IMMUNOLOGY - Roitt I. - Mir 2000

Chapter 23. Hypersensitivity - Type I

SKIN TESTS

Intradermal testing. Remarkably, the Skin test—the simplest of all allergy Diagnostics—yields a wealth of information regarding the immunopathology of allergic reactions. The classical atopic response features an immediate wheal-and-flare reaction, which occurs because the introduced allergen triggers the release of preformed mediators that increase vascular permeability, leading to local edema and pruritus (Fig. 23.15). A positive skin test generally correlates with a positive radioallergosorbent test (RAST) for allergen-specific serum IgE, as well as with positive challenge tests (such as the application of the allergen to the nasal or bronchial mucosa). A late-phase cutaneous response is less common, but when it does occur, it presents as a painful rather than itchy skin infiltrate.

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Fig. 23.15. Skin tests photographed 5 hours (left) and 20 minutes (right) after application. The test on the right demonstrates the typical end result of an immediate (type I) wheal-and-flare reaction. The late-phase cutaneous reaction (left) is clearly visible after 5 hours, particularly following a strong preceding immediate-type response. Dilutions of the allergen extract are indicated.

A positive skin test (the classic wheal-and-flare response) in individuals with various atopic conditions indicates that their IgE is bound to cutaneous mast Cells, even though clinical symptoms may manifest in the Nose or Bronchi. However, in a small subset of patients with a clear history of conditions such as allergic rhinitis, both skin tests and RAST results prove negative. Despite the absence of IgE in the skin and serum of such patients, an IgE-mediated response can still be observed in certain mucosal membranes. This is evidenced by a positive nasal provocation test and the detection of specific IgE in nasal secretions via RAST. When lymphocytes from these patients are stimulated with an allergen in vitro, they transform and begin producing cytokines, pointing to a T-Cell-mediated response to the allergen. While this does not strictly prove a direct role for delayed-type hypersensitivity in such pathological processes, it nevertheless demonstrates the presence of allergen-specific Th cells capable of providing "help" for the IgE response.

Skin prick/scratch testing. This test is performed by applying the allergen to slightly abraded "normal" skin. For instance, patients with atopic eczema (Fig. 23.16) whose serum contains IgE Antibodies against house dust mites show a positive skin test to mite allergen (Fig. 23.17). Interestingly, some patients with allergic rhinitis caused by exposure to house dust mites (Fig. 23.18) also develop basophilic infiltration when this allergen is applied to the skin; in other words, such infiltration is not exclusive to eczema.

Fig. 23.16. Atopic eczema on the arm of a child with allergies to rice and eggs.

Fig. 23.17. Skin tests with purified house dust mite antigen (Dermatophagoides pteronyssinus) in a patient with atopic eczema. 1. The antigen extract was applied to an unaffected area of skin that had been lightly scratched to remove the superficial keratin layer; the site was then covered, and the reaction was evaluated after 48 h. Eczematous changes are visible, and microscopic examination revealed infiltrates containing eosinophils and basophils.

2. Saline control. (Photos kindly provided by Dr. E. Mitchell.)

Fig. 23.18. The house dust mite—a major cause of allergic disease. Electron micrograph of a house dust mite, Dermatophagoides pteronyssinus, and its feces (bottom right), which serve as the primary source of the allergen. It is these particles, rather than the mite itself, that become airborne and enter the Lungs. (Photo kindly provided by Dr. R. Tovey.)

Early on in The Study of the late-phase cutaneous response, it was attributed to type III hypersensitivity (immune complex-mediated) and linked to precipitating IgG antibodies by analogy with allergic bronchopulmonary aspergillosis. However, precipitating antibodies are rarely detected in this reaction; as subsequent research has shown, it is fundamentally dependent on IgE.