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The skin prick test in the diagnosis of atopic allergy
Journal of the American Academy of Dermatology
Johansson (Pharmacia Diagnostics AB, Uppsala, Sweden), which, by detecting IgE antibodies to common inhalant allergens, can identify almost 100% of persons sensitized to common inhalants. 3 Children allergic only to food allergens or adults sensitized only to very special allergens, such as those occurring in occupational environments, will not be detected by Phadiatop, but these individuals often have increased total IgE levels. The next step would be to break down a positive test for atopy into groups of likely allergens by using mixed allergen disks. These disks can consist of allergens unique for a particular geographic region, a type of disease such as atopic eczema, or a particular age group of patients or be based on the prevalence of unique allergens in a given occupational environment. However, it is impossible to screen patients with all of the approximately 300 different allergens available for RAST. Phadiatop can also be used to identify a negative screening result when there is a need to exclude allergy conclusively. In contrast to its role in asthma and hay fever, little is known about the role of IgE in dermatologic disorders. However, IgE antibodies are thought to be
II
an important "trigger" in atopic eczema in childhood. Another area of interest is contact urticaria. IgE antibodies to proteins from the rubber tree, as present in latex, are found in an occupational allergy mainly manifesting as contact urticaria. 4 The route of sensitization could be through the skin. Further studies should be performed in this interesting field. In conclusion, atopic allergy can be diagnosed easily and reliably by determining IgE antibodies in serum by RAST. The importance of circulating IgE antibodies in dermatologic disorders should be studied further, but atopic eczema and contact urticaria are two entities for which a RAST-based diagnosis is of great help. REFERENCES 1. Bennich H, Ishizaka K, Johansson SGO, et al. Immunoglobulin E. A new class of human immunoglobulin. Bull WHO 1968;38:151. 2. Wide L, Bennich H, Johansson SGO. Diagnosis of allergy by an in vitro test for allergen antibodies. Lancet 1967; 2:1105. 3. Duc J, Peitrequin R, P6coud A. Value of a new screening test for respiratory allergy. Allergy 1988;43:332. 4. Axelsson IGK, Johansson SGO, Wrangsj6 K. IgE-mediated anaphylactoid reactions to rubber. Allergy 1987;42:46.
I
II I
The skin prick test in the diagnosis of atopic allergy Sten Dreborg, MD LinkOping, Sweden The factors that influence the results Ofskin prick tests are reviewed.The concentrationand compositionof allergen preparations, the test technique used, and the prevalenceof allergy in the populationstudied are emphasized. (J AM ACADDERMATOL1989;21:820-1.) The usefulness of the skin prick test (SPT) in the diagnosis of atopic allergy depends on standardization of the allergenic material, the equipment, and the technique used. Allergenic preparations of known composition should be used. The composition of allergens used for SPT can be investigated by crossed immunoelectrophoresis/ crossed radioimmunoelectrophoresis, rocket immuFrom the Faculty of Health Sciences, University of Link6ping. Reprint requests: Sten Dreborg,MD, Department of Pediatrics, University Hospital of Link6ping,S-581 8 5 Link6ping, Sweden.
16/o/1~904 82O
noelectrophoresis, immunoblotting, or similar immunochemical procedures. Calibration of the concentration of allergenic material in relation to a standard should be performed by radioallergosorbent (RAST) inhibition,l, 2 The in-house standard of the laboratory/company should be freeze-dried and compared with international standard preparations, when available) The potency should be expressed in international units (IU/ml) and in biologically meaningful units, such as the allergy units proposed by the Food and Drug Administration4 or the biological units (BU/ml) prescribed by the Nordic Council on
Volume 21 Number 4, Part 2 October 1989
Medicines.5, 6 Several different devices suitable for SPT have been proposed. The uncoated Phazet (Pharmacia AB, Uppsala, Sweden) needle,7 developed from the @sterballe needle,8has been shown to give the most reproducible results. 9 Furthermore, to obtain meaningful information, personnel must be trained to perform SPT with a reproducible technique. 1° For the proper use of tests for diagnosis and epidemiologic studies, it is essential that the sensitivity and specificity11 be well documented. Several problems are involved in such documentation. The diagnostic properties of SPT vary with the concentration or composition of allergen preparations, 1 the SPT technique, 12 the prevalence of disease in the sample studied, la and the definition of criteria for allergy (disease) to the allergen in question) 3 The frequency of positive test results is highly influenced by the allergen concentration and also by the SPT technique used. A traumatic SPT technique introduces more allergen into the skin and induces a more pronounced reaction than does an atraumatic technique, lo In samples of patients with a high prevalence of allergy (patients attending a pediatric allergy unit), a higher concentration of allergen must be used than in patients with a low prevalence of allergy (consecutive elderly persons in a community), t2 Criteria used to define a disease strongly influence the sensitivity and specificity of the SPT. The history is the basis of all diagnostic procedures. However, a diagnosis of mite, mold, animal, or grass pollen allergy 14 is difficult to establish based only on the history. We investigated the relevance of the conjunctival provocation test for confirming the diagnosis of rhinoconjunctivitis caused by allergy to dogs.15 To diagnose all patients with a positive history of dog allergy, 1 × 106 BU/ml (2.5 × 106 IU/ ml) was needed. Next, the sensitivity and specificity of different concentrations of allergen used in the SPT was investigated. Disease was defined by a positive history and a positive conjunctival provocation test result at a concentration of 1 × 106 BU/ml. An SPT with 1 X 106 BU/ml showed a high sensitivity and should be used for screening purposes, whereas 1 X 10 4 BU/ml showed a high specificity. In the fu-
SPT in diagnosis of atopic allergy 821 ture, similar documentation is needed not only for common inhalant allergens but also for other allergens, such as food allergens, 13 before meaningful epidemiologic studies can be begun. REFERENCES
1. Dreborg S, Einarsson R, Longbottom J. The chemistry and standardization of allergens. In: Weir DM, ed. Handbook of experimental immunology, vol 28. Edinburgh: Blackwell, 1986:1-28. 2. Yman L, Ponterius G, Brandt R. RAST based allergen assay methods. Dev Biol Stand 1975;29:151-65. 3. Norman PS. International units. In: Schaeffer M, Sisk C, Brede HD, eds. Regulatory control and standardization of allergenic extracts. Fourth International Paul Ehrlich Seminar, October 16-17, 1985, Washington, DC. Stuttgart: Gustav Fisher, 1987:175-82. 4. Baer H. Potency units for allergenic extracts in the USA. In: Schaeffer M, Sisk C, Brede HD, eds. Regulatory control and standardization of allergenic extracts. Fourth International Paul Ehrllch Seminar, October 16-i7, 1985, Washington, DC: Stuttgart: Gustav Fischer, 1987: 167-8. 5. Turkeltaub PC. Biological standardization based on quantitative skin testing: the ID 50 EAL method (intradermal dilution for 50 mm sum of erythema diameters determines standardization of allergenic extracts). Fourth International Paul Ehrlich Seminar, October 16-17, 1985, Washington, DC. Stuttgart: Gustav Fisher, 1987:169-73. 6. Nordic Council on Medicines. Registration of allergenic preparations. Nordic guidelines. 2nd ed. Uppsala: NLN Publications, 1988. 7. Dreborg S, Basomba A, Belin L, et al. Biological equilibration of allergenic preparations. Methodological aspects and reproducibility. Clin Allergy 1987;17:537-50. 8. Belin L, Dreborg S, Einarsson R, etal. Phazet--a new type of skin prick test. Calibration and stability. Allergy 1985; 40:60-3. 9. ~bsterballe O, Weeke B. A new lancet for skin prick testing. Allergy 1979;34:209-12. 10. Chanal I, Horst M, Segalen C, et al. Comparison between modified skin prick test with standardized allergen extracts and Phazet. J Allergy Clin Immunol 1988;82:878-80. 11. Galen RS, Gambino SR. Beyond normality. The predictive value and efficiency of medical diagnosis. New York: John Wiley & Sons, 1975. 12. Drcborg S. The skin prick test. Methodological studies and clinical applications [Dissertation]. Linkrping, Sweden: Link~ping University, 1987. 13. Dreborg S. Skin test in diagnosis of food allergy. Ann Allergy (in press). 14. Petersson G, Dreborg S, Ingestad R. Clinical history, skin prick test and RAST in the diagnosis of birch and timothy pollinosis. Allergy 1986;41:398-407. 15. Rim~s M, Dreborg S, Bjrrkst~n B, et al. Diagnosis of dog rkino-conjunctMtis (RC) by history (CH), skin prick test (SPT), RAST and nasal (NPT) and eonjunctivat (CPT) provocation tests. Allergy 1988;41:109.
Johansson (Pharmacia Diagnostics AB, Uppsala, Sweden), which, by detecting IgE antibodies to common inhalant allergens, can identify almost 100% of persons sensitized to common inhalants. 3 Children allergic only to food allergens or adults sensitized only to very special allergens, such as those occurring in occupational environments, will not be detected by Phadiatop, but these individuals often have increased total IgE levels. The next step would be to break down a positive test for atopy into groups of likely allergens by using mixed allergen disks. These disks can consist of allergens unique for a particular geographic region, a type of disease such as atopic eczema, or a particular age group of patients or be based on the prevalence of unique allergens in a given occupational environment. However, it is impossible to screen patients with all of the approximately 300 different allergens available for RAST. Phadiatop can also be used to identify a negative screening result when there is a need to exclude allergy conclusively. In contrast to its role in asthma and hay fever, little is known about the role of IgE in dermatologic disorders. However, IgE antibodies are thought to be
II
an important "trigger" in atopic eczema in childhood. Another area of interest is contact urticaria. IgE antibodies to proteins from the rubber tree, as present in latex, are found in an occupational allergy mainly manifesting as contact urticaria. 4 The route of sensitization could be through the skin. Further studies should be performed in this interesting field. In conclusion, atopic allergy can be diagnosed easily and reliably by determining IgE antibodies in serum by RAST. The importance of circulating IgE antibodies in dermatologic disorders should be studied further, but atopic eczema and contact urticaria are two entities for which a RAST-based diagnosis is of great help. REFERENCES 1. Bennich H, Ishizaka K, Johansson SGO, et al. Immunoglobulin E. A new class of human immunoglobulin. Bull WHO 1968;38:151. 2. Wide L, Bennich H, Johansson SGO. Diagnosis of allergy by an in vitro test for allergen antibodies. Lancet 1967; 2:1105. 3. Duc J, Peitrequin R, P6coud A. Value of a new screening test for respiratory allergy. Allergy 1988;43:332. 4. Axelsson IGK, Johansson SGO, Wrangsj6 K. IgE-mediated anaphylactoid reactions to rubber. Allergy 1987;42:46.
I
II I
The skin prick test in the diagnosis of atopic allergy Sten Dreborg, MD LinkOping, Sweden The factors that influence the results Ofskin prick tests are reviewed.The concentrationand compositionof allergen preparations, the test technique used, and the prevalenceof allergy in the populationstudied are emphasized. (J AM ACADDERMATOL1989;21:820-1.) The usefulness of the skin prick test (SPT) in the diagnosis of atopic allergy depends on standardization of the allergenic material, the equipment, and the technique used. Allergenic preparations of known composition should be used. The composition of allergens used for SPT can be investigated by crossed immunoelectrophoresis/ crossed radioimmunoelectrophoresis, rocket immuFrom the Faculty of Health Sciences, University of Link6ping. Reprint requests: Sten Dreborg,MD, Department of Pediatrics, University Hospital of Link6ping,S-581 8 5 Link6ping, Sweden.
16/o/1~904 82O
noelectrophoresis, immunoblotting, or similar immunochemical procedures. Calibration of the concentration of allergenic material in relation to a standard should be performed by radioallergosorbent (RAST) inhibition,l, 2 The in-house standard of the laboratory/company should be freeze-dried and compared with international standard preparations, when available) The potency should be expressed in international units (IU/ml) and in biologically meaningful units, such as the allergy units proposed by the Food and Drug Administration4 or the biological units (BU/ml) prescribed by the Nordic Council on
Volume 21 Number 4, Part 2 October 1989
Medicines.5, 6 Several different devices suitable for SPT have been proposed. The uncoated Phazet (Pharmacia AB, Uppsala, Sweden) needle,7 developed from the @sterballe needle,8has been shown to give the most reproducible results. 9 Furthermore, to obtain meaningful information, personnel must be trained to perform SPT with a reproducible technique. 1° For the proper use of tests for diagnosis and epidemiologic studies, it is essential that the sensitivity and specificity11 be well documented. Several problems are involved in such documentation. The diagnostic properties of SPT vary with the concentration or composition of allergen preparations, 1 the SPT technique, 12 the prevalence of disease in the sample studied, la and the definition of criteria for allergy (disease) to the allergen in question) 3 The frequency of positive test results is highly influenced by the allergen concentration and also by the SPT technique used. A traumatic SPT technique introduces more allergen into the skin and induces a more pronounced reaction than does an atraumatic technique, lo In samples of patients with a high prevalence of allergy (patients attending a pediatric allergy unit), a higher concentration of allergen must be used than in patients with a low prevalence of allergy (consecutive elderly persons in a community), t2 Criteria used to define a disease strongly influence the sensitivity and specificity of the SPT. The history is the basis of all diagnostic procedures. However, a diagnosis of mite, mold, animal, or grass pollen allergy 14 is difficult to establish based only on the history. We investigated the relevance of the conjunctival provocation test for confirming the diagnosis of rhinoconjunctivitis caused by allergy to dogs.15 To diagnose all patients with a positive history of dog allergy, 1 × 106 BU/ml (2.5 × 106 IU/ ml) was needed. Next, the sensitivity and specificity of different concentrations of allergen used in the SPT was investigated. Disease was defined by a positive history and a positive conjunctival provocation test result at a concentration of 1 × 106 BU/ml. An SPT with 1 X 106 BU/ml showed a high sensitivity and should be used for screening purposes, whereas 1 X 10 4 BU/ml showed a high specificity. In the fu-
SPT in diagnosis of atopic allergy 821 ture, similar documentation is needed not only for common inhalant allergens but also for other allergens, such as food allergens, 13 before meaningful epidemiologic studies can be begun. REFERENCES
1. Dreborg S, Einarsson R, Longbottom J. The chemistry and standardization of allergens. In: Weir DM, ed. Handbook of experimental immunology, vol 28. Edinburgh: Blackwell, 1986:1-28. 2. Yman L, Ponterius G, Brandt R. RAST based allergen assay methods. Dev Biol Stand 1975;29:151-65. 3. Norman PS. International units. In: Schaeffer M, Sisk C, Brede HD, eds. Regulatory control and standardization of allergenic extracts. Fourth International Paul Ehrlich Seminar, October 16-17, 1985, Washington, DC. Stuttgart: Gustav Fisher, 1987:175-82. 4. Baer H. Potency units for allergenic extracts in the USA. In: Schaeffer M, Sisk C, Brede HD, eds. Regulatory control and standardization of allergenic extracts. Fourth International Paul Ehrllch Seminar, October 16-i7, 1985, Washington, DC: Stuttgart: Gustav Fischer, 1987: 167-8. 5. Turkeltaub PC. Biological standardization based on quantitative skin testing: the ID 50 EAL method (intradermal dilution for 50 mm sum of erythema diameters determines standardization of allergenic extracts). Fourth International Paul Ehrlich Seminar, October 16-17, 1985, Washington, DC. Stuttgart: Gustav Fisher, 1987:169-73. 6. Nordic Council on Medicines. Registration of allergenic preparations. Nordic guidelines. 2nd ed. Uppsala: NLN Publications, 1988. 7. Dreborg S, Basomba A, Belin L, et al. Biological equilibration of allergenic preparations. Methodological aspects and reproducibility. Clin Allergy 1987;17:537-50. 8. Belin L, Dreborg S, Einarsson R, etal. Phazet--a new type of skin prick test. Calibration and stability. Allergy 1985; 40:60-3. 9. ~bsterballe O, Weeke B. A new lancet for skin prick testing. Allergy 1979;34:209-12. 10. Chanal I, Horst M, Segalen C, et al. Comparison between modified skin prick test with standardized allergen extracts and Phazet. J Allergy Clin Immunol 1988;82:878-80. 11. Galen RS, Gambino SR. Beyond normality. The predictive value and efficiency of medical diagnosis. New York: John Wiley & Sons, 1975. 12. Drcborg S. The skin prick test. Methodological studies and clinical applications [Dissertation]. Linkrping, Sweden: Link~ping University, 1987. 13. Dreborg S. Skin test in diagnosis of food allergy. Ann Allergy (in press). 14. Petersson G, Dreborg S, Ingestad R. Clinical history, skin prick test and RAST in the diagnosis of birch and timothy pollinosis. Allergy 1986;41:398-407. 15. Rim~s M, Dreborg S, Bjrrkst~n B, et al. Diagnosis of dog rkino-conjunctMtis (RC) by history (CH), skin prick test (SPT), RAST and nasal (NPT) and eonjunctivat (CPT) provocation tests. Allergy 1988;41:109.