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Antivenom skin test: Theory versus practice
Acta Tropica 109 (2009) 86
Contents lists available at ScienceDirect
Acta Tropica journal homepage: www.elsevier.com/locate/actatropica
Author’s reply
Antivenom skin test: Theory versus practice Dear Editor, The letter from Dr. Klaewsongkram raises an interesting point. Although clinical studies demonstrated that snake antivenom skin test was not predictive of early reactions, he criticized on the procedures of intradermal tests including inappropriate criteria for positive results and concentrations of antivenom used, as well as the lack of positive and negative controls for the test. He also suggested the studies correlating with clinical outcomes to optimize the conditions of the test before conclude that it is useless. Although the argument is theoretically sound, it is not supported by clinical data. The current skin test for snake antivenom is awfully inaccurate. Almost all patients with positive tests do not experience any reactions, while the great majority of cases with reactions have negative tests (Malasit et al., 1986; Rojnuckarin et al., 1998; Chen et al., 2000; Thiansookon and Rojnuckarin, 2008). This information strongly suggested that most the reactions are not mediated via IgE. It is difficult to imagine that varying a few millimeters of the cut-off point can change all of these to the opposite results. Furthermore, as the test shows very high rates of both false negative and false positive, either increases or decreases the concentration of the allergen are unlikely to improve the overall accuracy. Inclusion of the negative and positive controls may let us know that a particular intradermal test is invalid. However, this will not helpful in clinical decision-making. Apart from its accuracy, the role of the test is now in the context of improved antivenoms. The highly purified equine F(ab) 2 antivenoms display very low rate of early reactions. A study to predict these adverse events will require an enormous number of subjects. In addition, these side-effects can be easily managed (Chen et al., 2000; Thiansookon and Rojnuckarin, 2008). Prevention of these reactions using desensitization is not necessary and may even be harmful because it will delay the full doses of antivenom
DOI of original article:10.1016/j.actatropica.2008.09.007. 0001-706X/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.actatropica.2008.09.004
for hours. Therefore, it is more practical to administer antivenom with ‘universal’ precautions. Under close observation, medications can be given immediately when reactions occur. This precaution will never be avoidable, as the test, even after improvements, is unlikely to be 100% sensitive. A role of skin test in the countries using crude antivenoms remains to be determined. One previous study using an equine, whole-IgG antivenom showed that negative skin test was not helpful, but positive test might be able to predict the risk of anaphylaxis (Rojnuckarin et al., 1998). Contaminants may be the sources of IgE-mediated reactions. Nevertheless, an endeavor to supply better antivenoms with low adverse reactions would be more appealing than just a trial to predict them. References Chen, J.C., Bullard, M.J., Chiu, T.F., Ng, C.J., Liaw, S.J., 2000. Risk of immediate effects from F(ab)2 bivalent antivenin in Taiwan. Wilderness Environ. Med. 11 (3), 163–167. Malasit, P., Warrell, D.A., Chanthavanich, P., Viravan, C., Mongkolsapaya, J., Singhthong, B., Supich, C., 1986. Prediction, prevention, and mechanism of early (anaphylactic) antivenom reactions in victims of snake bites. Br. Med. J. (Clin. Res. Ed.) 292 (6512), 17–20. Rojnuckarin, P., Mahasandana, S., Intragumthornchai, T., Sutcharitchan, P., Swasdikul, D., 1998. Prognostic factors of green pit viper bites. Am. J. Trop. Med. Hyg. 58 (1), 22–25. Thiansookon, A., Rojnuckarin, P., 2008. Low incidence of early reactions to horsederived F(ab )(2) antivenom for snakebites in Thailand. Acta Trop. 105 (2), 203–205.
Ponlapat Rojnuckarin Chulalongkorn University, Faculty of Medicine, Rama IV Rd patumwan, Bangkok 10330, Thailand E-mail address: [email protected] 20 August 2008 Available online 20 September 2008
Contents lists available at ScienceDirect
Acta Tropica journal homepage: www.elsevier.com/locate/actatropica
Author’s reply
Antivenom skin test: Theory versus practice Dear Editor, The letter from Dr. Klaewsongkram raises an interesting point. Although clinical studies demonstrated that snake antivenom skin test was not predictive of early reactions, he criticized on the procedures of intradermal tests including inappropriate criteria for positive results and concentrations of antivenom used, as well as the lack of positive and negative controls for the test. He also suggested the studies correlating with clinical outcomes to optimize the conditions of the test before conclude that it is useless. Although the argument is theoretically sound, it is not supported by clinical data. The current skin test for snake antivenom is awfully inaccurate. Almost all patients with positive tests do not experience any reactions, while the great majority of cases with reactions have negative tests (Malasit et al., 1986; Rojnuckarin et al., 1998; Chen et al., 2000; Thiansookon and Rojnuckarin, 2008). This information strongly suggested that most the reactions are not mediated via IgE. It is difficult to imagine that varying a few millimeters of the cut-off point can change all of these to the opposite results. Furthermore, as the test shows very high rates of both false negative and false positive, either increases or decreases the concentration of the allergen are unlikely to improve the overall accuracy. Inclusion of the negative and positive controls may let us know that a particular intradermal test is invalid. However, this will not helpful in clinical decision-making. Apart from its accuracy, the role of the test is now in the context of improved antivenoms. The highly purified equine F(ab) 2 antivenoms display very low rate of early reactions. A study to predict these adverse events will require an enormous number of subjects. In addition, these side-effects can be easily managed (Chen et al., 2000; Thiansookon and Rojnuckarin, 2008). Prevention of these reactions using desensitization is not necessary and may even be harmful because it will delay the full doses of antivenom
DOI of original article:10.1016/j.actatropica.2008.09.007. 0001-706X/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.actatropica.2008.09.004
for hours. Therefore, it is more practical to administer antivenom with ‘universal’ precautions. Under close observation, medications can be given immediately when reactions occur. This precaution will never be avoidable, as the test, even after improvements, is unlikely to be 100% sensitive. A role of skin test in the countries using crude antivenoms remains to be determined. One previous study using an equine, whole-IgG antivenom showed that negative skin test was not helpful, but positive test might be able to predict the risk of anaphylaxis (Rojnuckarin et al., 1998). Contaminants may be the sources of IgE-mediated reactions. Nevertheless, an endeavor to supply better antivenoms with low adverse reactions would be more appealing than just a trial to predict them. References Chen, J.C., Bullard, M.J., Chiu, T.F., Ng, C.J., Liaw, S.J., 2000. Risk of immediate effects from F(ab)2 bivalent antivenin in Taiwan. Wilderness Environ. Med. 11 (3), 163–167. Malasit, P., Warrell, D.A., Chanthavanich, P., Viravan, C., Mongkolsapaya, J., Singhthong, B., Supich, C., 1986. Prediction, prevention, and mechanism of early (anaphylactic) antivenom reactions in victims of snake bites. Br. Med. J. (Clin. Res. Ed.) 292 (6512), 17–20. Rojnuckarin, P., Mahasandana, S., Intragumthornchai, T., Sutcharitchan, P., Swasdikul, D., 1998. Prognostic factors of green pit viper bites. Am. J. Trop. Med. Hyg. 58 (1), 22–25. Thiansookon, A., Rojnuckarin, P., 2008. Low incidence of early reactions to horsederived F(ab )(2) antivenom for snakebites in Thailand. Acta Trop. 105 (2), 203–205.
Ponlapat Rojnuckarin Chulalongkorn University, Faculty of Medicine, Rama IV Rd patumwan, Bangkok 10330, Thailand E-mail address: [email protected] 20 August 2008 Available online 20 September 2008