Infections may trigger or contribute to the pathogenesis of arthritis. Thus, vaccines may prevent arthritis by protecting against natural infections. Rubella-containing vaccines (e.g. MMR) can cause mild, acute, transient arthralgia or arthritis, rarely in children but very commonly in certain adult women (between 10-25% of adult female vaccinees without preexisting rubella immunity), usually beginning 1-3 weeks after vaccination and then persisting up to 3 weeks. Other vaccines currently routinely recommended to the general population in the U.S.* have not been shown to cause chronic arthralgia or arthritis.
Mild, acute, transient arthralgia occurs in approximately 25% of adult women without preexisting rubella immunity after rubella vaccination, and mild, acute, transient arthritis occurs in approximately 10%, usually beginning 1-3 weeks after vaccination and then persisting up to 3 weeks. Both are less common in men and rare in children .
The 2012 report by the Institute of Medicine (IOM) , now called the National Academy of Medicine (NAM), described four studies in women [3-6] and seven studies in children [7-13] that generally reported an increased risk of transient arthralgia after rubella or MMR vaccination. Also described are two studies assessing chronic arthralgia and arthritis in women [5, 6] and two studies assessing arthropathy in men [14, 15] after rubella or MMR vaccination; one study assessing the association between HPV vaccine and transient arthralgia ; one study assessing the association between hepatitis B vaccination and exacerbation of rheumatoid arthritis ; and two studies assessing the association between diphtheria or tetanus toxoid vaccination and chronic arthritis [15, 18]; however, these studies did not provide convincing evidence due to a lack of validity and precision. The IOM found no relevant studies of quality in the literature providing evidence of an association between any other vaccines and chronic arthropathy .
Most studies published since the 2012 IOM report did not show a statistically significant association between influenza and HPV vaccines and arthralgia [19-22]. One study found a relative risk of arthralgia of 2.0 (95% CI: 1.6-2.5) after receipt of a vero-cell culture-derived trivalent influenza vaccine , and another study found an odds ratio of grade 3 arthralgias of 2.68 (95% CI: 1.29-5.59) after receipt of the AS04-adjuvanted HPV-16/18 vaccine (Cervarix) among women in Korea . No association has been found between vaccination and arthritis [25-29]. Studies in patients with autoimmune inflammatory arthritis showed no change in disease severity or relapse rates after influenza vaccination [30-36].
Proposed Biological Mechanism
Environmental factors such as infections may trigger or contribute to the pathogenesis of arthritis; however, the exact mechanisms are still unclear [37-40].
Based on both cases reviewed and knowledge about the natural infection, the IOM concluded that there was some mechanistic evidence in support of a causal relationship between rubella vaccine in women and arthralgia [3, 41-43]; however, there was less evidence for a relationship between rubella vaccine in women and chronic arthralgia [43-45] or arthritis [42, 45]. There was little evidence for a relationship between rubella vaccine and arthropathy in men, transient arthralgia in children or chronic arthropathy in children [46, 47], for influenza vaccine and onset or exacerbation of arthropathy , or for hepatitis B vaccine and onset or exacerbation of arthritis [49, 50]. The IOM also concluded that there was no mechanistic evidence for an association between all other vaccines and arthralgia, arthritis or arthropathy.
* These conclusions do not necessarily consider vaccines recommended only for special populations in the United States such as Yellow Fever vaccine (international travelers) or Smallpox vaccine (military personnel).
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