What is the management approach for a rheumatoid arthritis (RA) flare accompanied by fever and chills?

Management of Fever with Chills in Rheumatoid Arthritis Flare

The immediate priority when an RA patient presents with fever and chills is to rule out infection before attributing symptoms to an RA flare, as infection is a life-threatening complication that mimics inflammatory disease activity and requires fundamentally different management.

Critical First Step: Exclude Infection

Before escalating immunosuppressive therapy, you must establish whether inflammatory RA activity or infection is causing the fever. This distinction is paramount because:

• Patients with RA, especially those on DMARDs or biologics, have significantly increased infection risk 1, 2
• Fever with chills in an RA patient on immunosuppression should be considered sepsis until proven otherwise
• Escalating immunosuppression in the setting of occult infection increases mortality

Diagnostic Approach to Fever in RA

Confirm the presence or absence of true inflammatory disease activity before any treatment adjustment 3:

• Clinical assessment: Examine for objective synovitis (joint swelling, warmth, effusion) versus subjective symptoms alone
• Laboratory markers: Check C-reactive protein and erythrocyte sedimentation rate 4, 2
• Imaging when uncertain: Consider ultrasonography to detect inflammatory activity if clinical assessment is equivocal 3
• Infection workup: Blood cultures, urinalysis, chest imaging, and assessment for other infection sources are mandatory before attributing fever to RA flare

When Fever Represents True RA Disease Activity

If infection has been excluded and inflammatory RA activity confirmed:

Immediate Management

Initiate systemic glucocorticoids as the first-line treatment for RA patients with active systemic features including fever 3:

• Glucocorticoids provide rapid control of systemic inflammation and fever 3
• Low to moderately high doses added to DMARD therapy are appropriate 5
• Taper glucocorticoids as rapidly as clinically feasible once control is achieved 5, 6

NSAIDs Have Limited Role

NSAIDs alone are inappropriate for RA patients with significant fever 3:

• NSAID monotherapy is inappropriate when physician global assessment of disease activity is ≥7/10 3
• Continuation of NSAID monotherapy beyond 1 month is inappropriate for patients with active fever 3
• NSAIDs may provide symptomatic relief but do not address underlying disease activity 7, 1

Disease-Modifying Therapy Adjustment

If fever persists despite glucocorticoids, escalate to biologic therapy 3:

• For patients with fever and features of poor prognosis, consider anakinra (IL-1 inhibitor) regardless of current therapy 3
• Anakinra is specifically recommended for patients who develop or sustain fever while receiving systemic glucocorticoids 3
• Methotrexate alone is inappropriate for initial management of active fever without active arthritis 3

Treatment Algorithm

1. Rule out infection first (blood cultures, imaging, comprehensive infectious workup)
2. Confirm inflammatory activity using clinical assessment, inflammatory markers, and ultrasonography if needed 3
3. Initiate systemic glucocorticoids for rapid control 3, 5
4. If inadequate response within 2 weeks, add or switch to biologic therapy (anakinra for systemic features) 3
5. Taper glucocorticoids aggressively once control achieved 5, 6
6. Optimize background DMARD therapy (typically methotrexate) for long-term disease control 5, 1

Common Pitfalls to Avoid

Do not assume fever equals RA flare in immunosuppressed patients - infection must be excluded first, as this error can be fatal 1, 2.

Do not continue NSAID monotherapy beyond 2 weeks in febrile RA patients - this delays appropriate therapy and worsens outcomes 3.

Do not overlook alternative diagnoses - conditions like familial Mediterranean fever can mimic RA flares with recurrent fever and arthritis 8, and other inflammatory diseases may coexist 3.

Do not escalate DMARDs without confirming inflammatory activity - if symptoms are not from active RA inflammation, DMARD escalation will be ineffective and increase toxicity risk 3, 9.

Monitoring and Follow-up

Reassess disease activity every 1-3 months until treatment target is reached 5:

• Use composite disease activity measures (DAS28, SDAI, or CDAI) 3, 2
• Target remission or low disease activity 5, 2
• Adjust therapy promptly if target not achieved 5