This post came from a question received in our simulation lab a couple of weeks ago. Mainly, there was a simulated patient with latrodectus envenomation, and there was a fair amount of discussion about skin testing prior to administration on antivenom. Now, when I say discussion, what really happened was some faculty said skin testing was recommended by the package insert and all of their prior readings, whereas the residents were simply asking “why?” Then both groups practiced their google-fu and were able to come up with abstracts to support their viewpoints.
So, yet again, it seems there might be a generational gap between evidence and practice, so I figured I would try to answer their question here. And yet, when I went to search, there haven’t been a large amount of RCTs for skin testing, which isn’t shocking for the toxicology literature.
However, there have been a few decent case series that do not show a benefit to skin testing, as well as a few case series that demonstrate the safety profile of latrodectus antivenom. Putting these together, one could logically make the case against skin testing for latrodectus antivenom. However, there have now been two case reports of deaths from latrodectus antivenom use, one in a young woman with a history of asthma who received an undiluted push dose of antivenom, and more recently a man, also with asthma, who received a diluted dose of antivenom but died after experiencing anaphylaxis. The authors feel his death was likely from PE, but it still happened secondary to antivenom.
This article from Thailand was a retrospective review of snake bites who received antivenom. Over a little more than nine years, there were a total of 254 cases, 211 of which received skin testing. Ten of these patients had positive skin tests, and received different treatment. Desensitization was used in 5, and “close observation” was used in the other 5, but they still received undiluted antivenom. There were no reactions in any of the 10 patients with positive skin tests. Conversely, 7 patients with negative skin tests had reactions to the antivenom, and two who did not receive skin testing also had reactions. So the sensitivity of skin testing in their paper is 0%, and the specificity was 96.4%. Not terribly helpful for making decisions in management.
The good news for the practicing physician is that the weight of the current evidence has led the WHO to recommend against skin testing (at least for snake antivenom) as it leads to delays in treatment and does not help in decision making.
Skin and conjunctival “hypersensitivity” tests will reveal IgE mediated Type I hypersensitivity to horse or sheep proteins. However, since the majority of early (anaphylactic) or late (serum sickness type) antivenom reactions result from direct complement activation rather than from IgE mediated hypersensitivity, these tests are not predictive. Since they may delay treatment and can in themselves be sensitising, these tests should not be used [level of evidence T].
They do have the caveat that they only recommend antivenom treatment in patients who the benefits of said treatment outweigh the risks of allergic reactions.
My personal practice is to not perform skin testing. There is a very small number of patients who I feel need antivenom that I would withhold treatment based on a positive skin test. And since preventive treatment has not been proven effective, again it would only serve to delay definitive care. If I had a patient with a known severe allergy history, I would probably pretreat them (or concurrently treat them), but I would also get epinephrine and advanced airway equipment to the bedside. The harms and costs of a single dose of steroids and antihistamines are exceedingly low, and you have less of a risk of some “expert” saying you were acting cavalier.
Thiansookon A, Rojnuckarin P. Low incidence of early reactions to horse-derived F(ab’)(2) antivenom for snakebites in Thailand. Acta Trop. 2008 Feb;105(2):203-5 [PMID 17996842]
Of note, skin testing doesn’t appear to work for drugs either, so maybe there’s no point in doing it for anything emergent. In this paper, the skin test for cephalosporins had a sensitivity of 0%, specificity of 97.5%, negative predictive value of 99.7%, and a positive predictive value of 0%. Nobody with positive skin tests reacted to the medication, and 4 people with negative tests did have immediate reactions.
Yoon SY, Park SY, Kim S, Lee T, Lee YS, Kwon HS, Cho YS, Moon HB, Kim TB. Validation of the cephalosporin intradermal skin test for predicting immediate hypersensitivity: a prospective study with drug challenge. Allergy. 2013 Jul;68(7):938-44 [PMID 23751142]
- Murphy CM1, Hong JJ, Beuhler MC. Anaphylaxis with Latrodectus antivenin resulting in cardiac arrest. J Med Toxicol. 2011 Dec;7(4):317-21. [PMC3550195]
- Nordt SP, Clark RF, Lee A, Berk K, Lee Cantrell F. Examination of adverse events following black widow antivenom use in California. Clin Toxicol (Phila). 2012 Jan;50(1):70-3 [PMID 22175789]
EBM Gone Wild