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.