Introduction: In adults, allergic reactions to insect stings are among the most frequent causes of anaphylaxis, a potentially life-threatening condition. Recurrent anaphylaxis following vespid stings may be prevented by allergen immunotherapy (AIT). The aim of this study was to evaluate the benefit of measuring venom-induced wheal area in intracutaneous skin tests (ICT), in comparison to various serological and clinical parameters, for the diagnosis of severe vespid venom allergy and during follow-up of AIT. Methods: We conducted a monocentric, retrospective evaluation of 170 patients undergoing AIT against vespid venoms. We scanned ICT wheals at baseline and at three time points after AIT initiation and measured wheal area using objective data analysis software. Results: We found that ICT histamine-induced and venom-induced wheal areas did not correlate. In addition, the venom-induced wheal area was independent from the minimal venom concentration required to elicit a wheal in an ICT and all other parameters. No correlation was found between wheal area and the severity of anaphylaxis. Wheal area standardized to the application of 0.1 μg/mL venom inversely correlated with anaphylaxis severity and positively correlated with venom-specific IgE levels. During AIT, mean areas of venom-induced wheals did not change. In contrast, venom-specific IgG and IgG4 levels, and the minimal venom concentration required to induce a positive ICT result increased, while the venom wheal area standardized to 0.1 μg/mL venom application and specific IgE levels decreased over time. Conclusion: Wheal area evaluation did not provide additional information over specific IgE analysis. We therefore recommend that ICTs are used only as a secondary measure for confirming serological test results.

Journal Section:
Clinical Allergy – Research Article
Keywords:
Allergy, Insect venom allergy, Intracutaneous test, Skin test reactivity
1.
Tejedor Alonso MA, Moro Moro M, Múgica García MV. Epidemiology of anaphylaxis. Clin Exp Allergy. 2015 Jun;45(6):1027–39.
2.
Grabenhenrich LB, Dölle S, Moneret-Vautrin A, Köhli A, Lange L, Spindler T, et al. Anaphylaxis in children and adolescents: the European anaphylaxis registry. J Allergy Clin Immunol. 2016 Apr;137(4):1128–37.e1.
3.
Schäfer T. Epidemiologie der Insektengiftallergie. Allergo J. 2009 Jul;18(5):353–8.
4.
Blank S, Seismann H, McIntyre M, Ollert M, Wolf S, Bantleon FI, et al. Vitellogenins are new high molecular weight components and allergens (Api m 12 and Ves v 6) of Apis mellifera and Vespula vulgaris venom. PLoS One. 2013 Apr;8(4):e62009.
5.
Yoon KA, Kim K, Kim W-J, Bang WY, Ahn N-H, Bae C-H, et al. Characterization of venom components and their phylogenetic properties in some aculeate bumblebees and wasps. Toxins. 2020 Jan;12(1):47.
6.
Przybilla B, Ruëff F, Walker A, Räwer H-C, Aberer W, Bauer CP, et al. Diagnose und Therapie der Bienen und Wespengiftallergie. Allergo J. 2011;20:318–39.
7.
Golden DBK. Anaphylaxis to insect stings. Immunol Allergy Clin North Am. 2015 May;35(2):287–302.
8.
Antonicelli L, Bilò MB, Bonifazi F. Epidemiology of hymenoptera allergy. Curr Opin Allergy Clin Immunol. 2002 Aug;2(4):341–6.
9.
Bilò MB, Bonifazi F. The natural history and epidemiology of insect venom allergy: clinical implications. Clin Exp Allergy. 2009 Oct;39(10):1467–76.
10.
Golden DB, Marsh DG, Freidhoff LR, Kwiterovich KA, Addison B, Kagey-Sobotka A, et al. Natural history of hymenoptera venom sensitivity in adults. J Allergy Clin Immunol. 1997 Dec;100(6):760–6.
11.
Sturm GJ, Kranzelbinder B, Schuster C, Sturm EM, Bokanovic D, Vollmann J, et al. Sensitization to hymenoptera venoms is common, but systemic sting reactions are rare. J Allergy Clin Immunol. 2014 Jun;133(6):1635–43.e1.
12.
Ruëff F, Bergmann K-C, Brockow K, Fuchs T, Grübl A, Jung K, et al. [Skin tests for diagnostics of allergic immediate-type reactions. Guideline of the German Society for Allergology and Clinical Immunology]. Pneumologie. 2011 Aug;65(08):484–95.
13.
Wood RA, Phipatanakul W, Hamilton RG, Eggleston PA. A comparison of skin prick tests, intradermal skin tests, and RASTs in the diagnosis of cat allergy. J Allergy Clin Immunol. 1999 May;103(5):773–9.
14.
McKay SP, Meslemani D, Stachler RJ, Krouse JH. Intradermal positivity after negative prick testing for inhalants. Otolaryngol Head Neck Surg. 2006 Aug;135(2):232–5.
15.
Lockey R, Benedict L, Turkeltaub P, Bukantz S. Fatalities from immunotherapy (IT) and skin testing (ST). J Allergy Clin Immunol. 1987 Apr;79(4):660–77.
16.
Lawrence MG, Woodfolk JA, Schuyler AJ, Stillman LC, Chapman MD, Platts-Mills TAE. Half-life of IgE in serum and skin: consequences for anti-IgE therapy in patients with allergic disease. J Allergy Clin Immunol. 2017 Feb;139(2):422–8.e4.
17.
Lerch E, Müller UR. Long-term protection after stopping venom immunotherapy: results of re-stings in 200 patients. J Allergy Clin Immunol. 1998 May;101(5):606–12.
18.
Saulite I, Hoetzenecker W, Guenova E, Schmid-Grendelmeier P, Glatz M. Skin test reactivity to hymenoptera venom after venom immunotherapy correlates inversely with the IgG/IgE ratio. Int Arch Allergy Immunol. 2017;174(3–4):190–9.
19.
Pucar F, Kagan R, Lim H, Clarke AE. Peanut challenge: a retrospective study of 140 patients. Clin Exp Allergy. 2001 Jan;31(1):40–6.
20.
Knight A, Shreffler W, Sampson H, Sicherer S, Noone S, Mofidi S, et al. Skin prick test to egg white provides additional diagnostic utility to serum egg white–specific IgE antibody concentration in children. J Allergy Clin Immunol. 2006 Apr;117(4):842–7.
21.
Sporik R, Hill DJ, Hosking CS. Specificity of allergen skin testing in predicting positive open food challenges to milk, egg and peanut in children: specificity of allergen skin testing. Clin Exp Allergy. 2000 Nov;30(11):1541–6.
22.
Hill DJ, Heine RG, Hosking CS. The diagnostic value of skin prick testing in children with food allergy. Pediatr Allergy Immunol. 2004 Oct;15(5):435–41.
23.
Hollstein MM, Matzke SS, Lorbeer L, Forkel S, Fuchs T, Lex C, et al. Intracutaneous skin tests and serum IgE levels cannot predict the grade of anaphylaxis in patients with insect venom allergies. JAA. 2022 Jul;15:907–18.
24.
Mueller HL. Diagnosis and treatment of insect sensitivity. J Asthma Res. 1966 Jan;3(4):331–3.
25.
Golden DBK, Kwiterovich KA, Kagey-Sobotka A, Valentine MD, Lichtenstein LM. Discontinuing venom immunotherapy: outcome after five years. J Allergy Clin Immunol. 1996 Feb;97(2):579–87.
26.
Rueff F, Wolf H, Schnitker J, Ring J, Przybilla B. Specific immunotherapy in honeybee venom allergy: a comparative study using aqueous and aluminium hydroxide adsorbed preparations. Allergy. 2004 Jun;59(6):589–95.
27.
van Halteren HK, van der Linden P-WG, Burgers SA, Bartelink AKM. Hymenoptera sting challenge of 348 patients: relation to subsequent field stings. J Allergy Clin Immunol. 1996 May;97(5):1058–63.
28.
Malling H-J. Skin prick testing and the use of histamine references. Allergy. 1984 Nov;39(8):596–601.
29.
Corallino M, Nico A, Kourtis G, Caiaffa MF, Macchia L. Skin testing technique and precision in stinging insect allergy. J Clin Nurs. 2007 Jul;16(7):1256–64.
30.
Gattinger P, Lupinek C, Kalogiros L, Silar M, Zidarn M, Korosec P, et al. The culprit insect but not severity of allergic reactions to bee and wasp venom can be determined by molecular diagnosis. PLoS One. 2018 Jun;13(6):e0199250.
31.
Ollert M, Blank S. Anaphylaxis to insect venom allergens: role of molecular diagnostics. Curr Allergy Asthma Rep. 2015 May;15(5):26.
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