Smythe M A, Umstead G S
Wayne State University, Detroit, MI.
DICP. 1989 Jan;23(1):13-8. doi: 10.1177/106002808902300102.
Phenytoin hepatotoxicity is a serious idiosyncratic reaction that occurs in less than one percent of patients. The onset of symptoms occurs early in therapy, usually within the first six weeks. Presenting symptoms often include fever, rash, lymphadenopathy, hepatomegaly, anorexia, and myalgias or arthralgias. Other significant findings that may develop throughout hospitalization are jaundice, periorbital or facial edema, and splenomegaly. The following alterations in liver function tests are associated with phenytoin hepatotoxicity: elevations in serum aminotransferases, lactic dehydrogenase, alkaline phosphatase, bilirubin, and prothrombin time. Rechallenges, lymphocyte stimulation test, and liver biopsy have been used to aid in the diagnosis. Rechallenge is the most definitive diagnostic approach; however, its use is limited by the potential of a fatal reaction. Although the exact mechanism of phenytoin hepatotoxicity is unknown, the majority of literature supports a hypersensitivity mechanism. The severity of this adverse effect ranges from self-limiting to fatal. Since 1965 six fatal cases have been reported. To date, sufficient evidence is not available to establish treatment guidelines. Discontinuation of phenytoin therapy is warranted.
苯妥英钠肝毒性是一种严重的特异质性反应，发生率低于1%的患者。症状通常在治疗早期出现，通常在最初六周内。常见症状往往包括发热、皮疹、淋巴结病、肝肿大、厌食以及肌痛或关节痛。在整个住院期间可能出现的其他显著表现有黄疸、眶周或面部水肿以及脾肿大。以下肝功能检查的改变与苯妥英钠肝毒性相关：血清氨基转移酶、乳酸脱氢酶、碱性磷酸酶、胆红素升高以及凝血酶原时间延长。再次用药试验、淋巴细胞刺激试验和肝活检已被用于辅助诊断。再次用药试验是最具决定性的诊断方法；然而，其应用受到致命反应可能性的限制。虽然苯妥英钠肝毒性的确切机制尚不清楚，但大多数文献支持超敏反应机制。这种不良反应的严重程度从自限性到致命不等。自1965年以来已报告了6例致命病例。迄今为止，尚无足够证据制定治疗指南。停用苯妥英钠治疗是必要的。
