Skin Tests
Skin prick tests (SPTs) are safe except in patients with a reliable history of near fatal anaphylaxifl. A positive test is very specific but has a poor positive predictive value (50% in children and 5% or less in adults). Thus, avoid using SPTs out of clinical context. A negative SPT, however, rules out IgE-mediated food allergy (negative predictive value near 100%). Intradermal skin tests have no role in diagnosis of food allergies. If suspected food allergy is associated with fresh and raw fruits or vegetables (e.g., OAS), then the prick-and-prick technique is used: A fresh food is peeled and pricked by SPT device, followed by pricking the patient’s skin.
RAST and Other Lab Investigations
RAST measures levels of food-specific IgE in the serum. These usually have only 80% of the sensitivity of SPTs and are more expensive, and the results are not immediately available, Order RAST testing only if SPTs cannot be performed (e.g., diffuse chronic skin disease, patient cannot stop antihistamines), produce results that are inconsistent with clinical history or are contraindicated. Recent studies have suggested some utility for capture allergen protein RAST (CAP-RAST, a more sensitive RAST test but with more false-positive results) in determining the level of risk of oral food challenges. This “risk stratification” can then be used to decide whether food challenge is contraindicated, should be done in a medical facility, or can be performed at home.
Food Challenges
DBPCFC is the gold standard for diagnosing AFR and is usually performed by an allergist/immunologist familiar with the management of anaphylaxis. A positive challenge does not necessarily identify the mechanism of the reaction (IgE-, non-IgE-, or non-immune-mediated reaction). Food challenges are contraindicated In suspected food-Induced anaphylaxis. Good history and consistent SPT are usually sufficient to establish a diagnosis without a food challenge. With vague history and inconclusive SPT, an open challenge may be indicated, followed, if positive, by a blinded challenge. Details of food-challenge techniques are available in standard allergy textbooks.
Other Tests
Other tests may be indicated for the diagnosis of AFR (immune and nonimmune). Serum tryptase levels are useful in some cases of food-induced anaphylaxis if serum is collected early after the event (1-2 hrs, but may be useful up to 6 hrs after anaphylaxis). CBC with differential counts in suspected chronic allergies and atopy (eosino-philia) or anemia associated with AFR (celiac disease and Reiner’s syndrome). Hydrogen breath tests can confirm lactose intolerance, and endoscopic biopsies are required to establish the diagnosis of eosraophilic syndrome of the GI tract.
IN VIVO AND IN VITRO DIAGNOSTIC TESTS FOR ALLERGY
Introduction
Since the characterization of IgE and its role in the pathophysiology of allergic symptoms, many clinical tests have be used to help detect specific antigen sensitivities. Two types of tests are widely used to detect the presence of IgE. One is skin testing and the other is the in vitro measurement of IgE. Both tests, however, are only adjuncts to thorough exposure history that indicates the presence of relevant IgE mediated symptoms or signs and the physical exam.
METHODS OF SKIN TESTS
Immediate Hypersensitivity Skin testing
Immediate hypersensitivity skin testing is the most sensitive and cost-effective method to screen existing IgE sensitivities that may be responsible for clinical symptoms. The antigen is directly applied to the skin surface by different methods. One is epicutaneous, and the other is intradermal.
Indications
Documentation of allergic sensitivity to specific allergens in patients with asthma, rhinitis, eczema, food allergy, drug allergy, or insect hypersensitivity. Monitoring of immunotherapy effects.
Contraindications
Skin tests should not be performed in patients who have had a recent severe allergic reaction, because test results are unreliable in these instance. Skin testing is usually postponed for 4-6 wks after the acute event.
Tests should not be performed on patients who have severe eczema or dermatographism because of difficulty in interpreting the results.
Medications to Avoid Skin Testing
Several medications can interfere with skin testing results. Antihistamines, both H1 and H2 blockers, should be discountinued for >72 hrs: fexofenadine (allegro) for 5-7 days; loratadine(Claritin) for 7 days; and certirizine (Zyrtec) for 7-10 days. Trycyclic antidepressants, which can have antihistaminic effects, should also be discontinued for 1 wk(taper if necessary!). Some atypical antipsychotic agents(e.g., risperidone, olanzapine, ziprasidone) also have antihistaminic effects and may interfere with skin testing.
Eplcutaneous Skin Tests
Epicutaneous skin tests include prick and puncture techniques. These methods introduce the antigen into the epidermis of the skin and thereby activate any IgE sensitized mast cells by the cross-linking of IgE molecules present on the mast cell surface.
Prick Skin Test
The prick skin test is performed by placing a small drop of allergen on the cleansed skin surface and passing a 25 or 26 gauge needle through the antigen at a 45 degree angle. The needle should be lightly pressed into the epidermis and then lifted, creating a break in the epidermis without causing bleeding.
Puncture Skin Test
The puncture skin test is performed by placing a small drop of the allergen extract on the cleansed skin surface and then puncturing the skin with a device a device at a perpendicular angle, penetrating 1-1.5 mm into the skin. Commercially available devices made of plastic allow for placement of multiple antigen test sites at one time. Each test antigen site should be place > 2 Cm apart.
Scratch Skin Test
The scratch skin test is performed by making abrasions on the skin and then applying the allergen extract to the site, allowing it to diffuse through the skin. Because of its poor standardization and reproducibility, this method has fallen out of favor and is rarely used.
Intradermal Skin Testing
Intradermal skin testing is more sensitive than the epicutaneous skin tests, but it is generally only performed if the epicutaneous test is negative. The test is performed using 25 to 27 gauge needles. A small amount of allergen extract (0.02-0.05 ml: 0.02 mL in Hymenoptera to avoid false-positive) is injected into the skin, creating a small bled 2-3 mm in diameter. Spaces between each injection site should be >2 cm. For patients with a negative prick-puncture test, the concentration of extract for intradermal testing should be between 100- and 1,000 fold more dilute than the concentration used for epicutaneous testing.
Test controls
Positive and negative test controls are routinely used for the skin test:
Positive Controls
For the positive control, histamine at 1 mg/mL for epicutaneous methods and 0.1 mg/mL for intradermal skin testing is used. A patient must have a positive response to the histamine control to proceed with the skin testing. Mast cell degramulators, such as an opiate, codein, or morphine sulfate, may also be used as positive controls.
Negative Controls
Diluents used to preserve the allergen extracts are used as negative controls. This will help detect any problems with technique, possible skin irritation reaction, or dermatographism.
Indications for Epicutaneous and Intradermal Skin Testing
Skin testing should always begin with epicutaneous testing. If the results of the epicutaneous tests are negative, and there is high clinical suspicion from history, there may be value in proceeding to intradermal skin testing in various situations.
Interpretation of Skin Test Results
The immediate hypersensitivity reaction can be quantified by measuring the diameter of the wheal and assocated erythema. Wheal size was found to be more specific than erythema size and to correlate better to clinical symptoms. The results should be measured at the peak of the reaction.
Praunsnltz-Kustner Test
The Praunsnitz-Kustner test is a passive transfer test and is of historical interest only. This test was the first method by which specific allergic sensitivities were determined before the knowledge of IgE. The serum of a patient with a specific allergy-e.g., to eggs-would be taken and placed on the marked location on the skin of another, nonallergic person.
Set Point titration
Set point titration is a method developed by RInkel in which serial dilutions of extract are tested using the intradermal method. Dilutions of allergenic extract increasing in fivefold concentrations are placed and observed fro a wheal reaction.