Eosinophilic Pleural Effusion Due to Dantrolene: Resolution With Steroid Therapy

South Med J. 2001;94(5) 

In This Article


Eosinophilic pleural effusion is defined as an exudative effusion containing more than 10% eosinophils. Of all pleural exudates, EPE comprises only 1% to 9%, with eosinophilia ranging from 10% to 90%.[6] Many cases are accompanied by peripheral eosinophilia as well. Causes of EPE are diverse and include malignancy, infection (including tuberculosis), air or blood in the pleural space (trauma, pneumothorax, post-thoracotomy), congestive heart failure, cirrhosis, connective tissue disease, hypersensitivity reactions, and medication side effects.[7,8,9,10] Twelve medications have been implicated in EPE, including dantrolene (Dantrium), nitrofurantoin (Macrodantin), bromocriptine (Parlodel), methotrexate (Rheumatrex), methysergide (Sansert), amiodarone (Cordarone), bleomycin (Blenoxane), procarbazine (Matulane), procainamide (Pronestyl), isotretinoin (Accutane), valproic acid (Depakote), and fluoxetine (Prozac).[3,4,11,12,13,14]

Molecular similarities between dantrolene and nitrofurantoin, an antibiotic implicated in pulmonary reactions such as pneumonitis and pleural effusion, provide plausible support for an allergic basis for EPE.[3,4,15,16] Further evidence in support of an allergic etiology for dantrolene-induced EPE includes (1) concomitant peripheral eosinophilia, (2) long-term administration of dantrolene, (3) reduction of symptoms and effusion with drug withdrawal, and (4) lack of an alternative explanation on extensive clinical evaluation.[4] Recurrence of effusion after rechallenge with dantrolene therapy would be powerful evidence for an allergic reaction, but no such cases have been reported.

In the five previously reported cases of dantrolene-associated EPE,[3,4] duration of administration of dantrolene ranged from 2 months to 12 years, with doses from 100 to 400 mg daily. This is consistent with our case, in which 400 mg/day had been prescribed for 5 years. Pleural fluid eosinophilia ranged from 36% to 70% among these five previous cases, similar to the 64% observed in our patient. The most unusual feature of our case was the rapid resolution of symptoms (2 days) and effusion (3 weeks) with steroid therapy, whereas some previous cases were said to resolve "slowly within several months" after medication withdrawal.[3,4] A recent text states that, after offending medication is stopped, most effusions improve "over a period of 6 months."[17] To our knowledge, our case represents the first report of prednisone administration in dantrolene-associated EPE. Recent documentation of biologically active eosinophil-derived proteins in high concentration in pleural fluid from 17 patients with EPE of various causes[18] suggests that inflammation underlies the pathogenesis of EPE. This may in part explain the favorable response to steroid therapy observed in our patient.


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