Q&A: Chronic Chikungunya Arthritis vs. Rheumatoid Arthritis

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Chronic chikungunya arthritis can resemble rheumatoid arthritis, but understanding their parallels and differences may offer insights into better diagnosis and treatment of both conditions, according to a review published in The American Journal of Medicine.

In this Q&A with author J. Kennedy Amaral, M.D., of the Federal University of Minas Gerais in Brazil, we discuss the clinical manifestations of chronic chikungunya arthritis as a rheumatoid arthritis mimic, along with differences between the conditions and treatment options.

What is the chikungunya virus and where is it most common?

Chikungunya virus is a single-stranded RNA virus belonging to the family Togaviridae and genus Alphavirus, that causes an acute febrile illness, chikungunya fever, transmitted to humans by Aedes species mosquitoes. Chikungunya virus was isolated in Tanzania in 1952 during a dengue-like outbreak. Since then, chikungunya virus has caused outbreaks in Africa, Asia, the Indian Ocean region, and Europe, with severe medical and economic effects. In December 2013, chikungunya virus was reported in the Americas on the island of Saint Martin. Since then, more than 2.9 million cases have been reported in 45 countries in North, Central, and South America.

During acute illness from chikungunya virus, patients have high fever, polyarthralgias or polyarthritis, maculopapular rash, headache, and myalgia that may last for weeks. Following resolution of acute infection, a number of patients develop chronic chikungunya arthritis that can resemble rheumatoid arthritis.

What were the main findings from your review?

Chronic chikungunya arthritis may be a post-infectious inflammatory process with clinical and pathogenic features that mimic rheumatoid arthritis. Emerging evidence demonstrates that low dose methotrexate, a widely available, relatively safe disease modifying drug in rheumatoid arthritis, could also be effective in chronic chikungunya arthritis. Given the growing disease burden associated with chronic chikungunya arthritis, it is important that the pathogenesis and treatment of chronic chikungunya arthritis continue to be elucidated. Rheumatoid arthritis provides insights into future directions for these investigations.

How does chronic chikungunya arthritis mimic rheumatoid arthritis?

In many patients, chronic chikungunya arthritis mimics rheumatoid arthritis clinically. Some studies report patients with chronic chikungunya arthritis whose clinical features are so similar to rheumatoid arthritis that they meet the 2010 ACR diagnostic criteria for rheumatoid arthritis.

Chronic chikungunya arthritis has been associated with high circulating levels of pro-inflammatory cytokines, including IL-6, GM-CSF, IFN-α, and IL-17. IL-6 is well-recognized in rheumatoid arthritisjoint inflammation and increases the production of cartilage-destroying enzymes. In chronic chikungunya arthritis, inflammatory cytokines and chemokines, plasma levels of IL-6 and GM-CSF have been found to be significantly higher in patients with persistent arthralgia compared with those who had recovered. In another study, the cytokine profile in chronic chikungunya arthritis, including IFNα, IL-5, IL-6, IL-10, and particularly IL-7 and IL-15, was similar to rheumatoid arthritis. The profile of elevated levels of cytokines such as IL-1β, tumor necrosis factor (TNF), IL-6, and IL-17 during Chronic chikungunya arthritis resembles that observed in rheumatoid arthritis.

Chronic chikungunya arthritis can develop into a form of arthritis that meets the ACR / EULAR criteria for rheumatoid arthritis, including joint deformities.

How do the two conditions differ?

In chronic chikungunya arthritis, it presents with medium and/or large joint asymmetric mono- or oligoarthritis (less commonly). The signs and symptoms include memory and concentration problems and asthenia/depression can be more predominant than in rheumatoid arthritis. The serologies include anti-CHIKV IgM and/or IgG antibodies.

In rheumatoid arthritis, the signs and symptoms include an association with pulmonary (interstitial) disease and/or rheumatoid nodules. Serologies include anti-cyclic citrullinated peptide antibodies (anti-CCP); rheumatoid factor (RF).

How is chronic chikungunya arthritis treated?

Some guidelines recommend starting the treatment of chronic chikungunya arthritis with corticosteroids and anti-inflammatories. However, in our studies, we recommend management with early use of methotrexate, due to the many cases of patients with deforming arthritis that we have received in our office.

Similarities in pathogenesis could explain why chronic chikungunya arthritis seems to respond to treatments effective in rheumatoid arthritis. In particular, methotrexate, a mainstay in the treatment of rheumatoid arthritis, has been investigated in chronic chikungunya arthritis.

Treatment during this phase includes supportive care, short-term opioid analgesics, paracetamol/acetaminophen, and non-steroidal anti-inflammatory drugs (NSAIDs). The mechanism by which the disease transitions in some, but not all patients, to chronic chikungunya arthritis is uncertain. Since studies suggest similarities with rheumatoid arthritis, in clinical features and cytokine expression, patients who develop chronic rheumatic symptoms have been treated with NSAIDs, corticosteroids, chloroquine, hydroxychloroquine, methotrexate, sulfasalazine, and/or biological agents such as etanercept or abatacept with some evidence of efficacy.

How can your findings help clinicians and benefit patients?

Many patients have received insufficient treatment for chronic chikungunya arthritis, progressing to joint deformities and disabling arthritis a few years after infection with the chikungunya virus.

Our studies recommend starting methotrexate early as a treatment for these patients. We encourage clinicians not to underestimate chronic chikungunya arthritis by treating patients with analgesics or corticosteroids.

Do you have anything else to add?

Chronic chikungunya arthritis can help us better understand the pathogenesis of rheumatoid arthritis as we study its similarities. Undeniably, infection by the chikungunya virus has precipitated a disease similar to rheumatoid arthritis. This may mean that there is a link between the two diseases. Chikungunya virus may enter the list of viruses involved in the etiopathogenesis of rheumatoid arthritis.

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REFERENCE

J. Kennedy Amaral, Joshua B. Bilsborrow,Robert T. Schoen. “Chronic Chikungunya Arthritis and Rheumatoid Arthritis: What They Have in Common.”The American Journal of Medicine. March 1, 2020. DOI: https://doi.org/10.1016/j.amjmed.2019.10.005