Atorvastatin-Associated Acute Pancreatitis: A Case Report

Introduction

Acute pancreatitis (AP) is a severe inflammatory condition caused by the premature activation of digestive enzymes within the pancreas, leading to autodigestion and tissue inflammation [1]. It is one of the leading causes of gastrointestinal hospitalizations in the United States, with an incidence of approximately 210 000 cases annually [2]. The clinical presentation of AP varies widely, ranging from mild inflammation to severe necrotizing pancreatitis associated with systemic organ failure and high mortality rates [1]. The most common causes of AP include gallstones, alcohol consumption, and hypertriglyceridemia. However, drug-induced pancreatitis (DIP) is a rare cause, accounting for less than 2% of cases [3].

From 2015 to 2017, 17 730 adverse drug reactions (ADRs) were reported in Saudi Arabia, with 11.11% being cardiovascular-related. Atorvastatin accounted for 9.7% of these ADRs, including muscle pain, fatigue, elevated liver enzymes, and increased bilirubin [4].

Statins, commonly used for hyperlipidemia, lower serum cholesterol and cardiovascular risk by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase. In 2018–2019, approximately 92 million individuals in the United States used statins [5,6]. The association between statin use and AP remains controversial, requiring further research to establish causality [7,8].

Case Report

INVESTIGATIONS:

The patient underwent a series of diagnostic investigations to determine the cause of acute pancreatitis (AP) and exclude other potential etiologies. An abdominal ultrasound of the liver and biliary tract revealed mild gallbladder wall thickening measuring up to 5.5 mm, which was likely reactive, without evidence of gallstones or pericholecystic fluid. The common bile duct (CBD) was non-dilated, and no biliary dilatation was observed. Laboratory investigations revealed significantly elevated pancreatic enzymes, with amylase at 3273 U/L and lipase at 2503 U/L, consistent with the diagnosis of AP. Liver function tests showed mildly elevated alanine aminotransferase (ALT) at 113 U/L and total bilirubin at 45.8 μmol/L, while alkaline phosphatase and creatinine levels were within normal limits. A lipid profile ruled out hypertriglyceridemia as a cause. Table 1 summarizes the laboratory findings.

TREATMENT AND OUTCOME:

Initial management consisted of supportive care, including hydration with lactated Ringer’s solution at 125 mL/hour and symptomatic treatment with metoclopramide for nausea and paracetamol for analgesia. Atorvastatin was promptly discontinued. The patient was maintained on a low-fat diet and closely monitored for symptom resolution.

During a 2-day hospital stay, pancreatic enzyme levels decreased significantly (lipase: 1147 U/L, amylase: 1733 U/L), and the patient’s abdominal pain improved. He was discharged with prescriptions for paracetamol for residual pain and pantoprazole 40 mg for gastroprotection. At follow-up, he reported complete resolution of symptoms, with no recurrence of AP.

Discussion

A 48-year-old man developed acute pancreatitis (AP) following atorvastatin use, with a Naranjo scale score of 6 (Table 2), indicating a probable adverse drug reaction [9]. The Naranjo scale has been widely utilized in epidemiological studies to assess the probability of adverse drug reactions in AP. For example, a study by Jones et al showed its utility in systematically identifying drug-induced AP cases, ensuring objective and reproducible assessments [1]. This supports its reliability in our case, where atorvastatin was identified as the probable causative agent.

Dyslipidemia, the condition for which the patient was prescribed atorvastatin, is known to be associated with hypertriglyceridemia, a recognized independent risk factor for AP. However, the patient’s triglyceride levels were within normal limits at the time of admission, ruling out hypertriglyceridemia as a potential contributor. This finding reinforces the likelihood that atorvastatin itself was the causative agent in this case.

A literature review reveals that statin-induced AP is not limited to atorvastatin; similar cases involving simvastatin and pravastatin show symptom resolution upon discontinuation, supporting a potential class effect of statins in inducing AP [3,5]. Our case report contributes to this evidence by demonstrating a clear temporal relationship between atorvastatin use and AP onset, along with rigorous exclusion of other etiologies, providing a strong model for diagnosing statin-induced AP.

Our approach emphasizes thorough clinical evaluation and detailed drug history for diagnosing medication-induced AP. Serum lipase and amylase levels rise to at least twice the normal limit upon admission, with lipase, which is more specific than amylase, declining over 7–14 days [8]. Timely intervention with supportive care, including analgesics and hydration, is essential to manage this severe adverse drug reaction [10].

Statins are part of a broader spectrum of medications linked to AP, including azathioprine, hydrochlorothiazide, and metronidazole [11]. According to the Badalov classification system, which ranks drugs inducing AP based on reported cases, re-challenge outcomes, and latency periods, statins are classified as class 3b or 4 [12]. This underscores the need for vigilance and proactive management in patients on statins presenting with unexplained gastrointestinal symptoms.

Conclusions

It is imperative that clinicians become more familiar with statins as a probable cause of acute pancreatitis (AP) and maintain a high index of suspicion in such cases, especially when patients present with AP of unknown etiology. A comprehensive review of the patient’s medication history is essential for identifying any potential links between statin use and the onset of AP symptoms. Furthermore, there is a clear need for prospective studies with large sample sizes to elucidate the exact relationship between statin use and the induction of AP. Such studies will provide deeper insights into the mechanisms by which statins may cause this serious adverse effect and guide the development of more effective management strategies to mitigate risks associated with statin therapy.