History of Drug-induced SMON

Around 1955, patients appeared complaining of loss of sensation or numbness in the feet after the gastro intistional disorder. Many patients also complained of impaired vision and difficulty in ambulation due to paralysis in the lower limbs. Thus, it became a social problem of a rare disease with an unknown cause.

Around 1957, large outbreaks occurred in various regions around Japan, suggesting it was a contagious disease. As a polio epidemic occurred from 1960 to 1961, it was sometimes called “adult polio.” A virus was suspected as the cause, and the discoveries of SMON virus were reported (but not proven in an additional study), which was picked up by the mass media. Since SMON was considered a contagious disease, patients were discriminated against and often suffered in society.

In June 1970, the true cause was revealed. SMON patients would sometimes experience a greenish tongue, stool, and urine, and an analysis of the green urine crystals revealed that the green substance was chinoform.

Chinoform was commonly used as an antiflatulent at that time. In August 1970, investigation results indicated that all SMON patients had been administered chinoform. SMON occurred earlier and was more severe in patients given a higher dose. Based on those findings, the Ministry of Health and Welfare made the decision to ban the use of chinoform at the Central Pharmaceutical Affairs Council held on September 7. After taking measures to discontinue marketing and suspend use of the drug, occurrences of SMON after September rapidly decreased, and are no longer found.

Chinoform (clioquinol) was developed as a bactericidal topical drug in Switzerland in 1899. It had been used as an oral medicine for intestinal sterilization since 1920s as it was assumed to not be absorbed through the intestines. However, a suspected case of SMON was found in 1935 in Argentina, so Switzerland designated chinoform as a deleterious substance. The Japanese government followed suit. However, the deleterious substance designation was cancelled in Japan in 1939, and production of the drug was expanded for the use in the army.

Japan was in a chaotic situation immediately after the World War II, so the Pharmaceutical Affairs Council of the Ministry of Health and Welfare simultaneously approved all drugs listed in both domestic and foreign pharmacopeias. Some indications were added for chinoform, and an increase of dose was also approved. The dose had been increased after establishment of a national system for public health insurance in 1961, and many over-the-counter products contained chinoform. There were 186 products containing chinoform, making it difficult to identify the cause of SMON. While chinoform was assumed not to be taken into the body, it was actually absorbed through the intestines, where it invaded nerve tissue, resulting in the onset of SMON. The onset of SMON was also confirmed by administering chinoform to dogs, experimentally.

Since chinoform was identified as a cause of SMON, anger grew among patients who had been treated as having a rare curious disease of unknown cause or a contagious disease. A liability suit was filed against the pharmaceutical company manufacturing and marketing chinoform and the government, which had approved its use. About 11,000 patients were identified as having SMON, and a reconciliation was reached in 1979 after the lawsuit had gone on for years, with the condition that the cause of SMON would be investigated and that permanent measures for patients would be taken.

For permanent measures, it was decided to investigate the causes of SMON, develop treatment methods, ensure outcomes through health check-ups and other means, and conduct health management. That work has been taken over by the Research Committee on SMON, organized by MHLW’s Research on Intractable Diseases Policy.

Research Committee on SMON: Research representative:
Masaaki Konagaya, Director, NHO Suzuka National Hospital
3-2-1 Kasado, Suzuka-shi, Mie-ken, 513-8501
Phone: +81-59-378-1321