Contents
26.1 Introduction . . . . 429
26.2 Skin Prick Test . . . . 429
26.3 Scratch Test . . . . 430
26.4 Scratch-Chamber Test . . . . 430
26.5 Chamber Test . . . . 430
26.6 Open Application Test . . . . 430
26.7 Rub Test . . . . 431
26.8 Factors Suppressing Immediate Skin Test Reactivity . . . . 431
26.9 Control Tests . . . . 431
References . . . . 432
26.1 Introduction
Immediate contact reactions comprise both immu- nologic (allergic) and nonimmunologic (non-aller- gic) reactions. Itching, burning, and tingling are the most usual subjective symptoms. Mild reactions ap- pear as redness only, but in stronger reactions, con- tact urticaria or eczematous dermatitis can be seen.
Skin tests are usually reliable in detecting immedi- ate allergies. Medication, such as acetylsalicylic acid and other prostaglandin inhibitors, and ultraviolet radiation readily abolish nonimmunological reactiv- ity. They have less influence on allergic reactions.
This chapter deals with the most usual and most use- ful skin tests, discussing their advantages and disad- vantages (Table 1).
26.2 Skin Prick Test
The skin prick test (SPT) is usually the most conven- ient and reliable method for detecting clinically sig- nificant, immunoglobulin E (IgE)-mediated allergy.
Large numbers of standardized allergens are avail-
able commercially. Self-made test material can also be used.
Drops of SPT allergen solutions are applied to the skin of the back or lower arm, 3–5 cm apart, and pierced with a special prick test lancet. Histamine di- hydrochloride, 10 mg/ml, is used as a positive control and the base solution as a negative control. After piercing the skin, the drops are wiped off with a soft tissue. After 15–20 min, the diameters or areas of the wheals are measured. Redness around the weal is usually not taken into consideration. The result is usually expressed as the mean of the longest diame- ter of the weal and the longest diameter perpendicu- lar to it. Reactions larger than 3 mm and at least half the size of that produced by histamine are regarded as positive [1–3]. Reactions at least the size of that by histamine are usually clinically relevant. Those smaller than half the size of the histamine reaction are usually not significant.
In a cheaper modification of the ordinary SPT, the lancet is first dipped in the allergen solution and, im-
Chapter 26
Skin Tests
for Immediate Hypersensitivity
Matti Hannuksela
26
Table 1.Skin tests for immediate hypersensitivity reactions
Test Remarks
Skin prick test (SPT) For immediate allergy.
Especially for standardized allergen solutions
Prick-by-prick For testing with fresh foods Scratch test For immunoglobulin E (IgE)-
mediated immediate allergy.
Non-standardized allergens Scratch-chamber test May be less sensitive than
scratch test
Open application test For both immunologic and nonimmunologic reactions Previously affected skin reacts more readily than healthy skin Skin application food test Resembles chamber test. An
alternative to open application test
Rub test Another modification of the open application test 26_429_432 05.11.2005 10:41 Uhr Seite 429
mediately after that, the skin is pricked [4]. No statis- tical difference has been noticed in the size of the wheals.
Another modification of the SPT is the prick-by- prick method used especially for testing with fresh foodstuffs [5, 6]. A piece of food is pricked with the lancet, immediately after which, the skin is pricked with the same lancet. The results are grouped as mentioned above.
쐽 The skin prick test is the standard skin test method for detecting immediate allergies.
Commercial standardized allergens are recommended. Skin from the back and the arm are the preferable test sites. The result is read after 15–20 min. Reactions greater than 3 mm and at least the size of hista- mine dihydrochloride, 10 mg/ml, are usual- ly clinically significant. Reactions smaller than half of that from histamine are con- sidered negative.
26.3 Scratch Test
This previously common method for detecting im- mediate allergy is still used when only non-standard- ized allergens are available. In SPT with, e.g., fresh meat, poultry, flours, spices, fruits, and vegetables, skin infection and other untoward effects are more likely than in a scratch test. Scratches approximately 5-mm long are made with a blood lancet or veni- puncture needle on arm or back skin 3–5 cm apart, and bleeding is avoided. Allergen solutions are ap- plied to the scratches for 5–10 min, after which, they can be wiped off with a soft tissue. Powdered aller- gens are mixed with a drop of physiological saline or 0.1N sodium hydroxide. Histamine dihydrochloride, 10 mg/ml, is the positive and saline or 0.1N sodium hydroxide is the negative control. The results are read 15–20 min after application. Only the longest diame- ter of the weal perpendicular to the scratch is meas- ured. Reactions equal to or greater than that from histamine are usually clinically significant. Spices like cinnamon and mustard also produce nonimmu- nologic contact urticaria reactions, often indistin- guishable from true allergic reactions. The signifi- cance of such reactions should be interpreted with caution.
26.4 Scratch-Chamber Test
In this test, the scratch with the allergen is covered with an 8-mm, or, preferably, a 12-mm Finn chamber (Epitest, Helsinki, Finland). This method has been used when fruits, vegetables, and other fresh foods have been tested [7]. The control substances and reading are the same as for the scratch test. In a study on apple allergy, the sensitivity of the scratch-cham- ber test has been found to be inferior to that of SPT [8].
쐽 The scratch test and its modification, the scratch-chamber test, are suitable for test- ing with non-standardized materials, such as meat, flours, fruits, vegetables, and spic- es. Covering the scratch with an epicutane- ous test chamber may decrease the sensi- tivity or specificity of the scratch test.
26.5 Chamber Test
In addition to the SPT, scratch test, and scratch- chamber test, the chamber test has been used in the diagnosis of immediate contact allergy. There might be two types of immediate allergy: that detected by the SPT, and that found by an occluded epicutaneous test (chamber test) [9, 10]. There seems to be three kinds of patients: those reacting to SPT only, those reacting to the chamber test only, and those reacting to both [9].
The test material is put into an ordinary patch test chamber (e.g., Finn chamber), moistened with phys- iological saline when needed, and applied to the back or upper arm for 15–20 min. The test is read some minutes after the removal of the test chamber. A weal-and-flare reaction is regarded as positive, and erythema without edema as unlikely to be positive.
One should keep in mind that materials such as cin- namon and mustard elicit readily nonimmunologic contact urticaria reactions. When testing materials of unknown irritancy, an appropriate number of con- trol cases should also be tested.
26.6 Open Application Test
This test is also known as the contact urticaria test, open patch test, and provocative test. It can be used
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for both immunologic (allergic) and nonimmuno- logic reactions. Immunologic reactions appear on the arms as readily as on the back skin. Nonimmuno- logic reactions, on the other hand, appear less readily on the ventral aspects of lower arms, while the back skin and the outer aspects of the upper arms are equally sensitive [11]. Allergic reactions are usually more readily produced on previously affected skin than on normal-looking, healthy skin [12]. Cosmetic creams may produce positive reactions on the cheek while the back skin shows no response.
Liquids, creams, and ointments are tested by spreading 0.1 ml of the test substance to an area of about 3×3 cm in size on the upper back or the outer aspect of the upper arm [13]. When testing a greater number of substances at the same time, 10-µl ali- quots are applied to 1×1-cm areas. After 15–60 min, the test materials are gently wiped off with a soft paper towel or tissue. Dry test materials, such as latex gloves and carbonless copy paper, are applied direct- ly to the skin moistened with two or three drops of water for better contact. Powders should be mixed with a proper vehicle. Petrolatum and water were the most popular vehicles some decades ago, but alcohol vehicles with propylene glycol may enhance the reac- tivity [14, 15].
The test is usually read at 20, 40, and 60 min.
When testing previously unknown substances, it is advisable to follow the result for 6–8 h at 1–2-h inter- vals. Nonimmunologic reactions tend to appear more slowly than allergic ones. The time of maximal reac- tivity depends on the substance itself and on the ve- hicle used [14].
In visual grading, redness and edema are usually assessed separately (+ weak, ++ moderate, +++
strong). However, objective measurements are pre- ferred. Erythema can be measured, e.g., with chro- mameter or with laser Doppler flowmeter.
쐽 The open application test, also known as the contact urticaria test, open patch test, and provocative test, is usually done on the upper back skin or on the outer aspects of the upper arms. Allergic reactions also ap- pear as readily on the lower arms. Aliquots of 0.1 ml are spread onto 3×3-cm areas.
When testing a greater number of sub- stances, 10-µl aliquots are applied to 1×1- cm areas. Allergic reactions usually appear usually within 15–20 min, but may last sev- eral hours.
26.7 Rub Test
In the rub test, the suspected substance is gently rubbed into slightly affected or healthy skin [7]. Rub- bing may enhance the reactivity compared to the open application test.
In the skin application food test (SAFT), 0.8 ml of liquid food or a solid piece of food is placed on a 4- cm2gauze and fixed onto the back skin with acrylic tape [16]. The test can also be performed by using patch test chambers (e.g., van der Bend or large Finn chambers). The results are followed up every 10 min, the maximal occlusion time being 30 min. The test results are highly reproducible.
쐽 The rub test and the skin application food test (SAFT) are modifications of the open application and chamber tests. The results are followed up for 30–40 min. The tests are used especially in cases of suspected food contact allergy.
26.8 Factors Suppressing Immediate Skin Test Reactivity
H1antihistamines suppress histamine-mediated skin test reactions for 1–4 days, astemizole for at least 3–4 weeks.
Over 10 mg of prednisone and equivalent doses of other glucocorticosteroids suppress allergic reac- tions to the extent that the result may not be relevant.
Non-steroidal anti-inflammatory drugs abolish the nonimmunologic reactivity for at least 3 days, but have no or little effect on allergic reactions.
Both ultraviolet A (UVA) and ultraviolet B (UVB) exposure weakens the skin reactivity for 2–3 weeks to substances producing nonimmunologic immediate reactions. On the other hand, UV usually shows no effect on the size of immediate allergic contact reac- tions.
26.9 Control Tests
When testing with non-standardized allergens, con- trol tests ought to be performed to detect false-posi- tive and non-relevant test results. It is advocated to use at least (20–)50 atopic control persons when test- ing substances causing IgE-mediated allergy.
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References
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2. Malling H-J (1985) Reproducibility of skin sensitivity us- ing a quantitative skin prick test. Allergy 40 : 400–404 3. Taudorf E, Malling H-J, Laursen LC, Lanner A, Weeke B
(1985) Reproducibility of histamine skin prick test. Aller- gy 40 : 344–349
4. Zawodniak A, Kupczyk M, Gorski P, Kuna P (2003) Com- parison of standard and modified SPT method. Allergy 58 : 257–259
5. Dreborg S, Foucard T (1983) Allergy to apple, carrot and potato in children with birch pollen allergy. Allergy 38 : 167–172
6. Rancé F, Juchet A, Brémont F, Dutau G (1997) Correlations between skin prick tests using commercial extracts and fresh foods, specific IgE, and food challenges. Allergy 52 : 1031–1035
7. Niinimäki A (1987) Scratch-chamber tests in food handler dermatitis. Contact Dermatitis 16 : 11–20
8. Osterballe M, Scheller R, Stahl Skov P, Andersen KE, Bindslev-Jensen C (2003) Diagnostic value of scratch- chamber test, skin prick test, histamine release and specif- ic IgE in birch-allergic patients with oral allergy syndrome to apple. Allergy 58 : 950–953
9. Susitaival P, Husman K, Husman L, Hollmén A, Horsman- heimo M, Hannuksela M, Notkola V (1994) Hand derma- toses in dairy farmers. In: McDuffie HH, Dosman JA, Sem- chuk KM, Olenchock SA, Senthilselvan A (eds) Human sustainability in agriculture: health, safety, environment.
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10. Morren M-A, Janssens V, Dooms-Goossens A, van Hoey- veld E, Cornelis A, De Wolf-Peeters C, Heremans A (1993) a-amylase, a flour additive: an important cause of protein contact dermatitis in bakers. J Am Acad Dermatol 29 : 723–728
11. Lahti A (1980) Non-immunologic contact urticaria. Acta Derm Venereol Suppl (Stockh) 91 : 1–49
12. Tosti A, Guerra L (1988) Protein contact dermatitis in food handlers. Contact Dermatitis 19 : 149–150
13. Lahti A (1997) Nonimmunologic contact urticaria. In:
Amin S, Lahti A, Maibach HI (eds) Contact urticaria syn- drome. CRC Press, Boca Raton, Florida, pp 5–10
14. Ylipieti S, Lahti A (1989) Effects of the vehicle on non-im- munologic immediate contact reactions. Contact Derma- titis 21 : 105–106
15. Lahti A, Poutiainen A-M, Hannuksela M (1993) Alcohol ve- hicles in tests for non-immunological immediate contact reactions. Contact Dermatitis 29 : 22–25
16. Oranje AP, Van Gysel D, Mulder PGH, Dieges PH (1994) Food-induced contact urticaria syndrome (CUS) in atop- ic dermatitis patients: reproducibility of repeated and du- plicate testing with a skin provocation test, the skin appli- cation food test (SAFT). Contact Dermatitis 31 : 314–318 Matti Hannuksela
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