OVERVIEW OF SKIN TESTING FOR ALLERGIC DISEASE

© H. Nolte, K. Kowal, L. DuBuske, 2007

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INTRODUCTION

The incidence of atopic disease has increased 10-fold in developed countries in the last two decades. Almost 30 percent of Americans have symptoms of upper respiratory allergy, including up to 40 percent of children and 10 to 30 percent of adults. Inflammatory processes involving IgE (IgE-mediated allergies) account for the majority of clinically significant environmental, food, and medication allergies.

There are three components to the diagnosis of an IgE-mediated allergic disorder. These are:

• Identifying the allergen, usually through a careful clinical history
• Demonstrating the presence of IgE specific to the allergen by skin testing or in vitro testing
• Establishing a causal relationship between exposure to the allergen and symptoms, either by history or with a challenge procedure

Thus, allergy testing is an important element in the evaluation of allergic disease; however, by itself, it is not sufficient to make a diagnosis. A positive test (skin or in vitro) must be supported by an appropriate clinical history of reactivity and, in some cases, allergen challenge to confirm that the suspected allergen causes symptoms.

This topic review will discuss general principles of skin testing, including indications, contraindications, factors influencing results, techniques, and accuracy. The two major methods of skin testing currently used, the prick/puncture technique and the intradermal technique, are described. This review includes the types of skin testing used in the diagnosis of IgE-mediated allergy. Other forms of skin testing, such as patch testing for contact dermatitis or atopy patch testing for eosinophilic gastrointestinal disorders, are reviewed separately.

OVERVIEW OF SKIN TESTING

Skin testing is the most rapid, sensitive, and cost effective testing modality for the detection of IgE-mediated disease. Results are obtained in less than an hour with minimal patient discomfort. However, there are some situations in which in vitro testing is preferable. (See "Contraindications" below).

Skin testing and other diagnostic procedures in the field of allergy (eg, challenges) should be performed by specialists trained in the methods and interpretation of the test results. Any procedure that involves the deliberate exposure of a patient to a substance that may cause significant harm should be undertaken by someone with expertise in the emergency treatment of allergic reactions and anaphylaxis. In addition, because each type of allergy has unique characteristics and implications for the patient's health, an allergy expert can be an invaluable source of information for both the patient and the primary provider.

General approach to testing

Testing may be very specific or more general, based upon the clinical setting:

• A focused approach is most appropriate for patients whose history and/or physical examination strongly indicates the identity of the specific offending allergen(s). As an example, a patient who developed urticaria and wheezing while taking penicillin would be evaluated with test for IgE specific to penicillin and its immediate derivatives.
• A broader approach would be utilized for a patient with perennial rhinitis and asthma symptoms. In this setting, it would be appropriate to test with a selected panel of outdoor and indoor allergens pertinent to the geographical region:
• Tree, grass, and weed pollens, with choices reflecting regional flora
• Molds, including Alternaria alternata, Penicillum notatum, Aspergillus fumigatus, and Cladosporium
• Dust mites, including Dermatophagoides pteronyssinus and Dermatophagoides farinae, and cockroach
• Animal danders, including cat pelt and dog epithelium

Terminology

A person with demonstrable IgE to a specific allergen is said to be "sensitized" to that allergen. Both skin testing and in vitro testing are used to demonstrate sensitization. However, a sensitized person is considered "allergic" to an allergen only if they react with representative symptoms when exposed to it.

This distinction is made because not all sensitized patients will develop actual symptoms on exposure. With some food skin tests, for example, the percentage of people who react to a food for which they have skin tested positive can be as low as 50 percent. Thus, food challenge procedures are often necessary to clarify a patient's status. By comparison, the proportion of individuals with positive pollen skin tests who truly react is much higher; therefore, a positive skin test and a history of symptoms during the appropriate season is sufficient to make the diagnosis. As a result, the confirmation of reactivity is crucial to making an accurate diagnosis and each type of allergy must be approached individually.

Pathophysiologic mechanism

Skin testing is a bioassay that detects the presence of allergen-specific IgE on a patient's mast cells. When allergen is introduced into the skin of a patient during skin testing, it comes into contact with cutaneous mast cells. Binding of the allergen occurs if the patient's mast cells are coated with IgE recognizing that specific allergen. If both IgE and allergen are present in sufficient quantities, then adjacent IgE molecules directed against the allergen may be cross-linked on the cell surface and initiate intracellular signaling.

These events lead to mast cell activation, release of the contents of intracellular granules (degranulation), and the de novo generation of inflammatory mediators. Degranulation releases pre-formed vasoactive mediators and enzymes, such as histamine, tryptase, chymase, and carboxypeptidase. Histamine is the major mediator of the wheal and flare response, but other mediators (eg, prostaglandin D2) are also involved, as the size of the wheal does not correlate directly with the concentrations of histamine released.

The clinical result of these cellular events is a positive skin test, or a transient "wheal-and-flare" reaction. This reaction consists of a central area of superficial skin edema (wheal) surrounded by erythema (flare). This pruritic reaction represents the immediate phase of the allergic reaction.

Late phase reactions (LPRs) may develop at skin test sites in some individuals. These consist of deep tissue swelling, warmth, pruritis, and erythema beginning one to two hours after testing and resolving in 24 to 48 hours. LPRs are mast cell-mediated and IgE-dependent, although they do not predict symptoms on exposure and are not used in allergy diagnosis.

INDICATIONS

Skin testing is useful in the diagnosis of a variety of IgE-mediated allergic disorders, including:

• Allergic asthma, rhinitis, and conjunctivitis. Skin testing using panels of indoor and outdoor allergens is the primary diagnostic modality for these conditions and is well-validated.
• Food allergy. Skin testing is considered the primary diagnostic technique for a variety of food allergies, although in vitro testing is also well-validated for several childhood food allergies. Subsequent challenge procedures are sometimes indicated to confirm allergy following testing.
• Some medication allergies. Skin testing is used in the diagnosis of IgE-mediated drug allergies; however, it has been validated and standardized only for the evaluation of penicillin allergy. For allergies to other medications, including other antibiotics, biologicals, chemotherapy agents, insulin, and drugs used in anesthesia, skin testing is often used as part of the evaluation, but the significance of a positive or negative result is not as well-defined.
• Venom allergies. For allergy to the venoms of Hymenoptera species (wasps, honey bees, yellow jackets, hornet, imported fire ants, and others), skin testing is the diagnostic test of choice and is well-validated.
• Latex allergy. Skin testing can be used to evaluate for latex allergy, however, there are currently no commercially-available latex skin test reagents in the United States. Some allergists produce their own extracts for testing, although the concentration of allergens in these preparations can vary dramatically, and the protein content should be measured and standardized to avoid systemic reactions. In vitro tests for lates are available in the United States, although the sensitivies of these tests are variable, ranging from 50 to 90 percent. In Canada and Europe, standardized latex reagents are available and skin testing is the diagnostic method of choice.

CONTRAINDICATIONS

Skin testing should not routinely be performed in patients who are at high risk for an anaphylactic reaction to testing, have experienced a recent anaphylactic event, are taking medications that may interfere with the treatment of anaphylaxis, or have certain skin conditions.

High risk patients

Patients who are at higher risk for an anaphylactic reaction in response to skin testing include:

• People with poorly controlled asthma and reduced lung function
• People with clinical histories of severe reactions to minute amounts of allergen

Patients with significant cardiovascular disease, including coronary artery disease and cardiac arrhythmias, and elderly patients may also present an enhanced risk potential for skin testing related to the adverse effects inherent in treating anaphylaxis in such patients.

In vitro allergy testing should be the initial diagnostic modality in such patients, or in the case of uncontrolled asthma, skin testing can be performed after symptoms have been stabilized.

Recent anaphylaxis

An episode of anaphylaxis within the previous month is a contraindication to skin testing because it may yield falsely negative results. Anaphylaxis can render the skin temporarily non-reactive. Full restoration of reactivity can take two to four weeks. This is especially important in assessing patients who have had anaphylaxis from insect stings. In vitro allergen testing may be more reliable during this refractory period if immediate diagnosis is necessary, because free allergen-specific IgE in the serum is less affected by anaphylaxis.

Presence of interfering medications

Beta 2-antagonists and angiotensin converting enzyme antagonists may inhibit the management of anaphylaxis. Thus, in vitro assessment of serum antigen-specific IgE may be the safest method of testing for individuals who cannot discontinue these medications.

Skin conditions

Patients with certain skin conditions, including dermatographism, urticaria, and cutaneous mastocytosis, cannot be skin tested because false positive results are common. Skin test results are also difficult to interpret in patients with atopic dermatitis affectin the areas where testing is performed, both because of changes in skin cellularity and the application of topical medication. However, patients with atopic dermatitis in other areas can be skin tested normally.

FACTORS AFFECTING RESULTS

The results of skin testing are influenced by various factors, including medications and physiologic characteristics of the patient, as well as the reagents and devices used.

Medications

The patient's full medication list should be reviewed in advance of testing. Several types of medications can interfere with skin testing, although only some are routinely discontinued. Non-interfering allergy medications that can be continued are also discussed below.

• H1 antihistamines can suppress skin reactivity for one to seven days, depending upon the specific drug. The general practice is to discontinue these agents seven days prior to testing. Older, non-selective antihistamines (eg, diphenhydramine) generally suppress skin reactivity for one to three days, whereas second-generation antihistamines (eg, cetirizine, loratadine) may blunt skin test for up to seven days. If a negative or weak response to the positive histamine control is obtained on a patient who was recently taking antihistamines, a longer medication-free period and repeat testing is suggested. H2 receptor antagonists (eg, ranitidine, cimetidine) are generally discontinued at least 48 hours before testing, as these medications may reduce the flare component of the response.
• Short-term systemic corticosteroids (30 mg daily for one week) should not suppress skin tests. Chronic and relatively high dose cortictosteroids (>20 mg/day) can partially suppress reactions. Although skin testing may be performed in these patients, a negative or small response to the positive histamine control suggests interference.
• Chronic topical steroids can partially suppress responses by locally reducing the number of skin mast cells. In this setting, skin testing should be performed on untreated skin.
• Inhaled corticosteroids do not affect the skin test response and may be taken by patient prior to testing.
• Treatment with omalizumab, and anti-IgE antibody used for asthma treatment, may depress skin reactivity for up to six months or longer after treatment has been discontinued.
• Some drugs prescribed for non-allergic diseases, including tricyclic antidepressants and phenothiazines, may block skin reactivity for up to two weeks. Muscle relaxants and antiemetic drugs can have antihistaminic properties that may also reduce skin test responses. Because many of these medications are difficult for patients to discontinue and/or have long half-lives, testing is often done despite them; however, interference must be considered if a weak or negative response is obtained. In such patients, assessment of allergen specific IgE in serum may be preferable.
• Decongestants, inhaled beta agonists, and cromolyn preparations do not affect skin testing.
• Limited data suggest that topical pimecrolimus has no effect on skin testing.
• Leukotriene receptor antagonists do not influence skin test responses.

Physiologic variables

Several physiologic characteristics of the patient should be considered, although the effects of these factors are usually minor.

• The age of the patient can affect the results of skin testing. Skin testing can be performed in people of any age. Infants have smaller positive reactions to histamine and allergens, although clear positives can be obtained in very young children. Skin reactivity increases gradually throughout childhood and plateaus in the mid-adolescent years. A gradual decline in reactivity is seen after the age of 50 to 60 years.
• The skin of the forearm generally produces smaller wheals than the skin of the back. This effect is more pronounced with allergens than with histamine, although it is rarely of significant clinical consequence. Performing testing on the arms has the advantage of allowing for the placement of a tourniquet proximal to the testing site in rare cases of anaphylaxis in response to testing. Tourniquets are applied in this setting to slow absorption of allergen into the central vasculature.
• The size of skin test reactions to some pollen antigens in sensitive patients may increase during the pollen season, although positive results are present throughout the year.

Technical variables

The results of skin testing can be influenced by the potency and quality of allergenic extracts, testing devices, and techniques.

• The major inhalant allergens are well characterized and standardized, except for molds.
• Most commercially-available food extracts are not standardized. However, extracts of milk, eggs, peanuts, soy, fish, shellfish, and tree nuts are reliable. In contrast, commercial extracts of fruits and vegetables are sometimes inadequate because the responsible allergen may be labile and altered during processing. Thus, in the event of a negative skin test for these foods, or when there is suspicion that the allergenicity of the food depends on its preparation (raw vs cooked), the fresh food should be used for skin testing using the "prick by prick" method (See "Prick by prick testing" below).

Conversely, false positive results can arise from naturally occuring histamine and other vasoactive amines in some allergen extracts (ie, insect venoms, molds, foods) as extracts produced in the United States are not dialyzed to remove histamine, which may occur as a natural contaminant, or from cross-reactivity with clinically irrelevant proteins. An example of the latter phenomenon can occur in foods containing the profilin protein Bet v 2, which can cause positive skin tests to foods in birch allergic patients without symptoms of food allergy. In the testing of non-standardized drug preparations, false positives can occur from irritating properties of the drug in question. If these issues are suspected, repeating the test in one or more volunteers to assure that the test is negative in others is sometimes required.

• The testing device used can influence the results, and the practitioner should consider the strenghts and weaknesses of different devices when deciding which method to use. This is of particular importance in research settings. As an example, multi-headed devices (those that allow for application of several antigens simultaneously) produce more false negatives than single headed devices; however, these devices may facilitate testing in children by allowing rapid application of multiple allergens.

ALLERGEN PREPARATION

The allergens relevant to human allergic disease are either glycoproteins and lipoproteins from other living organisms, or in the case of some drug and occupational allergens, a combination of small chemical moieties conjugated (or "haptenated") to serum proteins. Allergens have in common the ability to trigger the formation of IgE in genetically susceptible individuals. Hundreds of clinically significant allergens have been identified from tree, grass, and weed pollens, molds, dust mites, foods, parasites, animal danders, insect venoms, drugs, occupational chemicals, and other biologic materials.

At this time, the allergens used in clinical practice are obtained almost exclusively from natural sources. In some cases, the more important allergenic proteins from a given substance have been identified, cloned, sequenced, and produced through recombinant technology. However, recombinant allergens do not necessarily reproduce the clinical response observed to natural allergens. Allergens from natural sources are heterogeneous. Individual allergic patients can be sensitive to different allergens from the same source, and can even respond differently to isoallergens that are identical except for minor differences in primary amino acid composition or substituted side chains. Thus, although recombinant allergens offer the advantages of being readily available and uniform in composition, their use is currently limited to research settings.

The reliance on allergens derived from natural sources introduces immense variability into the commercial preparation of these products. Allergen content in plant, animal, and insect materials can vary because of the season, growth conditions, genetic differences between geographic regions, or other variables. For this reason, commercial allergen extracts are not uniform among manufacturers or between lots. Each preparation will detect a slightly different population of IgE antibodies.

Efforts have been made to "standardize" the commonly-used extracts. In standardized extracts, the important allergenic proteins have been identified and the manufacturer has verified their content to be within a specified range. Based upon clinical testing, the standardized extracts are labeled in biological potency units, termed allergy units (AU), biological allergy units (BAU), or in micrograms of major allergen content (for venoms). Currently, standardized versions of some pollen, dust mite, animal dander, and venom extracts are available, and their use is preferred over non-standardized extracts. Unstandardized products are labeled in protein nitrogen units (PNU) or weight of protein per volume.

The manufacturer and concentration of the skin test reagents used in testing must always be recorded in the patient record. Withouth this information, precise interpretation of the results by other providers is not possible.

CHOICE OF SKIN TEST METHOD

The two major methods of skin testing currently in use are the prick/puncture technique are the intradermal technique. In most cases, prick/puncture method is the appropriate initial procedure.

• The prick/puncture method is the primary diagnostic method and is the most appropriate initial test, in the absence of contraindications. (See "Contraindications" above). Prick/puncture testing is sensitive although not very specific; overall positive predictive accuracy is less than 50 percent if all types of allergens are considered together. Thus a positive prick test in consistent with possible allergy to that allergen, but allergy cannot be diagnosed until there is confirmation, either through convincing history or challenge, that symptoms develop upon exposure.
• Intradermal testing has much higher sensitivity but a higher rate of false positive results (ie, lower specificity). This type of testing carries a greater risk of inducing a systemic reaction, and therefore should only be performed after negative prick/puncture testing. Intradermal tests that are positive for inhalant allergens, in the context of negative skin prick tests, have low positive predictive value for the presence of symptoms upon allergen exposure. In contrast, the high sensitivity of intradermal tests is essential for the optimal detection of venom sensitivity, as failure to identify a venom allergy may lead to life threatening consequences. Intradermal testing is not currently used in the diagnosis of food or latex allergy in the United States, due to an unacceptably high rate of systemic reactions to testing.

PRICK/PUNCTURE METHOD

Technique

The prick/puncture of epicutaneous method of skin testing involves application of droplets of 1:10 or 1:20 weight/volume allergen extract solutions on the volar surface of the forearm or upper back, after the skin has been cleaned with a 70 percent alcohol solution. Each droplet contains a single allergen extract, although for screening purposes, mixes of closely related allergens (eg, four tree pollens) are sometimes used. One of a number of commercially available test devices are then used to prick through the droplets of allergen. Test should be placed at least two centimeters apart to avoid overlapping reactions.

Prick by prick testing

Prick-by-prick testing is a variation of epicutaneous skin testing in which fresh food is used as a source of the allergen, instead of a commercially-prepared extract. This is often done to evaluate allergies to fruits, many of which occur only in the fruit is eaten in the raw form. To perform this, the food and the patient's skin are both cleaned, and the test device is used to prick first the food and then the patient's skin. If a positive test is obtained using this method, the test should be repeated on a non-allergic individual, to assure that the result is not a false positive irritant response.

Controls

Both a positive control of histamine dichloride (10 mg/mL for epicutaneous use) and a negative control of diluent identical to that of the allergen extracts (usually glycerinated saline) should always be applied in order to verify that the patient's skin is normally responsive.

Definition of a positive test

A positive reaction appears as a raised wheal with surrounding erythema. A positive reaction is defined in one of two ways:

• It is defined most commonly as a wheal that is equal or larger in size to that associated with the histamine control, with the histamine control normally producing a wheal of at least three millimeters in diameter.
• Alternatively, a wheal diameter larger than three millimeters may be considered positive.

Positive results are recorded by measuring the greatest diameter of both the wheal and the erythema (separate measurements for each) in millimeters, at 10 minutes for the histamine control, and at 15 to 20 minutes for the allergen extracts. For research purposes, a more precise measurement is usually used, in which the longest wheal diameter (D) and the diameter perpendicular to D (d) are measured. The result is then expressed as a mean (D + d) / 2.

Skin test reactions usually begin to resolve within 30 minutes. A permanent visual record of the results can be made by tracing the reactions with a fine-tipped marker and transferring them to clear tape, which is then placed on paper.

Safety

Although allergy skin testing is considered a safe procedure, it is not without risk. It is recommended that full emergency equipment and medications, (including epinephrine) be present for treatment of the rare, yet potentially life-threatening anaphylactic event.

Generalized reactions can occur with prick/puncture skin testing. The systemic reaction rate for prick/puncture tests has been estimated at 33 reactions per 100,000 tests. One study examined systemic reactions to prick testing in infants and found a rate of 0,5 percent, all of which occured when fresh food was used.

A survey of fatal reactions related to skin testing and immunotherapy performed during 1990 to 2001 was returned by 25 percent (646) of members of the American Academy of Allergy, Asthma, and Immunology. There was one fatality due to skin prick testing, which was noted in a woman with allergic rhinitis, food allergy, and moderate persistent asthma that was not optimally controlled. This is the first reported fatality due to prick/puncture testing.

Accuracy

The exact sensitivity and specificity of skin prick testing are dependent on the allergens used as well as the different variables inherent in this bioassay. (See "Factors affecting results" above). For skin testing in general, the overall sensitivity is low, and often estimated at approximately 50 percent. Thus, a positive skin test only suggests the possibility of allergy. However, the negative predictive value of skin prick testing is very high and skin testing can exclude allergy with relative certainty. These characteristics are explained in more detail below.

Positive results

A positive skin test to a particular allergen, taken alone, only indicates the presence of IgE specific to that allergen. It still must be demonstrated that the patient develops symptoms upon exposure to the allergen.

When standardized inhalant extracts with high potency are used, prick/puncture tests generally have high sensitivity and specificity (>85 percent). The diagnostic efficacy is lower for molds and certain foods (See "Allergen Preparation" below for an explanation of standardization of extracts).

A positive skin test in the absence of a relevant clinical history may be indicative of sub-clinical sensitization (ie, may be a true positive) that may eventually become clinically apparent, or it may be a false positive reaction.

Compared with other allergens, the performance of inhalant extracts in the diagnosis of allergic rhinitis is superior. A large body of literature has examined this issue. The following are a few representative examples:

• The performance of skin prick testing for identifying respiratory allergy was studied using 10 pollen allergens, two house dust mite allergens, and one cat allergen. Testing was performed in 50 patients with asthma or allergic rhinitis (group 1), 50 without these conditions but with a positive immediate family history of the disorders (group 2), and 100 subjects without a personal or family history of asthma or allergic rhinitis (group 3). At least one positive test reaction (as defined by a mean wheal diameter of greater than or equal to 3 mm) was observed in 90, 46, and 29 percent of those in groups 1,2, and 3, respectively, with accuracy based in part on the allergen. A positive reaction to the cat allergen was associated with a sensitivity, specificity, and diagnostic accuracy of 90 percent, when compared to the clinical history.
• In one study of 365 consecutive patients aged 12 years or older, the predictive value of history alone for seasonal allergic rhinitis was found to be 82 to 85 percent, and that of history in combination with prick/puncture skin testing, 97 to 99 percent.

Skin testing for foods is much less reliable, and positive reactions that do not correlate to clinical reactivity are more common. This is discussed in detail separately.

Negative results

The negative predictive accuracy of prick/puncture skin testing is high. A negative skin test confirms the absence of an IgE-mediated reaction with greater than 95 percent accuracy. As previously described, the negative predictive accuracy of food testing using commercial extracts is lower.

INTRADERMAL METHOD

Technique

Intradermal skin testing is performed by injection of 0,02 to 0,05 mL of a 1:500 to 1:1000 weight/volume allergen extract into the skin. A 26 of 27 gauge needle, positioned at a 45 degree angle, is used to make a two to three mm "bleb" of extract intradermally. The technique is identical to that used to place the intradermal PPD test for tuberculosis.

An intradermal negative control is included, in order to control for reactions in response to the injection method. A positive histamine control is not needed if reactivity to histamine has already been demonstrated by prick method; however, if required, histamine can be injected intradermally at a dilute concentration of 0,001 mg/mL.

Intradermal tests are usually performed following negative prick/puncture tests. Because they are approximately 100- to 1,000-fold more sensitive, the starting test dose of intradermal extract solutions in patients with a preceding negative prick/puncture test should range between 100 and 1,000-fold more dilute than the prick/puncture test solution.

• End-point dilution technique. The technique of end-point dilution is variant of intradermal testing that is used to identify the concentration of an extract that produces a reaction of a defined size. The more sensitive an individual is to a given extract, the lower the concentration required to produce a reaction of a given size. End-point dilution is performed by injecting a series of dilutions of an extract into a patient's skin, until a specific diameter wheal or flare is obtained. It is not considered useful in determining starting or maintenance doses for immunotherapy.

This technique is commonly used among otolaryngology practitioners in the diagnosis of allergy, however, use among allergy specialists is rare, having been largely replaced by prick/puncture followed by standard intradermal testing. The technique may be useful for evaulation of patients in whom nasal or bronchial challenges must be performed, as it can be used to assess the initial concentration for challenge. It is also used for research purposes, especially in studies of immunotherapy efficacy, because it provides a more precise measure of a patient's sensitivity. It is used in commercial laboratories for standardizing the strength of extracts.

Safety

Intradermal testing is commonly performed with environmental allergens and drugs. It is not generally done with food allergens or latex, due to an unacceptably high rate of false positive results and systemic reactions with these allergens.

Systematic reactions can occur at a low rate (less than 0,5 percent of patients). Fatalities have been reported that were primarily caused by allergens no longer in common use. In addition, in one survey, five of six fatalities associated with skin testing were observed in patients who underwent intradermal testing without prior prick/puncture testing.

Accuracy

Intradermal tests are more reproducible than prick/puncture skin tests and are more sensitive. However, false-positive reactions are more common, and for some allergens, have been demonstrated to add little to diagnostic accuracy.

False positives may be related to naturally-occurring histamine, endotoxins, and other skin irritants in some mold, venom, and inhalant extracts. Intracutaneous bleeding can be falsely interpreted as a positive reaction.

SUMMARY

• The three components in the diagnosis of an IgE-mediated allergy are identification of the allergen, demonstration of IgE specific to that allergen, and confirmation that symptoms occur when the patient is exposed to the allergen. Skin testing is a diagnostic tool used in the second component.
• A positive skin test, in isolation, is not sufficient to make a diagnosis of allergy, as it must be demonstrated that the patient develops symptoms on exposure to that allergen.
• Skin testing is a bioassay that detects the presence of allergen-specific IgE on the surface of a patient's cutaneous mast cells. Allergen is pricked into the skin and if allergen-specific IgE is present on the patient's mast cells, the cells are activated and produce localized pruritus, swelling, and erythema. Skin testing should be performed by an allergy expert, as there is a small but definite risk of inducing an allergic reaction.
• The allergic diseases for which skin testing is useful in diagnosis include allergic asthma, rhinitis, and conjunctivitis, food allergy, some medication allergies, some venom allergies, and depending on the availability of testing reagents, latex allergy.
• Skin testing is contraindicated in patients who are a high risk for an anaphylactic reaction to testing, have experienced a recent anaphylactic event, are taking medications that may interfere with the treatment of anaphylaxis, or have certain skin conditions. Such patients should undergo in vitro allergy testing instead.
• The results of skin testing are influenced by medications, physiologic characteristics of the patient, the device used, and the allergen extract used. Antihistamines must be discontinued prior to testing.
• The allergens relevant to human disease are mostly proteins from other living organisms that are able to trigger the formation of IgE in genetically susceptible individuals. Allergens for testing are obtained from natural sources and are heterogenous. Efforts are underway to standardize their production around the world.
• There are two commonly used methods of skin testing for IgE-mediated disorders: prick/puncture and intradermal. Prick/puncture is performed first and is sensitive but not very specific. Intradermal testing is more sensitive, although false positives are common and it carries a higher risk of inducing an allergic reaction.
• Prick/puncture skin testing has low specificity if all allergens are considered together. However, if standardized, high potency extracts are used (eg, pollens), sensitivity and specificity are both excellent. In addition, the negative predictive value of skin prick testing is very high and skin testing can exclude allergy with relative certainty.
• Intradermal tests are usually performed following negative prick/puncture tests, and are approximately 100- to 1,000-fold more sensitive. Intradermal testing is not performed in the diagnosis of food or latex allergy, due to an unacceptably high rate of both false positives and systemic reactions to testing.