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Vaccination as a triggering agent for the development of rheumatoid arthritis

Dear Editor, Rheumatoid arthritis (RA) is an autoimmune disease of unknown aetiology. Current thinking on its etiopathogenesis is related to a close interplay between a genetically determined hyper-reactive innate immune system, a genetically predisposed adaptive immune system and some environmental factor(s). The environmental triggers that have been implicated in its etiopathogenesis include smoking, viruses and bacterial products. One of the triggering agents occasionally implicated in RA has been vaccination. Recently we saw a 46-year-old man with a 6-week history of symmetric inflammatory polyarthritis of insidious onset. There was history of a stray-dog bite on the left leg (category III), 1 week prior to the development of symptoms. He was given post-exposure rabies prophylaxis with purified vero-cell culture rabies vaccine (ABHAYRAB ) on days 0, 3 and 7. He was concomitantly vaccinated with intramuscular tetanus toxoid 1.0 mL on day 0. There was a strong family history of autoimmune diseases, including scleroderma, RA and hypothyroidism. On musculoskeletal examination there were 16 tender and 14 swollen joints, that included a wrist, six metacarpophalangeal, eight proximal interphalangeal, mid-tarsal and metatarsophalangeal joints bilaterally. The calculated Disease Activity (DAS)-28 value was 5.51. Investigation results were as follows: erythrocyte sedimentation rate (ESR) 24 mm at 1 h; high sensitivity-C-reactive proteins 16.7 mg/L; platelets 219 · 10/lL; rheumatoid factor (RF) 26.3 IU/mL (low titre positive); anticyclic citrullinated peptide (CCP) 121.92 U/mL and human leucocyte antigen (HLA) B27 positive. Radiograph of both hands and feet were normal. He was prescribed methotrexate, hydroxychloroquine and low-dose methylprednisolone 16 mg once a week and 4 mg daily which was tapered off over the period of the next 2 months. At 2 months follow-up he showed marked improvement with no swollen or tender joints and a DAS-28 value of 2.22 (remission). On second follow-up after 10 months he continued in remission (DAS-28 1.53). This case could be classified as RA according to 1987 criteria as well as 2010 revised criteria of the American College of Rheumatology. The onset of the symptoms was within 1 week of two vaccinations, namely rabies and tetanus toxoid. The temporal relationship of the administration of vaccines and the onset of RA suggested the possibility of a causal association. Tetanus and hepatitis B vaccines have been often implicated in triggering the development of RA. The relationship between immunisation and development of arthritis has three possible explanations. First, this could be simply a chance occurrence with no causal relationship. Second, the vaccination could precipitate a specific form of ‘reactive’ arthritis that is distinct from RA and that is usually self-limiting. The third possible mechanism could be through immunological perturbations caused by the vaccination that may actually trigger the development of RA. The patient reported here could have the third possible mechanism for his disease. It is known that killed vaccines can induce the formation of auto-antibodies like RF and autoimmunity in humans. Of course, appearance of RF by itself does not always lead to the development of RA in the post-immunisation period. However, a person with a strong family history of RA may have increased chances of developing RA in the post-immunisation period. The implicated mechanism for vaccines as a trigger for autoimmunity could be an antigen of either a recombinant vaccine or a live attenuated viral vaccine which may resemble the host antigen and trigger auto-immunity through molecular mimicry. There is also an association between the presence of HLA B27 and/or HLA DR1 or DR4 and the development of RA. However, HLA B27 expression is not a pre-requisite for arthritis linked to vaccines, although its presence may predict more prolonged and severe episodes. There are also coincidental suggestions that administration of multiple International Journal of Rheumatic Diseases 2011; 14: e8–e9