Pathophysiological aspects of dacarbazine-induced human liver damage

Hepatic Veno-occlusive Disease (VOD) and Budd Chiari syndrome (BCS) have been reported as fatal complications of Dacarbazine therapy. Peripheral eosinophilia and eosinophilic infiltrates after repeated Dacarbazine therapy in some cases were interpreted as evidence of an allergic drug reaction. Since no mention of an allergic drug reaction is to be found in other reports on veno-occlusive disease or Budd Chiari syndrome due to Dacarbazine, the pathophysiological mechanism of these fatal complications of Dacarbazine remain to be elucidated. We describe a case of VOD due to Dacarbazine which showed peripheral eosinophilia after the first cycle of Dacarbazine treatment with no prior possibility of sensibilization, along with signs of a toxic drug reaction. This observation suggests that peripheral eosinophilia, so far interpreted as a sign of an allergic reaction induced by Dacarbazine, can be observed together with obvious signs of toxic drug reaction, thus providing further evidence of a toxic mechanism of Dacarbazine-induced VOD or BCS.