New pathogenic hypotheses for spondyloarthropathies.

Pathogenic hypotheses for spondyloarthropathies are evolving. Several candidates have been added to the list of inciting microorganisms, and genes other than HLA-B27 are under scrutiny. Above all, the chiefly 'immunological' theory of spondyloarthropathies incriminating a cross-reaction between self-proteins and bacterial peptides is giving way to a more 'microbiological' concept in which latent bacteria residing within macrophagic or dendritic cells undergo reactivation through a process facilitated by HLA-B27. This molecule is prone to misfolding, which decreases the presentation of bacterial peptides to the immune system and stimulates the Nf-KB inflammation pathway within infected macrophages and/or dendritic cells. Migration of these infected cells from the mucous membranes to the tissues targeted by spondyloarthropathies, particularly the bone marrow located near entheses, may facilitate transient reactivation of dormant intracellular bacteria by creating a favorable cytokine environment. This environment may include high levels of TGFbeta and IL-10, noted also at other sites that enjoy immune privilege, such as the eye. The reactivation may be stopped by a local response of CD4+ and/or CD8+ T cells at the expense of local inflammation responsible for clinical manifestations. This scenario seems consistent with results from studies of murine models transgenic for the HLA-B27 antigen: exposure to bacteria is necessary to the development of spondyloarthropathy, but the disease occurs even when only the heavy chain of HLA-B27 is present (i.e., beta2-microgloblin is not indispensable). Improved understanding of the mechanisms that confer to some bacterial strains a strong potential for persisting within cells, including macrophagic cells, may open the way toward new treatment approaches capable of complementing antagonists of TNF-alpha and other monokines, which merely suspend the disease process, and antibiotic therapy, which fails to kill dormant bacteria located within cells. Pathogenic hypotheses for spondyloarthropathies are evolving. This review presents the most recent concepts. These concepts have not all received confirmation from experimental data. However, the high degree of consistency among them prompted us to consolidate them into a single picture. Although this approach may yield a motley composite of fact and speculation, it may open up new avenues of thought for rheumatologists interested in the links between chronic intracellular infections and inflammatory joint disease.

Clinical and functional status in 88 rheumatoid arthritis patients followed for 15 years or more by office-based (n = 41) or hospital-based (n = 47) physicians.

OBJECTIVE: To determine the very long-term clinical and functional outcomes in rheumatoid arthritis (RA) patients followed by office-based or hospital-based physicians. PATIENTS AND METHODS: A questionnaire including items on clinical outcomes (active disease, remission, burn-out) and the Health Assessment Questionnaire (HAQ) was mailed to 122 patients with RA of at least 15 years' duration; 61 were followed by office-based physicians and 61 by hospital-based physicians. In the 88 (72%) respondents, mean age was 63 +/- 13 years and mean disease duration was 20.1 +/- 8.7 years. RESULTS; None of the patients experienced burn-out of their disease, and only six (7%) met Pinals' remission criteria. However, 23 (26%) reported a current subjective remission with a mean duration of 8.5 +/- 5.9 months. Although the mean pain score in the 88 patients was 4.1 +/- 2.3, only 50 (56%) patients reported a physician visit during the last 6 months. HAQ scores varied widely, the mean being 1.11 +/- 0.84. Forty (46%) patients had a history of arthroplasty (knee or hip in 29 (33%)). Of the 34 nonrespondents, seven had died (at a mean age of 74 years), and in four of these seven the cause of death was infection or immobility-related complications; in the 27 survivors, disease activity was considered minimal by the physicians or patients, 11 (41%) patients believed they were in remission, and mean time since the last physician visit was 3.9 years. Conclusion. Although burn-out within 20 years of RA onset seems exceedingly rare, clinical activity is milder than in early RA; over one-fourth of our patients believed they were in remission and over one half had not seen a physician during the last 6 months. Functional outcomes varied widely across patients but were acceptable overall, a result that is partly ascribable to the favorable effects of surgery. No differences in functional outcomes were found between patients followed by office-based physicians and those followed by hospital-based physicians.