Chronic pancreatitis (CP) is a debilitating disease that is associated with approximately $150 million in healthcare expense annually.1 It is a complicated disease in that it is multifactorial, problematic to diagnose, and difficult to treat. The majority of patients with CP experience severe abdominal pain, and 50% will develop endocrine insufficiency and 80% will develop exocrine insufficiency within 5 years of diagnosis. Abdominal pain and other myriad symptoms lead to significant psychosocial and physical disability and reduced quality of life.2


A variety of pathogenic entities contribute to CP, all of which result in chronic inflammation, fibrosis, and irreversible damage to the pancreas. These etiologies can be remembered according to the mnemonic TIGAR-O: toxic-metabolic, idiopathic, genetic, autoimmune, recurrent, and obstructive.3 Toxic-metabolic triggers include chronic alcohol abuse, tobacco use, hypercalcemia, hyperlipidemia, uremia, and others. Chronic exposure to toxins is responsible for oxidative damage at the cellular level, resulting in parenchymal destruction and reduced pancreatic function.4

Idiopathic CP occurs in 2 patterns based on age: idiopathic chronic juvenile pancreatitis in the pediatric population (early onset) and idiopathic senile chronic pancreatitis in the elderly (late onset).5 One form of early-onset CP is tropical CP, also known as fibrocalculous pancreatic diabetes; this entity is most common in tropical, southern India.1 The bimodal age distribution in idiopathic CP is poorly understood, but environmental, genetic, and autoimmune factors are likely responsible. To relegate a case of CP as idiopathic requires that all other entities be excluded.4 

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Genetic causes of CP are the result of mutations primarily involving “premature activation of trypsinogen or failure to inactivate trypsin during pancreatic inflammation,” which ultimately damages the pancreas.5  Trypsin is the active form of the precursor enzyme trypsinogen. Trypsinogen is produced by and stored in the pancreas, and upon stimulation by cholecystokinin, it is released into the duodenum where it is converted to trypsin, an enzyme involved in the breakdown of protein. If this chain of events fails, trypsin promotes auto-digestion of acinar tissue, leading to pancreatitis. Genes directly or indirectly related to the trypsin pathway and underlying derangements in the development of CP include CFTR (codes for cystic fibrosis transmembrane regulator protein), PRSS1 (codes for cationic trypsinogen enzyme), SPINK1 (codes for pancreatic secretory trypsin inhibitor protein), CTRC (codes for chymotrypsin C enzyme), and CASR (codes for calcium sensing receptor protein).3,5

Autoimmune pancreatitis occurs in 2 patterns. Type 1 correlates with deposition of immunoglobulin G4 (IgG4) in pancreatic tissue, leading to subsequent damage to the pancreas. Infiltration of IgG4, however, is not confined to the pancreas; IgG4 may invade the bile duct, salivary glands, retroperitoneum, kidneys, and lymph nodes.5  Type 2, in contrast, is characterized by cellular infiltration of neutrophils, which damage the pancreatic ducts. Both types 1 and 2 respond to treatment with steroids.5

Recurrent pancreatitis is typified by repeated episodes of acute pancreatitis, resulting in cumulative tissue damage. Complete morphologic resolution rarely occurs following numerous attacks. Deposition of collagen and formation of scar tissue interfere with restoration of glandular structure and function, resulting in CP.4

Obstructive CP consists of segmental anatomic blockade in the ductal system by occlusive stones, tumors, or structural entities such as pancreas divisum. Obstruction of enzyme flux in and out of the ductal network results in accumulation of digestive enzymes within the pancreas. This dynamic process creates elevated intraductal and parenchymal pressures, mimicking a compartment syndrome and resulting in ischemic tissue damage.4,6

Clinical Presentation

Because many patients with CP display risk factors associated with certain etiologies, it is important that social and medical histories be explored for conditions predisposing patients to the disease.7

The most common symptom of CP is epigastric pain, often exacerbated by lying down and alleviated by leaning forward. Radiation to the back also occurs frequently. Pain is typically postprandial, and can be persistent or intermittent. Depending on disease severity, patients may also present with exocrine dysfunction, which manifests as malabsorption (weight loss, diarrhea, and steatorrhea), and endocrine disturbance presenting as hyperglycemia. Signs and symptoms vary depending on the etiology of CP.7

Physical examination in CP often reveals midline epigastric tenderness. Rigidity and rebound are rare. The presence of ascites suggests a pseudocyst, abscess, or other complication. Physical findings may prove beneficial in ruling out conditions that mimic CP (Table).7

Table. Differential Diagnoses for Chronic Pancreatitis7

Myocardial infarction
Pancreatic adenocarcinoma
Peptic ulcer disease

No single laboratory test is diagnostic of CP. Amylase and lipase are usually normal in chronic disease but may be elevated in early disease stages or during an acute exacerbation. In late-stage CP, amylase and lipase may be low, signaling exocrine insufficiency, although this is not sensitive or specific.3,7 Laboratory data are of further value in determining precise etiologies of CP, especially metabolic toxins, and in monitoring disease flares or complications. For example, elevated liver enzymes may suggest alcohol abuse. Azotemia may indicate uremic pancreatitis. Hypercalcemia may indicate calcium deposition in the pancreas. Abnormal blood glucose levels are associated with loss of endocrine function. Elevated white blood cell counts may indicate pancreatic infection or necrosis.7

This article originally appeared on Clinical Advisor