Chronic pancreatitis (CP) is a progressive inflammatory disease of the pancreas, characterized by irreversible morphologic changes and gradual fibrotic replacement of the gland. Loss of exocrine and endocrine function results from parenchymal fibrosis. The primary symptoms of CP are abdominal pain and maldigestion. Because of diagnostic and therapeutic challenges, an interdisciplinary management strategy is required.
Abdominal pain occurs in 50% to 80% of cases and is responsible for most hospitalizations related to this illness. Pancreatic pain is dull or boring in quality and worsens after eating. The pain is located in the epigastric area and often radiates to the back. There may be associated nausea and vomiting with exacerbations of pain. Two patterns of abdominal pain have been described in CP. Type A pain is characterized by short relapsing episodes lasting days to weeks, separated by pain-free intervals. Type B pain implies prolonged, severe, unrelenting pain. Recent study suggests that type B pain is associated with worse quality of life, greater healthcare need and disability. Pain exacerbations are not always associated with elevations of serum amylase and lipase levels. Previously, results of some studies suggested diminishment of pancreatic pain with progression of CP. However, subsequent large prospective studies refuted this notion and findings suggest progression of disease may in fact lead to a state where pain management is less effective. There are several proposed pathogenic mechanisms of pancreatic pain in CP, including intraductal hypertension, neural inflammation, upregulation of pain mediators, and proliferation of unmyelinated nerve fiber, neurohormonal changes, and abnormal feedback mechanisms. Concomitant gastroparesis, and complications of CP can contribute to abdominal pain and appropriately investigated if suspected. Some patients develop nonvisceral (central) pain, often after years of narcotic dependency.
Gradual pancreatic fibrosis produces a steady deterioration in enzyme output, leading to steatorrhea and weight loss. Clinically apparent steatorrhea does not occur until 90% of pancreatic function has been lost. The sudden development of steatorrhea suggests main pancreatic duct obstruction by inflammatory strictures, stones, or cancer. Endocrine insufficiency does not occur until late in the disease course. Pancreatic diabetes requires insulin and is typically brittle because of concomitant glucagon deficiency. Weight loss in CP is multifactorial, related to maldigestion, fear of eating, anorexia, nausea, and vomiting. Severe or rapid weight loss is a red flag for pancreatic cancer.
Heavy and prolonged alcohol use is a common cause of CP. In contrast to other causes, alcohol-related CP is associated with more-severe pain, extensive calcification and ductal changes, and more rapid progression to endocrine and exocrine insufficiency. Most patients experience recurrent episodes of acute pancreatitis for several years before CP develops. Interestingly, only 3% of alcoholics develop CP, implying the presence of cofactors that amplify the effect of alcohol. A high-fat diet and smoking might also contribute to pancreatic disease in alcoholics. Smoking adversely affects pancreatic bicarbonate and water secretion, induces oxidative stress, and increases the rate of pancreatic calcification. Indeed, there have been several studies that demonstrated smoking as an independent risk factor for both development and progression of chronic pancreatitis.
Tropical pancreatitis is endemic to certain developing regions, such as India, Africa, and South America. Episodic abdominal pain begins in childhood and is followed by rapid progression to endocrine and exocrine insufficiency. Nutritional factors such as micronutrient deficiencies (zinc, copper, and selenium) may be involved in the pathogenesis of tropical pancreatitis. Causes of obstructive CP include pancreatic adenocarcinoma, neuroendocrine tumors, and intrapapillary mucinous tumors. Autoimmune pancreatitis is a recently described disorder which resides on the continuum of IgG4 related sclerosing disease. Pancreatic involvement often presents with obstructive jaundice or acute recurrent pancreatitis due to pancreatic swelling and ductal strictures compressing the bile duct or pancreatic duct. Laboratory features include an elevated immunoglobulin IgG4 level. Imaging features include focal or diffuse pancreatic enlargement and a narrowed pancreatic duct. The clinical and radiographic features of the disease improve rapidly with corticosteroid therapy.
Important discoveries have been made in the genetic basis of pancreatic disease. Hereditary pancreatitis is a rare autosomal dominant disease that causes recurrent painful episodes of acute pancreatitis in childhood, leading to CP and pancreatic cancer in adulthood. Hereditary pancreatitis occurs through a mutation of the cationic trypsinogen gene (PRSS1), leading to loss of autoregulation of activated trypsin. Additionally, studies have demonstrated a high prevalence of CFTR gene mutations in patients presenting with idiopathic acute and chronic pancreatitis. Although 85% of cystic fibrosis patients have the severe form of cystic fibrosis, with respiratory disease and pancreatic insufficiency, the remaining 15% possess lower sweat chloride levels and might express other phenotypes, including pancreatitis. Most patients who present with pancreatitis as the sole phenotypic feature of cystic fibrosis have one or two mild CFTR mutations. Other susceptibility genes that have been established include the pancreatic secretory trypsin inhibitor gene (SPINK1), the chymotrypsinogen C gene (CTRC), and the calcium sensing receptor gene (CASR).
Severe hypercalcemia is known to trigger episodes of acute pancreatitis through trypsin-mediated mechanisms and can progress to CP. Chronic renal failure is associated with an increased prevalence of CP, perhaps related to a direct toxicity of uremia on the pancreas. Hypertriglyceridemia and gallstones rarely cause CP.
Ten percent to 30% of patients with CP possess no identified risk factors. Idiopathic CP has a bimodal age presentation. Early-onset idiopathic CP manifests with severe abdominal pain in childhood, with relatively few structural and functional changes. Late-onset idiopathic CP manifests in late adulthood, often with minimal pain and pronounced exocrine insufficiency.
A commonly used etiologic classification of CP is Toxic Idiopathic Genetic Autoimmune Recurrent Obstructive (TIGAR-O) system that reflects different underlying mechanisms of pancreatic injury.
Advanced CP is most easily diagnosed with a pancreatic-protocol CT scan. The cardinal CT features of CP are pancreatic atrophy, calcifications, and main pancreatic duct dilation. Using these criteria, CT has a sensitivity of 74% to 90% and a specificity of 84% to 100%. Additionally, CT can detect CP complications, including pseudocysts, splenic artery pseudoaneurysm, and biliary obstruction. The finding of pancreatic head enlargement suggests pancreatic cancer or an inflammatory mass.
The diagnosis of early (minimal change) CP is more challenging. ERCP involves the endoscopic injection of contrast into the pancreatic duct via the papilla of Vater for fluoroscopic imaging. ERCP ductal changes are graded from equivocal (class I) to severe (class IV) (Cambridge classification). Although ERCP is considered accurate for early CP, it carries a 5% to 10% risk of acute pancreatitis. The role of ERCP in the diagnosis of chronic pancreatitis has recently decreased because safer and less-invasive techniques are available.
EUS is a minimally invasive test that allows a close sonographic inspection of the head, body, and tail of the pancreas from gastric and duodenal stations. The finding of five or more EUS criteria has been an approximate sensitivity of 75% and specificity of 80% for CP in studies incorporating ERCP as reference standard.