Mathelier-Fusade P, Leynadier F
Service Médecine interne, Hôpital Rothschild, Paris.
Presse Med. 1993 Oct 2;22(29):1363-5.
Intolerance to sulfonamides is very frequent in HIV-infected subjects and 10 times more common than in the general population. There are 2 types of intolerance to sulfonamides: early reactions with urticaria or angioedema, which are IgE-dependent, and late reactions with febrile rash, which occur between the 6th and 12th days of treatment and represent the vast majority of allergic manifestations in HIV-infected subjects. Clinically, these reactions resemble serum sickness, but all physiopathological hypotheses point to toxic process. The degradation of sulfonamides has two different pathways: the N-acetylation pathway which is genetically determined and saturable, and the cytochrome P450 pathway which produces toxic hydroxylamine metabolites "detoxified" by glutathione. In HIV-infected subjects detoxication is thought to be incomplete due to an acquired deficiency of glutathione and probably increased in the presence of a slow acetylation profile.
在HIV感染患者中,对磺胺类药物不耐受的情况非常常见,其发生率比普通人群高10倍。磺胺类药物不耐受有两种类型:一种是早期反应,表现为荨麻疹或血管性水肿,属于IgE依赖型;另一种是晚期反应,表现为发热性皮疹,发生在治疗的第6至12天,是HIV感染患者中绝大多数过敏表现的类型。临床上,这些反应类似于血清病,但所有生理病理假说都指向毒性过程。磺胺类药物的降解有两条不同途径:一条是由基因决定且可饱和的N - 乙酰化途径,另一条是细胞色素P450途径,该途径产生的有毒羟胺代谢产物由谷胱甘肽“解毒”。在HIV感染患者中,由于获得性谷胱甘肽缺乏,解毒过程被认为是不完全的,而且在慢乙酰化型存在时可能会增强。