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).