human serum albumin for the more dilute solutions used for intradermal testing.
Because of safety issues involved in allergy skin testing, tests should never be performed unless properly trained personnel and emergency equipment to treat systemic reactions are available. In particular, patients receiving beta-adrenergic-blocking agents for treatment of hypertension or heart disease should be advised of this risk, because they are less likely to respond to epinephrine in the case of anaphylaxis. Skin testing should be avoided in these patients until a substitute treatment can be found (Executive Committee, American Academy of Allergy, 1989).
The methods for interpreting skin tests are not well defined. It is known that an immediate skin test response to histamine reaches a peak at about 8–10 minutes; for agents such as codeine that act directly to cause histamine release from mast cells, peak response comes at 10–15 minutes, whereas allergens elicit responses in 15–20 minutes. At the time of peak response, the diameter of the wheal and flare is measured; sometimes a permanent record is obtained by outlining the size of the reaction with a pen and then blotting the marks onto cellophane tape, which is stored on paper.
Generally, a wheal 3 mm or greater in diameter is considered a positive test using the skin prick method. However, a grading system has been established (Bousquet, 1988) in which erythema (redness of the skin) and a wheal of less than 5 mm in diameter is a negative test. A 2+ reaction is a 5- to 10-mm wheal with 21–30 mm of erythema; this size response is often elicited by histamine control. A 3+ reaction is a 5- to 10-mm wheal with pseudopods and erythema of 31–40 mm. A 4+ reaction is a wheal of 15 mm or greater within any pseudopods and erythema of 40 mm or more. Other investigators have found that if a control site is completely negative, wheals of 1–2 mm with flare and itching are likely to represent a positive response. Although these reactions indicate immunologic sensitization, they do not necessarily indicate the presence of clinically relevant allergic symptoms.
From 2 to 8 percent of individuals with no personal history of allergy or respiratory disease exhibit positive skin test responses with intradermal testing. These positive tests may indicate the presence of specific IgE antibodies but not the presence of clinical allergy. A true false-positive test occurs as a result of irritant reactions; in the case of intradermal testing, it may be produced by the so-called splash response when air is injected into the skin. Occasionally, a false-positive reaction is the result of nonspecific enhancement, through the axon reflex, from a nearby strong allergic reaction. For this reason, skin tests should be placed at least 2–5 cm apart, and the positive histamine control should be at some distance from the allergen test