"Many patients have symptoms that are mistakenly assumed to be caused by allergy, such as fainting, but there is no evidence of a true immediate hypersensitivity reaction," the review authors write. "These patients can be revaccinated in appropriate settings, with a waiting period of at least 15 minutes as per the guidelines of the Advisory Committee on Immunization Practices.

A 4-step protocol for allergy testing is as follows:
Step 1. When the history is convincing for anaphylaxis, a skin-prick test should be done with use of a 1:10 dilution of the vaccine or components as well as positive (histamine) and negative controls, and the tests should be read in 15 minutes. Any reagent causing a positive response, defined as a wheal at least 3 mm greater than the negative control, surrounded by a flare, should not be retested. A wheal without flare is considered a negative test, and the next dose should be tested.
Step 2. When the history is not convincing for anaphylaxis, or when there is a negative response to 1:10 dilution, a skin-prick test with use of the full-strength vaccine should be applied for any vaccines or components with a negative prick test at the 1:10 dilution and read at 15 minutes (as in step 1).
Step 3. An intradermal skin test with use of a 1:100 concentration should be applied for any vaccines for which prick testing has not yielded a positive result.
Step 4. An intradermal skin test with use of a 1:10 concentration should be applied for any reagents for which previous steps have not elicited a positive result, unless it is determined that a 1:10 concentration is too irritating to provide useful results (eg, influenza vaccine). Because irritant reactions are extremely common, intradermal skin testing should seldom or never be performed with use of undiluted vaccines.
"Decisions about additional vaccination should be made on the basis of a case-by-case risk/benefit analysis as guided by the algorithm," the review authors write. "The options for revaccination include (1) withholding subsequent doses of suspected or implicated vaccines for patients who have serologic evidence of immunity, are at low risk for disease or serious complications from disease, or are at risk for life-threatening complications from the vaccine, (2) revaccination with minimal precautions for patients without evidence of immediate hypersensitivity, (3) revaccination with alternative vaccines that do not contain the component to which the patient has evidence of allergy, or (4) revaccination with special precautions for patients who have incomplete immunity and are at risk for disease."
Specific recommendations to guide revaccination for patients with immediate-type reactions are as follows:

• If skin tests are negative and there is no history of anaphylaxis, the patient can be given the vaccine in a single dose and observed for 1 hour.
• When available, alternative preparations that do not contain the suspected allergen should always be used.
• When testing is inconclusive and appears to implicate more than 1 vaccine, then the next series of vaccines should be done individually, on separate days, to reduce risk and to help determine which vaccine caused the reaction.
• When results of skin tests are negative and there is a history of anaphylaxis or other serious reactions, the patient should be given 10% of the dose of the full-strength vaccine and observed for 30 to 60 minutes, followed by administration of the remainder of the vaccine if there are no signs of a reaction. The patient should then be observed for 1 hour.
• If results of skin test are positive for the vaccine and/or one of the vaccine components and there is an absolute need for vaccination, the patient should then receive escalating doses of the vaccine as recommended by the American Academy of Pediatrics. This should be performed in a well-equipped clinic with skilled personnel or possibly in the intensive care unit. Each subsequent dose (increasing from 0.05 mL of 1:10 dilution through a range of doses to 0.20 mL of full strength) should be given at 15- to 30-minute intervals when there are no signs of an adverse reaction.
• The interval between doses is based on clinical judgment, ranging from 15 minutes to 1 hour for cases when the interval for the original reaction was longer. With any signs of an adverse reaction, the protocol should be aborted and treatment provided. Subsequently, additional doses of the offending vaccine should be withheld. Alternatively, some allergists premedicate with antihistamines and oral corticosteroids before administering the offending vaccine, but this has never been studied or proved effective for vaccine allergy.
• After the 1-hour observation period, patients who have not had a reaction can generally return home. However, any patient who had positive results on skin tests and then successfully completed this protocol is still considered to be allergic to the vaccine.

"All suspected hypersensitivity reactions to vaccines, both immediate and delayed, should be reported to the Vaccine Adverse Event Reporting System (www.vaers.hhs.gov) so that the true burden of this problem can be assessed.

Study Highlights

• A 4-step protocol for allergy testing is as follows:
• Step 1:
  • Skin-prick test with use of a 1:10 dilution of the vaccine or components when the history is convincing for anaphylaxis.
  • The test should include positive (histamine) and negative controls.
  • Positive response is defined as a wheal at least 3 mm greater than the negative control, surrounded by a flare, at 15 minutes.
  • Any reagent causing a positive response at 15 minutes should not be retested.
  • A wheal without flare is considered a negative result, and the next dose should be tested.
• Step 2:
  • When the history is not convincing for anaphylaxis, or when there is a negative response to 1:10 dilution, a skin-prick test with use of the full-strength vaccine should be applied and read as in step 1.
• Step 3:
  • For any vaccines for which a prick testing result is negative, an intradermal skin test with use of a 1:100 concentration should be applied.
• Step 4:
  • An intradermal skin test with use of a 1:10 concentration should be applied for any reagents for which steps 1 through 3 have been negative, unless it is determined that a 1:10 concentration is too irritating to provide useful results (eg, influenza vaccine).
• Specific recommendations to guide revaccination for patients with immediate-type reactions are as follows:
  • If skin tests are negative and there is no history of anaphylaxis, administer the vaccine in a single dose and observe the patient for 1 hour.
  • Alternative preparations that do not contain the suspected allergen should always be used when available.
  • When testing is inconclusive and appears to implicate more than 1 vaccine, then the next series of vaccines should be done individually, on separate days. This should help reduce risk and identify which vaccine caused the reaction.
  • When results of skin tests are negative and there is a history of anaphylaxis or other serious reactions, the patient should be given 10% of the dose of the full-strength vaccine.
  • If there are no signs of a reaction within 30 to 60 minutes, the remainder of the vaccine can be given, and the patient should be observed for 1 hour.
  • If results of skin test are positive for the vaccine and/or 1 of the vaccine components and there is an absolute need for vaccination, the patient should then receive escalating doses of the vaccine as recommended by the American Academy of Pediatrics.
  • Dose escalation (increasing from 0.05 mL of 1:10 dilution through a range of doses to 0.20 mL of full strength) should be performed in a well-equipped clinic with skilled personnel or possibly in the intensive care unit.
  • Each subsequent dose should be given at 15- to 30-minute intervals when there are no signs of an adverse reaction.
  • The interval between doses is based on clinical judgment, ranging from 15 minutes to 1 hour for cases when the interval for the original reaction was longer.
  • The protocol should be aborted if there are any signs of an adverse reaction, and treatment should be provided.
  • Additional doses of the offending vaccine should subsequently be withheld.
  • Although some allergists premedicate with antihistamines and oral corticosteroids before administering the offending vaccine, this has never been studied or proved effective for vaccine allergy.
  • After the 1-hour observation period, patients who have not had a reaction can generally return home.
  • Any patient with positive results of skin testing who then successfully completed this protocol is still considered to be allergic to the vaccine.

Pearls for Practice

• For patients with signs and symptoms consistent with immunoglobin E–mediated reactions to vaccine or its components, allergy testing may be indicated, especially when future doses of the suspect vaccine(s) will be needed. A 4-step protocol facilitates this process, which should preferably be performed by an allergist, using the specific vaccine, from the same maker, that is suspected of causing the reaction.
• Decisions about additional vaccination should be based on patient-specific risk/benefit analysis as guided by the algorithm. Options for revaccination include withholding subsequent doses of suspected or implicated vaccines for patients with serologic evidence of immunity, are at low risk for disease or serious complications from disease, or are at risk for life-threatening complications from the vaccine.