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.

    Figure 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. Smoking has recently emerged as a risk factor for chronic pancreatitis, also increasing 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 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 mellitus) 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. 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 chronic pancreatitis, it is important to consider:

  • BM to check for raised glucose, secondary to reduce endocrine dysfunction
  • Serum calcium to assess for any 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 cases.

Imaging

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

  • Abdominal USS – typically the first line imaging in suspected chronic pancreatitis
    • This can show evidence of underlying causes of any pancreatitis and also investigate for other intra-abdominal pathology
  • CT abdomen-pelvis 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, especially if the diagnostic can be made through clinical features alone
  • 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

Figure 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 any pancreatic duct stones causing the chronic disease
  • Endoscopic Ultrasound (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-on-chronic pancreatitis, which the patient must be warned about pre-intervention.

Surgical Approaches

The purpose of surgery is to relieve any obstruction and remove mass lesions, whilst preserving pancreatic tissue wherever 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.
    • 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*
  • 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

*The fluid will have a high amylase concentration on biochemical analysis; surgical intervention is often required for this complication


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 and patients usually respond well to steroids in exacerbations or relapses.

Key Points

  • Chronic pancreatitis is caused by chronic alcohol excess in most cases
  • Reduced faecal elastase is the most appropriate initial investigation however CT imaging can also be useful to confirm
  • Management is mainly based around symptom control, optimising analgesia and nutritional support

Quiz

Question 1 / 3
Which of the following is a known cause of chronic pancreatitis?

Quiz

Question 2 / 3
Which of the following is the most appropriate initial test to investigate for chronic pancreatitis?

Quiz

Question 3 / 3
Which of the following blood results is not commonly seen in severe cases of chronic pancreatitis?

Results

Further Reading

Chronic Pancreatitis
Braganza JM at al., The Lancet

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