Azacitidine-associated hyperthermia and interstitial pneumonitis in a patient with myelodysplastic syndrome

The DNA hypomethylating agent azacitidine was approved by the United States Food and Drug Administration after the drug demonstrated superiority over the best supportive care for treatment of myelodysplastic syndrome in patients unable to undergo stem cell transplantation. Mild adverse reactions, both hematologic and nonhematologic, are not uncommon; however, severe adverse effects are rare. We describe a 55-year-old woman who was treated with azacitidine for myelodysplastic syndrome and experienced hyperthermia that was not attributable to other causes. The patient's treatment course was further complicated by interstitial pneumonitis and hypoxic respiratory failure that ultimately led to acute respiratory distress syndrome. Hyperthermia develops when discord occurs between metabolic heat production and heat dissipation. The process of temperature regulation can be altered by drugs such as succinylcholine, phenothiazines, monoamine oxidase inhibitors, atropine, benztropine, antihistamines, cocaine, Ecstasy, amphetamines, and haloperidol. The hyperthermia in this patient was refractory to antipyretic therapy and was not due to other drug-induced hyperthermic syndromes. She eventually responded to high-dose methylprednisolone. The Naranjo adverse drug reaction probability scale score indicated that the association between azacitidine and hyperthermia was probable. Clinicians should be aware of this rare, severe, potential adverse effect of azacitidine.