Etoposide-induced posterior reversible encephalopathy syndrome

Abstract

Dear Editor, Posterior reversible encephalopathy syndrome (PRES) is an uncommon but distinct neurological condition recognized by characteristic clinical and radiological findings [1]. The clinical manifestation ranges from headache to severe encephalopathy [2]. It is associated with various conditions including hypertension, preeclampsia/eclampsia, cytotoxic therapies, and sepsis [1]. We report on a patient who developed PRES after treatment with etoposide for secondary hemophagocytic lymphohistiocytosis. A 22-year-old previously healthy Caucasian male initially presented to the emergency roomwith a 5-day history of flu-like illness, sore throat, nausea, vomiting, and diarrhea. He acutely decompensated and developed hypovolemic shock. His physical examination revealed splenomegaly, peripheral edema, and diffuse maculopapular skin rash. Laboratory evaluation showed pancytopenia and transaminitis. His serological studies were positive for acute Epstein–Barr virus infection. Given his unexplained pancytopenia, a bone marrow biopsy was performed that revealed hemophagocytic lymphohistiocytosis (HLH) with no evidence of concurrent lymphoma or leukemia. Further evaluation with serum IL-2 levels and NK cell activity assays was consistent with a diagnosis of secondary HLH. He was started on therapy with etoposide and improved clinically. However, within a week, he started complaining of generalized severe headache and developed hypertensive urgency. He also developed cortical blindness. The neurological workup was unremarkable other than the blindness, and imaging with MRI revealed findings consistent with PRES with vasogenic edema and noncommunicating hydrocephalus (Fig. 1a, b). Despite his cytopenias, an emergent ventriculostomy with ventriculoperitoneal (VP) shunting was performed.With continued supportive therapy, our patient completely recovered his visual function after 3 weeks. A follow-up MRI showed complete resolution of the cerebral abnormalities. Since etoposide was thought to be a causative agent, further therapy was withheld. His HLH and cytopenias also resolved completely and he continues to do well with no evidence of disease 1 year later. Patient was on other medications, besides etoposide during the treatment course, which are: micafungin, acyclovir, calcitriol, insulin (Lantus), lansoprazole, levofloxacin, cefepime, vancomycin, cotrimoxazole, atovaquone, and methotrexate (intrathecal). Some of the chemotherapeutic agents that have been reported to be associated with PRES are cyclosporin, tacrolimus, methotrexate, cisplatin, cytarabine, vincristine, bevacizumab, and dexamethasone [1, 3, 4, 5]. Our patient presented with PRES within a week of starting therapy with etoposide for the treatment of his HLH. Patient received P. Khanal (*) : F. Awan :V. Nguyen Georgia Health Science University, Augusta, GA, USA e-mail: docpkhanal@gmail.com