DELAYED REACTIONS
Delayed reactions are defined as reaction that develop hours or days
after vaccination, and are very unlikely to be mediated by IgE. Delayed
urticaria and/or angioedema, as well as non-specific skin rashes, have
been reported in 5% to 13% of patients receiving vaccines containing
toxoids but several studies suggest that most of these generalized
reactions result from a nonspecific activation of the immune system by a
significant amount of microbial substances and will not relapse on
re-exposure to the same vaccine17.
Delayed reactions are usually self-limiting conditions that do not
contraindicate the administration of future doses of the same
vaccine18. Of these, local reactions are the most
frequent and are commonly non-allergic such as pain, redness and
swelling, that develops within hours and days at the vaccination site
after immunization and do not require any allergy workup. Instead,
contact dermatitis, subcutaneous nodules and maculopapular exanthema are
local type IV hypersensitivity reactions and usually occur more than 12
hours after vaccination19.
Soreness, redness and/or swelling at the injection site are generally
mild and could result from nonspecific inflammation induced by injection
itself or other components used as adjuvants. Large injection site
reactions are less common and usually occur within 24-72 hours following
immunization and disappear in a few days17,20.
Swelling that measure at least 10 cm and extend beyond the elbow or knee
is defined as extensive limb swelling17, it is usually
painless and occur commonly within the first 24 hours after vaccination
and his responsible mechanism is still poorly understood. They occur
more frequently after polysaccharide pneumococcal vaccine, diphtheria,
tetanus toxoids, and acellular pertussis (aP) -containing vaccines.
Local reactions could also result from an Arthus reaction, a type III
hypersensitivity, that develop only in previously immunized patients
occurring typically after the fourth or fifth
injection20.
Subcutaneous nodules have been described in up to 19% of patients
receiving vaccines containing aluminum hydroxide1 and
they typically develop weeks after injection. Although these lesions
usually regress spontaneously within a few weeks, few cases of
persistent nodules more than 6 months have been
reported21.
Patch testing with aluminum chloride hexahydrate 2% and/or elemental
aluminium should be used to investigate the presence of a type IV
hypersensitivity22. Positive results were demonstrated
in 95% of children with persistent itching subcutaneous nodules and
tend to disappear over time, suggesting a loss of
hypersensitivity23. However, delayed-type
hypersensitivity to Aluminum causing an injection site nodule, is not
usually a contraindication to subsequent vaccination.
In all these cases the administration technique is important and a
deeper injection has been associated with a lower rate of local
reactions, especially in children younger than 3
years1.
Aminoglycoside antibiotics (neomycin, gentamicin, streptomycin and
kanamycin) might be contained in many vaccines to avoid contamination of
the culture with bacteria or fungi, including MMR, polio and influenza.
Although they can theoretically cause immediate allergic reactions to
containing vaccines, they are commonly implicated in delayed
hypersensitivity reactions such as contact
dermatitis17. Administration of vaccines containing
gentamicin, neomycin, streptomycin and kanamycin is contraindicated in
case of anaphylaxis from such antibiotics, whereas patients suffering
from allergic contact dermatitis can be safely vaccinated.
Concurrent systemic viral infections that may predispose to delayed
cutaneous reactions after immunization practice have been observed in
children17. The mechanisms by which viral infections
modify immune responses to drugs are not clear, widespread activation of
T cells with a lower threshold of T cell reactivity and high cytokine
levels may be involved21.