What is the best approach for a patient with symmetric inflammatory arthritis, fever, and dizziness?

Immediate Diagnostic Workup and Management for Symmetric Inflammatory Polyarthritis with Fever

This patient requires urgent exclusion of infection before any immunosuppressive therapy, followed by immediate initiation of systemic glucocorticoids if infection is ruled out, as escalating immunosuppression in the setting of occult infection increases mortality. 1

Critical First Step: Rule Out Infection

• Perform comprehensive infectious workup immediately including blood cultures, urinalysis with culture, chest imaging, and any site-specific cultures based on examination findings 1
• The presence of fever with new-onset symmetric polyarthritis demands infection exclusion before considering inflammatory arthritis treatment, as fever with chills in the context of inflammatory disease can represent either septic arthritis, systemic infection, or disease activity 1
• Do not empirically add antibiotics if the patient is hemodynamically stable and initial workup is negative, as this provides no benefit 1

Clinical Assessment for Rheumatoid Arthritis

Once infection is excluded, this presentation is highly suggestive of rheumatoid arthritis given:

• Symmetric polyarthritis affecting multiple joints is the hallmark presentation of RA, typically involving small joints of hands and feet 2, 3
• Morning stiffness lasting ≥1 hour reflects significant inflammatory burden and is a typical sign of RA 4, 2
• Acute onset with fever can occur in approximately 25% of RA patients who present with acute or subacute onset rather than the more typical insidious pattern 3
• Systemic symptoms including fever represent active systemic features that require aggressive management 1

Confirm Inflammatory Synovitis

• Perform joint ultrasonography to confirm inflammatory synovitis, as this is recommended when fever is present and traditional clinical assessment may be unreliable 1
• Examine for objective joint swelling, tenderness to palpation, and warmth in the affected joints 3
• Urgent rheumatology referral is indicated when small joints of hands or feet are affected, even if acute-phase reactants are normal or RF is negative 2

Immediate Treatment Algorithm

If Infection is Ruled Out and Inflammatory Arthritis Confirmed:

Step 1: Initiate Systemic Glucocorticoids Immediately

• Prednisone is first-line therapy for RA patients with active systemic features including fever 1, 5
• Glucocorticoids provide rapid control of systemic inflammation and fever, typically achieving defervescence within 2-5 days 1
• Prednisone is FDA-approved for rheumatoid arthritis as adjunctive therapy for acute episodes or exacerbations 5
• Do not continue NSAID monotherapy beyond initial assessment in patients with active fever, as this is inappropriate 1

Step 2: Plan DMARD Initiation Within Days

• Methotrexate 15-25 mg weekly should be initiated as soon as systemic features are controlled, as aggressive early management improves patient functioning, quality of life, and survival 4
• However, do not initiate methotrexate as initial management for patients with active fever without addressing the systemic features first with glucocorticoids 1

Step 3: Escalate if Fever Persists Despite Glucocorticoids

• If fever persists after 1-2 weeks of systemic glucocorticoids, initiate anakinra (IL-1 receptor antagonist) as this is specifically recommended for RA patients with active fever and features of poor prognosis 1
• The median time to defervescence with appropriate therapy is 2-5 days; persistent fever beyond this in a stable patient warrants escalation 1

Diagnostic Testing to Perform

• Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) to confirm diagnosis and guide prognosis 2, 6
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as these provide the best information about acute phase response and correlate with clinical assessment 3
• Complete blood count to assess for anemia of chronic disease and rule out hematologic complications 3
• HLA-DRB1 testing may be considered as certain alleles significantly increase lifetime risk and determine autoantigen recognition 2

Differential Diagnosis Considerations

• Acute rheumatic fever typically affects large joints (knees, ankles, elbows, wrists) with migratory polyarthritis; involvement of small joints of hands and feet is much less common 2
• Crystal arthropathies, polymyalgia rheumatica, and vasculitis can mimic RA activity and should be considered if infectious workup is negative 1
• The symmetric small joint involvement with morning stiffness >1 hour strongly favors RA over these alternatives 2, 3

Monitoring and Follow-Up

• Reassess disease activity every 1-3 months using composite measures (DAS28, SDAI, or CDAI) until treatment target is reached 4, 1
• Target low disease activity (SDAI ≤11 or CDAI ≤10) or remission (SDAI ≤3.3 or CDAI ≤2.8) within 6 months 4
• Daily clinical evaluation if hospitalized looking for new symptoms or signs that might indicate infection or other complications 1
• Taper prednisone once remission is achieved to minimize long-term glucocorticoid toxicity 4

Critical Pitfalls to Avoid

• Never escalate immunosuppression without ruling out infection first, as this dramatically increases mortality risk 1
• Do not delay glucocorticoid initiation once infection is excluded, as rapid control of systemic inflammation prevents organ damage and improves outcomes 1
• Do not use methotrexate alone for initial management of fever without glucocorticoids, as this is inappropriate and ineffective 1
• Do not continue to escalate therapy if inflammatory activity cannot be objectively confirmed, as this leads to unnecessary toxicity 1