Chikungunya virus is a virus of the Togaviridae family, transmitted by Aedes mosquitoes, that causes acute febrile illness in infected humans. The virus was first isolated during an epidemic, originally suspected to be dengue, in Tanzania, Africa, in 1953. The acute phase of the disease, called chikungunya fever (CHIKF), is characterized by high fever, rash, headache, severe polyarthralgia, and myalgia that follow an incubation period of 5 to 7 days.
“Chikungunya” means “the one bowing” in the Madoke language, a Tanzanian dialect. CHIKF may have been present in periodic epidemics since the 1700s in Africa, Asia, and the new world. In the modern era, when the disease was recognized in Tanzania in the 1953, infection occurred in both an enzootic life cycle and in local outbreaks in Africa and Asia. The epidemiology of chikungunya fever changed during a major epidemic in Kenya in 2004. As a result of urbanization, crowding, increased travel, and vector adaptation, chikungunya virus began to occur in explosive, largescale epidemics affecting millions of people in Africa, then Asia, Europe, and Oceania, spreading to more than 45 countries. In 2013, the first autochthonous causes were reported in Americas.
The time course of chikungunya arthritis is variable. In some patients, inflammatory arthritis begins during acute CHIKF and is unremitting. In other patients, the illness is biphasic; acute illness is followed by temporary remission of symptoms and then persistent arthritis. Following the acute phase, 59% of patients develop chronic symptoms, primarily chronic CHIK arthritis. These patients can have painful, destructive inflammatory arthritis that often mimics rheumatoid arthritis and related disorders. During recent widespread epidemics, chronic CHIK arthritis has caused substantial morbidity, disability, and in some cases, irreversible joint destruction.
According to a recent systematic review, published at Arthritis Care & Research, that examined 131 articles on the treatment of chronic arthritis of chikungunya, the optimal treatment of chronic rheumatic manifestations of CHIKF represents an unanswered challenge for physicians around the world and a spectrum of treatment options, including NSAIDs, corticosteroids, hydroxychloroquine, sulfasalazine, methotrexate and biological agents, alone or in combination, have been considered.
Dr. Kennedy Amaral, a Brazilian rheumatologist, together with Dr. Robert Schoen and Dr. Ravi Sutaria, Yale University, included in this review retrospective studies, prospective studies, and randomized controlled trials that used MTX alone or in combination therapy for the treatment of chronic CHIKV arthritis. The studies identified included four retrospective studies, one prospective study and one randomized clinical trial. Three studies were conducted in France or French territories (including one study on Martinique Island) and three were conducted in India.
For example, in a randomized 24-week clinical trial, Ravidran and Alias evaluated 72 patients with persistent CHIKF arthritis with inadequate response to HCQ. Subjects received either triple combination therapy (methotrexate 15 mg / week, sufassalazine 1 g per day and hydroxychloroquine 400 mg per day) versus continued monotherapy with hydroxychloroquine (400 mg / day). At the end of 24 weeks, the combination therapy group had significant improvement in DAS28ESR compared to the subjects who remanded on HCQ (3.39 ± 0.87 versus 4.74 ± 0.65, p <0.0001) and in self-reported disability (HAQ 1.14 ± 0.31 vs. 1.88 ± 0.47, p <0.0001). Good EULAR response (85% vs. 14%) and VAS pain scores (46 ± 6,13 vs. 60.8 ± 11.6) were also significantly better in patients with combined therapy, (p <0.0001, for both comparisons).
According to Dr. Amaral, “patients with chronic arthritis of chikungunya develop can develop joint deformities, depression, disease similar to rheumatoid arthritis, fibromyalgia and other rheumatic syndromes. This makes treating this form of arthritis an urgency for the scientific community because the disease can cause outbreaks on virtually every continent where the mosquito vector is present. As of September, 2017, among the five Brazilian federative regions, the Northeast had the highest number of reported cases and confirmed deaths with more than 400,000 cases and 278 deaths. Ceará, in the Northeast, reported more than 106.435 probable CHIKF cases.”
According to the authors “in spite of the limited data available, our systematic review supports our belief that MTX should receive further study for the treatment of chronic chikungunya arthritis. There is a need for larger scale, statistically rigorous, randomized prospective studies of MTX monotherapy, using quantifiable outcome measures. Given the self-limited nature of chikungunya, even in chronic arthritis patients, further studies should be placebo controlled. In addition, larger scale, carefully conducted studies can better evaluate safety. In the studies we reviewed, there were no reports that MTX, as an immunosupressive, worsened this viral infection, but the data available is insufficient to exclude this possibility.”