Reevaluating the timing of specific immunoglobulin E measurement after anaphylaxis
Main Article Content
Keywords
anaphylaxis, anergic period, cefaclor, hypersensitivity reaction, ImmunoCAP
Abstract
The anergic period is defined as a period of around 3–6 weeks following a systemic allergic reaction when skin test results are negative. Therefore, most guidelines recommend that physicians should conduct skin test 6 weeks after an immediate hypersensitivity reaction. However, in vitro tests, including serum-specific immunoglobulin E (IgE) measurement, are generally deemed unaffected by the anergic period. Here, we present a case of a patient with initial cefaclor-specific IgE negativity, but when tested immediately after confirmed anaphylaxis to cefaclor, the results converted to positive after the resolution of the anergic period, 8 weeks post reaction. In patients with a strong clinical suspicion of drug-induced anaphylaxis, repeating in vitro tests after the anergic period may be warranted, even if the initial results are negative. Further investigation is needed to assess whether ImmunoCAP values, similar to skin test reactivity, exhibit significant short-term variability.
References
2 Romano A, Atanaskovic-Markovic M, Barbaud A, Bircher AJ, Brockow K, Caubet JC, et al. Towards a more precise diagnosis of hypersensitivity to beta-lactams–an EAACI position paper. Allergy. 2020;75(6):1300–15. 10.1111/all.14122
3 Romano A, Valluzzi RL, Caruso C, Zaffiro A, Quaratino D, Gaeta F. Evaluating immediate reactions to cephalosporins: Time is of the essence. J Allergy Clin Immunol Pract. 2021;9(4):1648–57 e1. 10.1016/j.jaip.2020.11.032
4 Mohamed OE, Baretto RL, Walker I, Melchior C, Heslegrave J, McKenzie R, et al. Empty mast cell syndrome: Fallacy or fact? J Clin Pathol. 2020;73(5):250–6. 10.1136/jclinpath-2019-206157
5 Kleine-Tebbe J, Jakob T. Molecular allergy diagnostics using IgE singleplex determinations: Methodological and practical considerations for use in clinical routine: Part 18 of the Series Molecular Allergology. Allergo J Int. 2015;24:185–97. 10.1007/s40629-015-0067-z
6 Golden DBK, Wang J, Waserman S, Akin C, Campbell RL, Ellis AK, et al. Anaphylaxis: A 2023 practice parameter update. Ann Allergy Asthma Immunol. 2024;132(2):124–76. 10.1016/j.anai.2023.09.015
7 Li PH, Chiang V, Yeung HH, Au EY. Caution against temporary tolerance and negative skin testing during the anergic period following systemic reactions. J Investig Allergol Clin Immunol. 2022;32(2):157–8. 10.18176/jiaci.0724
8 Aun MV, Kalil J, Giavina-Bianchi P. Drug-induced anaphylaxis. Immunol Allergy Clin North Am. 2017;37(4):629–41. 10.1016/j.iac.2017.06.002
9 Sim DW, Yu JE, Koh YI. Diagnostic accuracy of skin test in patients with cefaclor-induced anaphylaxis. J Allergy Clin Immunol Pract. 2025. 10.1016/j.jaip.2025.02.009
10 Lee JH, Park CS, Pyo MJ, Ryang Lee A, Shin E, Yoo YS, et al. Intradermal testing increases the accuracy of an immediate-type cefaclor hypersensitivity diagnosis. The World Allergy Organ J. 2022;15(4):100643. 10.1016/j.waojou.2022.100643
11 Mayorga C, Celik G, Rouzaire P, Whitaker P, Bonadonna P, Rodrigues-Cernadas J, et al. In vitro tests for drug hypersensitivity reactions: An ENDA/EAACI Drug Allergy Interest Group position paper. Allergy. 2016;71(8):1103–34. 10.1111/all.12886
12 Nam YH, Lee SH, Rhyou HI, Lee YS, Park SH, Lee YH, et al. Proper cut-off levels of serum specific IgE to cefaclor for patients with cefaclor allergy. Yonsei Med J. 2018;59(8):968–74. 10.3349/ymj.2018.59.8.968
13 Vultaggio A, Matucci A, Virgili G, Rossi O, Fili L, Parronchi P, et al. Influence of total serum IgE levels on the in vitro detection of beta-lactams-specific IgE antibodies. Clin Exp Allergy. 2009;39(6):838–44. 10.1111/j.1365-2222.2009.03219.x
14 Fernandez TD, Torres MJ, Blanca-Lopez N, Rodriguez-Bada JL, Gomez E, Canto G, et al. Negativization rates of IgE radioimmunoassay and basophil activation test in immediate reactions to penicillins. Allergy. 2009;64(2):242–8. 10.1111/j.1398-9995.2008.01713.x