1 December 1993

Open any rheumatology textbook and it will tell you that rheumatoid arthritis (RA) results from the interaction between a susceptible host and an unidentified environmental trigger. It seems highly unlikely, however, that all cases of RA will be attributable to a single environmental factor. It is more credible that a number of agents are capable of triggering the immunological process which is manifested clinically as RA. A rational approach to the primary prevention and treatment of the disease will be precluded until all these causes are found. It is therefore necessary to follow up all plausible aetiological clues.

One such clue is the apparent triggering of RA by immunisation. We were intrigued that, in response to a direct question, 19 (3%) of the first 588 patients notified to the Norfolk Arthritis Register' 2 reported having a tetanus immunisation in the 6 weeks before the onset of their arthritis. Twelve of the 19 patients satisfied the 1987 ARA criteria for RA3 (table) when they were first seen, 8 were seropositive and 5 have developed radiological erosions in the first year. In addition one patient reported having an immunisation against influenza and another against hepatitis B. Neither of these patients satisfied the 1987 ACR criteria for RA. There are three possible explanations for this apparent, but uncontrolled, association between immunisation and the development of arthritis:

1- That it represents the chance occurrence of two common phenomena-namely arthritis and immunisation. A 6 week period-incidence of tetanus immunisation of 3% is equivalent to an annual immunisation rate of 28%. Since tetanus immunisation need be given no more often than once every 10 years 4 the maximum annual immunisation rate in adults if everyone were fully covered should not exceed 10%. It is possible, however, that tetanus immunisation is a surrogate marker for some other factor such as trauma-which is actually the trigger for RA. Alternatively the immunisations may have been given opportunistically when the patients attended their general practitioners with prodromal features of arthritis. Further investigations are in progress to explore these possibilities.

2- That immunisation precipitates a specific form of arthritis which is distinct from RA. The tenth revision of the International Classification of Diseases 5 includes, for the first time, a code (M02.2) for post-immunisation arthropathy as a sub-heading under the code for reactive arthropathy (M02). This might lead to the conclusion that post-immunisation arthropathy was a recognised disease entity but the case is far from proven.

3- That immunisation is one of the factors which can initiate RA. Infectious agents have long been the favourite candidates as potential triggers for RA.6 7 However, attempts to isolate organisms directly from synovium and/ or synovial fluid have, with a few exceptions, been unsuccessful.