Immunological basis of Chlamydia induced reactive arthritis.

Introduction A small proportion of patients who present with clinical symptoms of urethritis or cervicitis later develop inflammatory arthritis and, for an unfortunate minority, this can be the beginning of a persistent and disabling disease. This illness is now termed reactive arthritis, rather than the older term, Reiter’s disease. Reiter described a triad of urethritis, conjunctivitis, and arthritis in first world war soldiers in the trenches following attacks of dysentery, and mistakenly believed that it was due to infection with a novel spirochaete. However, others had previously described the same syndrome, and the triad has no specific pathological significance; patients can have the same arthritis whether they have conjunctivitis or not, and urethritis is not infrequently absent, particularly in cases triggered by gut infection. Because of the emphasis on urethritis in the definition of Reiter’s disease, it has often been assumed subsequently that Reiter’s disease is synonymous with sexually acquired reactive arthritis (SARA), whereas in Reiter’s report the index cases followed gut infection. For all these reasons the term reactive arthritis is to be preferred and avoids unnecessary categories such as “incomplete” Reiter’s disease. There are many advantages, from a rheumatological view, in studying the pathogenesis of reactive arthritis. Unlike, for instance, rheumatoid arthritis, the onset is sharply defined rather than insidious, and is the result of an identifiable antigenic challenge (in the form of an infectious organism) to the host immune system. It has also been clear for some time that host factors influence who develops arthritis, HLA-B27 being the best described of these, and that the same factors play a part in the whole family of arthritic conditions which make up the seronegative spondyloarthropathies (table 1). There is, therefore, an expectation that exploration of the host:pathogen interaction in reactive arthritis may provide valuable insights into the pathogenesis of related forms of arthritis. Genitourinary infections which trigger reactive arthritis Of the sexually acquired infections, the evidence implicating Chlamydia trachomatis as a cause of reactive arthritis is strongest. The infection is not always symptomatic, and rheumatologists greatly value the help of colleagues in genitourinary medicine in tracking down chlamydial infection in patients with unexplained acute synovitis. There are also reports of the involvement of mycoplasmas, particularly Ureaplasma urealyticum. These organisms are clearly capable of causing arthritis, and a septic arthritis due to mycoplasma infection in immunodeficiencies in which patients lack antibody is well described. 6 Individual “reactive arthritis” cases have been reported in which Mycoplasma genitalium, now thought to be a significant cause of nongonococcal, non-chlamydial urethritis, has been identified in the joint by polymerase chain reaction (PCR) or culture. 9 Less clear is the extent of mycoplasma infection in classic reactive arthritis. Problems in establishing such an association include the possibility of dual infection by chlamydiae and mycoplasmas, and the carriage of mycoplasmas in the genitourinary tract of normal individuals. As discussed in detail below, finding an organism in joint tissue or fluid, particularly when using highly sensitive PCR based tests, can no longer be regarded as definitive proof that the organism is responsible for the arthritis. Infection by gonococcus also gives rise to an inflammatory arthritis which is sometimes loosely referred to as “reactive,” although the occasional isolation of the organism by culture has often led to gonococcal arthritis being classified with other forms of septic arthritis. In any case this arthritis does not share the extra-articular features or the HLA-B27 association of classic reactive arthritis, and cannot be regarded as being within the spondyloarthropathy grouping. Again dual gonococcal and chlamydial infection can cause confusion.