GE 2007;132:2022; Am J Gastro 2006;101:2379; Lancet 2003;361:1447

Cause: Many causes of acute pancreatitis (AP) have been identified (Nejm 1994;330:1198; Gastroenterol Clin North Am 1999;28:571). In most regions of the world, gallstones are the leading cause of AP, and alcohol is a close second. Idiopathic pancreatitis (10-25% of the total) places third on the list, though some of these cases represent a failure to diagnose gallstone disease and microlithiasis (Nejm 1992;326:589). Hypertriglyceridemia is a relatively common cause of AP and is seen when TG levels are >1000 mg/dL. Pancreatitis occurs more often in type V hyperlipidemia and less often in types I and IV (Gastroenterol Clin North Am 1990;19:783). A bewildering number of drugs have been implicated in AP (Clin Gastroenterol Hepatol 2007;5:648). These include AZA/6-MP, L-asparaginase, 5-aminosalicylic acid compounds (mesalamine, olsalazine, sulfasalazine), didanosine (an antiretroviral), valproic acid, furosemide, cimetidine, famotidine, thiazides, lisinopril, codeine (Am J Gastro 2000;95:3295), antibiotics (tetracycline, metronidazole, nitrofurantoin, erythromycin, sulfonamides, pentamadine), and NSAIDs (ibuprofen, sulindac, celecoxib) (Arch IM 2000;160:553).

Diagnostic ERCP is associated with a 3-9% risk of AP, and rates may be higher with sphincterotomy or sphincter of Oddi manometry. Blunt trauma to the abdomen can cause AP by disrupting the duct. Infections are always listed as a cause of AP, but in adult practice they are uncommon. Mumps, coxsackievirus, CMV, Campylobacter, hep A, and hep B have all been implicated. HIV-infected pts have a high incidence of pancreatitis associated with a variety of infections and drugs. The association of hyperparathyroidism with AP has received more attention than it deserves and is very infrequent (0.23% of 800 consecutive pts with hyperparathyroidism in 1 series) (Brit J Surg 1986;73:282). Occurrence of AP following cardiac surgery is thought to be related to ischemia. Emboli and vasculitis are rare causes. Scorpion venom (BMJ 1970;1:666), bites of certain spiders and the Gila monster lizard, organophosphorous insecticides, and methanol are rare toxic causes of AP. A rare familial form (hereditary pancreatitis) is associated with recurrent bouts of AP leading to chronic pancreatitis and caused by mutations in the cationic trypsinogen gene (Gut 1999;45:317). Autoimmune pancreatitis (a cause of chronic pancreatitis, see p 192) can have an acute presentation. Other obstructive disorders, such as pancreatic cancer or ampullary cancer, may obstruct the duct and cause AP. In pancreas divisum, the dorsal and ventral ducts of
the pancreas do notfuse, and the larger dorsal duct (Santorini duct) drains through the minor papilla. If the minor duct is relatively stenotic, AP may result. Sphincter of Oddi stenosis or dysfunction (p 210) may also result in AP. Choledochal cysts (p 212) and mucinous duct ectasia (p 198), and anomalous union of the pancreaticobiliary duct (Gastro Endosc 1999;50:189) are infrequent causes.

Penetrating peptic ulcer rarely presents as AP. Crohn’s disease, cystic fibrosis, and hypothermia usually present with other sx. Postpartum pancreatitis appears to be largely biliary in nature (Mayo Clin Proc 2000;75:361).

Epidem: The disorder is common with an incidence of 24/100,000 per yr in the U.K. (Brit J Surg 1987;74:398). The incidence has risen over the last 40 yr for unclear reasons. The disorder is more common in men than in women.

Pathophys: (Surg Clin N Am 1999;79:699) The means by which the numerous causes of pancreatitis result in a similar clinical illness has notbeen determined. Biliopancreatic reflux appears to be the important initiating event in gallstone pancreatitis (Gut 1995;36:803). There appear to be genetic predispositions to pancreatitis caused by mutations in genes that normally function to limit the destruction of the pancreas caused by activation of trypsin from trypsinogen. The shared characteristic of the many causes of AP is premature activation of proteolytic enzymes (such as trypsin from trypsinogen) and their inappropriate retention in the acinar cell. Subsequent injury to the acinar cell causes release of cytokines and activation of the complement system. Inflammatory cells are recruited into the pancreas and result in further release of inflammatory mediators (such as platelet activating factor [PAF], TNF, IL-1, and IL-6). These cause local tissue edema, cell necrosis, and the distant, systemic effects of hypotension, fever, hypoxia, leaky capillaries, and ARDS. Improved understanding of the cascade may allow for therapeutic interventions.

Pancreatitis is classified as interstitial, edematous pancreatitis if the pancreatic tissue remains viable. It is classified as necrotizing pancreatitis (which is more severe) if pancreatic tissue becomes nonviable.

Sx: The most common sx is upper abdominal pain, which is usually epigastric and radiates to the back. Pain is generally constant and can be severe. Nausea and vomiting are common.

Si: Fever is common and does notnecessarily imply infection. Hypotension and tachycardia may be associated with volume depletion. Abdominal tenderness is greatest in the epigastrium but can be present in any area of the abdomen where the inflammatory process tracks. In more severe cases, there is distention, rigidity, percussion tenderness, or loss of bowel sounds. An upper abdominal mass may be felt if the pt develops a phlegmon or pseudocyst. Bluish discoloration of the flanks (Grey Turner sign) and of the periumbilical area (Cullen sign) is rarely seen and is due to hemorrhage in severe, necrotizing disease. The lung fields can show evidence of effusions or atelectasis. The skin may show eruptive xanthomata (reddish-yellow papules of a few mm, especially on extensor surfaces) if the cause is hyperlipidemia. Tender red skin nodules from fat necrosis are rarely seen.

Diff Dx: See Approach to Acute Abdominal Pain (p 4). The dx of AP is made on the basis of the hx, physical exam, and laboratory studies and is selectively confirmed by imaging studies such as CT. In mild cases presenting late in the illness, the laboratory studies may be less helpful and the imaging is more important.

The cause of pancreatitis is usually evident from the initial H&P, labs, and the abdominal US. However, in 10-25% of cases the cause is notimmediately evident. About 50% of these idiopathic cases never recur, but many do and require a more extensive evaluation. There is a range of expert opinions regarding the evaluation of so-called recurrent AP (compare GE 2001;120:708 to J Clin Gastro 2003;37:238). The evaluation usually begins with CT scan to look for tumor or chronic pancreatitis. If this is negative, many experts proceed to EUS and/or ERCP to look for chronic pancreatitis, tumors, pancreas divisum (which is then treated by dorsal duct sphincterotomy), annular pancreas, choledochocele, and anomalous union of the pancreaticobiliary duct. EUS is the preferred initial test because it is less risky. Some experts evaluate the sphincter of Oddi by manometry, but others do notbecause of risk. At the ERCP, bile is aspirated and examined by microscopy for cholesterol monohydrate crystals or bilirubinate granules. If these studies are negative, tests for gene defects (see Pathophys) or testing for autoimmune pancreatitis are undertaken (with IgG4 levels). Many experts skip biliary microscopy and recommend biliary sphincterotomy and/or cholecystectomy if ERCP/MRCP and/or EUS is negative. The approach will vary with the local expertise in the various available modalities.

Lab: Amylase is a sensitive predictor of AP, but false-positive elevations may be seen due to pancreatic cancer, mesenteric infarction, bowel obstruction, perforated ulcer, and renal failure. Salivary amylase causes false positives that can be easily identified by amylase fractionation. Macroamylasemia causes a high serum amylase in the absence of pancreatitis and can be detected by fractionation. Lipase is more specific than amylase but can be elevated in perforated ulcer, ischemia, or obstruction (though typically such elevations are less than 3 times normal). Lipase is cleared more slowly and can be helpful if pts present days after the event. All pts should have at least a daily CBC and CMP early in the course of the illness to assess renal function, electrolytes, calcium, glucose, and liver function. Elevations of AST/ALT (<3 × normal) and bilirubin may suggest gallstones as the etiology. Triglycerides should be obtained to exclude hypertriglyceridemia as the etiology.