Emergency Medicine

Chronic Pancreatitis

Etiology, clinical presentation, pain management, and the use of interventional ultrasound in chronic pancreatitis are among the topics discussed.

By Nasir Hussain, MD, and Bernard Karnath, MD

Chronic pancreatitis is defined as a continuing inflammatory and fibrosing process involving the pancreas that leads to progressive destruction of the parenchyma, resulting in irreversible loss of pancreatic exocrine and endocrine function. Serum amylase and lipase are unreliable markers of chronic pancreatitis because they may be normal, unlike in acute pancreatitis. Lack of histologic confirmation of the disease has made the diagnosis and classification of chronic pancreatitis difficult. The diagnosis must be based on clinical findings and imaging studies such as plain abdominal x-ray, computed tomography (CT), ultrasound, endoscopic ultrasound (EUS), or endoscopic retrograde cholangiopancreatography (ERCP).

What are the causes of chronic pancreatitis?

In 70% to 90% of cases, chronic pancreatitis results from alcoholism. Usually, the consumption of alcohol in amounts exceeding 150 grams daily for five years or longer is required to cause symptomatic chronic pancreatitis. However, amounts of less than 50 grams daily over a prolonged period of time may also result in the disease. Since only 5% to 15% of people who drink alcohol develop pancreatitis, some other cofactor such as genetics or diet must play an important role.

It is not clear how alcohol causes chronic pancreatitis. Direct toxic effects, protein plugs from pancreatic secretions, and recurrent attacks of acute pancreatitis are possible mechanisms.

Obstruction of the main pancreatic duct by tumors, strictures, or anatomic variants such as pancreas divisum is another possible cause of chronic pancreatitis. Cholelithiasis is a common cause of acute pancreatitis, and recurrent or relapsing pancreatitis due to gallstones can also result in chronic pancreatitis.

Cystic fibrosis, an autosomal recessive disorder, accounts for a small percentage of patients with chronic pancreatitis. It is the most common cause of exocrine pancreatic insufficiency in children. Mutation of the serine protease inhibitor Kazal type 1 gene increases the propensity for developing pancreatitis; it seems to be one of the factors that can cause tropical pancreatitis, seen in areas of Indonesia, India, and Africa. Malnutrition, toxic metabolites of cassava, and other etiologic cofactors are considered to be the cause of tropical chronic pancreatitis.

Hyperlipidemia, most often familial, may cause chronic pancreatitis after repeated attacks of acute pancreatitis. Triglyceride levels above 1000 mg/dl are usually required to initiate acute pancreatitis.

The Japanese have described a distinct type of chronic pancreatitis associated with autoantibodies in the blood, elevated levels of serum IgG, association with other autoimmune disorders such as primary biliary cirrhosis and inflammatory bowel disease, diffuse enlargement of the pancreas, and irregular narrowing of the main pancreatic duct. Autoimmune pancreatitis usually produces mild symptoms and responds well to glucocorticoid therapy.

In up to 20% of cases of chronic pancreatitis, the cause is unclear. The disease is called idiopathic pancreatitis in these cases.

How do patients with chronic pancreatitis present?

Chronic pancreatitis is four times more common in men than in women. However, idiopathic chronic pancreatitis occurs more often in women. In a long-term follow-up study by Cavallini et al, the mean age at presentation was 40.8 years (+/-11.3 years). Age at presentation in the familial form of the disease is much lower, as is the case in alcohol-induced chronic pancreatitis. After the onset of symptoms there is, on average, a delay of 1.5 years before the diagnosis of chronic pancreatitis is established.

Pain is a common presenting feature of chronic pancreatitis. The presentation of patients with relapsing chronic pancreatitis may be similar to that of acute pancreatitis, and it may be difficult clinically to differentiate between the two conditions. Early in the disease process the pain may be intermittent, but as the disease progresses the pain may become more constant.

The pain is located mostly in the epigastrium and radiates to the back. The most commonly noted type of chronic pain is dull, constant, epigastric pain with associated back pain, often made worse by eating or the supine position. Patients may present with acute exacerbations of epigastric pain.

Other common symptoms include anorexia, nausea, vomiting, constipation, flatulence, and weight loss. Patients may develop exocrine dysfunction of the pancreas with steatorrhea, malabsorption, and weight loss. Patients with chronic pancreatitis may also develop endocrine dysfunction that manifests clinically as diabetes mellitus.

What are the possible causes of the pain that patients experience in chronic pancreatitis?

Various theories have been presented to explain the etiology of the pain in chronic pancreatitis. Hypertension of the pancreatic duct and damage to the nerve endings have been justified by the observed response to surgical or endoscopic decompression and operative resection of the pancreas. Pain may start due to inflammation, which can be severe, as in acute pancreatitis, or it may be of milder intensity with pain-free periods. Pain tends to be more severe during the initial years of presentation.

Other sources of pain may be a complication of the disease, such as pseudocyst, and obstruction of biliary or duodenal drainage, which should respond well to surgery. Obstruction of the pancreatic duct is another possible cause of pain. It may develop due to stenosis or calcification and may be present as a late complication in 80% of cases.

What are the long-term complications of chronic pancreatitis?

Addiction to narcotics is a serious potential complication of chronic pancreatitis. Chronic pain with recurrent exacerbations is quite common. Pain management in such patients is often complicated by frequent visits to the emergency department and clinics, requiring referral to specialty pain management clinics in many cases.

Steatorrhea, a late complication of the disease, signifies a profound loss in pancreatic exocrine function, resulting in lipase deficiency. It may be present in 80% of cases. Weight loss occurs as a result of malabsorption and is worsened by the avoidance of food, which exacerbates the pain. Vitamin B12 deficiency may be present in 40% of patients with alcohol-induced chronic pancreatitis and nearly all patients with pancreatitis due to cystic fibrosis.

Diabetes, also a late manifestation of the disease, occurs less frequently than steatorrhea because islet cells are more resistant to damage than exocrine tissue. It is often complicated by hypoglycemic episodes caused by an inadequate glucagon response during insulin therapy.

Patients with chronic pancreatitis may also develop pleural and pericardial effusions and ascites. Such effusions have a high amylase level. Gastrointestinal bleeding may occur from peptic ulceration, gastritis, a pseudocyst eroding into the duodenum, or ruptured varices secondary to splenic vein thrombosis from inflammation of the tail of the pancreas. Edema of the head of the pancreas or inflammation around the intrapancreatic portion of the common bile duct may result in biliary obstruction and jaundice. Chronic obstruction may lead to cholangitis and ultimately to biliary cirrhosis. Other complications may include subcutaneous fat necrosis, bone pain secondary to intramedullary fat necrosis, and inflammation of the large and small joints.

Pancreatic calcification may be present in as many as 75% of cases. In the follow-up study by Cavallini, calcification was present in 12% of patients at the time of diagnosis and the percentage increased over time. Nearly 20% of patients with chronic pancreatitis remain calcification-free.

Pancreatic pseudocyst is also a recognized complication of chronic pancreatitis. In the Cavallini study, 9.6% of patients had pseudocyst early in the course of chronic pancreatitis; the percentage rose to 38.1% at five years, 47.8% at 10 years, and 54% at 15 years. Pancreatic inflammation appears to increase the risk of pancreatic adenocarcinoma, and pancreatic cancer is a significant late complication of chronic pancreatitis.

Which diagnostic studies are indicated?

Serum amylase and lipase levels may increase during acute exacerbations of chronic pancreatitis, but in advanced cases they may be normal ("burnt-out pancreas"). As the disease progresses, patients may develop endocrine dysfunction of the pancreas and serum and urine glucose may be elevated. Uncontrolled diabetes will result in elevated HbA_1c.

Patients with exocrine pancreatic dysfunction may develop malabsorption and steatorrhea. Excess fecal fat can be demonstrated with the Sudan stain. Stool quantification of fecal fat is unnecessary given the appropriate history. Patients with chronic malabsorption may also develop electrolyte and trace element deficiencies that can be confirmed by appropriate blood tests. A deficiency of serum B₁₂ is fairly common in patients with chronic pancreatitis caused by alcohol and cystic fibrosis; a serum B₁₂ level should be checked in such patients.

Plain x-rays of the abdomen showing pancreatic calcifications are diagnostic in the appropriate clinical setting. However, calcifications may be found in only 30% of patients with chronic pancreatitis, particularly early in the course of the disease. Computed tomography provides detailed images of the pancreas and is more sensitive than plain abdominal x-rays, with a reported 90% sensitivity and 85% specificity in the detection of chronic pancreatitis. A CT scan may easily reveal pancreatic enlargement, ductal dilatation, or pseudocyst.

Endoscopic retrograde cholangiopancreatography is considered the gold standard for diagnosing chronic pancreatitis. The disadvantage of ERCP is that it is invasive. Magnetic resonance cholangiopancreatography is relatively safe and noninvasive, but it may not be accurate in the diagnosis of early chronic pancreatitis. Ultrasonography may also reveal abnormalities but with a lower sensitivity and specificity.

What is the role of EUS in the diagnosis of chronic pancreatitis?

Endoscopic ultrasound was introduced in the early 1980s to improve imaging of the pancreas. Because it uses higher frequencies and the images are not compromised due to intervening bowel and fat, EUS produces higher-resolution images, a distinct advantage over abdominal ultrasound. Compared to ERCP, EUS has a very low risk of complications; it also provides detailed images of the pancreatic parenchyma, another advantage over ERCP, in which images are limited to the ductal system. To date, EUS is the most promising imaging study for the diagnosis of chronic pancreatitis.

There is growing evidence that EUS findings in the pancreatic parenchyma and ductal system correlate with histologic changes in chronic pancreatitis. Transgastric pancreatic biopsy is also possible under EUS guidance. With a large-channel endoscope, it is also possible to perform EUS-guided transgastric drainage of pancreatic pseudocyst. Celiac plexus block or neurolysis under EUS guidance is very effective in controlling pain in patients with pancreatic cancer. In patients with pain due to chronic pancreatitis, the response is variable.

Limitations of EUS include the fact that it is obviously dependent on the experience of the endosonographer. Also, to what extent interpretations of EUS findings might vary among clinicians has not been studied carefully. Lastly, EUS is largely unavailable outside of large medical centers.

What treatment options are available for a patient with chronic pancreatitis?

Management of patients with chronic pancreatitis includes emotional and psychological treatment for alcohol and narcotic dependence, pain control, and replacement of lost exocrine and endocrine functions of the pancreas. Some complications of chronic pancreatitis also require surgical or endoscopic interventions. Surgical intervention is needed, for example, for patients with chronic pancreatitis complicated by pseudocyst, pancreatic fistula, or duodenal or common bile duct obstruction. Nearly 70% of patients with chronic pancreatitis undergo surgery at some point in the course of the disease.

It is extremely important that patients stop drinking. In addition to pancreatitis, other complications of chronic alcoholism may be present. Successful treatment requires a team approach involving a chemical dependency counselor and a psychologist trained in cognitive therapy. Patients may also need help in quitting smoking; smokers with pancreatitis have worse clinical outcomes than nonsmokers, including a higher incidence of pancreatic cancer.

Antioxidants have also been used to improve the healing process in pancreatitis. However, there is no proven benefit of their use.

For patients with steatorrhea, treatment consists of a low-fat diet. Pancreatic enzyme replacement may also be given orally before meals. Replacement of pancreatic enzymes, especially lipase, is the mainstay of treatment for malabsorption. Antisecretory therapy, in the form of acid suppressive therapy with H2-receptor antagonists or proton pump inhibitors, can reduce acid-induced secretin release from the duodenum and consequent pancreatic stimulation. Some patients with secondary diabetes will respond to oral hypoglycemics, but most will require insulin. Control of diabetes will also allow for control of serum triglycerides in patients with hypertriglyceridemia.

What are some pain management strategies for chronic pancreatitis?

Pain is the symptom that most often requires treatment in chronic pancreatitis. The first step in pain control is to identify treatable causes of pain associated with chronic pancreatitis, such as pseudocyst, duodenal obstruction, common bile duct obstruction, and peptic ulcer disease. Adequate treatment of these complications may alleviate or at least minimize the patient's pain.

Management of chronic pain due to pancreatitis is challenging. Treatment should start with simple analgesics; later, if necessary, narcotic analgesics may be used. As noted earlier, addiction to narcotics is a serious potential problem. It may be difficult to differentiate between real pain and drug-seeking behavior. Whenever narcotic analgesics are used, the least potent formulation should be tried initially.

Tricyclic antidepressants can be a helpful adjunct for pain control and in the treatment of depression, if present. The role of pancreatic enzyme replacement in pain management remains unproven. Percutaneous and EUS-guided block or neurolysis of the celiac nerve plexus, when effective, is short-lived. Surgical resection of the splanchnic nerve is being studied; initial results have shown modest alleviation of pain.

In carefully selected patients, endoscopic relief of pancreatic obstruction due to a stone or stricture may result in alleviation of pain in 70% to 80% of cases. Surgical techniques to improve pain include decompression of the main pancreatic duct with or without resection of a portion of the pancreas. In 65% to 85% of patients with intractable pain and a dilated pancreatic duct, substantial relief is obtained by lateral pancreaticojejunostomy, sometimes with resection of a portion of the head of the pancreas.

Is there a role for complementary medicine in the management of chronic pancreatitis?

Mind-body therapeutic techniques have been used in the treatment of abdominal pain, but the evidence for their effectiveness is limited due to the small number of studies that have been done and their suboptimal quality. However, there is no reported harm in this type of treatment. Herbal products and acupuncture have also been used in the treatment of abdominal pain and the pain of chronic pancreatitis, but because of the lack of evidence on their effectiveness, they are not standard care.