The principle of skin prick tests is that the skin weal and flare reaction to an allergen demonstrates the presence of mast-cell-fixed antibody, which is mainly IgE antibody. IgE antibody is produced in plasma cells, and is distributed in the circulation to all parts of the body, so that sensitization is generalized and therefore can be demonstrated by skin testing. In the presence of specific IgE antibody, mast cells in the skin release histamine, which in turn causes a visible weal and flare reaction in the skin.
The procedure involves a drop of allergen solution being placed on the skin, which is then pricked with a hypodermic needle. Two control solutions should also be used: the diluent, in order to detect false-positive reactions; and a positive control (e.g., a histamine solution), to enable comparison with a positive result of an allergen solution. The skin prick test induces a response that reaches a peak in 8-9 min for histamine and 12-15 min for allergens. The size of the weal reaction (and not the larger red flare) is measured.
There are numerous problems with skin prick tests, including:
1. There is no agreed definition about what constitutes a positive reaction.
2. The size of the weal depends to some extent on the potency of the extract.
3. Antihistamines and tricyclic antidepressants suppress the histamine-induced weal and flare response of a skin test. The suppressive effect of antihistamines may last from a week up to several months for some of the more recently introduced nonsedating antihistamines.
4. False-positive tests: skin prick test reactivity may be present in subjects with no clinical evidence of allergy or intolerance. This is sometimes described as 'asymptomatic hyper-sensitivity' or 'subclinical sensitization.' Whilst many with positive skin prick tests will never develop the allergy, some subjects with positive skin prick tests do develop symptoms later. However, since the test cannot identify those who are going to develop symptoms, the skin test information is of no practical value.
5. False-positive results: skin prick test reactivity may persist after clinical evidence of intolerance has subsided. For example, in a study of children with egg allergy, it was noted that 5 out of 11 who grew out of egg allergy had persistently positive skin prick tests after the allergy had disappeared.
6. False-negative tests: skin prick tests are negative in some subjects with genuine food allergies.
7. Skin prick tests mainly detect IgE antibody. However, many adverse reactions to food are not IgE mediated, in which case skin prick tests can be expected to be negative. Taking cows'
milk protein intolerance as an example, patients with quick reactions often have positive skin prick tests to cows' milk protein, but those with delayed reactions usually have negative skin prick tests.
8. False-negative results are a problem in infants and toddlers, when the weal size is much smaller than later in life.
9. There is a poor correlation between the results of provocation tests (e.g., double-blind food challenges) and skin prick tests. For example, in one study of 31 children with a strongly positive (weal >3 mm in diameter) skin prick test to peanut, only 16 (56%) had symptoms when peanuts were administered.
10. Commercial food extracts (sometimes heat treated) and fresh or frozen raw extracts may give different results (more positives with raw foods), reflecting the fact that some patients are allergic to certain foods only when taken in a raw state. In others the reverse is the case.
Skin prick tests are mainly used in research studies. The results of skin tests cannot be taken alone, and standard textbooks on allergy acknowledge that ''the proper interpretation of results requires a thorough knowledge of the history and physical findings.'' The problems in clinical practice are, for example, whether or not a subject with atopic disease (eczema, asthma, or hay fever) or symptoms suggestive of food intolerance will benefit from attempts to avoid certain foods or food additives. However, skin prick test results are unreliable predictors of response to such measures.
Skin test results are known to be misleading in cases of inhalant allergy (e.g., allergy to dust mites or grass pollen) but skin prick tests for food allergy are especially unreliable because of the large number of false-positive and false-negative reactions.
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