting small-duct disease.

Fig 2 - CT scans in chronic pancreatitis. A - Calcification in the region of the pancreas. B - Large psuedocyst formation

Fig 2 – CT scans in chronic pancreatitis. A – Calcification in the region of the pancreas. B – Large psuedocyst formation


Management

Initial Management

Analgesia is the mainstay of the initial management of chronic pancreatitis, with simple analgesia plus an opioid usually being sufficient. In those with long-term pain, strong opioid analgesia is ideally best avoided as it is often insufficient and may lead to long-term dependence; instead, tricyclic antidepressants (TCAs) may be useful.

Complications of chronic pancreatitis should be addressed as appropriate (discussed below). Pancreatic enzyme supplements are often trialed in an attempt to relieve the pain of chronic pancreatitis, which may be particularly beneficial in small duct disease.

Definitive Management

The definitive management of chronic pancreatitis is typically avoidance of the precipitating factor such as alcohol, management of chronic pain, and nutritional support often with enzyme supplements. Endoscopic and surgical management are possible in a select few patients to target the underlying cause.

Endoscopic

Endoscopy can be utilised in several ways in the treatment of chronic pancreatitis:

  • ERCP – can be used for diagnostic and therapeutic purposes and may be used to extract pancreatic stones.
  • EUS – can be used to facilitate the drainage of any pseudocysts that have formed; a bile duct stent can also be placed to relieve distal duct stricture. This is a temporary measure and should not be left for longer for 4-6 weeks as they tend to become blocked.
  • Endoscopic Pancreatic Sphincterotomy – might be beneficial in patients with papillary stenosis associated with high sphincter and pancreatic duct pressures. These treatments are generally used for large duct pancreatitis.

It is also important to note that many endoscopic procedures have a risk of inducing an acute pancreatitis.

Surgical Approaches

The purpose of surgery is the relieve any obstruction and remove mass lesions, whilst preserving pancreatic tissue where possible.

A lateral pancreaticojejunostomy (side to side anastomosis of the pancreatic duct to the jejunum) provides relief in many patients but pain does tend to reoccur, as the head of the pancreas still remains in situ.

A pancreaticoduodenectomy (commonly termed a Whipple’s procedure) is indicated in paraduodenal pancreatitis or if neoplasia cannot be excluded. The procedure involves resection of the pancreatic head, gallbladder and bile duct, the pyloric antrum, and the first and second portions of the duodenum, with the tail of the pancreas anastamosed with the duodenum and the body of the stomach anastamosed to distal duodenum.

A total pancreatectomy is the removal of the entire pancreas, however is commonly associated with morbidity secondary to the loss of pancreatic function and reduced quality of life; in approximately one-third of patients, it does not provide analgesia.

Fig 3 - Pancreaticoduodenectomy (Whipple's procedure). A: Pre-procedure, B: Post-procedure.

Fig 3 – Pancreaticoduodenectomy (Whipple’s procedure). A: Pre-procedure, B: Post-procedure.

Steroids

Steroids are effective at reducing symptoms in chronic pancreatitis with an autoimmune aetiology only. A high dose of prednisolone is used initially to bring symptoms under control; a low dose maintenance regime is then used.


Complications

  • Pseudocyst – discussed here.
  • Steatorrhoea and Malabsorption
    • Poor exocrine pancreatic function can lead to malabsorption and steatorrhoea. This can initially be treated with enzyme replacements (including lipases), such as Creon®, which are typically administered with meals.
    • If symptoms do not resolve, a low-fat diet, PPI or increase in lipase dose should then be trialed.
    • Patients are at risk of becoming deficient in the fat soluble vitamins (A, D, E and K), hence regular clotting function and bone density checks are advised.
  • Diabetes
    • Loss of endocrine function in chronic pancreatitis means patients become prone to developing diabetes mellitus.
    • Simple insulin regimes are usually preferred so as to avoid hypoglycaemia caused by a deficiency of glucagon.
  • Effusions
    • Where there has been disruption of the main pancreatic duct, ascites and pleural effusions may occur.
    • The fluid will have a high amylase concentration on biochemical analysis. Surgical intervention is required for this complication.
  • Pancreatic Malignancy 
    • Pancreatic malignancy is a risk in those who have had the disease for 20 years or more. New or evolving symptoms should therefore undergo investigation.

Prognosis

Chronic pancreatitis is associated with significant morbidity and reduced quality of life. It is a difficult condition to manage effectively*. In some patients, the disease may eventually ‘burn out’ after many years of pain, resulting in residual endocrine and exocrine insufficiencies.

A third of patients with chronic pancreatitis will die within 10 years and the risk is further increased in those who continue to drink alcohol.

*Chronic pancreatitis due to an autoimmune aetiology is exempt from this however and patients usually respond well to steroids in exacerbations or relapses.

Further Reading

Chronic Pancreatitis
Braganza JM at al., The Lancet

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