Chikungunya virus-associated long-term arthralgia: a 36-month prospective longitudinal study

Abstract

Background: Arthritogenic alphaviruses, including Chikungunya virus (CHIKV), are responsible for acute fever and arthralgia, but can also lead to chronic symptoms. In 2006, a Chikungunya outbreak occurred in La Réunion Island, during which we constituted a prospective cohort of viremic patients (n = 180) and defined the clinical and biological features of acute infection. Individuals were followed as part of a longitudinal study to investigate in details the long-term outcome of Chikungunya.

Methodology/principal findings: Patients were submitted to clinical investigations 4, 6, 14 and 36 months after presentation with acute CHIKV infection. At 36 months, 22 patients with arthralgia and 20 patients without arthralgia were randomly selected from the cohort and consented for blood sampling. During the 3 years following acute infection, 60% of patients had experienced symptoms of arthralgia, with most reporting episodic relapse and recovery periods. Long-term arthralgias were typically polyarthralgia (70%), that were usually symmetrical (90%) and highly incapacitating (77%). They were often associated with local swelling (63%), asthenia (77%) or depression (56%). The age over 35 years and the presence of arthralgia 4 months after the disease onset are risk factors of long-term arthralgia. Patients with long-term arthralgia did not display biological markers typically found in autoimmune or rheumatoid diseases. These data helped define the features of CHIKV-associated chronic arthralgia and permitted an estimation of the economic burden associated with arthralgia.

Conclusions/significance: This study demonstrates that chronic arthralgia is a frequent complication of acute Chikungunya disease and suggests that it results from a local rather than systemic inflammation.

Figure 1. Diagram of the clinical study.

“unable”: patients who were reached but unable to answer to the questionnaire, “lost”: patient lost of follow up until the end of the study, “temporally lost”: not reached at a specific timepoint, “death”: dead patients.

Figure 2. Evolution and characterization of arthralgia in CHIKV patients.

(A) Percentage of patients with arthralgia among participating patients, (B) localization of arthralgia among patients with arthralgia, (C) number of arthralgia sites among the 76 patients answering at every time point and having arthralgia, (D) complete model presenting the probability for one joint to be painful depending on its previous state.

Figure 3. Distinctive markers in serum of patients with arthralgia (ART+ in black) versus patients without arthralgia (ART−, in white) at M36.

SD: standard deviation, results of Mann Whitney test are shown. * p<0.05, q = 0.056.