Successful Methotrexate Treatment of Chronic Chikungunya Arthritis

J. Kennedy Amaral, MD; Clifton O. Bingham, III, MD; Robert T. Schoen, MD, MBA


J Clin Rheumatol. 2020;26(3):119-124. 

In This Article

Abstract and Introduction


Chikungunya (CHIK) is an emerging tropical and subtropical, vector-borne, viral infection. The illness is spread by Aedes mosquitoes, which also transmit dengue fever, yellow fever, and Zika virus infection.[1] Chikungunya is caused by chikungunya virus (CHIKV), a single-stranded RNA alphavirus, the family that includes Ross River fever.[2] The CHIKV was first isolated in 1952 in Tanzania during a febrile, polyarthritis outbreak, initially attributed to dengue fever.[3] The word "chikungunya" means "that which bends up" in the local dialect.[4] In retrospect, chikungunya fever (CHIKF) has been frequently misdiagnosed as dengue fever but was probably widespread in the 18th and 19th century, causing outbreaks in Africa, Asia, especially India, Southeast Asia, and also in the southern United States.[4,5]

The modern reemergence of a global CHIK epidemic began in Kenya in 2004 (500,000 cases).[6] The disease occurred in the Indian Ocean (Reunion Island) in 2005 (250,000 cases)[7] and then India in 2006 (1.4 million cases).[6] Following the recent global spread of the Aedes mosquito vectors, CHIK was reported in Africa, southern Europe, and Southeast Asia.[8]

There have been recorded CHIK epidemics in the Americas as long ago as the 1800s.[5] After a long absence, CHIK infection returned to the new world in Saint Martin in 2013.[3] Since then, 2.9 million cases have been reported from 45 Western hemisphere countries.[1] Beginning in 2014, Brazil (500,000 cases) and Colombia (1 million cases) have experienced this epidemic.[9,10]

Chikungunya infection causes a biphasic illness. The initial phase, CHIKF, occurs in 97% of infected individuals.[11] After an incubation period of 1 to 12 days, CHIKF causes acute febrile illness, polyarthralgia, polyarthritis, arthritis, headache, fatigue, and maculopapular rash, as well as gastrointestinal symptoms, including vomiting, diarrhea, and abdominal pain.[12]

Following the acute phase, 59% of patients develop chronic persistent symptoms, primarily chronic CHIK arthritis.[13] These patients can have with painful, potentially destructive disabling inflammatory arthritis that often mimics rheumatoid arthritis (RA) and related disorders.[14] During recent widespread epidemics, chronic CHIK arthritis has caused substantial morbidity, disability, and, in some cases, irreversible joint destruction.[15,16]

Treatment of acute CHIKF is usually symptomatic management of acute viral infection.[17] Some patients require hospitalization for dehydration or other comorbidities. There is interest in vaccine prevention and antiviral therapies for CHIKF, but no effective agent has been demonstrated.

For CHIK arthritis, there is a lack of consensus as to appropriate treatment. For many patients, the later musculoskeletal manifestations of CHIK infection such as arthritis may also be self-limited.[17] But for chronic arthritis patients and more severely and chronically affected individuals (the patients who are likely to present to a rheumatologist for treatment), there is a need for a safe and effective disease-modifying strategy. Glucocorticoids, nonsteroidal anti-inflammatory drugs (NSAIDs), antimalarials, and disease-modifying antirheumatic drugs (DMARDs) have all been used with limited reports of success.[18–20]

From 2014 to the present, Pernambuco and 5 other states in northeastern Brazil have experienced a CHIK epidemic with 500,000 cases reported.[9,21] During the past year, one of us (J.K.A.) treated 50 Brazilian chronic CHIK arthritis patients, during this regional CHIK epidemic. We believe that this experience can inform other rheumatologists about the management of chronic CHIK arthritis patients. In this report, we first describe the clinical spectrum of arthritis in our patients, focusing on those with chronic CHIK arthritis that we define as arthritis lasting more than 12 weeks after disease onset. Next, we report our experience treating chronic CHIK arthritis with methotrexate (MTX) in this group. In our patients, MTX rapidly reduced pain and clinical signs of disease. Although our study is retrospective, and we have no comparable control group, we believe that the success of our MTX intervention in chronic CHIK arthritis justifies its evaluation of MTX in a larger, randomized, placebo-controlled trial.