IDIOSYNCRATIC NEUROTOXICITY: CLiOOUINOL AND BISMUTH

During the 1960's there were 1000·2000 cases of subacute myelo-optic neuropathy (SMON) a y~r djagnosed in Japan, but from 1935 to 1977 there were only 10 c2ses with full features and II with some featuresofSMON reported in the rest of the world. This unusual distribution of thedisease has not been explained but studies in Japan have implicated clioquinol. Two variants of SMON have been noted. Some patients w'ho present with acu~ eocephaJopathy and features of globaJ amnesia have only taken c.lioquinol for I day. All patients reoover when the drug is stopped. The other variant is optic atrophy which occurs in children with acrodermatitis enteropathica ~hen they have taken high doses of cli9Quinol for a long time. The green discoloration of the tongue seen in pat~nts with Sl\:1PN strongly. suggests an association with cJiQquinol but the poor correlation between the consumption of the drug and the distribution o(the disease remains to be explained. Perhaps S9me other factors influence the toxicity of clioquinol in certain people. It is unlikely ~hat these include genetic influen~. Similarities exist between clioquinol as a cause ofS~ON and a d,sease recently recogniZ;ed in Australia and France - bismuth encephalopathy. The disease exists where overall bismuth consumption is high but there is no correlation between the intake in individuals and development of the disease. However·, unlike SMON, the severity of disease correlates well with high blood le.vels of bismuth. The reason for the raised blood levels in some individuals still remains a mystery, as does the mechanism of absorption of the insoluble bismuth salts. 'It is hard enough to recognise that a drug itself sometimes has unpleasant side-effects; and even harder to detect toxicity whtch depends on some additional variabte.' Edilorial: LaRCel I : IIS7 (19 Apr 19110)

6 lNPHARMA 17 May 1980 0156-2703/80/0517-0006 $00.50/ 0 C ADIS Press