Pleurisy and bilateral pleural effusions after administration of atorvastatin
Atorvastatin is a commonly prescribed statin used to lower cholesterol. It works by inhibiting HMGCoA reductase and increasing the expression of low-density lipoprotein (LDL) receptors in the liver. This, in turn, leads to a reduction in LDL serum levels and a significant decrease in cardiovascular mortality.[1-3] The most common side effects of atorvastatin include muscle pain, myopathy, rhabdomyolysis, and elevations of hepatic enzyme.[4-6] We report only the second case of atorvastatin-induced pleural effusions, presenting as pleurisy, and the first case from Ethiopia. Informed written consent was taken from the patient to use the clinical data for this case presentation.
A 68-year-old healthy male visited his primary care physician for a routine office visit. He had no history of hypertension, diabetes, or tobacco use. His physical examination and baseline laboratories including renal and liver function were all normal. His lipid profile showed the following: Serum cholesterol: 167 mg/dl (<200 mg/dl), HDL: 43 mg/dl (>60 mg/dl), and LDL: 118 mg/dl (<130 mg/dl). Despite these results, he was started on atorvastatin 40 mg once daily.
Two weeks after initiation of treatment, he developed left-sided and then subsequent right-sided pleuritic chest pain. He had no fever, chills, pharyngitis, rhinorrhea, cough, or dyspnea. He returned to his primary care physician who obtained a normal CBC; a CXR at the time showed a moderate sized left-sided pleural effusion [Figure 1].
The patient was then referred to a pulmonologist for further evaluation. A chest CT was obtained and revealed bilateral pleural effusions, left greater than right, with no other abnormalities.
Other laboratory investigations included a normal echocardiogram and negative ANA and RF. Left-sided thoracentesis was performed and the pleural fluid was found to be a lymphocytic transudate with negative cytology, Gram stain, and GeneXpert testing.
Despite the above investigations, the exact cause of the pleural effusions was not identified. The possibility of atorvastatin-induced pleurisy/pleural effusions was considered and the drug was discontinued. His bilateral pleuritic chest pain subsided after 1 week and a repeat CXR 1 month later showed significantly reductions in the bilateral pleural effusions. After 3 months, repeat CXR and chest ultrasound were both normal [Figure 2].
We report only the second case of atorvastatin-induced pleural effusions, presenting as pleurisy, and the first case from Ethiopia. We believe our patient had this association based on the temporal onset of symptoms, the otherwise negative evaluation, and the resolution of findings once atorvastatin was discontinued.
In general, drug-induced pleural reactions may occur in the absence of parenchymal lung disease and usually manifest as pleurisy and pleural effusions. The pathologic mechanism remains unknown, but hypersensitivity, oxidative stress of the mesothelial cells, fluid retention, and chemical inflammation have all been postulated.[8,9] To make the diagnosis, clinicians should meticulously review medication use and inquire about a temporal relationship between drug exposure and symptoms. Resolution of symptoms after drug discontinuation, reappearance after drug reuse, and evidence of pleural fluid eosinophilia help to confirm the diagnosis. Treatment is two-fold: Drainage of the pleural fluid to relieve dyspnea and discontinuation of the offending drug. Rarely, corticosteroid administration is required.
Clinicians need to consider the relationship between atorvastatin and pleural effusions, presenting as pleurisy, when evaluating patients with unexplained pleural disease.