Skin testing in allergy

Skin tests are used in addition to a directed history and physical exam to exclude or confirm IgE-mediated diseases such as allergic rhinitis, asthma, and anaphylaxis to aeroallergens, foods, insect venoms, and certain drugs. There are two types of skin testing used in clinical practice. These include percutaneous testing (prick or puncture) and intracutaneous testing (intradermal). Prick testing involves introducing a needle into the upper layers of the skin through a drop of allergen extract and gently lifting the epidermis up. Other devices are available for prick testing. Intracutaneous (intradermal) testing involves injecting a small amount of allergen (0.01–0.02 mL) into the dermis. The release of preformed histamine from mast cells causes increased vascular permeability via smooth muscle contraction and development of a wheal; inflammatory mediators initiate a neural reflex causing vasodilatation, leading to erythema (the flare). Prick testing methods are the initial technique for detecting the presence of IgE. They may correlate better with clinical sensitivity and are more specific but less sensitive than intradermal testing. Sites of skin testing include the back and the volar aspect of the arm. Although the back is more reactive, the difference is minimal. By skin testing on the arm, the patient can witness the emergence and often sense the pruritus of the skin test reaction. Because more patients are sensitized (have IgE antibodies and positive skin test reactions) than have current symptoms, the diagnosis of allergy can be made only by correlating skin testing results with the presence of clinical symptoms.

Skin tests are used in addition to a directed history and physical exam to exclude or confirm IgEmediated diseases1 such as allergic rhinitis,2 asthma,3 and anaphylaxis4 to aeroallergens,5 foods,6 insect venoms,7 and certain drugs.8 Skin testing attempts to detect the presence of allergen-specific IgE bound to mast cells by eliciting mast cell degranulation to the specific allergen being tested. This may help confirm the suspicion that a patient’s symptoms are related to immediate hypersensitivity to this allergen. Currently, two types of skin testing are used in clinical practice. These include percutaneous testing (prick or puncture) and intracutaneous testing (intradermal). Prick testing involves introducing a needle into the upper layers of the skin through a drop of allergen extract and gently lifting the epidermis up. Several other percutaneous skin testing implements are available commercially. Intracutaneous (intradermal) testing involves injecting a small amount of allergen (0.01–0.02 mL) into the dermis.

Prick testing methods are the initial technique for detecting the presence of IgE. They may correlate better with clinical sensitivity and are more specific but less sensitive than intradermal testing.9–11 In addition, intradermal testing carries a slightly higher risk of a systemic reaction (0.05% versus 0.03% for a prick test), although the risk is still low. Because of this risk, testing should begin with prick testing, and then proceed to intradermal testing if prick testing is negative and there remains a high degree of clinical suspicion. In the past 30 years, six fatalities have been attributed to intradermal testing; five of these patients had asthma and a lack of prior prick testing. One fatality from prick testing has ever been identified; this patient received over 90 prick tests to food allergens at one time and had preexisting asthma.12 Intradermal testing has not proven beneficial in the diagnosis of food allergy; therefore, the risk to patients is not justified. A physician should always be available to give emergency treatment if necessary, and patients should be observed for at least 20 minutes after testing

H1-receptor antagonists should be held for a minimum of 24–72 hours before skin testing based on the specific pharmacokinetics of each drug. Other drugs with antihistaminic properties, such as metoclopramide, histamine-2 receptor blockers, and tricyclic antidepressants, may affect test results and should be held before testing if possible.13 Refer to Table 1 for the elimination half-lives (t 1⁄2) of several commonly prescribed medications. Short courses of oral corticosteroids will not affect testing results; however, topical corticosteroids may decrease or inhibit skin reactivity. These should not be applied to the test site for at least 1 week before testing. Patients receiving immunotherapy may have decreased skin reactivity. Leukotriene antagonists do not significantly affect skin test reactivity.
2-Adrenergic agonists, decongestants, theophylline, and cromolyn will not affect skin testing

Sites of skin testing include the back and the volar aspect of the arm. Although the back is more reactive, the significance of this is minimal.10 Use of the arm as the test site has the advantage of being able to place a tourniquet above the site should a systemic reaction occur. Skin chosen for testing should be clear of dermatitisThe skin chosen is cleaned with alcohol. Allergen extracts, positive control (histamine), and negative control (saline or allergen diluent) are placed 2–5 cm apart. One source of skin testing error is placing sites too close together resulting in spread of one allergen extract to another site and inability to accurately record the extent of erythema from two positive sites close together. False negative or positive reactions may occur with insufficient or excessive skin penetration. If prick testing reveals minimal or equivocal reaction to an allergen, one might choose to proceed with intradermal testing with a 100- to 1000-fold dilution of allergen extract.

Standardized extracts should be used to facilitate comparisons between clinicians. Note that use of standardized doses does not always confer equal potency. One study found that the content of major allergen varied significantly among the 12 standardized extracts tested. Extracts should be refrigerated at 4°C. They should contain glycerin to decrease the loss of potency that occurs with time

Testing should be graded within 15–20 minutes.15 Several different grading systems exist, one of which is shown in Table 2. The mean diameter of the wheal and erythema are recorded with the presence or absence of pseudopodia. Physicians should quantitate the actual size on the data sheet and not solely a grade so that results might be better shared among practitioners. Clinicians also are urged to use a comprehensive data sheet recording the brand of extract, dilutions used, device chosen, mean diameters of wheal and erythema, and specific grading system key. 

Interpretation of skin tests may be more difficult in patients with dermatographism. False positive reactions with dermatographism can be distinguished from true positive reactions that are secondary to IgE because the former fade more quickly. Special attention should be paid to the difference between the sizes of the reactions from allergen extracts compared with the negative control. No significant differences in skin test reactivity have been noted for gender. Infants and the elderly, however, may have decreased skin reactivity and thus smaller wheal size. Additionally, darkly pigmented skin can have larger histamine wheals compared with light skin.