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Highly concentrated botulinum preparation for cosmetic injections can result in severe illness

November 22, 2006

An examination of 4 cases of botulism following cosmetic injections to the face indicates that the adults received a highly concentrated, unlicensed preparation that resulted in toxin levels up to 40 times the estimated human lethal dose, according to a report in the November 22/29 issue of JAMA.

Botulism is a rare paralytic illness caused by the toxins of the spore-forming bacterium Clostridium botulinum and toxin-producing strains of Clostridium baratii and Clostridium butyricum. Botulism, left untreated, may result in respiratory failure and death, according to background information in the article. Two botulinum toxin preparations are licensed in the United States by the U.S. Food and Drug Administration for clinical use, BOTOX (crystalline toxin type A); and Myobloc/Neurobloc (toxin type B). Although botulinum toxin A is available by prescription for cosmetic and therapeutic use, no cases of botulism with detectable serum toxin have previously been attributed to cosmetic or therapeutic botulinum toxin injections. On November 27, 2004, four suspected botulism case-patients with a link to cosmetic botulinum toxin injections were reported to the Centers for Disease Control and Prevention.

Daniel S. Chertow, M.D., M.P.H., of the CDC, Atlanta, and colleagues investigated various aspects of the four suspected cases of botulism. They found that clinical characteristics of the four case-patients were consistent with those of naturally occurring botulism. All case-patients had been injected with a highly concentrated, unlicensed preparation of botulinum toxin A, intended for laboratory research, labeled accordingly, and not licensed or intended for human use.

Clinic staff had diluted a 100-µg vial of pure neurotoxin with diluent and drew up the resulting solution into syringes for clinical use. The physician working at the clinic administered 4 case-patients (including himself) 4 to 6 injections of this toxin solution in the facial area. All the patients eventually reported symptoms of progressive weakness and cranial neuropathies (abnormality of the nerves that control a number of functions, including movement of the facial muscles and swallowing), with two patients experiencing shortness of breath.

The researchers report the patients may have received doses 2,857 times the estimated human lethal dose by injection. Pretreatment serum toxin levels in 3 of the 4 case-patients were equivalent to 21 to 43 times the estimated human lethal dose; pretreatment serum from the fourth epidemiologically linked case-patient was not available. A 100-µg vial of toxin taken from the same manufacturer's lot as toxin administered to the case-patients contained a toxin amount sufficient to kill approximately 14,286 adults by injection if disseminated evenly.

"Botulism is a potentially fatal disease, which invariably presents with acute bilateral cranial neuropathies, regardless of exposure mechanism. Early recognition of botulism, treatment in an intensive care setting, provision of mechanical ventilation when indicated, and rapid administration of antitoxin (optimally within 12 hours of presentation) have been associated with improved clinical outcome. Suspected cases of botulism should be reported immediately to local health authorities to facilitate rapid epidemiological investigation, provision of antitoxin when indicated, and prevention of further cases," the researchers write.

"Physicians and patients must be aware of the hazards associated with illegitimate use of unlicensed botulinum toxin products. Only licensed products should be used clinically. Entities inappropriately marketing, selling, or using unlicensed botulinum toxin products should be sought and subjected to full criminal and civil penalties. The Code of Federal Regulations should be modified to reduce the weight threshold of individual shipments subject to regulation and should require researchers to provide legal documentation of credentials and adequate laboratory facilities prior to shipment of toxin," the authors conclude.

JAMA and Archives Journals