Clozapine-Induced Peripheral and Pleural Fluid Eosinophilia

OBJECTIVE: To present a case of clozapine-induced peripheral and pleural fluid eosinophilia (PFE). CASE SUMMARY: A 28-year-old man who was taking clozapine for bipolar disorder presented with a 2-week history of increasing shortness of breath. A large right-sided pleural effusion was identified, and eosinophilia was noted in peripheral and pleural fluid. An extensive workup ruled out other etiologies of PFE, and an objective causality assessment revealed that an adverse reaction to clozapine was probable. Clozapine was discontinued and the patient had complete resolution of symptoms, peripheral eosinophilia, and pleural effusion. DISCUSSION: Drug-induced pleural disease is uncommon. Nearly 30 drugs have been implicated as causation of pleural disease. Much less common is PFE, with only 8 drugs implicated since 2004. Clozapine is a second-generation antipsychotic approved for treatment of resistant schizophrenia. It is often also used to treat bipolar disorder. Common adverse effects include tachycardia, somnolence, weight gain, and sialorrhea. Uncommon adverse reactions include pancreatitis and agranulocytosis. Through 2009, 11 cases of clozapine-induced pleural effusion, with and without polyserositis, have been reported; however, pleural fluid studies to demonstrate eosinophilia have not been done. CONCLUSIONS: To our knowledge, this is the first documented report of clozapine-induced peripheral eosinophilia and PFE. Clinicians should consider clozapine as a possible cause of these reactions.