16 Skin Testing: Intradermal
16.1 Getting into (not under) Someone’s Skin
Intradermal testing is another skin testing technique that can be used to diagnose allergies, either alone as a single intradermal test, together with skin prick testing (see Chapter 17 on blended techniques), or in a sequential fashion to determine a potential suggested point for immunotherapy or as done with testing for venomous stinging insect allergy. It is also used in conjunction with skin prick testing as part of the testing technique to evaluate patients with some medication allergies, such as penicillin or local anesthetic allergies. This technique involves needles, is more technique-dependent so more skill and experience are needed in placing these tests, and can cause mild discomfort. Like skin prick testing, there should be little to no bleeding and, though the risk of severe allergic reactions is slightly elevated, anaphylaxis is rare. Even if the practitioner chooses not to practice this type of skin testing, it’s still helpful to be familiar with it, especially if he/she chooses to pursue adding testing for venoms or medication in the future.
16.2 Serious Stuff
Who’s a good candidate for skin testing? As with skin prick testing, patients with symptoms suggestive of immunoglobulin E (IgE)-mediated allergic disease, having no medical contraindications listed in Chapter 14, and who have discontinued any interfering medications.
What does this test tell? Whether or not IgE is present to (an) antigen(s). These tests are not perfect, require more skill to perform than skin prick testing, and are technique-dependent. It does not tell if a patient has allergy (see Chapter 3). The evidence doesn’t support a clear demonstration of superiority of skin prick testing over single or sequential intradermal techniques and vice versa.
How does this test differ from skin prick testing? What is the technique? Instead of an applicator device, a special short beveled needle is used to inject a tiny amount of fluid into the intradermal layer of the skin, similar to a purified protein derivative (PPD) test for tuberculosis. Roughly 0.01 to 0.03 mL of fluid is used to raise a 4-mm wheal. The testing procedure is discussed in more detail in this chapter.
What fluid is used for injection? Fluids used for injection are either the prepared positive, negative, and if indicated, glycerin controls, as well as one or more diluted preparations of antigen. What dilutions of antigen are used, as well as how to prepare them and the controls, are discussed later in the chapter.
How long does this test take? When can this test be read? After injection, wait for 10 minutes, although there may be some variation in that timing among practitioners. Then the test results can be read as either positive or negative and the wheal sizes can be recorded.
What is a negative test? What does it tell? Physical spreading of the injected fluid alone will cause enlargement of the wheal usually by 1 mm so a negative test will measure 5 mm wheal size at 10 minutes. It indicates the absence of sensitivity.
What is a positive test? What does it tell? A positive test is growth of the wheal beyond what would be expected from physical spreading alone by at least 2 mm. So a positive test would show a growth of the wheal to at least 7 mm or greater than the negative control. The exception to this is if a glycerin control is used and there is a positive result for that test. In that case, a positive test is at least 7 mm and at least 2 mm larger than the wheal produced from the glycerin control. Generally, a positive test result confirms the presence of IgE to (an) antigen(s). A positive test by itself only indicates allergen sensitization, NOT allergy.
What’s the negative control? And what’s a glycerin control? Why would you need that? Intradermal testing is a little bit more complicated. As mentioned before, different dilutions of antigens may be used in this testing. The negative control is whatever liquid the antigen concentrate is being diluted in, generally phenolated normal saline (PNS).
The glycerin control is basically one or more diluted preparations of 50% glycerin. Remember—each antigen concentrate contains 50% glycerin and diluting those down will create solutions with different concentrations of glycerin. In patients with glycerin sensitivity, a wheal and flare response can occur if the injected dilution contains a high amount of glycerin concentration to irritate their skin. Without a glycerin control to let you know the patient being tested has glycerin sensitivity, antigen testing reactions may be read as falsely positive.
So, can the glycerine be used or the test results can be read if the patient has a positive glycerin control? And what dilution of glycerin should be used? Yes! If the patient has a positive glycerin control, test results can be read, only the alteration is of the threshold needed for a positive response for any testing dilution that is the same or more concentrated/stronger than the glycerin control. For antigen dilutions that are equivalent or stronger than the glycerin control, a positive response is at least 7 mm and at least 2 mm larger than the wheal produced from the glycerin control. Tested antigen dilutions that are weaker than the glycerin control contain lower amounts of glycerin and the positive test criteria for those do not have to be altered.
Do you need a positive and negative control? Yes, because to make sure the skin reacts as expected. You need to confirm that it will react to histamine appropriately and that it won’t react to things it shouldn’t. See Chapter 14. You also need to know if there is glycerin sensitivity.
What’s the positive control? The positive control is a diluted histamine solution prepared for intradermal testing. There are different concentrations of histamine made for different types of testing. Make sure to use the correct one. Generally, a diluted solution of aqueous histamine phosphate 0.275 mg/mL is used. Several preparation instructions are provided in this chapter.
What antigens to test? See Chapters 5 to 9. Try to tailor tests according to the patient. Include any relevant exposures. These tests are also used as part of protocols to test for medication allergies and venoms. Do not use these tests for food or chemical allergy testing.
Where to test the patient (in the office)? Same as skin testing—most commonly the volar surface of the forearm, arm, and back are used.
Could anaphylaxis really happen during intradermal testing? Yes! It’s rare and unlikely, but patients may experience a variety of adverse events while testing. See Part 5, Allergy Emergencies, but the practitioner must be prepared to handle anaphylaxis if he/she chooses to do any form of skin testing.
16.3 Tools of the Trade (What Are Needed)
Short-beveled allergy testing syringes; larger syringes may be need for treatment board preparation (▶Fig. 16.1a, b).
Alcohol swabs or 70% isopropyl alcohol/gloves/skin marker/record sheet or electronic medical record (EMR) entry.
Histamine prepared for intradermal skin testing.
Negative control (PNS or some other liquid used as diluent); if needed, glycerin control(s).
Testing/treatment board prepared with antigen dilutions (▶Fig. 16.2).
Emergency supplies (See Part 5, Allergy Emergencies)
Wheal measuring device.
16.4 Shocking Information (How to Actually Do This!)
16.4.1 Preparation of Dilutions for the Testing/Treatment Board
Since various dilutions of antigens are used not just for patient testing, but also for immunotherapy, the procedure to make these dilutions are outlined in this section. Concentrated antigen is never used in intradermal testing. This procedure is also used to prepare histamine and glycerin controls.
To prepare the board, antigen concentrates are needed, syringes for mixing, and either 5-mL vials prefilled with 4 mL of PNS or 10-mL vials prefilled with 9 mL of PNS.
All dilutions or immunotherapy vials (anything considered to be mixed or “compounded” for allergy testing and treatment purposes) must be prepared according to USP 797 guidelines, either under an ISO Class 5, primary engineering control (PEC) (▶Fig. 16.3), OR in a dedicated allergenic extracts compounding area (AECA) by appropriately trained and regularly evaluated staff. See further details in Part 8.
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