The most common cause of acute pancreatitis is gallstone pancreatitis (GP), which represents 45% of cases [3]. There are three types of gallstones: black, brown, and yellow stones. Black stones are related to active hemolysis. Brown stones are the sequelae of chronic biliary-based infections often in the setting of biliary obstruction. Yellow cholesterol stones are the most common; risk factors include female sex, pregnancy, obesity, physical inactivity, and overnutrition [4]. GP presentation typically includes cholestatic liver tests. An alanine aminotransferase (ALT) enzyme elevation three times the upper limit of normal in the setting of AP is associated with a positive predictive value of 95% for GP. A subset of GP is microlithiasis-induced pancreatitis. In these cases, cholestatic liver tests are noted; however abdominal imaging does not reveal evidence of biliary obstruction or gallstones. EUS can be useful in diagnosing subtle pancreatobiliary-based sludge. The management of biliary pancreatitis is discussed at length in a separate chapter.

Alcoholic pancreatitis accounts for an estimated 30% of cases. Interestingly, only 5–10% of chronic alcoholics develop acute pancreatitis [5]. Following AP management, alcohol cessation is recommended. In patients with continued alcohol abuse, there is an increased risk for RAP. Other less common causes of toxin-induced pancreatitis include methanol, organophosphate exposure, and scorpion venom.

Idiopathic pancreatitis (IP), where no definitive etiology can be ascertained, occurs in an estimated 15–25% of AP cases. IP is considered when an extensive negative workup has occurred which often includes serological workup, CT, MRCP, and/or EUS studies. It should be noted that smoking represents an independent risk factor for acute pancreatitis [6].

Hypertriglyceridemia pancreatitis (HTGP) represents 3% of AP cases and often can lead to RAP. HTGP can be genetic or acquired [7]. Familial hypertriglyceridemia increases the risk for AP and therefore family history represents a potential risk factor. Acquired HTG occurs in the context of diabetes mellitus (DM), hypothyroidism, pregnancy, nephrotic syndrome, steroid use, beta-blockers, and tamoxifen use. Typically triglyceride levels over 1000 mg/dL significantly increase the risk for HTGP. Management includes aggressive hydration, analgesia, and IV insulin with IV dextrose. Plasmapheresis filters and effectively removes triglycerides. It is often reserved for TG levels greater than 1000 mg/dL with evidence of hypocalcemia and/or end-organ damage. Long-term management includes the use of fibrates, as well as optimizing predisposing comorbidities such as diabetes or hypothyroidism. Given that predisposing conditions such as DM or familial HTG can be difficult to control, HTGP patients often have an increased risk for RAP and severe pancreatitis-related morbidity.

Hypercalcemia is associated with acute pancreatitis in 1.5% of cases. Excess calcium is thought to promote pancreatitis via calcium-mediated activation of trypsinogen and pancreatic duct (PD) calcification deposition. Risk factors include hyperparathyroidism, malignancy, and numerous alternative etiologies of chronic hypercalcemia. Initial management includes IV hydration and treatment of the underlying etiology.

Medication-induced pancreatitis represents an estimated 1–2.5% of AP cases. Medication-induced pancreatitis literature ranges from case reports to larger observational studies to medication rechallenge trials [8]. The commonly associated drugs include azathioprine, estrogen, 5-ASA, sulfasalazine, metronidazole, pentamidine, didanosine, l-asparaginase, valproic acid, sulindac, salicylates, hydrochlorothiazide, and furosemide. The key management strategy is cessation of the offending medication and monitoring for RAP.

Due to extensive genetics research, hereditary pancreatitis (HP) is an increasingly diagnosed cause of RAP [9]. PRSS1 is a gain of function serine protease mutation that leads to autosomal dominant inheritance. The serine protease inhibitor Kazal type 1 (SPINK1) mutation leads to increased pancreatitis susceptibility. Mutation of the CFTR gene also leads to HP via an autosomal recessive inheritance pattern. Key clinical risk factors include a family history of pancreatitis, presentation of RAP, and/or young age of initial presentation. HP is important to diagnose early on due to the increased risk for developing chronic pancreatitis and pancreatic cancer.

Acquired structural and congenital pancreatic abnormalities can increase the risk for AP. Pancreatic malignancy and pancreatic cysts such as main duct intraductal papillary mucinous neoplasms (IPMNs) can obstruct the pancreatic duct and lead to AP. Management involves surgical resection depending on lesion location and/or malignancy staging. Pancreatic divisum is estimated to arise in 10% of the general population [10]. RAP is noted in a subset of 8–10% of these patients. Minor duct papillotomy can be performed in these patients to facilitate pancreatitis duct drainage.