In his lecture, Professor ALAN SILMAN (ARC epidemiology unit, Manchester university) asked "Is rheumatoid arthritis an infectious disease?" If an infectious cause could be identified, then this would raise the possibility of preventing or treating it, he said.
Diseases were often viewed as having an environmental or genetic cause. Professor Silman said that all diseases required both factors. In twin studies, RA concordance occurred in 15 per cent of monozygotic and 4 per cent of dizygotic twins. This suggested that some genetic factor contributed to the disease but that it was not the sole cause. Environmental factors could play a part, even in utero.
In terms of environmental factors, it was interesting to see that there was a similar prevalence of RA across Europe, the US, Australia, Japan and some other countries. A dramatic similarity had been found in many studies whereas for other diseases, such as cancer or heart disease, there were large differences in prevalence. There were exceptions, for example, there were some native American Indians who had very high rates of RA and some rural African populations with very low rates. This could be due to genetic factors.
If RA had an infectious cause, clustering over time might be expected. A population register in Norfolk had shown no evidence of time clustering nor higher rates in overcrowded areas with poor socio-economic conditions. This did not support evidence for an infectious cause. However, on the same register, there were some "hot spots" of disease clustering but this was not apparent for the vast majority of cases.
Population data for many countries, including the UK, had shown a recent decline in the incidence of RA. Could this be explained by birth cohort (ie, the year in which a person was born and not the current year), suggesting exposure to a causative agent early in life, Professor Silman asked. It did appear that older cohorts had a higher incidence of RA for the same age. This was consistent with an infectious cause, he said.
RA certainly appeared to be a very recent disease, being first described exactly 200 years ago. This might suggest a link to vaccines. It was also possible that people were genetically susceptible to the disease and that, as result of an unknown trigger, a person developed RA. A specific example of this was a person who had developed RA on the day after having a yellow fever vaccine.
Other evidence for an infectious cause included a higher incidence of cat ownership prior to RA development, suggesting that an infection was caught from cats.
Another theory was that an antigen in tetanus immunisations precipitated the disease. A study had shown that onset of RA had occurred in 3.2 per cent of people who had received the injection six weeks prior to onset compared with 1.2 per cent of controls.
Blood transfusion was also under suspicion. A history of transfusion was higher in RA cases than controls. Could this be linked to transmission of an infectious agent? Transmission of the Epstein Barr virus could not be ruled out.
It was suggested that RA was inversely related to allergies such as hayfever. RA was a TH-1 mediated disease and allergies were TH-2 mediated. Professor Silman said that it was a reasonable suggestion that the TH-2 response caused a dying down of the TH-1 response.
Asked how the different prevalence of disease in males and females could occur if the cause was infectious, Professor Silman said that this could be explained by a variation in immune response between the sexes.
Professor Silman concluded that there must be an environmental factor to RA; however, there was likely to be a considerable heterogeneity making identification of the cause difficult. Pathologically, infection seemed to be the most likely initiating event, he said.
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