Botox-Related Illnesses: Public Citizen Urges Consideration of Botulism Caused by FDA-Approved Products

In April 2024 the Centers for Disease Control and Prevention (CDC) issued a health advisory (hereafter, advisory) indicating that it was investigating adverse effects in clusters of people related to what the agency characterized as “counterfeit or mishandled botulinum toxin injections.”[1] The Food and Drug Administration (FDA) has approved several botulinum toxin products — including onabotulinumtoxinA (BOTOX, BOTOX COSMETIC) and abobotulinumtoxinA (DYSPORT) — to treat certain medical conditions (such as spasticity) and for the temporary smoothing of certain facial wrinkles.

Following the CDC health advisory, Public Citizen’s Health Research Group issued a press statement[2] and sent a letter to the CDC and the FDA urging both agencies to consider in their investigations that iatrogenic botulism can occur due to recommended doses of approved botulinum toxin products,[3] as emphasized in a petition that we submitted to the FDA in 2023[4] (see the March 2024 issue of Worst Pills, Best Pills News for details).[5]

Iatrogenic botulism is a complication of treatment with botulinum toxins due to their potential to spread beyond injection sites, resulting in breathing distress, progressive muscle paralysis and other serious symptoms. Our letter highlighted discrepancies between some information in the advisory and the CDC’s 2021 guidelines for diagnosis and treatment of botulism.[6]

Public Citizen’s letter

The CDC advisory mentioned that the agency was investigating clusters of 22 people who experienced adverse reactions from “counterfeit or mishandled botulinum toxin injections.”[7]

In our letter to the CDC and FDA we urged these agencies to fully consider the possibility that at least some of the identified cases may be related to recommended doses of approved and properly administered botulinum toxin drugs.[8] We also criticized the CDC for noting in the advisory that “low doses of injected toxins are not likely to reach circulation or produce botulism with its life-threatening manifestations,” a statement that downplays the potential risks of low-dose injections of these drugs as discussed in our FDA petition.

Our letter also discussed that the advisory seemed to limit botulism symptoms to symmetric cranial nerve palsies, possibly followed by a descending symmetric flaccid paralysis. In contrast, the CDC clinical guidelines state that up to 15% of botulism patients in large case series have reported asymmetry or unilateral neurologic deficits.[9]

These guidelines also acknowledge diagnostic challenges caused by “variations in the spectrum of signs and symptoms of botulism [that] were highlighted in the delayed recognition of a large foodborne botulism outbreak, in which some patients initially received diagnoses of myasthenia gravis, stroke, or psychiatric disorders.” Furthermore, our petition discussed published case reports showing that patients with iatrogenic botulism may present with asymmetric muscle weakness or asymmetric ptosis.[10],[11]

The CDC advisory reported that six people received the botulism antitoxin — the only specific therapy for botulism — to treat suspected botulism, but none of the patients had a laboratory-confirmed diagnosis of botulism demonstrating the existence of botulinum toxin in their serum (presumably using either mouse bioassay [MBA] or mass spectrometry, as mentioned in the advisory).

Our letter discussed that the MBA test may not be sufficiently sensitive to detect low levels of the toxin. In fact, a U.S. laboratory-confirmed iatrogenic botulism case cited in the CDC advisory had a negative MBA test result for serum samples collected on the fifth day after the onset of symptoms and prior to the administration of the antitoxin.[12] Instead, the diagnosis of iatrogenic botulism was confirmed in that patient using a highly sensitive test (matrix-assisted laser desorption/ionization time-of-flight mass spectrometry), whose results were available 19 days after specimen collection.

For these reasons, we urged the CDC to revise its advisory to encourage clinicians to err on the side of suspecting iatrogenic botulism in all patients experiencing adverse effects consistent with the distant spread of the toxin, including asymmetric neurological deficits, within hours to weeks after receiving botulinum toxin injections. We also asked the CDC to promptly follow its own guidelines that recommend the administration of botulinum antitoxin as quickly as possible to all people with signs or symptoms that are suggestive of botulism instead of waiting until they develop neurologic weaknesses.

The CDC investigation

According to the CDC’s April 2024 advisory, the agency investigated 22 people in 11 U.S. states who had experienced adverse reactions from “counterfeit or mishandled botulinum toxin injections.”

In June 2024, however, after closing its investigation, the CDC announced that only 17 people had experienced harmful reactions following injections with counterfeit products from unverified sources or from individuals who were not following state or local requirements.[13] These 17 cases were reported in nine states: California (2), Colorado (1), Florida (1), Illinois (2), Kentucky (1), New Jersey (1), New York (3), Tennessee (3) and Texas (3). The symptoms reported by these people included blurry vision and double vision, difficulty breathing or swallowing, drooping eyelids, dry mouth, fatigue, generalized weakness or slurred speech, all of which are suggestive of iatrogenic botulism.

It is unknown why the CDC has not disclosed any details about the five remaining cases it was investigating in April 2024 and whether these patients were not included in the June 2024 announcement because they had developed adverse effects that are suggestive of iatrogenic botulism due to injections with legitimate botulinum toxin products or for other reasons.

As of September 2024, the only other publicly available information about this issue is from a July 2024 article in Morbidity and Mortality Weekly Report by researchers from the CDC and some state health departments. This article only discussed the seven patients from Kentucky, Tennessee and New York who were included in the CDC investigation. The article noted that these patients had received botulinum toxin injections by unlicensed persons in nonmedical settings.[14] However, the investigation did not include why these illnesses occurred, including whether they were confirmed to involve injections of counterfeit botulinum toxin, according to the article.

Public Citizen urges the CDC to be more transparent about all the cases it has investigated and to disclose whether any of the patients received recommended doses of FDA-approved botulinum toxins. Likewise, we urge the FDA to promptly grant our 2023 petition to strengthen the safety warnings for these products.

What You Can Do

Do not use any botulinum toxin drug to smooth wrinkles or to treat any condition that is not approved by the FDA. If you are considering any of these products for an FDA-approved use, discuss with your clinician whether their potential benefits outweigh their risks.

Seek medical help immediately if you develop any weakness or serious adverse effects (such as those affecting your breathing, eyelids, speech or swallowing) within hours to weeks after injections with these drugs because you may need to receive botulinum antitoxin to stop the progression of symptoms.

Never receive any botulinum toxin injections from an unlicensed person.
 

References

[1] Centers for Disease Control and Prevention. Health Alert Network (HAN). Health Advisory. Adverse effects linked to counterfeit or mishandled botulinum toxin injections. April 23, 2024. https://emergency.cdc.gov/han/2024/han00507.asp. Accessed September 3, 2024.

[2] Public Citizen. CDC should promptly facilitate administration of botulinum antitoxin to people with illnesses linked to counterfeit “Botox.” April 17, 2024. https://www.citizen.org/news/cdc-should-promptly-facilitate-administration-of-botulinum-antitoxin-to-people-with-illnesses-linked-to-counterfeit-botox/. Accessed September 3, 2024.

[3] Public Citizen. Letter to the CDC and FDA regarding recent health advisory on clusters of patients with adverse events from certain botulinum toxin injections. April 30, 2024. https://www.citizen.org/wp-content/uploads/2680.pdf. Accessed September 3, 2024.

[4] Public Citizen. Petition to the FDA to strengthen safety warning for Botox and related drugs and remove misleading claims from Botox/Botox Cosmetic labeling. December 12, 2023. https://www.citizen.org/wp-content/uploads/2671.pdf. Accessed September 3, 2024.

[5] Public Citizen urges FDA to strengthen warning on labeling of BOTOX and related drugs. Worst Pills, Best Pills News. March 2024. https://www.worstpills.org/newsletters/view/1586. Accessed August 28, 2024.

[6] Rao AK, Sobel J, Chatham-Stephens K, et al. Clinical guidelines for diagnosis and treatment of botulism, 2021. MMWR Recomm Rep. 2021;70(2):1-30.

[7] Centers for Disease Control and Prevention. Health Alert Network (HAN). Health Advisory. Adverse effects linked to counterfeit or mishandled botulinum toxin injections. April 23, 2024. https://emergency.cdc.gov/han/2024/han00507.asp. Accessed September 3, 2024.

[8] Public Citizen. Letter to the CDC and FDA regarding recent health advisory on clusters of patients with adverse events from certain botulinum toxin injections. April 30, 2024. https://www.citizen.org/wp-content/uploads/2680.pdf. Accessed August 28, 2024.

[9] Rao AK, Sobel J, Chatham-Stephens K, et al. Clinical guidelines for diagnosis and treatment of botulism, 2021. MMWR Recomm Rep. 2021;70(2):1-30.

[10] Baig MA, Nogar J. A case of asymmetric cranial nerve palsy due to iatrogenic botulism. Asia Pac J Med Toxicol. 2021;10(4):149-150.

[11] Hovseth K, Badillo R, Schaeffer S, et al. Atypical botulism presentation following botulinum toxin with phenol therapy. In: North American Congress of Clinical Toxicology. Washington, D.C.; 2011:561.

[12] Halai UA, Terashita D, Kim M, et al. Notes from the field: Intestinal colonization and possible iatrogenic botulism in mouse bioassay-negative serum specimens - Los Angeles County, California, November 2017. MMWR Morb Mortal Wkly Rep. 2018;67(43):1221-1222.

[13] Centers for Disease Control and Prevention. Investigation update on harmful reactions linked to counterfeit "Botox." June 24, 2024. https://www.cdc.gov/botulism/outbreaks/harmful-reactions-botox-injections/details.html. Accessed September 3, 2024.

[14] Thomas CM, McElroy R, Yackley J, et al. Notes from the field: Illnesses after administration of presumed counterfeit botulinum toxin in nonmedical settings - Tennessee and New York City, March 2024. MMWR Morb Mortal Wkly Rep. 2024;73(27):609-611.