Principles of Allergy Skin Testing

  • Özlem Naciye Şahin
  • Cemal Cingi
  • Jennifer Derebery


For the diagnosis of allergic rhinitis (AR), the allergen-specific IgE is assumed to be the factor responsible for eliciting inflammation and the symptoms. Therefore, the objective of the diagnostic test is to determine whether IgE-mediated allergy is involved in a sensitized patient who has symptoms consistent with allergy. Interestingly, the recognition of IgE specifically does not indicate allergic symptoms. In addition, many people may be sensitized and not allergic clinically. In patients with AR symptoms, testing is necessary for the diagnosis of IgE-mediated reactions. For IgE specificity, a skin prick tests or a blood test (in vitro test) can be used. Presently, skin prick tests are the gold standard for the detection of allergies due to their non-invasiveness and affordability. The skin prick test for AR is reproducible and should be executed using thorough methods. Briefly, skin prick tests should be recorded by measuring the widest diameter of erythema at the test site 10–15 min after test application. A positive score is recorded based on EAACI recommendations. The interpretation must be backed by clinical history to verify diagnosis. False positives may occur by weak extract potency, poor technique, and/or current medication. The IgE-mediated response to skin prick test is reliant on acute phase mediators, which precedes the late response. The acute reaction will typically be seen within 10–15 min of skin test application, while the late phase reaction may be seen within 2–6 h of testing and subsides at 24 h. The late phase reaction is associated with an influx of T cells, rather than IgE-mediated. In this chapter, principles of allergy skin testing are presented.


Allergic rhinitis Allergen-specific IgE Allergy skin testing Principles Acute reaction Late phase reaction 


  1. 1.
    Kerkhof M, Droste JH, de Monchy JG, Schouten JP, Rijcken B. Distribution of total serum IgE and specific IgE to common aeroallergens by sex and age, and their relationship to each other in a random sample of the Dutch general population aged 20-70 years. Dutch ECRHS Group, European Community Respiratory Health Study. Allergy. 1996;51(11):770–6.PubMedGoogle Scholar
  2. 2.
    Scadding G, Hellings P, Alobid I, Bachert C, Fokkens W, van Wijk RG, Gevaert P, Guilemany J, Kalogjera L, Lund V, Mullol J, Passalacqua G, Toskala E, van Drunen C. Diagnostic tools in Rhinology EAACI position paper. Clin Transl Allergy. 2011;1(1):2. Scholar
  3. 3.
    Nelson HS, Rosloniec DM, McCall LI, Ikle D. Comparative performance of five commercial prick skin test devices. J Allergy Clin Immunol. 1993;92(5):750–6.PubMedGoogle Scholar
  4. 4.
    Engler DB, DeJarnatt AC, Sim TC, Lee JL, Grant JA. Comparison of the sensitivity and precision of four skin test devices. J Allergy Clin Immunol. 1992;90(6 Pt 1):985–91.PubMedGoogle Scholar
  5. 5.
    Williams AJ, Baghat MS, Stableforth DE, Cayton RM, Shenoi PM, Skinner C. Dysphonia caused by inhaled steroids: recognition of a characteristic laryngeal abnormality. Thorax. 1983;38(11):813–21.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Bilo BM, Rueff F, Mosbech H, Bonifazi F, Oude-Elberink JN. Diagnosis of Hymenoptera venom allergy. Allergy. 2005;60(11):1339–49.PubMedGoogle Scholar
  7. 7.
    Devillers AC, de Waard-van der Spek FB, Mulder PG, Oranje AP. Atopy patch tests with aeroallergens in children aged 0-3 years with atopic dermatitis. Allergy. 2008;63(8):1088–90.PubMedGoogle Scholar
  8. 8.
    Bousquet J. Pathophysiology of skin tests. In: Frew DA, editor. Position Paper: allergen standardization and skin tests. Accessed 3 Aug 2015.
  9. 9.
    Friedman MM, Kaliner M. Ultrastructural changes in human skin mast cells during antigen-induced degranulation in vivo. J Allergy Clin Immunol. 1988;82(6):998–1005.PubMedGoogle Scholar
  10. 10.
    Holgate ST, Benyon RC, Lowman MA, Church MK. Activation of human mast cells after immunoglobulin E-dependent and neuropeptide stimulation. Prog Clin Biol Res. 1989;297:103–12.PubMedGoogle Scholar
  11. 11.
    Shalit M, Schwartz LB, von Allmen C, Atkins PC, Lavker RM, Zweiman B. Release of histamine and tryptase during continuous and interrupted cutaneous challenge with allergen in humans. J Allergy Clin Immunol. 1990;86(1):117–25.PubMedGoogle Scholar
  12. 12.
    Fleekop PD, Atkins PC, von Allmen C, Valenzano MC, Shalit M, Zweiman B. Cellular inflammatory responses in human allergic skin reactions. J Allergy Clin Immunol. 1987;80(2):140–6.PubMedGoogle Scholar
  13. 13.
    Shalit M, Campbell DE, von Allmen C, Atkins PC, Douglas SD, Zweiman B. Neutrophil activation in human inflammatory skin reactions. J Allergy Clin Immunol. 1987;80(1):87–93.PubMedGoogle Scholar
  14. 14.
    Frew AJ, Kay AB. The relationship between infiltrating CD4+ lymphocytes, activated eosinophils, and the magnitude of the allergen-induced late phase cutaneous reaction in man. J Immunol. 1988;141:4158–64.PubMedGoogle Scholar
  15. 15.
    Leiferman KM, Fujisawa T, Gray BH, Gleich GJ. Extracellular deposition of eosinophil and neutrophil granule proteins in the IgE-mediated cutaneous late phase reaction. Lab Invest. 1990;62(5):579–89.PubMedGoogle Scholar
  16. 16.
    Gronneberg R, Dahlen SE. Interactions between histamine and prostanoids in IgE-dependent, late cutaneous reactions in man. J Allergy Clin Immunol. 1990;85:843–52.PubMedGoogle Scholar
  17. 17.
    Reshef A, Kagey-Sobotka A, Adkinson NF Jr, Lichtenstein LM, Norman PS. The pattern and kinetics in human skin of erythema and mediators during the acute and late-phase response (LPR). J Allergy Clin Immunol. 1989;84(5 Pt 1):678–87.PubMedGoogle Scholar
  18. 18.
    Shalit M, Valone FH, Atkins PC, Ratnoff WD, Goetzl EJ, Zweiman B. Late appearance of phospholipid platelet-activating factor and leukotriene B4 in human skin after repeated antigen challenge. J Allergy Clin Immunol. 1989;83(3):691–6.PubMedGoogle Scholar
  19. 19.
    Zweiman B. Mediators of allergic reactions in the skin. Clin Allergy. 1988;18:419–35.PubMedGoogle Scholar
  20. 20.
    Warner JA, Pwnkovski MM, Plaut M, Norman PS, Lichtenstein LM. Identification of histamine releasing factor(s) in the late phase of cutaneous IgE-Mediated reactions. J Immunol. 1986;136:2583–7.PubMedGoogle Scholar
  21. 21.
    Bousquet J, Lebel B, Dhivert H, Bataille Y, Martinot B, Michel FB. Nasal challenge with pollen grains, skin-prick tests and specific IgE in patients with grass pollen allergy. Clin Allergy. 1987;17(6):529–36.PubMedGoogle Scholar
  22. 22.
    Heinzerling L, Mari A, Bergmann KC, Bresciani M, Burbach G, Darsow U, Durham S, Fokkens W, Gjomarkaj M, Haahtela T, Bom AT, Wöhrl S, Maibach H, Lockey R. The skin prick test—European standards. Clin Transl Allergy. 2013;3(1):3. Scholar
  23. 23.
    Tatar EC, Sürenoğlu UA, Saylam G, Işık E, Ozdek A, Korkmaz H. Is there any correlation between the results of skin-prick test and the severity of symptoms in allergic rhinitis? Am J Rhinol Allergy. 2012;26(1):e37–9. Scholar
  24. 24.
    Dreborg S. Methods for skin testing. EAACI Position paper. Allergy. 1989;44(Suppl 10):22–30.Google Scholar
  25. 25.
    Dreborg S, Frew A. Allergen standardization and skin tests. EAACI Position paper. Allergy. 1993;48(Suppl 14):49–82.Google Scholar
  26. 26.
    Masse MS, Granger Vallee A, Chiriac A, Dhivert-Donnadieu H, Bousquet-Rouanet L, Bousquet PJ, et al. Comparison of five techniques of skin prick tests used routinely in Europe. Allergy. 2011;66:1415–9.PubMedGoogle Scholar
  27. 27.
    Malling H-J. Reproducibility of skin sensitivity using a quantitative skin prick test. Allergy. 1985;40:400–4.PubMedGoogle Scholar
  28. 28.
    van Kampen V, de Blay F, Folletti I, Kobierski P, Moscato G, Olivieri M, Quirce S, Sastre J, Walusiak-Skorupa J, Raulf-Heimsoth M. EAACI position paper: skin prick testing in the diagnosis of occupational type I allergies. Allergy. 2013;68(5):580–4. Epub 2013 Feb 15.CrossRefGoogle Scholar
  29. 29.
    Bousquet J, Heinzerling L, Bachert C, Papadopoulos NG, Bousquet PJ, Burney PG, et al. Practical guide to skin prick tests in allergy to aeroallergens. Allergy. 2012;67(1):18–24. Epub 2011 Nov 4.CrossRefPubMedGoogle Scholar
  30. 30.
    Goldberg A, Confino-Cohen R. Timing of venom skin tests and IgE determinations after insect sting anaphylaxis. J Allergy Clin Immunol. 1997;100(2):182–4.PubMedGoogle Scholar
  31. 31.
    Rueff F, Bergmann KC, Brockow K, Fuchs T, Grubl A, Jung K, Klimek L, Musken H, Pfaar O, Przybilla B, Sitter H, Wehrmann W. Skin tests for diagnostics of allergic immediate-type reactions. Guideline of the German Society for Allergology and Clinical Immunology. Pneumologie. 2011;65(8):484–95.PubMedGoogle Scholar
  32. 32.
    Bernstein IL, Storms WW. Practice parameters for allergy diagnostic testing. Joint Task Force on Practice Parameters for the Diagnosis and Treatment of Asthma. The American Academy of Allergy, Asthma and Immunology and the American College of Allergy, Asthma and Immunology. Ann Allergy Asthma Immunol. 1995;75(6 Pt 2):543–625.PubMedGoogle Scholar
  33. 33.
    Nelson HS, Knoetzer J, Bucher B. Effect of distance between sites and region of the body on results of skin prick tests. J Allergy Clin Immunol. 1996;97(2):596–601.PubMedGoogle Scholar
  34. 34.
    Carr WW, Martin B, Howard RS, Cox L, Borish L. Comparison of test devices for skin prick testing. J Allergy Clin Immunol. 2005;116(2):341–6.PubMedGoogle Scholar
  35. 35.
    Nelson HS, Kolehmainen C, Lahr J, Murphy J, Buchmeier A. A comparison of multiheaded devices for allergy skin testing. J Allergy Clin Immunol. 2004;113(6):1218–9.PubMedGoogle Scholar
  36. 36.
    Demoly P, Bousquet J, Manderscheid JC, Dreborg S, Dhivert H, Michel FB. Precision of skin prick and puncture tests with nine methods. J Allergy Clin Immunol. 1991;88(5):758–62.PubMedGoogle Scholar
  37. 37.
    Piette V, Bourret E, Bousquet J, Demoly P. Prick tests to aeroallergens: is it possible simply to wipe the device between tests? Allergy. 2002;57(10):940–2.PubMedGoogle Scholar
  38. 38.
    Oppenheimer J, Nelson HS. Skin testing. Ann Allergy Asthma Immunol. 2006;96(2 Suppl 1):S6–S12.PubMedGoogle Scholar
  39. 39.
    Konstantinou GN, Bousquet PJ, Zuberbier T, Papadopoulos NG. The longest wheal diameter is the optimal measurement for the evaluation of skin prick tests. Int Arch Allergy Immunol. 2010;151(4):343–5.Google Scholar
  40. 40.
    Pepys J. Skin testing. Br J Hosp Med. 1975;14:412.Google Scholar
  41. 41.
    Demoly P, Michel F, Bousquet J. In vivo methods for study of allergy. Skin tests, techniques and interpretation. In: Middleton E, Reed C, Ellis E, Adkinson N, Yunginger J, Busse W, editors. Allergy, principles and practice. 5th ed. St Louis: Mosby Co.; 1998. p. 530–9.Google Scholar
  42. 42.
    Simons FE. Advances in H1-antihistamines. N Engl J Med. 2004;351:2203–17.PubMedGoogle Scholar
  43. 43.
    Isik SR, Celikel S, Karakaya G, Ulug B, Kalyoncu AF. The effects of antidepressants on the results of skin prick tests used in the diagnosis of allergic diseases. Int Arch Allergy Immunol. 2010;154:63–8.PubMedGoogle Scholar
  44. 44.
    Sibbald B, Barnes G, Durham SR. Skin prick testing in general practice: a pilot study. J Adv Nurs. 1997;26:537–42.PubMedGoogle Scholar
  45. 45.
    Valyasevi MA, Maddox DE, Li JT. Systemic reactions to allergy skin tests. Ann Allergy Asthma Immunol. 1999;83:132–6.PubMedGoogle Scholar
  46. 46.
    Cantani A, Micera M. Can skin prick tests provoke severe allergic reactions? Eur Rev Med Pharmacol Sci. 2000;4:145–8.PubMedGoogle Scholar
  47. 47.
    Eleuterio Gonzalez J, Leal de Hernandez L, Gonzalez Spencer D. Anaphylactic reaction caused by the performance of skin tests: report of a case. Rev Alerg Mex. 1997;44:74–6.PubMedGoogle Scholar
  48. 48.
    Lierl MB. Isolated late cutaneous reactions to allergen skin testing in children. Ann Allergy Asthma Immunol. 2000;84:294–8.PubMedGoogle Scholar

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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Özlem Naciye Şahin
    • 1
  • Cemal Cingi
    • 2
  • Jennifer Derebery
    • 3
  1. 1.Department of PediatricsAcıbadem Mehmet Ali Aydınlar Medical FacultyIstanbulTurkey
  2. 2.Eskişehir Osmangazi University, Medical FacultyDepartment of OtorhinolaryngologyEskisehirTurkey
  3. 3.Department of Otolaryngology-Head and Neck SurgeryHouse Ear Clinic and Institute, David Geffen School of Medicine, University of California at Los AngelesLos AngelesUSA

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