Workgroup Report by the Joint Task Force Involving American Academy of Allergy, Asthma & Immunology (AAAAI); Food Allergy, Anaphylaxis, Dermatology and Drug Allergy (FADDA) (Adverse Reactions to Foods Committee and Adverse Reactions to Drugs, Biologicals, and Latex Committee); and the Centers for Disease Control and Prevention Botulism Clinical Treatment Guidelines Workgroup—Allergic Reactions to Botulinum Antitoxin: A Systematic Review

Abstract

Background. Naturally occurring botulism is rare, but a large number of cases could result from unintentional or intentional contamination of a commercial food. Despeciated, equine-derived, heptavalent botulinum antitoxin (HBAT) is licensed in the United States. Timely treatment reduces morbidity and mortality, but concerns that botulinum antitoxin can induce anaphylaxis exist. We sought to quantify the allergy risk of botulinum antitoxin treatment and the usefulness of skin testing to assess this risk.Methods. We conducted a systematic review of (1) allergic reactions to botulinum antitoxin and (2) the predictive value of skin testing (ST) before botulinum antitoxin administration. We searched 5 scientific literature databases, reviewed articles' references, and obtained data from the HBAT manufacturer and from the Centers for Disease Control and Prevention. Anaphylaxis incidence was determined for HBAT and previously employed botulinum antitoxins. We calculated the positive predictive value (PPV) and negative predictive value (NPV) of ST for anaphylaxis related to HBAT and other botulinum antitoxins.Results. Seven articles were included. Anaphylaxis incidence was 1.64% (5/305 patients) for HBAT and 1.16% (8/687 patients) for all other botulinum antitoxins (relative risk, 1.41 [95% confidence interval, .47-4.27]; P = .5). Observed values for both PPV and NPV for HBAT-ST (33 patients) were 100%. Observed PPVs and NPVs of ST for other botulinum antitoxins (302 patients) were 0-56% and 50%-100%, respectively. There were no reports of fatal anaphylaxis.Conclusions. Considering the <2 % rate of anaphylaxis, fatal outcomes, modest predictive value of ST, resource requirements for ST, and the benefits of early treatment, data do not support delaying HBAT administration to perform ST in a mass botulinum toxin exposure. Anaphylactic reactions may occur among 1%-2% of botulinum antitoxin recipients and will require epinephrine and antihistamine treatment and, possibly, intensive care.

Safety and Improved Clinical Outcomes in Patients Treated With New Equine-Derived Heptavalent Botulinum Antitoxin

“…Reports on botulinum antitoxin products employed in previous decades cite rates of anaphylaxis and serum sickness of 1–2% and 1–4%, respectively; rates varied with number of vials administered [18–21]. With HBAT, we observed anaphylaxis and serum sickness rates of 0% and <1%, respectively.…”

“…Historically, for older equine-derived botulinum antitoxin formulations, skin sensitivity testing before administration was recommended [23, 24]. Although skin testing was predictive of an allergic reaction in a single patient in our analysis, other studies suggest that the positive predictive value is low [18, 19, 25]. In clinical trials of 56 healthy adults, despite negative skin testing with horse dander immunoglobulin E and HBAT before HBAT administration, 2 subjects experienced hypersensitivity reactions including urticaria [4].…”

Characterization of a highly neutralizing single monoclonal antibody to botulinum neurotoxin type A

“…Although equine anti-BoNT polyclonal sera are able to efficiently neutralize all seven known BoNT toxinotypes, their use can cause dramatic side effects. 13,[49][50][51][52][53] Alternative therapeutic antitoxin approaches, such as mAbs or peptide inhibitors, 6 are currently explored to reduce the risks of serum sickness and cardiac arrest. Human anti-BoNT immune globulins obtained from vaccinated donors have been developed for the treatment of infant botulism, but their production is not easily scalable.…”

Wound Botulism Caused by Botulinum Neurotoxin Type A in a Chronic Parenteral Drug Abuser

“…As a result, this action decreases the amount of free neurotoxin able to block neurosignaling at the NMJ. However, heptavalent botulinum antitoxin does not work on neurotoxin that has already been internalized by the receptor [ 21 ]. The antitoxin is provided by the CDC and local health officials are alerted when reports of botulinum toxicity surface.…”