CHAPTER 219 Allergy Testing and Immunotherapy

The primary methods of allergy skin testing are (1) single skin prick tests (SPT; pricking the skin at a 45-degree angle through previously placed allergens); (2) skin puncture tests (puncturing the skin at a 90-degree angle through previously placed allergens); and (3) using preloaded multiple-allergen testing devices that apply multiple allergens simultaneously. All three of these tests are confined to the epidermis. Multiple-allergen applicators have gained in popularity because of their safety, ease of use, and test reproducibility and readability. The three that are commercially available are the Multi-Test II (Lincoln Diagnostics, Decatur, Ill; Fig. 219-1), Quintest (Hollister-Stier Laboratories, Spokane, Wash; Fig. 219-2), and Omni (Greer Laboratories, Lenoir, NC).

Figure 219-1 Lincoln Diagnostics Multi-Test.

(Courtesy of Lincoln Diagnostics, Decatur, Ill.)

Figure 219-2 Hollister-Stier Quintest.

(Courtesy of Hollister-Stier Laboratories, Spokane, Wash.)

Although considered an SPT, Multi-Test II is comparable with an intradermal (ID) test using a 1 : 1000 dilution of allergen. Several studies have shown that a positive ID skin test (1 : 100 dilution) after a negative SPT (using 1 : 20 concentrates) has little or no clinical significance; thus it is not recommended (see later discussion).

As opposed to the prick and puncture tests, the ID test goes deeper, into the dermis.

Older scratch testing methods are not as reproducible or reliable as SPT and are not recommended.

In vitro blood tests (e.g., radioallergosorbent test [RAST[) are performed by a reference laboratory. No “kits” are available for office testing because this procedure involves just the drawing and testing of a blood sample. It is the test of choice for patients exhibiting dermographism, hyporeactive skin, poorly controlled asthma, eczema, or any skin condition limiting the placement of skin tests.

The identification of allergens helps direct patient avoidance measures and medical therapy; it also provides the basis for immunotherapy. As Nelson and colleagues (1996) state, “Immunotherapy provides the only potentially curative treatment available because of its unique ability to change the natural history of allergic respiratory disease and Hymenoptera sensitivity. Many suggest that starting immunotherapy is a reasonable option that can provide safe and cost effective management for a substantial number of patients.” Starting immunotherapy earlier in allergic conditions may prevent (rather than just reduce) the inflammatory response, prevent the development of asthma in children with rhinitis, and allow treatment to begin at lower levels of patient sensitivity. It may be the only safe modality for patients whose jobs require alertness and who cannot tolerate antihistamines (e.g., pilots, truck drivers). It is accepted that a positive SPT or in vitro test does not necessarily mean clinical sensitivity, so correlation with the clinical history is essential if immunotherapy is to be successful.

Screening for Allergies

It is appropriate and cost effective to screen patients for allergies with a limited set of 6 to 10 allergens before applying a complete geographic panel of allergens (Fig. 219-3). A typical screen consists of a positive (histamine) and negative (glycerol-saline) control; house dust mite mix; cat; and the most tree, grass, weed, and mold allergens of the geographic area. Physicians and patients reluctant to rely on only six allergens for screening may use a second panel of eight allergens consisting of dog; cockroach; feathers; silk; and secondary tree, grass, weed, and mold preparations.

Figure 219-3 A typical screening panel with six allergens.

Always check the positive and negative control sites before interpreting the response to the allergens. When all screening test sites are negative (excluding the positive control; see Fig. 219-13), the probability of allergy is less than 3%. Approximately 50% of patients with rhinitis tested by Multi-Test or an in vitro test will have negative findings. These patients have nonallergic rhinitis. Identification of nonallergic triggers is critical for medical care. Decongestants (not antihistamines), nasal steroids, and nasal astemizole are the appropriate medications indicated for nonallergic rhinitis. However, roughly 50% of patients with rhinitis have an allergic basis to their symptoms. Many patients have mixed rhinitis, meaning they have both allergic and nonallergic rhinitis simultaneously.

As noted, allergy screening can be performed using either SPT or in vitro methods. Phadiatop (Pharmacia & Upjohn Diagnostics, Uppsala, Sweden) and the Multiple Inhalant Allergy screen (MIA; LabCorp, Burlington, NC) are two RAST screens using 10 allergens. In vitro screens usually have ±10 of the most common allergens, including tree, grass, weed, and molds from a geographic area; house dust mite; and cat. In vitro screens are performed by the various laboratories. A blood sample is sent to the company for testing. There is no office “kit.”

When the aforementioned screening tests are negative, no further testing is needed. Screening is very cost effective in selecting out the nonallergic patient. (The Blue Cross/Blue Shield usual and customary reimbursement for SPTs is currently $7.00 per allergen. The negative and positive controls are not reimbursed, hence the $42 payment. The $15 to $25 fee for in vitro testing varies from company to company.)

A history of symptoms in early spring generally correlates with positive skin tests to tree allergens. Summer symptoms correlate with grass sensitivity, and fall symptoms correlate with weed sensitivity. In the warmer climates there is much overlap. Year-round (perennial) symptoms correlate with house dust mite, mold, or insect or animal sensitivity. Perennial symptoms with seasonal exacerbations frequently occur in the same patient.

Equipment

For Skin Testing

• Multiple allergen applicators and loading docks (Multi-Test II, Quintest, Greer)

• Individual applicators for the occasional testing of one or two allergens (Duotip [Lincoln Diagnostics], Morrow Brown Needle [Alkaline Corporation, Oakhurst, NJ]); or a tip from a multiple-allergen applicator can be broken off and used separately

• Alcohol sponges to clean the testing site

• 30 to 50 standardized or 1 : 20 weight/volume [w/v] allergen concentrates identified for the specific geographic locale by published data or suggested by providers of allergy diagnostics (house dust mite comes only as a 1 : 100 dilution as the concentrate)

• Histamine phosphate (2.75 mg/mL) for the positive control and saline for the negative control

• Recording form (Fig. 219-4)

• Black skin-marking pen

• Timer capable of timing at least 20 minutes

• Millimeter ruler

• EpiPen, Ana-Kit, or epinephrine; and albuterol

• Resuscitation equipment in the rare event of anaphylactic reaction (the same as that for giving any injections in the office; see Chapter 220, Anaphylaxis)

• Disposable tuberculin syringes fitted with a 26- or 27-gauge needle for the “vial test” (see the section on Intradermal Testing and the Vial Test)

Figure 219-4 Sample recording form.

(Courtesy of Lincoln Diagnostics, Decatur, Ill.)

For Radioallergosorbent Testing or Other in Vitro Tests

• Equipment for drawing blood

• Mailing packages or instructions provided by the RAST laboratory

Technique

Skin Prick and Puncture Tests

Skin prick tests are performed by placing a drop of allergen concentrate (usually 1 : 20 w/v) on the arm or back, then pressing a needle through the drop into the epidermis at a 45-degree angle. The tip of the needle is then lifted up, producing the pricking sensation. If performed correctly, no bleeding should occur (Figs. 219-5 and 219-6A). The skin puncture test is similar, but the skin is punctured at a 90-degree angle (Fig. 219-6B). Several skin testing devices were listed previously. The use of Multi-Test II is described in detail here because it has been found to be safe, easily learned, reproducible, and reliable. A videotape of the procedure is available from Lincoln Diagnostics.

Figure 219-5 Method for percutaneous skin prick testing. A, The drop of allergen is placed on the skin and a 27-gauge needle (bevel up) is placed through the allergen drop into the superficial epidermis. B, The needle pricks the skin at a 45-degree angle, allowing allergen to come in contact with sensitized mast cells located in the epidermis, and then is lifted up. The dermis is not violated and bleeding at the site is nonexistent or minimal.

Figure 219-6 A, Skin prick test (45-degree angle). B, Skin puncture test (90-degree angle). In both methods, only the epidermis is penetrated.

Multi-Test Applicator Method

Multi-Test II is a sterile, disposable, multiple-test applicator used to apply eight allergens simultaneously. Although considered an SPT, its reliability is comparable to ID techniques using a 1 : 1000 dilution of allergen. Laboratories that supply the allergen concentrates will help determine the most relevant allergens for the patient’s geographic area based on established patterns. The system consists of plastic applicators and the Dipwell tray (Fig. 219-7).

Figure 219-7 Plastic applicators in the Dipwell tray.

Loading the Dipwell Tray

1 Establish a master list of allergen panels (each containing eight allergens) to be tested and enter them on the recording form. It is crucial to load each allergen in the same test well each time. Make copies of this list for recording test results and refer to it when replenishing allergens.

2 Label (number) each panel A, B, C, D, etc.

3 Allergen panels are made by adding 1 mL (enough for 100 applications) of each allergen concentrate (1 : 20 w/v in 50% glycerin or standardized extract) to each well numbered 1 through 8. Applicator heads are numbered 1 through 8 also and correspond to the numbered wells. Each Dipwell tray accommodates three allergen panels, each with eight testing heads (see Fig. 219-7).

4 Panel A (screening panel) contains the positive control in well A1 and the negative control in well A8. A2 through A7 contain the most common tree, grass, weed, and mold allergens from a geographic area, plus house dust mite mix and cat.

note: This panel will identify over 95% of those in the allergic population. A negative (except for the positive control) screen indicates a nonallergic cause of rhinitis or asthma. No further allergy testing is indicated. This reduces the cost of total allergy testing. When the screen is positive, additional allergens of the geographic area are tested (usually 30 to 40). An additional panel can also be used to check for allergies to common foods (e.g., milk, corn, wheat, egg, soy, sugar, baker’s yeast, and pork).

5 Trays are stored in the refrigerator and stack easily.

Application of Multi-Test

1 Place the Dipwell tray, which has been filled as noted previously, on a flat surface with the “cradle” for the “T” handle facing away from you.

2 Remove the sterile applicator from the package (held with the blue dot at the top) by pulling the label at the blue dot. This positions the “T” handle away from you for correct placement in the Dipwell tray (Fig. 219-8).

3 Place the applicator in the loaded Dipwell tray (see Fig. 219-7). The applicator now has the allergen on the respective tips.

4 Cleanse the skin with an alcohol wipe and allow it to dry.

5 Mark (number) the test sites on the skin corresponding to the placement of the applicators (A, B, C, D, etc.) with a black skin-marking pen.

6 Apply panel A (screening panel) to the volar surface of the forearm (supported with a pillow to keep the arm flat) with the “T” handle toward the patient’s head (Fig. 219-9). Apply with a rocking motion, to and fro and side to side. When applied with correct pressure, a footprint of each testing head will be visible. No bleeding should occur; if it does, reduce the amount of pressure applied. The correct amount of pressure will be realized after several applications.

7 A positive reaction to any one of the tree, grass, weed, or mold allergen(s) is followed by testing all remaining significant allergens of the area suggested by history. Total number is variable from area to area, usually 20 to 40. These are placed on the patient’s back with the patient lying face down and can be applied at this visit (Fig. 219-10). Sites must be kept flat to prevent allergens from running and contaminating other sites. Hairy sites should be avoided because this interferes with readability.

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