I) CHILDREN WITH A SUSPECTED ALLERGIC REACTION TO A VACCINE
Confirmation by allergy workup is recommended both to identify the culprit allergen from the vaccine components, in order to avoid the risk of cross-reactivity with other vaccines or foods24, both to manage subsequent administrations if further doses are needed avoiding unnecessary restrictions against vaccine use. A complete list of all potential allergens in vaccines can be found at the website of the Institute for Vaccine Safety of the John Hopkins University25.
An algorithm to select and manage vaccination of patients who refer a previous suggestive allergic reaction to a vaccine is proposed in Fig 1. If a vaccinee manifests an adverse event suggestive for a hypersensitivity reaction, it is mandatory to evaluate the clinical history to identify whether is present any risk factor as for e.g. food allergy, severe uncontrolled asthma, mastocytosis etc. It has to be evaluated the precise temporal relationship and thus the type of reaction (immediate or delayed), the brand of vaccine (necessary for the exact vaccine components list), the presence of comorbidities and the need for further doses in order to evaluate the individual risks/benefits ratio.
As stated above, IgE-mediated reactions can be suspected on the basis of the short time interval between vaccination and the onset of symptoms, conventionally within 4 hours26. The allergy workup in case of a suspected immediate-hypersensitivity reaction provides for complete vaccine skin testing in a setting equipped to treat anaphylaxis. First, it has to be performed a prick test with full-strength vaccine followed, in case of negative result, by intradermal test with 0.02 ml of vaccine diluted 1:100 and, if negative, 1:10 dilution could follow, although some authors described irritant false-positive reactions with this concentration27. Positive and negative control testing are recommended. The sensitivity and specificity of skin tests with vaccines in confirming or discarding allergy to a vaccine or its components have not been established, however, if skin testing proves negative, it is very unlikely for the patient to have IgE against the vaccine or its components17. In drug allergy, more than one year after an IgE-mediated reaction, there might be very little remaining circulating IgE with a consistent risk for false negative skin testing results28 and the same should be taken into account for IgE reactions to vaccines.
The next step is to assess sensitisation to the components of the vaccine, with the aim of preventing reactions with other vaccines containing the same components17, in Tab 2 are listed the main vaccine components which can elicit an allergic reaction. Prick test and/or specific IgE to components present in the suspected vaccine are limited (food proteins and tetanus toxoid). To note, interpretation of specific IgE results needs expertise because for some constituents, e.g. ovalbumin and gelatine, the predictive capacity for reaction to vaccines is rather low and false positive results may occur. There are much more individuals allergic and sensitized to a given allergen, than those who react clinically on the exposure to a minute amount of the same allergen present in the vaccine composition. In regards to serum specific IgE to vaccine microbial antigens production, this is mostly part of the regular immune response and has a limited predictive value for an allergic reaction1.
When the culprit allergen is identified, an alternative brand free from the offending ingredient should be preferred in case the patient needs additional doses.
Non-protected patients with negative skin testing results can be immunized with a full-strength dose. In case of history suggestive for anaphylaxis, a split dose strategy with initial 10% of the vaccine dose followed 30 minutes later by the remaining 90% of the dose is a more cautious option1.
Patients positive skin testing should undergo desensitization in graded doses. Increasing vaccine doses are administered every 15-30 minutes after providing that there are no signs of allergic reaction (0.05 ml of 1:10 dilution, following 0.05 ml, 0.1 ml, 0.15 ml and 0.2 ml of a 0.5 ml full strength vaccine)26. Patients who have successfully undergone this protocol still must be considered allergic to the vaccine and this procedure should be repeated in case of boosters. It is mandatory that patients suspected for an allergic reaction to a vaccine, must only be managed in a controlled setting where prompt treatment of anaphylaxis by experienced staff is available1.
In case of suspicion for a delayed reaction, the vaccine in most cases can be administered in a conventional manner29. Patch testing, although not essential for therapeutic decisions, might help in identifying the culprit component and avoiding it when alternative apten-free brands are available. Various vaccine aptens are commercially available for patch testing: aluminium chloride hexahydrate 2%, elemental aluminium (an empty aluminium metal Finn chamber), polysorbate 80, formaldehyde 1%, kanamycin sulphate, polymyxin B, gentamycin, phenoxyethanol 1%, neomycin and phenol. Patch tests should be removed at 48 hours and read at 72 and/or 96 hours or 1 week (the latter might be necessary in case of sensitization to aluminium salts).