16-27: Chronic Pancreatitis

GENERAL CONSIDERATIONS

The prevalence of chronic pancreatitis in the United States is 25–99 per 100,000 population with a peak in persons aged 46–55 years. Chronic pancreatitis occurs most often in patients with alcoholism (45–80% of all cases). The risk of chronic pancreatitis increases with the duration and amount of alcohol consumed, but pancreatitis develops in only 5–10% of heavy drinkers. Tobacco smoking is a risk factor for idiopathic chronic pancreatitis and has been reported to accelerate progression of alcohol-associated chronic pancreatitis. About 2% of patients with hyperparathyroidism develop pancreatitis. In tropical Africa and Asia, tropical pancreatitis, related in part to malnutrition, is the most common cause of chronic pancreatitis. By contrast, in Western societies, obesity can lead to pancreatic steatosis, which may lead ultimately to pancreatic exocrine and endocrine insufficiency and an increased risk of pancreatic cancer. A stricture, stone, or tumor obstructing the pancreas can lead to obstructive chronic pancreatitis. Autoimmune pancreatitis is associated with hypergammaglobulinemia (IgG₄ in particular), often with autoantibodies and other autoimmune diseases, and is responsive to corticosteroids. Affected persons are at increased risk for various cancers. Type 1 autoimmune pancreatitis (lymphoplasmacytic sclerosing pancreatitis, or simply autoimmune pancreatitis) is a multisystem disease, typically in a patient over age 60, characterized by lymphoplasmacytic infiltration and fibrosis on biopsy, associated bile duct strictures, retroperitoneal fibrosis, renal and salivary gland lesions, and a high rate of relapse after treatment. It is the pancreatic manifestation of IgG₄-related disease. Type 2 (“idiopathic duct-centric chronic pancreatitis”) affects the pancreas alone, typically in a patient aged 40–50 years, and is characterized by intense duct-centric lymphoplasmacytic infiltration on biopsy, lack of systemic IgG₄ involvement, an association with inflammatory bowel disease in 25% of cases, often a tumor-like mass, and a low rate of relapse after treatment. Between 10% and 30% of cases of chronic pancreatitis are idiopathic, with either early onset (median age 23) or late onset (median age 62). Genetic factors may predispose to chronic pancreatitis in some of these cases and include mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, the pancreatic secretory trypsin inhibitory gene (PSTI, also known as the serine protease inhibitor, SPINK1), the chymotrypsin-C (CTRC) gene, and the genes for carboxypeptidase A1 (CPA1) and possibly uridine 5′-diphosphate glucuronosyltransferase (UGT1A7). Mutation of the cationic trypsinogen gene on chromosome 7 (serine protease 1, PRSS1) is associated with hereditary pancreatitis, transmitted as an autosomal dominant trait with variable penetrance. In addition, a variant in an X-linked gene CLDN2, which encodes claudin-2, has been associated with chronic pancreatitis; its presence on the X chromosome may partly explain the male predominance of chronic pancreatitis. Variants in the gene ...