Chronic pancreatitis is persistent inflammation of the pancreas that results in permanent structural damage with fibrosis and ductal strictures, followed by a decline in exocrine and endocrine function. It can occur as the result of chronic alcohol abuse but may be idiopathic. Initial symptoms are recurrent attacks of pain. Later in the disease, some patients develop malabsorption and glucose intolerance. Diagnosis is usually made by imaging studies such as ERCP, endoscopic ultrasonography, or secretin pancreatic function testing. Treatment is supportive, with dietary modification, analgesics, and enzyme supplements. In some cases, surgical treatment is helpful.
In the US, less than half of cases result from alcoholism, and 15 to 25% are idiopathic. However, recent data suggest that alcohol is becoming less of a cause. Less common causes include hereditary pancreatitis, autoimmune pancreatitis, hyperparathyroidism, and obstruction of the main pancreatic duct caused by stenosis, stones, or cancer. In India, Indonesia, and Nigeria, idiopathic calcific pancreatitis occurs among children and young adults (tropical pancreatitis).
Similar to acute pancreatitis, the mechanism of disease may be ductal obstruction by protein plugs. The protein plugs may result from excess secretion of glycoprotein-2 or a deficiency of lithostatin, a protein in pancreatic fluid that inhibits Ca precipitation. If obstruction is chronic, persistent inflammation leads to fibrosis and alternating areas of ductal dilation and stricture, which may become calcified. Neuronal sheath hypertrophy and perineural inflammation occur and may contribute to chronic pain.
After several years, progressive fibrosis leads to loss of exocrine and endocrine function. Diabetes develops in 20 to 30% of patients within 10 to 15 yr of onset.
Symptoms and Signs
Most patients present with episodic abdominal pain. About 10 to 15% have no pain and present with malabsorption. Pain is epigastric, severe, and may last many hours or several days. Episodes typically subside spontaneously after 6 to 10 yr as the acinar cells that secrete pancreatic digestive enzymes are progressively destroyed. When lipase and protease secretions are reduced to < 10% of normal, the patient develops steatorrhea, passing greasy stools or even oil droplets, and creatorrhea (the presence of undigested muscle fibers in the feces). Symptoms of glucose intolerance may appear at this time.
Diagnosis can be difficult because amylase and lipase levels are frequently normal because of significant loss of pancreatic function. In a patient with a typical history of alcohol abuse and recurrent episodes of acute pancreatitis, detection of pancreatic calcification on plain x-ray of the abdomen may be sufficient. However, such calcifications typically occur late in the disease and then are visible in only about 30% of patients. In patients without a typical history, pancreatic cancer must be excluded as the cause of pain: abdominal CT is recommended. CT can show calcifications and other pancreatic abnormalities (eg, pseudocyst or dilated ducts) but still may be normal early in the disease. MRCP is now frequently used for diagnosis and can show masses in the pancreas as well as provide more optimal visualization of ductal changes consistent with chronic pancreatitis.
The primary options for patients with normal CT findings include ERCP, endoscopic ultrasonography, and secretin pancreatic function testing. These tests are quite sensitive, but ERCP precipitates acute pancreatitis in about 5% of patients.
Late in the disease, tests of pancreatic exocrine function become abnormal. A 72-h test for stool fat is diagnostic for steatorrhea but cannot establish a cause. The secretin test collects pancreatic secretions via a duodenal tube for analysis but is done in only a few centers. Levels of serum trypsinogen and fecal chymotrypsin and elastase may be decreased. In the bentiromide test and the pancreolauryl test, substances are given orally, and urine is analyzed for cleavage products generated by pancreatic enzymes. All such exocrine tests are less sensitive than ERCP or endoscopic ultrasonography early in the disease.
A relapse requires treatment similar to acute pancreatitis with fasting, IV fluids, and analgesics. When feeding resumes, the patient must eschew alcohol and consume a low-fat (< 25 g/day) diet (to reduce secretion of pancreatic enzymes). An H2 blocker or proton pump inhibitor may reduce acid-stimulated release of secretin, thereby decreasing the flow of pancreatic secretions. Too often, these measures do not relieve pain, requiring increased amounts of opioids, with the threat of addiction. Medical treatment of chronic pancreatic pain is often unsatisfactory.
Pancreatic enzyme supplementation may reduce chronic pain by inhibiting the release of cholecystokinin, thereby reducing the secretion of pancreatic enzymes. Supplementation is more likely to be successful in mild idiopathic pancreatitis than in alcoholic pancreatitis. Enzymes are also used to treat steatorrhea. Various preparations are available, and a dose providing at least 30,000 U of lipase should be used. Nonenteric coated tablets should be used, and they should be taken with meals. An H2 blocker or proton pump inhibitor should be given to prevent acid breakdown of the enzymes.
Favorable clinical responses include weight gain, fewer bowel movements, elimination of oil droplet seepage, and improved well-being. Clinical response can be documented by showing a decrease in stool fat after enzyme therapy. If steatorrhea is particularly severe and refractory to these measures, medium-chain triglycerides can be provided as a source of fat (they are absorbed without pancreatic enzymes), reducing other dietary fats proportionally. Supplementation with fat-soluble vitamins (A, D, K) should be given, including vitamin E, which may minimize inflammation.
Surgical treatment may be effective for pain relief. A pancreatic pseudocyst, which may cause chronic pain, can be decompressed into a nearby structure to which it firmly adheres (eg, the stomach) or into a defunctionalized loop of jejunum (via a Roux-en-Y cystojejunostomy). If the main pancreatic duct is dilated > 5 to 8 mm, a lateral pancreaticojejunostomy (Puestow procedure) relieves pain in about 70 to 80% of patients. If the duct is not dilated, a partial resection is similarly effective; either distal pancreatectomy (for extensive disease at the tail of the pancreas) or Whipple procedure (for extensive disease at the head of the pancreas) is done. Operative approaches should be reserved for patients who have stopped using alcohol and who can manage diabetes that may be intensified by pancreatic resection.
Some pseudocysts can be drained endoscopically. Endoscopic ultrasound-guided denervation of the celiac plexus with alcohol and bupivacaine may provide pain relief. If there is significant stricture at the papilla or distal pancreatic duct, ERCP with sphincterotomy, stent placement, or dilatation may be effective.
Oral hypoglycemic drugs rarely help treat diabetes caused by chronic pancreatitis. Insulin should be given cautiously because the coexisting deficiency of glucagon secretion by α-cells means that the hypoglycemic effects of insulin are unopposed and prolonged hypoglycemia may occur.
Patients are at increased risk of pancreatic cancer. Worsening of symptoms, especially with development of a pancreatic duct stricture, should prompt an evaluation for cancer. Evaluation may include brushing strictures for cytologic analysis or measuring serum markers (eg, CA 19-9, carcinoembryonic antigen).
Last full review/revision September 2012 by Steven D. Freedman, MD, PhD
Content last modified November 2012