Reactive arthritis (Reiter's syndrome)

Mayo Clinic overview

Nat Rev Rheumatol. 2011 Nov 22;8(1):55-9. doi: 10.1038/nrrheum.2011.173. Chlamydia-induced ReA: immune imbalances and persistent pathogens. Gracey E, Inman RD. Source Toronto Western Hospital, 399 Bathurst Street, Toronto, ON M5T 2S8, Canada. Abstract Reactive arthritis (ReA), an inflammatory arthritic condition that is commonly associated with Chlamydia infections, represents a significant health burden, yet is poorly understood. The enigma of this disease is reflected in its problematic name and in its ill-defined pathogenesis. The existence of persistent pathogens in the arthritic joint is acknowledged, but their relevance remains elusive. Progress is being made in understanding the underlying mechanisms of ReA, whereby an imbalance between type 1 and type 2 immune responses seems to be critical in determining susceptibility to disease. Such an imbalance occurs prior to the initiation of an adaptive immune response, suggesting that innate cellular and molecular mechanisms in ReA should be prioritized as fruitful areas for investigation. 1)

Arthritis Rheum. 2010 May;62(5):1203-7. Combination antibiotics for Chlamydia-induced arthritis: breakthrough to a cure?2) Rihl M, Kuipers JG, Köhler L, Zeidler H. Comment on: Arthritis Rheum. 2010 May;62(5):1298-307.

Editorial Reactive arthritis (ReA) and its association with an extra-articular bacterial infection have first been described almost a century ago. From the view of the entry site of the pathogen, there is a post-urethritic and a post-dysenteric ReA form mainly caused by Chlamydia trachomatis and Enterobacteria (such as Yersinia, Salmonella, or Shigella), respectively. In addition, numerous other but less frequent organisms have been implicated in ReA, including Chlamydophila pneumoniae causing respiratory tract infections at the primary site (1).

In order to cause ReA, a pathogen must be specifically equipped, i.e. it needs to be an obligate or facultative intracellular organism, travel from mucosal surfaces to the joint, modify its metabolic state in order to evade the host defense mechanism, and survive as a persistent agent. Given all this, Chlamydia trachomatis is the best studied pathogen. This is also because epidemiological work has established this pathogen as the most common organism leading to ReA in the course of a urogenital infection (2).

Jd, C., E. Lr, et al. (2010). “Combination antibiotics as a treatment for chronic Chlamydia-induced reactive arthritis.” Arthritis Rheum. 3)

BACKGROUND:: Chlamydia trachomatis (Ct) and Chlamydophila (Chlamydia) pneumoniae (Cpn) are known triggers of reactive arthritis (ReA). These chlamydial species exist in a persistent metabolically active infection state in the synovium suggesting that persistent chlamydiae may be susceptible to antimicrobial agents. The goal of this study was to investigate whether a six-month course of combination antibiotics is an effective therapy for patients with chronic Chlamydia-induced ReA. METHODS:: This study was a 9-month, double-blind, triple-dummy prospective trial assessing a 6-month course of combination antibiotics as a treatment for Chlamydia-induced ReA. Eligible patients were age 18 to 70 years, fulfilled the European Spondyloarthropathy Study Group (ESSG) Criteria, and had disease duration equal to or longer than 6 months. Subjects had to be polymerase chain reaction (PCR)-positive for Ct or Cpn in order to be randomized to therapy; randomization was performed in a 1:1:1 fashion. Treatment was for 6 months; the 3 groups included doxycycline 100mg twice daily and rifampin 300mg daily, azithromycin 500mg daily x 5 days then twice weekly and rifampin 300mg daily, or matching placebos. The primary efficacy endpoint was to assess the number of responders in the combination antibiotic group vs. placebo at month 6 compared to baseline. Responders were defined as those subjects who improved 20% or more in at least 4 of 6 variables without worsening in any one variable. RESULTS:: 80 subjects were screened and 42 were randomized to treatment (27 to combination antibiotics and 15 to placebo). Subjects in each group had similar demographics and baseline characteristics. At month 6, 17/27 subjects (63%) randomized to combination antibiotics were responders compared to 3/15 (20%) on placebo (P-value = 0.01). Secondary efficacy endpoints showed similar results with significant improvement in the modified swollen joint count, tender joint count, physician global assessment (P-values 0.0007, 0.002, and 0.0009, respectively), and a trend with the erythrocyte sedimentation rate (P-value = 0.07) in those patients on combination antibiotics compared to placebo. 6/27 (22%) subjects on combination antibiotics experienced complete resolution of their symptoms whereas 0/15 subjects on placebo achieved this endpoint. There were significantly more subjects who became PCR negative at month 6 in the active therapy group than in the placebo group (P-Value = 0.03). Adverse events (AE's) were mild; there were no significant differences between the groups. CONCLUSION:: These data suggest that a 6-month course of combination antibiotics is an effective therapy for chronic Chlamydia-induced ReA.

Evidence of infectious cause

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Full text of above paper may be useful


Chlamydia-induced ReA: immune imbalances and persistent pathogens.
Gracey E, Inman RD
Nat Rev Rheumatol8p55-9(2011 Nov 22)
Combination antibiotics for Chlamydia-induced arthritis: breakthrough to a cure?
Rihl M, Kuipers JG, Köhler L, Zeidler H
Arthritis Rheum62p1203-7(2010 May)
Combination antibiotics as a treatment for chronic Chlamydia-induced reactive arthritis: a double-blind, placebo-controlled, prospective trial.
Carter JD, Espinoza LR, Inman RD, Sneed KB, Ricca LR, Vasey FB, Valeriano J, Stanich JA, Oszust C, Gerard HC, Hudson AP
Arthritis Rheum62p1298-307(2010 May)
Vitamin D discovery outpaces FDA decision making.
Marshall TG
Bioessays30p173-82(2008 Feb)
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