Ever-increasing diversity of drug-induced pancreatitis

Abstract

With over 100000 hospital admissions per annum, acute pancreatitis remains the leading gastrointestinal cause of hospitalization in the United States and has far-reaching impact well beyond. It has become increasingly recognized that drug-induced pancreatitis (DIP), despite accounting for less than 3% of all cases, represents an important and growing though often inconspicuous cause of acute pancreatitis. Nevertheless, knowledge of DIP is often curtailed by the limited availability of evidence needed to implicate given agents, especially for non-prescription medications. Indeed, the majority of available data is derived from case reports, case series, or case control studies. Furthermore, the mechanism of injury and causality for many of these drugs remain elusive as a definitive correlation is generally not established (< 10% of cases). Several classification systems have been proposed, but no single system has been widely adopted, and periodic updates are required in light of ongoing pharmacologic expansion. Moreover, infrequently prescribed medications or those available over-the-counter (including herbal and other alternative remedies) are often overlooked as a potential culprit of acute pancreatitis. Herein, we review the ever-increasing diversity of DIP and the potential mechanisms of injury with the goal of raising awareness regarding the nature and magnitude of this entity. We believe this manuscript will aid in increasing both primary and secondary prevention of DIP, thus ultimately facilitating more expedient diagnosis and a decrease in DIP-related morbidity.

Keywords: Acute pancreatitis; Drug-induced pancreatitis; Etiology; Inflammation; Mechanism of action; Pharmacology.

Figure 1

Flow diagram to help identify the potential cause of acute pancreatitis, including cases of drug-induced pancreatitis. ERCP: Endoscopic retrograde cholangiopancreatography; FDA: Food and Drug Administration.

Figure 2

The Naranjo adverse drug reaction probability scale[17].

Figure 3

Proposed drug-induced pancreatitis probability assessment scale in which a total summative score of > 9: highly probable, 6-8: probable, 3-5: possible, and ≤ 2: doubtful. ERCP: Endoscopic retrograde cholangiopancreatography; EUS: Endoscopic ultrasound; MRCP: Magnetic resonance cholangiopancreatography.

Figure 4

The proposed mechanisms leading to pancreatic insult in drug-induced pancreatitis.