Anitvenom Use for Latrodectism

Latrodectism is a series of clinical signs and symptoms resulting from the bite of a widow spider, or spider. There are various species of widow spiders found across the globe including (black widow), Latrodectus geometricus (brown widow), and Latrodectus hasselti (red-back widow spider). The of a widow spider ultimately results in calcium-mediated release of such as , dopamine, , glutamate, GABA, and some neuropeptides. Symptoms of a widow spider envenomation are classified by a grading system that ranges from no symptoms or local pain at envenomation site to systemic pain and vital signs abnormalities such as hypertension, diaphoresis, nausea, or myalgias of the back, chest, and abdomen. Latrodectus (AV) is available as a purified horse serum that has been suggested for use in patients with a grade 3 envenomation.1

Most attempts to review the effectiveness of the Latrodectus AV are via retrospective studies, with only a few randomized controlled trails published. Exposures and treatments for latrodectism reported to the National Data System (NPDS) were reviewed by Monte and colleagues in 2011 and demonstrated that AV use was associated with a shorter duration of symptoms (<24 hours) in patients with moderate/severe , however there was no difference in symptom duration between those who received benzodiazepines or calcium compared to AV.2

Dart and colleagues performed a randomized, double-blind, placebo controlled trial with a total of 24 patients to receive either the black widow AV or placebo. There was no statistical difference in treatment failure, but there was a decrease in the median time to decreased pain (p=0.03).3 The RAVE-II study by Isbister and colleagues was another randomized, placebo controlled trial that examined the effectiveness of the red-back widow AV on pain and systemic symptom reduction at 2, 4, and 24 hours post administration in 227 patients. There was no statistically significant difference demonstrated between the AV and placebo groups for any time point or for pain vs. systemic systems.4 Finally, there have been two randomized trials comparing IV vs. IM administration of Latrodectus AV. The RAVE study by Isbister and colleagues demonstrated no difference in pain improvement or systemic system improvement within 2 hours of either IV or IM administration of AV in 126 patients.5 However, Ellis and colleagues suggested that IV administration of AV resulted in better pain control at 24 hours in 31 patients.6

While most reports of adverse effects relating to Latrodectus AV use are mild to moderate with reports of hypersensitivity reactions and serum sickness, there have been two case reports of anaphylactoid reactions to the black widow spider AV in a boy and man. Both patients reported a negative skin test, and the latter died of a cardiac arrest.7,8

Overall, the clinical data surrounding the use of Latrodectus AV is controversial and its use is not routinely recommended. Symptoms of grade 3 envenomation are consideration for its use, but not absolute indications. Availability of the AV also limits its use.

References: 1. Hoffman RS, Howland MA, Lewin NA, et al, ed. Goldfrank’s Toxicologic Emergencies. 10th ed. New York: McGraw-Hill Education; 2015. 1462-65 2. Monte AA, Bucher-Bartelson B, Heard KJ. A US perspective of symptomatic Latrodectus spp. envenomation and treatment: a National Poison Data System review. Ann Pharmacother. 2011 Dec;45(12):1491-8 3. Dart RC, Bogdan G, Heard K, et al. A randomized, double-blind, placebo-controlled trial of a highly purified equine F(ab)2 antibody black widow spider antivenom. Ann Emerg Med. 2013 Apr;61(4):458-67 4. Isbister GK, Page CB, Buckley NA, et al. Randomized controlled trial of intravenous antivenom versus placebo for latrodectism: the second Redback Antivenom Evaluation (RAVE-II) study. Ann Emerg Med. 2014 Dec;64(6):620-8 5. Isbister GK, Brown SG, Miller M, et al. A randomised controlled trial of intramuscular vs. intravenous antivenom for latrodectism--the RAVE study. QJM. 2008 Jul;101(7):557-65 6. Ellis RM, Sprivulis PC, Jelinek GA, et al. A double-blind, randomized trial of intravenous versus intramuscular antivenom for red-back spider envenoming. Emerg Med Australas. 2005 Apr;17(2):152-6. 7. Hoyte CO, Cushing TA, Heard KJ. Anaphylaxis to black widow spider antivenom. Am J Emerg Med. 2012 Jun;30(5):836 8. Murphy CM, Hong JJ, Beuhler MC. Anaphylaxis with Latrodectus antivenin resulting in cardiac arrest. J Med Toxicol. 2011 Dec;7(4):317-21