What is the role of synovitis in the pathophysiology of reactive arthritis (ReA)?

Updated: Dec 24, 2020
  • Author: Carlos J Lozada, MD; Chief Editor: Herbert S Diamond, MD  more...
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Synovitis in ReA is mediated by proinflammatory cytokines. Native T cells under the influence of transforming growth factor (TGF)-β and other cytokines, such as interleukin (IL)-6, differentiate into Th17 effector cells, which then produce IL-17. IL-17 is one of the major cytokines elevated in the synovial fluid of these patients. [19, 20] Deficiencies in regulatory mechanisms can result in increased proinflammatory cytokine production and worse outcome. [21]

The Toll-like receptors (TLRs) recognize different extracellular antigens as part of the innate immune system. [22] TLR-4 recognizes gram-negative lipopolysaccharide (LPS). Studies in mice and humans showed abnormalities in antigen presentation due to downregulation of TLR-4 costimulatory receptors in patients with ReA. Subsequent studies implicated TLR-2 polymorphism associated with acute ReA; however, its role is still disputed. [15, 23]

Molecular evidence of bacterial DNA (obtained via polymerase chain reaction [PCR] assay) in synovial fluids has been found only in Chlamydia -related ReA, and a single placebo-controlled trial of a tetracycline derivative (ie, lymecycline) has shown a reduction in the duration of acute Chlamydia -related, but not enteric-related, ReA. [24] This suggests that persistent infection may play a role, at least in some cases of chlamydial-associated ReA.

In a subsequent trial, the combination of doxycycline and rifampin was superior to doxycycline alone in reducing morning stiffness and swollen and tender joints in patients with undifferentiated spondyloarthropathy. [25]

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