Vaccination of Children and Adolescents With Rheumatic Diseases

Laura Dell'Era; Susanna Esposito; Fabrizia Corona; Nicola Principi


Rheumatology. 2011;50(8):1358-1365. 

In This Article

Vaccine-related Risk of Autoimmune Reactions

As vaccines are usually intended for healthy children, their adverse effects are less well accepted than those of drugs administered to the sick. Consequently, even rare adverse reactions to vaccines are greatly magnified and can significantly modify acceptance by physicians and parents. In the case of the development of autoimmunity and autoimmune disease, the manifestations are rare, may be non-specific, and are often so mild that they are not reported.[10] Furthermore, the time between vaccination and the occurrence of autoimmunity can vary from days to even years, and may be further extended by the fact that some vaccines require multiple administrations.[10] It is therefore difficult to define a causal relationship, although one has been supposed in some cases.[11]

The vaccines with the largest number of reports of RD induction are the HBV, influenza and measles, mumps and rubella (MMR) vaccines. There are reports of > 10 patients developing RA, ReA and vasculitis after HBV vaccination, and a small number have described the exacerbation of SLE, SS, cryoglobulinaemia, polyarthralgia and myalgia.[12–23] Only a few of these case reports involved young children.[12,18–22] Given the millions of doses of HBV vaccine given to children, the number of autoimmune diseases associated with HBV vaccine is very small. However, all of the case–control studies that have analysed the safety of HBV vaccine in large groups of subjects have found no increase in the incidence of autoimmune manifestations after its administration.[21,22] Furthermore, no differences have been found between the autoantibody profiles of 6-year-old children who had received HBV vaccine at birth and unvaccinated controls.[23] These data fully justify the conclusion of various experts (including those of the World Health Organization) that the risk of HBV vaccine-induced autoimmune reactions is no more than theoretical.[24]

Vasculitis, HSP and, very rarely, ReA and cryoglubulinaemia have been described after the administration of influenza vaccine.[25–32] Case reports suggest that influenza vaccination can induce autoimmune disease, as in the case of two patients with HSP in whom aPLs appeared.[25,26] However, the possible relationship between influenza vaccine and the recurrence of vasculitis was specifically addressed in a retrospective study of inactivated influenza vaccine in 230 adolescents and adults with ANCA-associated vasculitis,[27] which found no increase in the relapse rate of patients vaccinated during the preceding year in comparison with unvaccinated patients. Furthermore, controlled studies of children with active arthritis receiving influenza vaccine have shown that vaccination does not worsen the clinical situation, and that the few cases of increased joint involvement can be attributed to expected fluctuations in disease activity.[28] Finally, Guillain–Barré syndrome occurred with one swine influenza vaccine in 1976, but this association has not been observed since then.[29–32]

MMR vaccines contain live viruses that can trigger an immune-mediated disease, such as subacute sclerosing panencephalitis (SSPE), although this is much less common than after actual infection.[33] However, autoimmune complications after the administration of measles vaccines have been reported very rarely.[34] Arthralgia and acute transient arthritis have been described in ~10–25% of children receiving MMR vaccines: these have been associated with the rubella component as joint involvement is common after rubella infection.[35] However, chronic arthritis seems very rare and studies of adult women have clearly shown that those who have received rubella vaccine are at no risk of developing it.[36,37]

There are very few data concerning the other vaccines. Koshcheeva et al.[38] and Kashef et al.[39] have, respectively, studied diphtheria and tetanus vaccines and found that they do not interfere with the activity of the underlying disease. It has also been shown that the administration of meningococcal C or meningococcal B vaccine does not aggravate the disease activity of JIA or increase relapse frequency.[40–42] Similarly, no worsening in clinical parameters, and no disease flares or changes in the doses of medications have been observed after the administration of hepatitis A[43] or varicella vaccine.[44]

Global evaluations of suspected autoimmune manifestations (including RD) after vaccination indicate that those that are really related to the vaccine are extremely rare in the healthy population, and generally have a short course, a spontaneous resolution and benign prognosis. Moreover, children with RDs are at no significantly increased risk of the reactivation or recurrence of their underlying disease. All the characteristics of the autoimmune problems theoretically related to vaccination suggest that their pathogenesis is due to transient mechanisms. Although the risk factors for these reactions have not yet been identified, there is the possibility that autoimmune diseases may recur when a patient is given a booster dose of the same vaccine. Some experts would suggest that a vaccine should be avoided if it has previously caused a disease relapse.


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