Valproic acid

Shaib FH, MD; Patel B, MD--Division of Pulmonary and Critical Care Medicine, University of Texas Health Sciences Center, Houston

Introduction: Drug induced pulmonary disease and especially pleural effusions are well documented in the literature. Pleural effusions secondary to drugs are frequently eosinophilic, and usually occur within days to years of institution of therapy. Only one case of Valproic acid induced eosinophilic pleural effusion with peripheral eosinophilia has been reported (l). We report a case of bilateral eosinophilic pleural effusions secondary to valproic acid with no peripheral eosinophilia.

Case Presentation: A 38 year old man with a history of seizure disorder and schizophrenia was admitted to our hospital for evaluation of bilateral pleural effusions. He resides in an institution for the mentally ill. He has no known exposure to tuberculosis and has had negative yearly Tuberculin skin tests. The patient demonstrated no symptoms, signs, or laboratory data suggestive of an infectious process. There is no history of trauma or prior thoracentesis. He was on multiple antiepileptic medications including Valproic acid. Laboratory data revealed a normal white blood cell (WBC) count with a normal differential and no peripheral eosinophilia. The chest radiograph (CXR) revealed large bilateral pleural effusions that layered freely. The CXR obtained 11 months prior to presentation was normal and another at 4 months prior to presentation revealed a moderate new right-sided pleural effusion. Computed tomography scan of the chest showed large bilateral pleural effusions and absence of parenchymal and mediastinal abnormalities. The patient underwent a left thoracentesis revealing an exudate with 45% eosinophils (table 1). Thoracentesis and a pleural biopsy were performed on the right side. The fluid showed similar characteristics with 67% eosinophils. The biopsy demonstrated lymphoplasmacytic infiltrate within the pleura and adipose tissue and multiple eosinophils within the mesothelial lining. No granulomas or tumors were identified. The bacterial, fungal, and mycobacterial cultures and PCR on the pleural fluid and biopsy were negative after 8 weeks. Valproic acid was suspected as the etiology of the pleural effusions and consequently discontinued. A marked decrease in the effusions were noted with only minimal blunting of both costophrenic angles on the CXR at 3 weeks and a complete resolution of the pleural fluid at 10 weeks.

Table 1--Characteristics of the Pleural Fluid

Discussion: Air and blood in the pleural space are the most common causes of eosinophilic pleural effusions. Other causes include malignant and infectious processes. Drugs should always be considered in the differential of eosinophilic pleural effusions. In this case, the absence of other causes for the eosinophilic pleural effusion and its complete resolution after withdrawal of valproic acid supports a causative relationship of this drug with the development of the pleural effusions. This is the second case reported of an eosinophilic pleural effusion secondary to valproic acid, and the first case report where the patient had no associated peripheral eosinophilia.

Conclusion: Valproic acid must be included in the list of drugs causing eosinophilic pleural effusions with or without peripheral eosinophilia.

References

(1) Kaufman J, O'Shaughnessy IM. Eosinophilic pleural effusion associated with valproic acid administration. South Med J 1995 Aug: 88(8): 888-2

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