Dupuy O, Flocard F, Vial C, Rode G, Charles N, Boisson D, Flechaire A
Service de médecine interne, HIA Desgenettes, Lyon, France.
Rev Med Interne. 1995;16(1):67-72. doi: 10.1016/0248-8663(96)80667-9.
Prescribed since 1948 to control chronic alcoholism, disulfiram may cause severe toxicity as report in three cases of acute motive axonal polyneuritis. Disulfiram toxicity may present different clinical aspects: 1) Cytolytic hepatitis with fatal evolution in 30% of cases (fulminant hepatitis), and full recovery for the other 70%. The onset of the symptoms usually occurs as early as 15 days to a maximum of 6 months (most within 2 months) after initiation of treatment. 2) Severe optic neuritis with full recovery in 2 months. 3) Peripheral neuropathy usually dose dependent, with different clinical presentations: polyneuritis with sensory, motor, or both deficits, and few cases of tetraplegia. 4) Encephalopathy frequently associated with one of the precedent symptoms, having a favorable outcome (probably resulting in inhibition of dopamine-beta-hydroxylase by disulfiram). The mechanism of toxicity (direct or idiosyncractic) remain unclear. Disulfiram has been used safely in millions of people since 1948, and we have only few cases reports of severe toxicity. From a practical point of view, treated patients should benefit by a neurological examination once a month, ophtalmological examination every 2 months, and hepatic enzymes monitored twice a month during the 2 first months. This is the price to prevent and to detect side effects of disulfiram therapy.
自1948年以来,双硫仑一直被用于控制慢性酒精中毒,但据报道,在三例急性运动性轴索性多神经炎病例中,它可能会导致严重毒性。双硫仑毒性可能呈现不同的临床症状:1)细胞溶解性肝炎,30%的病例会发展为致命性肝炎(暴发性肝炎),其余70%可完全康复。症状通常在治疗开始后最早15天至最长6个月(大多数在2个月内)出现。2)严重视神经炎,2个月内可完全康复。3)周围神经病变通常与剂量有关,有不同的临床表现:感觉、运动或两者均有缺陷的多神经炎,以及少数四肢瘫痪病例。4)脑病常与上述症状之一相关,预后良好(可能是双硫仑抑制了多巴胺-β-羟化酶所致)。毒性机制(直接或特异质性)尚不清楚。自1948年以来,数百万患者安全使用了双硫仑,我们仅有少数严重毒性的病例报告。从实际角度来看,接受治疗的患者应每月进行一次神经学检查,每2个月进行一次眼科检查,并在最初2个月内每月监测两次肝酶。这是预防和检测双硫仑治疗副作用的代价。