Botox resistance and COVID‐19 vaccines: Is type B Botox a viable solution?

As previously reported by Azzam et al, an association between COVID-19 vaccines and decreased efficacy of botulinum injections has come to light.1 While this was a small case series, there is acknowledgment within the field that some patients are reporting a decreased effect or shorter duration of response. Previously considered a rare event, little has been published regarding botulinum resistance (secondary non-response) in cosmetic patients. The aim of this discussion is to not only highlight a case of secondary non-response following COVID vaccination but also to initiate discussion on management. Our patient is a 54-year-old female who has been receiving cosmetic botulinum injections for 5 years at intervals of 3–6 months without issue. However, in the winter of 2021, she reported a lack of response. When reviewing the patients' COVID-19 vaccination and botulinum type A (BTXA) injection timeline (Table 1), the patient received BTXA injections within days (2–14 days) of all three doses of the COVID vaccine. Most notably, the patient received the booster vaccine on 11/14/21 and had BTXA injection on 11/16/21 with no response and experienced a new complication of injection site reactions with exuberant erythema and subcutaneous edema lasting 3–4 days. There are only two reported cases of cutaneous hypersensitivity reactions to BTXA following COVID-19 vaccination; however, these included generalized facial edema rather than localized reaction and no lack of response was noted.2 Antibodies directed against BTXA are generally classified into neutralizing antibodies (Nabs, formed against the binding site of heavy chain on core neurotoxin) and non-neutralizing antibodies. It is worth noting that the patients in the case series,1 and our patient all received abobotulinumtoxinA (Dysport) which a meta-analysis in 2020 found to have a higher incidence of development of Nabs (7.4%) versus onabotulinumtoxinA (Botox) (0.3%).3 While neutralizing antibody testing was considered in this patient, it was felt to be of low clinical utility as the presence or absence of neutralizing antibodies does not definitively correlate to lack of response.4 Initial management of our patient included a trial of alternate and higher dose BTXA product injections (onabotulinumtoxinA (Botox), incobotulinumtoxinA (Xeomin)) as detailed in Table 1. No response was noted, and the patient developed injection site reactions with each trial. At that time, a review of the literature showed efficacy and safety of botulinum type B (BTXB, RimabotulinumtoxinB (Myobloc)) injections for cosmesis.5 Our patient was treated with a total of 38 Botox equivalent units to the glabella but reported minimal response. Notably, she again developed injection site reactions to BTXB. These injection site reactions perhaps serve as a marker of a robust immune response. While it is thought that type A toxin and type B toxin do not cross-react, the heavy chain of both serotypes share some homogeneity of structure6 thus cross-reactivity is possible though not yet documented. Given the impact of COVID-19 vaccinations in the COVID-19 pandemic, vaccination should not be discouraged. However, guidelines regarding the timing of neurotoxin injections and vaccinations requires further research. For patients who develop secondary non-response, a trial of BTXB may be warranted. Our patient remains hopeful that her immunity against botulinum toxin will wane; however, it is unclear the timeline of such waning and the possibility of response in the future. One case series of seven dystonia patients with secondary non-response showed average duration of Nabs positivity of 30 months (10–78 months). While six of these patients became seronegative and exhibited response to repeat trial of BTXA injection, three of those patients subsequently stopped responding and upon testing showed reemergence of antibody positivity.4 Further research is needed to appropriately counsel patients who develop non-response. Acknowledgment of Dr. Meghan O'Brien and Dr. Jean Carruthers for their expert opinions. The authors have no conflicts of interest to disclose. The authors confirm that the ethical policies of the journal, as noted on the journal's author guidelines page, have been adhered to. No ethical approval was required as this is a review article with no original research data. All photos presented in the article were obtained and published with the patient consent. Data sharing is not applicable to this article as no new data were created or analyzed in this study.