Approach
There is no specific antiviral treatment and management is mainly supportive.[75] Most people can be treated as outpatients. A review of global clinical management guidelines found variations in treatment recommendations for severe disease and when at-risk populations (such as pregnant women and infants) should be referred to specialised care, suggesting an urgent need for more research to inform evidence-based care and standardisation across regions.[29]
Non-pharmacological treatment during the acute phase
Patients will have increased metabolic demands during their illness. Appropriate hydration and proper nutrition should be ensured.[75]
Rest is important.[75] Patients may need to have time off work or be confined to less strenuous activities, depending on their clinical condition. Excessive movement of acutely inflamed joints should be avoided; however, strict immobilisation is not indicated. Relative rest with passive mobilisation of joints and encouragement of isometric muscle contractions may be helpful. Physiotherapy and occupational therapy may be indicated during the recovery phase.
Warm or cold compresses and baths with warm or cold water may provide relief of joint symptoms.[48][76]
Pharmacological therapy in the acute phase
Paracetamol is the treatment of choice for the management of fever and pain during the acute phase.[75] Caution should be used among patients consuming over-the-counter medicines (as they may already contain paracetamol) and among patients with liver disease (including alcohol users).
Although not available in several countries due to risk of agranulocytosis, metamizole remains in use in several countries as an analgesic/antipyretic, and short-term administration seems to be safe.[77] Where available, metamizole can be used for symptomatic control in the acute phase of viral infection in adults.[65]
Aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) should be used with caution during the initial weeks of disease, and not until other infections have been excluded.[75] These drugs can worsen haemorrhagic manifestations (which are uncommon in patients with chikungunya virus infection, but are of concern in patients who may have a co-infection with dengue). Aspirin and other salicylates may also trigger Reye's syndrome, a potentially lethal steatohepatitis associated with cerebral oedema, among patients with viral syndromes; therefore, aspirin should be avoided in children and adolescents. If other conditions have been ruled out and there is persistence of symptoms beyond 3 to 4 weeks, a trial of an appropriate NSAID can be justified. There is no specific NSAID recommended. Whichever NSAID is chosen, its efficacy should be re-evaluated in 7 to 10 days and another agent should be tried if there is no response to the initial choice. Treatment should not exceed 3 to 4 weeks. NSAIDs and aspirin should not be administered to pregnant women.
Tramadol and opioid analgesics (e.g., hydrocodone, oxycodone, morphine) can be considered in select cases when pain does not respond to NSAIDs. Morphine should be reserved for patients with very severe pain. Opioids should be used for the minimum period possible and de-escalated promptly to either an NSAID or paracetamol.[48]
If joint pain does not respond to analgesics, neuropathic pain may be present. If the patient is found to have a neuropathic component to their pain (confirmed using the Douleur Neuropathique 4 [DN4] questionnaire), amitriptyline or gabapentin are indicated.[48] Tramadol may also be useful in cases where neuropathic pain is present.
The only indication for the acute use of corticosteroids early in the course of infection is progressive neurological compromise (e.g., encephalopathy, uveitis, optic neuritis, acute demyelinating encephalomyelitis, or neuropathy). Use of corticosteroids for control of arthritis or other rheumatological symptoms at the beginning of the disease can be associated with recurrence of the symptoms. In patients with polyarticular manifestations that persist beyond 3 to 4 weeks and that do not respond to NSAIDs, a trial of corticosteroids is reasonable.[63][76][78]
In acutely ill patients who require hospitalisation, appropriate management of fluid, electrolyte, and acid-base disturbances is indicated.
Use of NSAID-embedded patches or gels may provide relief in cases of sinovitis, bursitis, arthralgias, and arthritis. Topical, as opposed to oral/systemic, NSAIDs are acceptable early in the course of the condition. When bursitis or arthritis is associated with fluid collections not responsive to other measures, aspiration and infiltration with corticosteroids can be used.
Pharmacological therapy in the chronic phase
There are a lack of clinical trials that support treatment recommendations in patients with chronic manifestations of infection; however, recommendations are available from French and Brazilian guidelines.[48][76]
In patients who develop symptoms resembling rheumatoid arthritis at least 12 weeks after the beginning of the disease, disease-modifying anti-rheumatic drugs (DMARDs) are indicated, particularly in patients who test positive for the presence of anti-cyclic citrullinated peptide (anti-CCP) antibodies. The DMARD of choice is hydroxychloroquine. Methotrexate is a second-line option.[48] Alternative choices include leflunomide and sulfasalazine monotherapy, but at this point a rheumatology specialist should be involved.[48][60][76][79][80] While there are a lack of data comparing hydroxychloroquine and methotrexate, hydroxychloroquine is often recommended first-line as it has a better adverse effect profile compared with methotrexate, which is associated with hepatotoxicity and myelotoxicity. If pain persists after an 8-week trial of hydroxychloroquine, sulfasalazine may be added. If combination treatment is not effective, the patient can be switched to methotrexate. A systematic review found that triple therapy with methotrexate in combination with hydroxychloroquine and sulfasalazine was superior to monotherapy with hydroxychloroquine alone; however, further research is required before this treatment can be recommended.[81]
Patients with symptoms resembling a spondyloarthropathy 12 or more weeks after the beginning of the disease should be treated preferentially with NSAIDs. Methotrexate and sulfasalazine can be used as second-line agents. Biological agents such as tumour necrosis factor-alpha inhibitors (e.g., infliximab) should be used only in refractory cases.[76][82]
For patients with undifferentiated polyarthritis (inflammation of multiple joints that does not resemble rheumatoid arthritis or spondyloarthopathy) 12 or more weeks after the disease onset, NSAIDs are also the first choice of therapy, followed by corticosteroids. Refractory cases can be treated with methotrexate.[76][83]
DMARDs should only be prescribed by a specialist and treatment managed under the supervision of a rheumatologist. Clinical and laboratory monitoring is required before and during treatment. Patients should be assessed every 6 weeks. The visual analogue scale is often used to assess pain severity. Treatment should be ceased when the patient is pain free.
Treatment of complications
Topical corticosteroids, cycloplegic agents, and medications to relieve intra-ocular pressure are useful in anterior uveitis.[67] Treatment with corticosteroids is indicated in cases of encephalopathy, uveitis, optic neuritis, acute demyelinating encephalomyelitis, or neuropathy.[58][59][66][67]
Specialist consultation
When there are doubts about the diagnosis or concerns about co-infection with other viruses, and in cases of persistent fever or atypical manifestations, infectious disease consultation is appropriate. In cases of meningitis or meningoencephalitis, a neurology consultation is indicated. A rheumatology consultation is recommended for patients with rheumatoid arthritis-like symptoms, spondyloarthropathy, or chronic undifferentiated polyarthrtitis.
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