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Allied Health: Articles of Interest

Skin testing: part I – from the beginning …
By Jeanette Arnold, CFNP

Charles Blackley, MD, is credited with first utilizing diagnostic skin testing in 1865 when he produced a wheal and flare in a patient sensitive to grass pollen, by applying an occlusive bandage containing grass pollen to skin which had been scarified with a lancet. In 1911, Leonard Noon, MD, investigated the significance of allergen extract concentration on symptom causality by placing progressive concentrations of grass pollen into sensitized patients’ conjunctiva. He is credited with developing the Noon unit, used today to describe antigenic potency.

In 1924, the skin test prick (STP) method of testing was introduced. This method decreased the incidence of dermatographism and false positive reactions, was better tolerated, less painful and produced more uniform results than scarification techniques. Scarification continued to be utilized despite advances in testing methodology until after the late 1970s when several technique-comparative studies were published. Subsequently, skin test prick (STP), skin test puncture and intradermal (ID) skin testing became and have remained the gold standard for immediate (IgE antibody specific) hypersensitivity testing.

Skin test prick has been defined as placing a drop of purified allergenic extract onto the patient’s cleansed skin. A needle is introduced through the drop of extract and the skin beneath the drop is gently lifted to allow antigen introduction without inducing bleeding. Testing method drawbacks include increased likelihood of contamination between drops of extract and marked variability in test results dependant on tester proficiency. Wiping the needle with alcohol between pricks increases the likelihood of inadvertent needle stick; using new needles for each successive droplet increases overall cost. Subsequently, STP has largely been replaced with the skin test puncture method.

With the skin test puncture method, disposable devices such as the Duotip or DermaPik are either dipped in antigenic extract or introduced through a drop of antigen placed on cleansed skin. The skin is then superficially punctured with the device perpendicular to the skin with either a twisting or rocking motion. Individual tests should be placed at least two centimeters apart to avoid contamination and help clarify interpretation. This technique can produce false negatives if the plastic tines are not placed firmly enough and produces slightly more dermatographism but diminishes the risk of inadvertent needle stick.

Intradermal skin testing is more sensitive and has better reproducibility but is more painful to perform. It also has a higher likelihood of producing anaphylaxis, compounded by the number of tests performed simultaneously. ID testing is usually reserved for clarification of selectively significant negative P/P tests and for special testing needs such as testing for medications, anesthetics or insect venoms. In this technique, a 26- or 27-guage syringe is introduced almost parallel to the skin of the upper arm or forearm with skin held taut and needle bevel down. The needle should penetrate just deeply enough to cover the bevel of the needle and 0.02 milliliters should be injected intradermally in order to produce a 2-3 millimeter superficial bleb. Some of the most common errors with this type of testing include producing too large a bleb which can confound interpretation and injecting too deeply, producing a false negative.

Both prick and puncture testing should be placed on the upper portion of the back or mid-portion of the forearm. ID testing can be placed on the forearms or upper arms. Skin tests for inhalants should be interpreted 15-20 minutes after application. Results are interpreted by comparison to a [positive] histamine control and a [negative] glycerin (or sometimes normal saline) control. Interpretation of positive skin tests varies, but the majority agree that for test results to correlate clinically, the test wheal and flare must be at least as big or bigger than the positive control and at least three millimeters greater than the negative control.

The most accurate method of interpretation is to record actual cross diameter measurements of wheal and flare in millimeters and divide by two. Another method includes tracing outlines of wheal and flare reactions and capturing them on cellophane tape. A grading scale of 0-4 is also sometimes used where a +4 reaction includes a wheal with pseudopods and flare at least as large as the histamine control. A +3 reaction is > three millimeter wheal with flare as large as the histamine but without pseudopods. A +2 reaction is a flare of at least 21 millimeters. A +1 reaction has a flare of less than 21 millimeters but is significantly larger than the negative control. A negative reaction is one that has no reaction or is similar to the negative control.

Testing results are also dependant upon extract potency, patient age, race, test site choice, season, concomitant medications and underlying disease processes. Standardized extracts, including several grass pollens, cat dander, dust mites, short ragweed and stinging insect venoms, have recently become available and are easily obtained from reliable sources. Typically, African-American patients produce a larger wheal than do Caucasian patients. The upper back is more reactive than the lower back and the forearm is more reactive proximally than distally. Patients are more likely to have a stronger reaction if tested during grass pollen season.

Anaphylaxis during skin test P/P is relatively rare, however, incidence of reactions (including fatalities) is slightly higher with intradermal testing. The incidence of fatality and adverse outcome is slightly higher in patients who were tested or received immunotherapy while taking beta-blockers or ACE inhibitors, although with today’s cardio-selective beta blockers, this seems to be less of a problem. Recent position statements by the JCAAI suggest, “special precautions should be considered” in test patients who are currently taking beta-blockers or MAOI’s.

Medications which can inhibit testing include oral and topical H1 and H2 antagonists (such as eye drops and nasal sprays), tricyclic antidepressants, tranquilizers and anti-emetics. Patients should defer testing at least one week and as long as six weeks following an anaphylactic event, as anaphylaxis depletes neurogenic mediators and may produce a false negative reaction to testing. Literature suggests a decreased skin response in patients with eczema, chronic renal failure, cancer patients, spinal cord injuries and peripheral neuropathy.

In-vitro testing (RAST) is used when skin testing is prohibited (i.e. certain skin conditions, dermatographism and those on prohibitive medications that cannot be discontinued). It is considered less specific and more expensive than skin testing but has recently provided more reliable data with less dependence on individual lab performance. We continue to strive for development of testing methods that deliver reproducible, clinically significant results with better patient tolerance.

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