JOURNAL OF THE LOUISIANA STATE MEDICAL SOCIETY
Fosphenytoin Induced Toxic Epidermal Necrosis After Traumatic Brain Injury
Karen George, MD, Hollis O'Neal, Jr., MD, Terrell Caffery, MD, Joel Mosley, MD, Jefferey Littleton, MD, Mandi Musso, PH.D
Background: Primary seizure prophylaxis currently carries a level II recommendation from the brain trauma foundation. We present a case of toxic epidermal necrolysis following seizure prophylaxis with fosphenytoin, illustrating the potential risks of this protocol. Case Report: We present a case of an individual treated with fosphenytoin for seizure prophylaxis following a traumatic brain injury. The patient developed toxic epidermal necrolysis and subsequent complications including sepsis, hypotension, and acute respiratory distress syndrome. Conclusion: While it is common practice to give seizure prophylaxis for the first week after severe traumatic brain injury, recent research reports that primary seizure prophylaxis may not provide any benefit in decreasing early post-traumatic seizures and may be associated with worse outcomes. Seizure prophylaxis after seven days is not recommended by the BrainTrauma Foundation but is often prescribed by physicians. This case reports highlights the potential for severe adverse events, questioning the utility of seizure prophylaxis.
INTRODUCTION
epidermal necrosis and detachment that affects the mucous membranes, SJS involves <10% body surface area, TEN involves >30%, and 10-30% surface area detachment is considered SJS-TEN overlap. The incidence of TEN is approximately 1-2 cases per million, 11 and varies slightly depending on regional prescribing habits. 12 A higher association has been noted in certain populations with immunodeficiencies and genetic susceptibilities. 13,14 Most notably, the presence of the human leukocyte antigen HLA-B*1502 in Han Chinese is associated with the risk of SJS/TEN in those given certain AEDs. 14 While these reactions are rare, they are potentially fatal, with mortality rates as high as 12% for SJS and 49% with TEN. 15 While fosphenytoin is believed to have the same pharmacologic and toxicologic effects as phenytoin, 7 it is important to investigate the safety and utility of the prodrug, and it is important to bemindful of both the prodrug and the active drug. On their website, the FDA lists similar warnings for fosphenytoin as phenytoin. 9 However, to the best of our knowledge, this case report is the first to illustrate TEN as a result of primary seizure prophylaxis with fosphenytoin (Cerebyx). In the discussion, safety of fosphenytoin for seizure prophylaxis is reviewed.
Phenytoin is an anticonvulsant medication used in the treatment of tonic-clonic status epilepticus and to treat or prevent seizures after neurosurgery. 1 There is mixed evidence regarding the use of phenytoin for primary seizure prophylaxis in patients with traumatic brain injury; 2-5 however, the Brain Trauma Foundation has issued a level II recommendation for the use antiepileptic drugs in seizure prophylaxis for the first seven days after a traumatic brain injury. 6 Phenytoin has poor solubility in water and requires a high pH when injected, which cause a number of problems during intravenous administration including pain, soft tissue injury, and in some instances, cardiovascular collapse. 7 In 1996, the Food and Drug Administration (FDA) approved the use of fosphenytoin (Cerebyx), a phenytoin prodrug, as an anticonvulsant. Fosphenytoin is believed to be completely and rapidly converted into phenytoin, but infusion site pain is better tolerated 7 and there is a lower risk of cardiovascular complications. 8 Phenytoin has been associated with numerous side effects and potentially adverse outcomes. The FDA has issued warnings of infusion-related hypotension, drug reaction with eosinophilia and systemic symptoms (DRESS)/Multiorgan Hypersensitivity, local toxicity such as Purple Glove Syndrome, and serious dermatologic reactions. 9 Of interest to the current case, aromatic anticonvulsants have been associated with Stevens Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN). 10 SJS and TEN are part of the spectrum of T-cell mediated drug hypersensitivity reactions. 11 While both reactions involve
CASE REPORT
A 54-year-old Chinese male with no past medical history and on no medications presented to an outside hospital with a head injury after a slip and fall on a patch of ice. On initial
J La State Med Soc VOL 169 SEPTEMBER/OCTOBER 2017 119
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