与吕弗勒综合征相关的苯妥英钠相关性免疫缺陷

Lazoglu A H, Boglioli L R, Dorsett B, Macris N T

Department of Medicine, Lenox Hill Hospital, New York, New York, USA.

Ann Allergy Asthma Immunol. 1995 Jun;74(6):479-82.

BACKGROUND

Phenytoin is one of the most commonly prescribed drugs in the United States. Its use is associated with a myriad of adverse reactions, including: eosinophilia, selective IgA deficiency and panhypogammaglobulinemia, pseudolymphoma, Stevens-Johnson syndrome, and interstitial pneumonia.

OBJECTIVE

To report a case of immunodeficiency manifest by panhypogammaglobulinemia and a low helper-to-suppressor ratio secondary to phenytoin crossreactivity with phenobarbital and carbamazepine complicated by hepatotoxicity, eosinophilia, and fleeting pulmonary infiltrates.

METHODS

Case report; immunoglobulin levels, T and B cell studies, and radiologic evaluation of patient.

RESULTS

A 37-year-old Oriental female taking phenytoin and phenobarbital for seizure prophylaxis after resection of a grade IV astrocytoma of the left frontal lobe, developed a rash, elevated liver function tests, and cervical lymphadenopathy with parotid gland enlargement. The abnormalities resolved with discontinuation of the drugs and the patient was discharged on carbamazepine. Eight weeks later the patient was readmitted with fever, slowed mentation, elevated liver function tests, and panhypogammaglobulinemia. Clonazepam was substituted for carbamazepine and the patient subsequently developed a rash and further elevation of her liver function tests. The clonazepam was discontinued and the patient was treated with methylprednisolone. She subsequently developed Loeffler's syndrome and a T cell deficiency with a decreased helper-to-suppressor cell ratio. She was treated with increased doses of methylprednisolone and granulocyte stimulating factor with complete resolution of her symptoms.

CONCLUSIONS

Phenytoin is associated with a myriad of side effects, including, rash, eosinophilia, panhypogammaglobulinemia, pseudolymphoma, Stevens-Johnson syndrome, immunosuppression in brain tumor patients, and rarely, pulmonary complications such as Loeffler's syndrome. Cross-reactivity with other anticonvulsant agents capable of forming arene oxide intermediates occurs in the cytochrome P-450 system.

背景

苯妥英是美国最常用的处方药之一。其使用与多种不良反应相关，包括：嗜酸性粒细胞增多、选择性IgA缺乏和全丙种球蛋白低下血症、假性淋巴瘤、史蒂文斯 - 约翰逊综合征以及间质性肺炎。

目的

报告一例免疫缺陷病例，该病例表现为全丙种球蛋白低下血症以及由于苯妥英与苯巴比妥和卡马西平交叉反应继发的辅助性T细胞与抑制性T细胞比例降低，并伴有肝毒性、嗜酸性粒细胞增多和短暂性肺部浸润。

方法

病例报告；对患者进行免疫球蛋白水平、T细胞和B细胞研究以及放射学评估。

结果

一名37岁的东方女性，在左额叶IV级星形细胞瘤切除术后服用苯妥英和苯巴比妥预防癫痫发作，出现皮疹、肝功能检查结果升高以及伴有腮腺肿大的颈部淋巴结病。停药后异常情况消失，患者出院时服用卡马西平。八周后患者因发热、精神状态迟缓、肝功能检查结果升高和全丙种球蛋白低下血症再次入院。用氯硝西泮替代卡马西平，随后患者出现皮疹且肝功能检查结果进一步升高。氯硝西泮停药，患者接受甲泼尼龙治疗。随后她出现吕弗勒综合征和T细胞缺陷，辅助性T细胞与抑制性T细胞比例降低。她接受了加大剂量的甲泼尼龙和粒细胞刺激因子治疗，症状完全缓解。