PDF(Pubmed)
Abstract：
Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine (Phe) metabolism, resulting from the deficient activity of phenylalanine hydroxylase that converts Phe to tyrosine in the liver, leading to elevated levels of Phe. Pegvaliase is an innovative and effective enzyme replacement therapy for reducing Phe concentration, but it has been associated with severe drug-induced hypersensitivity adverse events (HAEs). Limited data is available on the management of these HAEs, thus, we aimed to present a case report of a successful management strategy. The patient was a 28-year-old Caucasian male with classical PKU, who was otherwise healthy. Due to poor metabolic control, the pegvaliase treatment was initiated. The titration phase was uneventful, with transient and mild side effects, localized to the injection site. After the patient was on a maintenance dose of pegvaliase and had no reactions to the drug, we discontinued the H1-antihistamine. In the following days, within minutes after receiving the pegvaliase injection, an acute hypersensitivity reaction occurred that required emergency treatment. H1-antihistamine treatment was reintroduced. Four days after the incident he received pegvaliase under medical supervision and did not experience any symptoms. In conclusion, cautious reintroduction of pegvaliase in a hospital setting can be safely performed after HAE due to the discontinuation of H1-antihistamines. HAEs could be successfully mitigated by scheduling daily antihistamines administration closer to the pegvaliase injection. This approach can enable PKU patients to maintain their access to an effective and quality-of-life-improving therapy.
摘要：
苯丙酮尿症（PKU）是一种常染色体隐性遗传性先天性苯丙氨酸（Phe）代谢错误，由于苯丙氨酸羟化酶的活性不足，在肝脏中将Phe转化为酪氨酸，导致Phe水平升高。Pegvaliase是一种创新和有效的酶替代疗法，用于降低Phe浓度，但它与严重的药物诱导的超敏反应不良事件(HAEs)相关.有关这些HAE的管理的数据有限，因此，我们的目的是提出一个成功的管理策略的案例报告。患者是一名28岁的白人男性，患有典型的PKU，本来健康的人。由于代谢控制不佳,开始了聚乙二醇酶治疗.滴定阶段平安无事,有短暂和轻微的副作用，定位到注射部位。在患者服用维持剂量的pegvalidase并且对药物没有反应后，我们停止了H1-抗组胺药.在接下来的日子里,在接受pegvaliase注射后几分钟内，发生急性超敏反应，需要紧急治疗。重新引入H1-抗组胺治疗。事件发生四天后，他在医疗监督下接受了pegvaliase，没有任何症状。总之,由于H1-抗组胺药的停药,HAE后可安全地在医院环境中谨慎重新引入pegvaliase.HAE可以通过安排每日抗组胺药给药更接近聚乙二醇戊酶注射来成功缓解。这种方法可以使PKU患者保持获得有效和改善生活质量的治疗。
