Drug-Induced Acute Pancreatitis: Underdiagnosis and Overdiagnosis

Abstract

As the incidence of acute pancreatitis continues to rise, establishing the etiology in order to prevent recurrence is important [1, 2]. Although the etiology of acute pancreatitis is not difficult in the majority of patients, almost a quarter of patients are initially labeled as having idiopathic acute pancreatitis [3]. When confronted with a patient with acute pancreatitis and no clear etiology defined as an absence of a history of alcoholism, absence of imaging demonstrating gallstones (ultrasound and/or MRI), and a normal triglyceride level, it is reasonable to consider a drug as the cause of acute pancreatitis. When considering a particular medication as causing acute pancreatitis, often the first step is a literature search. Data from pharmaceutical companies and/or the Food and Drug Administration (FDA) is not helpful. Typically, these sources cite many medications as causing acute pancreatitis despite the fact that the evidence provided does not have sufficient detail as to demonstrate causation. Published case reports, if detailed properly, can give more definitive information as to the diagnosis of acute pancreatitis and whether other causes besides drugs have been properly ruled out. A recent thorough review of the literature found over 100 drugs implicated in causing acute pancreatitis [4]. While some of these case reports are well written, many case reports represent poorly written experiences of the clinician simply implicating a drug without a careful evaluation. The case reports are plagued by a combination of failing to provide the definitive diagnosis of acute pancreatitis and clarity in ruling out more common causes of acute pancreatitis such as alcoholism, gallstones, and hypertriglyceridemia. Due to problems in the literature, many patients with important causes of acute pancreatitis that need to be recognized such as gallstones, hypertriglyceridemia, and tumors, are falsely labeled as having drug-induced acute pancreatitis. This has resulted in the overdiagnosis of drug-induced pancreatitis. Conversely, some patients with idiopathic recurrent pancreatitis are not recognized as being on a medication that is causing their pancreatitis. This has resulted in the under-diagnosis of drug-induced pancreatitis. There have been multiple attempts to critically review the literature and determine which drugs have the best evidence as causing acute pancreatitis [4–7]. The more recent critical reviews [4, 7] utilize a classification system of the published case reports based on the level of evidence for each drug implicated as causing acute pancreatitis. Both of these reviews describe the best evidence of a particular drug causing acute pancreatitis if there is a either a positive rechallenge, a larger number of case reports for a particular drug and/or a consistent latency among the reports for a particular drug. A positive rechallenge is where the drug is stopped after a patient is found to have acute pancreatitis. After resolution of the pancreatitis, when the drug is restarted, acute pancreatitis develops again. This finding typically is reported as the clinicians caring for the patient made an error and did not blame the drug for causing acute pancreatitis. Despite a lack of a rechallenge, a drug may also be strongly suspected if there is a consistent latency among the case reports between initiating the drug and the onset of acute pancreatitis. A consistent latency may be a sign that the drug has a common mechanism of action. The Class I drugs, those with the most evidence causing acute pancreatitis, include mesalamine, amiodarone, S. Tenner (&) Medical Education and Research, Division of Gastroenterology, Maimonides Medical Center, Department of Medicine, State University of New York-Health Sciences Center, 2211 Emmons Ave, Brooklyn, NY 11235, USA e-mail: DrTenner@BrooklynGI.com