Chikungunya arthritis persists but virus undetectable

Arthritis Rheum 2017; doi:10.1002/art.40384.

Arthritis Rheum 2017; doi:10.1002/art.40383.

One-quarter of Latin American patients who were infected with chikungunya virus had persistent arthritis almost 2 years later, despite the finding that there was no detectable virus in the synovial fluid.In a follow-up study of a prospectively enrolled cohort of 485 patients with chikungunya during an epidemic in Colombia in 2014-2015, 123 (25%) had ongoing joint pain after a mean of 20 months, which was less than the 48% that had been predicted. On a multivariate analysis, these factors were associated with persistent joint pain:

  • College education, OR 5.53 (95% CI 1.13 to 27.17, P=0.0353)
  • Headache, OR 2.17 (95% CI 1.16 to 4.07, P=0.0157)
  • Knee pain, OR 4.69 (95% CI 1.91 to 11.51, P=0.0007)
  • Missed work, OR 5.23 (95% CI 2.87 to 9.52, P<0.0001)
  • Normal activities disrupted, OR 8.80 (95% CI 3.89 to 19.89, P<0.0001)
  • Initial symptoms persisting for 4 days or more, OR 2.69 (95% CI 1.57 to 4.60, P=0.0003)
  • Initial joint pain persisting for 4 weeks or more, OR 2.39 (95% CI 1.40 to 4.08, P=0.0014)

In extensive synovial fluid analyses of 38 of the patients, there was no detectable virus on PCR, culture, or mass spectrometry. For this analysis, patients were a median of 22 months post-infection, and had an average of 5.5 and 3 tender and swollen joints, respectively. Global disease activity on a 100-point scale was 93, and the Disease Activity Score in 28 joints was 4.52. The researchers performed various tests on a subset of their cohort with serologically confirmed viral infection, seeking evidence of the virus itself in cultures of synovial fluid, as well as viral RNA using PCR, and viral proteins with mass spectrometry. All were negative. With no evidence of viral persistence, potential mechanisms for arthritis included epigenetic changes to host DNA, as has been observed with Epstein Barr virus infection, modification of macrophages, and molecular mimicry, according to the authors.

This finding suggests that chikungunya virus may cause arthritis through induction of potential host autoimmunity, suggesting a role for immunomodulating medications in the treatment of chikungunya virus arthritis. Various immunosuppressants such as methotrexate and hydroxychloroquine and biologics such as adalimumab and etanercept have been tried.