Assessing the risk of immunosuppressive treatments

Progressive Multifocal Leukoencephalopathy (PML) is a rare and often fatal opportunistic demyelinating disorder secondary to central nervous system infection by the polyomavirus John Cunningham (JC), a common infecting agent in human populations, with 50–70% of healthy individuals having antibodies to the virus. Although human immunodeficiency virus (HIV) infection remains the most common predisposing factor for PML, which can occur also in association with hematologic malignant neoplasms or iatrogenic immunosuppression in the setting of organ transplantations, recently JC virus has been recognized as an important pathogen in patients with autoimmune and rheumatic diseases receiving immunosuppressive treatments. Following the availability of new biologic drugs, additional cases of PML have been reported in dermatologic patients as well. In particular, the occurrence of PML in psoriatic patients who had been taking efalizumab in the absence of any other concurrent immunosuppressive agents resulted in the decision of European Medicine Agency (EMEA) in February 2009 to recommend suspension of the marketing authorization for this drug in Europe. Some months later the manufacturer of the drug decided to voluntarily withdraw the product from the U.S. market. Since PML can occur as a potential side effect of different immunosuppressive drugs, including conventional treatments for psoriasis, and in consideration of the future development of new immunosuppressive biological agents, dermatologists need to become familiar with opportunistic infections including PML.