Overview of skin testing for allergic disease
- Hendrik Nolte, MD, PhD
Hendrik Nolte, MD, PhD
- Allergy and Asthma Unit
- Bispebjerg University Hospital, Copenhagen, Denmark
- Krzysztof Kowal, MD
Krzysztof Kowal, MD
- Department of Allergy and Internal Diseases
- University Medical School, Bialystok, Poland
- Lawrence DuBuske, MD
Lawrence DuBuske, MD
- Clinical Professor of Medicine
- George Washington University School of Medicine, Washington, DC
- Section Editors
- Bruce S Bochner, MD
Bruce S Bochner, MD
- Editor-in-Chief — Allergy and Immunology
- Section Editor — Adult Allergy; Asthma
- Samuel M Feinberg Professor of Medicine
- Northwestern University Feinberg School of Medicine
- Robert A Wood, MD
Robert A Wood, MD
- Editor-in-Chief — Allergy and Immunology
- Section Editor — Pediatric Allergy
- Professor of Pediatrics
- Johns Hopkins University School of Medicine
Immunoglobulin E (IgE)-mediated allergies account for the majority of clinically significant environmental, food, and medication allergies. Skin testing is an important element in the diagnosis of IgE-mediated allergy.
This topic review will discuss general principles of skin testing used in the diagnosis of IgE-mediated allergy, including indications, contraindications, factors influencing results, techniques, and accuracy. The two major methods of skin testing used, the prick/puncture technique and the intradermal technique, are described. The use of skin testing to diagnose specific disorders is presented in the appropriate topic reviews. (See "Diagnostic evaluation of food allergy" and "Allergic rhinitis: Clinical manifestations, epidemiology, and diagnosis", section on 'Skin testing'.)
Other forms of skin testing, such as patch testing for contact dermatitis or atopy patch testing for eosinophilic gastrointestinal disorders, are reviewed separately. (See "Patch testing" and "Allergy testing in eosinophilic esophagitis".)
ROLE IN DIAGNOSIS
There are three components to the diagnosis of an immunoglobulin E (IgE)-mediated allergic disorder. These are:
●Identification of the possible culprit allergen(s), usually through a careful clinical history.
- 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; 75:543.
- Heinzerling L, Mari A, Bergmann KC, et al. The skin prick test - European standards. Clin Transl Allergy 2013; 3:3.
- Ruëff F, Bergmann KC, Brockow K, et al. [Skin tests for diagnostics of allergic immediate-type reactions. Guideline of the German Society for Allergology and Clinical Immunology]. Pneumologie 2011; 65:484.
- Bernstein IL, Li JT, Bernstein DI, et al. Allergy diagnostic testing: an updated practice parameter. Ann Allergy Asthma Immunol 2008; 100:S1.
- Horsmanheimo L, Harvima IT, Harvima RJ, et al. Histamine release in skin monitored with the microdialysis technique does not correlate with the weal size induced by cow allergen. Br J Dermatol 1996; 134:94.
- Agarwal K, Zetterström O. Diagnostic significance of late cutaneous allergic responses and their correlation with radioallergosorbent test. Clin Allergy 1982; 12:489.
- Dolovich J, Hargreave FE, Chalmers R, et al. Late cutaneous allergic responses in isolated IgE-dependent reactions. J Allergy Clin Immunol 1973; 52:38.
- Grönneberg R, Dahlén SE. Interactions between histamine and prostanoids in IgE-dependent, late cutaneous reactions in man. J Allergy Clin Immunol 1990; 85:843.
- dos Santos RV, Magerl M, Mlynek A, Lima HC. Suppression of histamine- and allergen-induced skin reactions: comparison of first- and second-generation antihistamines. Ann Allergy Asthma Immunol 2009; 102:495.
- Devillier P, Bousquet J. Inhibition of the histamine-induced weal and flare response: a valid surrogate measure for antihistamine clinical efficacy? Clin Exp Allergy 2007; 37:400.
- Dreborg S. The skin prick test in the diagnosis of atopic allergy. J Am Acad Dermatol 1989; 21:820.
- Pearlman DS, Grossman J, Meltzer EO. Histamine skin test reactivity following single and multiple doses of azelastine nasal spray in patients with seasonal allergic rhinitis. Ann Allergy Asthma Immunol 2003; 91:258.
- Jones JD, Temino VM, Dworski R, et al. Use of olopatadine ophthalmic solution and reactivity of histamine skin testing. Allergy Asthma Proc 2008; 29:636.
- Kupczyk M, Kupryś I, Bocheńska-Marciniak M, et al. Ranitidine (150 mg daily) inhibits wheal, flare, and itching reactions in skin-prick tests. Allergy Asthma Proc 2007; 28:711.
- Andersson M, Pipkorn U. Inhibition of the dermal immediate allergic reaction through prolonged treatment with topical glucocorticosteroids. J Allergy Clin Immunol 1987; 79:345.
- Gradman J, Wolthers OD. Suppressive effects of topical mometasone furoate and tacrolimus on skin prick testing in children. Pediatr Dermatol 2008; 25:269.
- Pipkorn U, Hammarlund A, Enerbäck L. Prolonged treatment with topical glucocorticoids results in an inhibition of the allergen-induced weal-and-flare response and a reduction in skin mast cell numbers and histamine content. Clin Exp Allergy 1989; 19:19.
- Noga O, Hanf G, Kunkel G. Immunological and clinical changes in allergic asthmatics following treatment with omalizumab. Int Arch Allergy Immunol 2003; 131:46.
- Corren J, Shapiro G, Reimann J, et al. Allergen skin tests and free IgE levels during reduction and cessation of omalizumab therapy. J Allergy Clin Immunol 2008; 121:506.
- Rao KS, Menon PK, Hilman BC, et al. Duration of the suppressive effect of tricyclic antidepressants on histamine-induced wheal-and-flare reactions in human skin. J Allergy Clin Immunol 1988; 82:752.
- Isik SR, Celikel S, Karakaya G, et al. The effects of antidepressants on the results of skin prick tests used in the diagnosis of allergic diseases. Int Arch Allergy Immunol 2011; 154:63.
- Spergel JM, Nurse N, Taylor P, ParneixSpake A. Effect of topical pimecrolimus on epicutaneous skin testing. J Allergy Clin Immunol 2004; 114:695.
- Olson R, Karpink MH, Shelanski S, et al. Skin reactivity to codeine and histamine during prolonged corticosteroid therapy. J Allergy Clin Immunol 1990; 86:153.
- Simons FE, Johnston L, Gu X, Simons KJ. Suppression of the early and late cutaneous allergic responses using fexofenadine and montelukast. Ann Allergy Asthma Immunol 2001; 86:44.
- Hill SL 3rd, Krouse JH. The effects of montelukast on intradermal wheal and flare. Otolaryngol Head Neck Surg 2003; 129:199.
- Cuhadaroglu C, Erelel M, Kiyan E, et al. Role of Zafirlukast on skin prick test. Allergol Immunopathol (Madr) 2001; 29:66.
- Des Roches A, Paradis L, Bougeard YH, et al. Long-term oral corticosteroid therapy does not alter the results of immediate-type allergy skin prick tests. J Allergy Clin Immunol 1996; 98:522.
- Spector SL. Effect of a selective beta 2 adrenergic agonist and theophylline on skin test reactivity and cardiovascular parameters. J Allergy Clin Immunol 1979; 64:23.
- Munro CS, Higgins EM, Marks JM, et al. Cyclosporin A in atopic dermatitis: therapeutic response is dissociated from effects on allergic reactions. Br J Dermatol 1991; 124:43.
- Joint Task Force on Practice Parameters, American Academy of Allergy, Asthma and Immunology, American College of Allergy, Asthma and Immunology, Joint Council of Allergy, Asthma and Immunology. The diagnosis and management of anaphylaxis: an updated practice parameter. J Allergy Clin Immunol 2005; 115:S483.
- Skassa-Brociek W, Manderscheid JC, Michel FB, Bousquet J. Skin test reactivity to histamine from infancy to old age. J Allergy Clin Immunol 1987; 80:711.
- Ménardo JL, Bousquet J, Rodière M, et al. Skin test reactivity in infancy. J Allergy Clin Immunol 1985; 75:646.
- Song WJ, Lee SM, Kim MH, et al. Histamine and allergen skin reactivity in the elderly population: results from the Korean Longitudinal Study on Health and Aging. Ann Allergy Asthma Immunol 2011; 107:344.
- de Vos G, Nazari R, Ferastraoaru D, et al. Discordance between aeroallergen specific serum IgE and skin testing in children younger than 4 years. Ann Allergy Asthma Immunol 2013; 110:438.
- 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; 97:596.
- Sin BA, Inceoglu O, Mungan D, et al. Is it important to perform pollen skin prick tests in the season? Ann Allergy Asthma Immunol 2001; 86:382.
- Anhoej C, Backer V, Nolte H. Diagnostic evaluation of grass- and birch-allergic patients with oral allergy syndrome. Allergy 2001; 56:548.
- Carr WW, Martin B, Howard RS, et al. Comparison of test devices for skin prick testing. J Allergy Clin Immunol 2005; 116:341.
- Masse MS, Granger Vallée A, Chiriac A, et al. Comparison of five techniques of skin prick tests used routinely in Europe. Allergy 2011; 66:1415.
- Engler DB, DeJarnatt AC, Sim TC, et al. Comparison of the sensitivity and precision of four skin test devices. J Allergy Clin Immunol 1992; 90:985.
- Montalvo A, Martín S, Mesa A, et al. [Comparative study of 3 types of lancets for performing prick tests]. Allergol Immunopathol (Madr) 1996; 24:58.
- Nelson HS, Kolehmainen C, Lahr J, et al. A comparison of multiheaded devices for allergy skin testing. J Allergy Clin Immunol 2004; 113:1218.
- Nelson HS, Lahr J, Buchmeier A, McCormick D. Evaluation of devices for skin prick testing. J Allergy Clin Immunol 1998; 101:153.
- Dykewicz MS, Lemmon JK, Keaney DL. Comparison of the Multi-Test II and Skintestor Omni allergy skin test devices. Ann Allergy Asthma Immunol 2007; 98:559.
- Hamilton RG, Adkinson NF Jr. 23. Clinical laboratory assessment of IgE-dependent hypersensitivity. J Allergy Clin Immunol 2003; 111:S687.
- Matsson P, Hamilton RG, Adkinson NF Jr, et al. Evaluation methods and analytical performance characteristics of immunologic assays for human immunoglobulin E (IgE) antibodies of defined allergen specificities. Wayne (PA): National Committee on Clinical Laboratory Standards (NCCLS). Approved guideline 1997; 17:24.
- Oppenheimer J, Nelson HS. Skin testing: a survey of allergists. Ann Allergy Asthma Immunol 2006; 96:19.
- Adinoff AD, Rosloniec DM, McCall LL, Nelson HS. Immediate skin test reactivity to Food and Drug Administration-approved standardized extracts. J Allergy Clin Immunol 1990; 86:766.
- Pepys J. Skin testing. Br J Hosp Med 1975; 14:412.
- Tschopp JM, Sistek D, Schindler C, et al. Current allergic asthma and rhinitis: diagnostic efficiency of three commonly used atopic markers (IgE, skin prick tests, and Phadiatop). Results from 8329 randomized adults from the SAPALDIA Study. Swiss Study on Air Pollution and Lung Diseases in Adults. Allergy 1998; 53:608.
- Sampson HA. Role of immediate food hypersensitivity in the pathogenesis of atopic dermatitis. J Allergy Clin Immunol 1983; 71:473.
- Crobach MJ, Hermans J, Kaptein AA, et al. The diagnosis of allergic rhinitis: how to combine the medical history with the results of radioallergosorbent tests and skin prick tests. Scand J Prim Health Care 1998; 16:30.
- Bousquet J, Lebel B, Dhivert H, et al. Nasal challenge with pollen grains, skin-prick tests and specific IgE in patients with grass pollen allergy. Clin Allergy 1987; 17:529.
- Sampson HA. Update on food allergy. J Allergy Clin Immunol 2004; 113:805.
- Dolen WK. Skin testing techniques. Immunol Allergy Clin North Am 2001; 21:273.
- Nadarajah R, Rechtweg J, Corey JP. Introduction to serial endpoint titration. Immunol Allergy Clin North Am 2001; 21:369.
- Lin SY, Mabry RL. Allergy practice in the academic otolaryngology setting: results of a comprehensive survey. Otolaryngol Head Neck Surg 2006; 134:25.
- Williams PB, Nolte H, Dolen WK, et al. The histamine content of allergen extracts. J Allergy Clin Immunol 1992; 89:738.
- Nelson HS, Oppenheimer J, Buchmeier A, et al. An assessment of the role of intradermal skin testing in the diagnosis of clinically relevant allergy to timothy grass. J Allergy Clin Immunol 1996; 97:1193.
- 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; 103:773.
- Lockey RF, Benedict LM, Turkeltaub PC, Bukantz SC. Fatalities from immunotherapy (IT) and skin testing (ST). J Allergy Clin Immunol 1987; 79:660.
- Bernstein DI, Wanner M, Borish L, et al. Twelve-year survey of fatal reactions to allergen injections and skin testing: 1990-2001. J Allergy Clin Immunol 2004; 113:1129.
- Lockey RF, Nicoara-Kasti GL, Theodoropoulos DS, Bukantz SC. Systemic reactions and fatalities associated with allergen immunotherapy. Ann Allergy Asthma Immunol 2001; 87:47.
- Bagg A, Chacko T, Lockey R. Reactions to prick and intradermal skin tests. Ann Allergy Asthma Immunol 2009; 102:400.
- Norrman G, Fälth-Magnusson K. Adverse reactions to skin prick testing in children - prevalence and possible risk factors. Pediatr Allergy Immunol 2009; 20:273.
- Pitsios C, Dimitriou A, Stefanaki EC, Kontou-Fili K. Anaphylaxis during skin testing with food allergens in children. Eur J Pediatr 2010; 169:613.
- Pitsios C. Generalized allergic reactions during skin testing. Pediatr Allergy Immunol 2010; 21:557.
- Ricketti PA, Unkle DW, Cleri DJ, Ricketti AJ. Delayed anaphylaxis secondary to allergy skin testing. Ann Allergy Asthma Immunol 2013; 111:420.
- ROLE IN DIAGNOSIS
- OVERVIEW OF SKIN TESTING
- Advantages over in vitro tests
- Biologic mechanism
- Sensitization versus clinical allergy
- General versus focused testing
- High risk for anaphylaxis
- Recent anaphylaxis
- Skin conditions
- FACTORS AFFECTING RESULTS
- Medications that should be discontinued
- - Beta blockers and ACE inhibitors
- Physiologic variables
- Technical variables
- - Quality of the extract
- - Skin test device
- ALLERGEN PREPARATION
- SKIN TESTING METHODS
- Prick/puncture method
- - Technique
- Definition of a positive test
- Prick-by-prick testing with fresh food
- - Accuracy and interpretation
- Positive results
- Negative results
- Intradermal method
- - Technique
- Definition of a positive test
- End-point dilution technique
- - Accuracy
- Intradermal testing and high-risk allergens
- Overall incidence of systemic reactions
- Anaphylaxis with prick/puncture testing
- INFORMATION FOR PATIENTS