In an adult with persistent joint pain, swelling, and stiffness lasting more than 4–6 weeks after the febrile phase of chikungunya infection, what is the appropriate diagnostic work‑up and treatment plan for chikungunya‑induced rheumatoid‑like arthritis?

Chikungunya-Induced Rheumatoid-Like Arthritis: Diagnostic Work-Up and Treatment

Immediate Diagnostic Approach

In an adult with persistent joint pain, swelling, and stiffness lasting more than 4–6 weeks after chikungunya infection, confirm the diagnosis with chikungunya IgG and IgM serology, obtain baseline inflammatory markers (CRP and ESR), and perform bilateral hand, wrist, and foot radiographs to assess for erosive changes. 1, 2

Essential Laboratory Work-Up

• Chikungunya serology is the cornerstone diagnostic test: IgM positivity may persist for months to years in chronic chikungunya arthritis, and higher IgG/IgM levels correlate with symptom persistence at 13 years post-infection 1
• Inflammatory markers (CRP and ESR) should be measured at baseline, as they are typically markedly elevated in active chikungunya-induced inflammatory arthritis 3, 4
• Complete blood count with differential to assess for cytopenias before initiating disease-modifying therapy 5
• Comprehensive metabolic panel including liver and renal function to ensure safety before starting DMARDs 5
• Rheumatoid factor (RF) and anti-CCP antibodies to differentiate chikungunya arthritis from true rheumatoid arthritis: notably, no anti-CCP seroconversion occurs in chikungunya-induced arthritis even after 13 years, which is a critical distinguishing feature 1
• Antinuclear antibodies (ANA) may be positive in some cases of persistent chikungunya arthritis, but this does not indicate seroconversion to a primary autoimmune disease 1

Imaging Studies

• Bilateral hand, wrist, and foot radiographs at baseline to document erosive changes: longitudinal studies demonstrate that chikungunya can cause progressive radiographic joint damage, bone erosions, and cartilage destruction up to 13 years post-infection 1, 2
• Ultrasound with Power Doppler or MRI with contrast should be considered when clinical examination shows persistent synovitis, as these modalities detect synovial inflammation and structural damage more sensitively than plain radiographs 2, 4
• Repeat radiographs at 6 and 12 months to monitor for progression of erosive disease 5, 2

Clinical Assessment and Disease Activity Monitoring

• Perform a 28-joint count examination assessing metacarpophalangeal joints, proximal interphalangeal joints, wrists, elbows, shoulders, and knees for tenderness and swelling 5
• Document morning stiffness duration: stiffness lasting ≥30 minutes (ideally ≥1 hour) indicates inflammatory arthritis 5
• Use composite disease activity measures such as the Simplified Disease Activity Index (SDAI) or Clinical Disease Activity Index (CDAI) to quantify disease severity and guide treatment decisions 5
• Reassess disease activity every 4–6 weeks with repeat inflammatory markers to monitor treatment response 5, 1

Treatment Algorithm

First-Line Therapy for Persistent Symptoms (>6 weeks)

Start methotrexate 15 mg weekly as first-line disease-modifying therapy, escalating to 20–25 mg weekly as tolerated, combined with short-term low-dose prednisone (10–20 mg daily) as bridge therapy for 2–4 weeks. 5, 1, 4

• Methotrexate is the anchor DMARD for chikungunya-induced chronic inflammatory arthritis, as chronic chikungunya arthritis shares clinical and pathophysiologic similarities with rheumatoid arthritis 1, 2, 4
• In the Reunion Island cohort, 5 patients required ongoing methotrexate therapy at 13 years post-infection, demonstrating the need for sustained disease-modifying treatment in severe cases 1
• Short-term glucocorticoids provide rapid symptom relief while awaiting DMARD effect, then taper and discontinue once disease control is achieved 5, 4

Screening Before Biologic Therapy

• Hepatitis B, hepatitis C, and tuberculosis screening are mandatory before initiating any biologic agent 5

Second-Line Therapy for Inadequate Response

• If inadequate response after 3 months of methotrexate monotherapy, escalate to triple DMARD therapy (methotrexate + hydroxychloroquine + sulfasalazine) or add a TNF inhibitor 5
• In the Reunion Island cohort, 3 patients required TNF-blocker therapy at 13 years, indicating that some cases of chikungunya-induced arthritis behave like refractory inflammatory arthritis requiring biologic therapy 1

Treatment Target

• The therapeutic goal is sustained remission (SDAI ≤3.3) or low disease activity (SDAI ≤11) 5
• Adjust therapy every 3 months based on disease activity assessment until target is achieved 5

Critical Pitfalls and Clinical Pearls

• Do not dismiss persistent symptoms as "post-viral syndrome": longitudinal data demonstrate that at least 23.3% of patients with chikungunya-related inflammatory arthritis have persistent symptoms at 13 years, with significant ongoing pain, fatigue, and disability 1
• Absence of anti-CCP antibodies does not exclude severe erosive disease: chikungunya arthritis causes bone erosions and joint damage without anti-CCP seroconversion, distinguishing it from classic rheumatoid arthritis 1, 2
• Persistent chikungunya IgM positivity (observed in some patients at 13 years) may indicate residual viral antigen-driven chronic inflammation and correlates with worse outcomes 1
• Older age at infection is a key risk factor for chronic arthritis: patients over 60 are at highest risk for persistent symptoms 3, 4
• Early DMARD therapy is critical: the success of early disease-modifying therapy in rheumatoid arthritis—preventing irreversible joint damage—underscores the urgent need for similar aggressive treatment in chikungunya arthritis, particularly given documented radiographic progression over years 2, 4
• Analgesics and NSAIDs alone are insufficient: in the absence of published guidelines, physicians often limit treatment to symptomatic care, but this approach fails to prevent progressive joint damage 6, 3

Differential Diagnosis Considerations

• Exclude septic arthritis if monoarticular involvement with high fever: joint aspiration is mandatory 7
• Exclude Lyme arthritis in endemic areas: Lyme typically presents as large-joint monoarthritis (especially knee) with positive serology, treated with doxycycline or amoxicillin for 28 days 7
• Exclude crystal arthropathies: synovial fluid analysis for monosodium urate or calcium pyrophosphate crystals is essential, as gout/pseudogout can coexist with viral arthritis 7
• Distinguish from primary rheumatoid arthritis: negative anti-CCP at baseline and no anti-CCP seroconversion over time strongly favors chikungunya-induced arthritis over true RA 1

Long-Term Monitoring Strategy

• Repeat CRP/ESR every 4–6 weeks during active treatment adjustment 5
• Repeat hand, wrist, and foot radiographs at 6 and 12 months to monitor radiographic progression 5, 2
• Assess functional status using the Health Assessment Questionnaire Disability Index at least annually 5
• Monitor for extra-articular manifestations: while rare in chikungunya arthritis compared to RA, systemic complications can occur 4