REACTIVE ARTHRITIS

doi:10.1016/S0889-857X(05)70008-9

Rheumatic Disease Clinics of North America

Volume 24, Issue 2, 1 May 1998, Pages 261-273

https://doi.org/10.1016/S0889-857X(05)70008-9 Get rights and content

The fact that “reactive arthritis” is being addressed in an issue on infectious arthritis suggests that the time is right to consider this subject in a less traditional way. For the last several years, information has been accumulating that makes it clear that antigens from the infectious triggers are actually often present in the joint. In fact, in many cases, especially in chlamydia-associated disease, there is also increasing evidence that DNA, RNA, chlamydia-like bodies, and thus likely live organisms are also present in the joint. Where then does “reactive” disease end and actual infectious joint disease begin? How do the genetic background, cellular and humoral responses and other factors contribute to the very different clinical pictures? Does the presence of actual bacteria in joints make things easier or more complex? Certainly it does not seem that the presence of organisms implies ready response to current antibiotic regimens. Are these organisms traditionally associated with reactive arthritis found only in this disease? It seems not. Then what separates the various clinical responses associated with the same organism, such as chlamydia?

This article focuses on clinical implications and briefly examines the development of the concept of reactive arthritis, attempts to put some of the developments of the last few years in perspective, and ends by leaving many fascinating questions for investigation.

Section snippets

BACKGROUND

The current term, “reactive arthritis, ” was suggested by Ahvonen et al in the 1960s¹ and has served an important purpose in directing attention to the many similarities among the arthritic responses to a number of enteric and genital pathogens. A key part of the initial formulation was that these arthropathies were inflammatory yet sterile and were felt to be a response to a distant infection in contrast to the well-recognized infectious arthritis. Several common features included other

ARE THERE DIFFERENCES BETWEEN ENTERIC AND GENITAL INFECTION–ASSOCIATED REACTIVE ARTHRITIS?

Differences have long been recognized between post-enteric and post–genital infection reactive arthritis. Post-dysenteric reactive arthritis is described equally in men and women, whereas post-chlamydial disease is reported much more often in men. Prognosis is generally felt to be better after enteric infections than after sexually acquired disease. The possibility has been raised that reinfection is more common in the latter.¹⁸ Csonka followed patients with reactive arthritis in a venereal

RECENT SEARCHES FOR INFECTIOUS ANTIGEN OR DNA IN JOINTS

Antigens of the enteric pathogens, Yersinia enterocolitica, Salmonella enteritidis, and Salmonella typhimurium have been identified in joints using immunohistochemistry on synovial tissue or synovial fluid.31, 36, 62

Reports by Ford and Schulzer have also noted preferential synovial lymphocyte transformation in response to enteric and other pathogens as further support for antigen presence in the joint.²³ Attempts to identify DNA or RNA of enteric pathogens in the joint have generally been

RELATION OF GENES TO INFECTION IN

REACTIVE ARTHRITIS

How may HLA–B27, the genetic predisposition described earlier, be related to the role of the infectious agents? Because the major function of the class I antigens is to present antigenic peptides to cytotoxic lymphocytes, most have considered that this action is in some way involved in the arthritis. Other ideas also need consideration, including those generated by the fascinating studies of Kapasi and Inman and others that suggest that B27 may also influence handling of

MIGRATION OF INFECTION FROM PRIMARY SITES TO JOINTS

If bacteria or their antigens lodge in joints, how do they arrive there? Do they disseminate widely and only persist at certain sites, and thus, does the pattern of dissemination or the manner in which they are handled after spread have the most influence on disease? Studies over many years have shown that joints behave in many ways like part of the reticuloendothelial system and are prime sites for lodging of circulating infectious agents or other particles.71, 73 At least some such

THE BIOLOGY OF CHLAMYDIA IN THE JOINT

The potentially important concept of persistent chlamydial infection at various sites has been proposed in the work of Byrne, Beatty, and Kuo7, 8, 13, 46 and has been extended to joint disease by the work of Rahman et al⁶⁹ and Koehler et al.⁴⁰ Such infection may be inapparent in that organisms seem to be able to exist in a relatively metabolically inactive form that is difficult to culture yet viable.

Beatty et al6, 7 have observed and studied a similar altered chlamydial development in vitro,

TREATMENT

As noted previously, 3-month treatment with antibiotics, although beneficial in chlamydia-associated reactive arthritis, ⁵⁰ is not invariably effective⁹ and to date has not been helpful in enteric infection–associated disease. Although still controversial, most agree that short-term treatment with tetracycline does not help established chlamydia-associated reactive arthritis.3, 52 Sexual partners need to be evaluated and probably treated in genitourinary associated disease. One brief report

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