What is the appropriate management for a patient presenting with high fever and arthralgia?

Management of High Fever with Arthralgia

The immediate priority is to exclude septic arthritis and other life-threatening infections through urgent joint aspiration if monoarticular involvement is present, followed by systematic evaluation for infectious causes (particularly arboviral infections in travelers), acute rheumatic fever, and Adult-Onset Still's Disease based on specific clinical patterns. 1

Immediate Assessment and Red Flags

Critical Exclusions Requiring Urgent Intervention

• Septic arthritis must be excluded immediately in any monoarticular presentation with fever through joint aspiration and synovial fluid analysis before initiating any immunosuppressive therapy 2, 1
• Systemic inflammatory response syndrome signs (temperature >38°C or <36°C, heart rate >90 beats/min, respiratory rate >20 breaths/min) require immediate medical evaluation 3
• New cardiac findings (changing murmurs, signs of heart failure) raise concern for infective endocarditis and require urgent echocardiography 2, 1
• Altered mental status, severe headache, or neck stiffness suggest encephalitis and warrant emergency neurological evaluation 2, 3

Travel and Exposure History

• Recent travel to tropical regions within 2-14 days strongly suggests arboviral infection, particularly dengue (4-8 day incubation) or chikungunya (2-3 day incubation) 2
• Fresh-water exposure 4-8 weeks prior with fever, urticarial rash, and eosinophilia suggests Katayama syndrome (acute schistosomiasis) 2
• Tick exposure with fever, arthralgia, and inoculation eschar suggests rickettsial infection 2

Diagnostic Algorithm Based on Clinical Patterns

Pattern 1: High-Spiking Quotidian Fever (>39°C with Late Afternoon/Evening Peaks)

This pattern occurs in 95.7% of Adult-Onset Still's Disease cases and should trigger specific evaluation 1:

• Classic triad: High-spiking quotidian fever + evanescent salmon-pink maculopapular rash (appears with fever spikes) + symmetric polyarthritis affecting wrists, knees, ankles (93.5% sensitive for AOSD) 1
• Laboratory findings: Marked leukocytosis with left shift, elevated ESR/CRP, markedly elevated ferritin with low glycosylated fraction (<20%) 1
• Wrist radiographs specifically recommended to evaluate for characteristic findings 1
• Management: NSAIDs first-line for mild disease; prednisone 0.5-1 mg/kg for moderate-severe disease; consider methotrexate or IL-1/IL-6 inhibitors for refractory cases 1

Pattern 2: Migratory Polyarthritis Affecting Large Joints

This pattern is classic for acute rheumatic fever and requires specific diagnostic criteria 2, 1:

• Revised Jones Criteria: Evidence of preceding Group A Streptococcal infection (throat culture, rapid antigen test, or elevated anti-streptolysin O/anti-DNase B titers) PLUS either 2 major criteria OR 1 major + 2 minor criteria 2, 1
• Major criteria: Carditis, polyarthritis, chorea, erythema marginatum, subcutaneous nodules 2, 1
• Minor criteria: Polyarthralgia (only in moderate/high-risk populations), fever, elevated ESR/CRP, prolonged PR interval on ECG 2, 1
• Mandatory echocardiography to evaluate for carditis, including Doppler assessment for subclinical valvular regurgitation 2, 1
• Management: Aspirin or NSAIDs for arthritis; penicillin prophylaxis for secondary prevention 1

Pattern 3: Fever with Polyarthralgia in Returned Travelers

Arboviral infections are the most common cause in this scenario 2:

• Dengue fever: Characterized by fever, headache, retro-orbital pain, myalgia, arthralgia (particularly back pain), and rash; transmitted by day-biting Aedes mosquitoes 2
• Chikungunya: Similar presentation with prominent polyarthralgia; increasingly reported in travelers from Asia, Africa, and recently Europe 2
• Diagnosis: PCR if <5-7 days of symptoms; IgM capture ELISA if >5-7 days; note cross-reaction with other flavivirus vaccines (yellow fever, Japanese encephalitis, tick-borne encephalitis) 2
• Management is supportive: Hydration, antipyretics (avoid aspirin in dengue due to bleeding risk), analgesics for pain 2

Pattern 4: Recurrent Self-Limited Episodes

Consider autoinflammatory syndromes, particularly in specific ethnic backgrounds 1:

• Familial Mediterranean Fever: Self-limited episodes (typically <72 hours) of peritonitis, pleuritis, and acute monoarthritis; more common in Mediterranean populations 1
• Protracted febrile myalgia syndrome in FMF patients: Severe myalgia, fever, abdominal pain, diarrhea, arthralgia lasting 4-6 weeks; may require anakinra if corticosteroid-resistant 4
• TRAPS: Longer fever attacks, ocular involvement, centrifugal erythematous patches 1

Mandatory Initial Laboratory Evaluation

First-Line Tests (Obtain in All Patients)

• Complete blood count with differential (evaluate for leukocytosis with left shift, eosinophilia, or cytopenias) 1
• ESR and CRP (markedly elevated in AOSD, ARF, and bacterial infections) 1
• Blood cultures if septic arthritis suspected (obtain before antibiotics) 1
• Joint aspiration with synovial fluid analysis (cell count, Gram stain, culture) if monoarticular involvement 1

Second-Line Serologic Testing (Based on Clinical Suspicion)

• ANA, rheumatoid factor, anti-CCP antibodies (evaluate for systemic lupus erythematosus, rheumatoid arthritis) 1
• Ferritin with glycosylated fraction (markedly elevated ferritin with low glycosylated fraction suggests AOSD) 1
• Anti-streptolysin O and anti-DNase B titers (if ARF suspected) 2, 1
• Arboviral serologies or PCR (if travel history to endemic areas) 2

Imaging Studies

• Plain radiographs of affected joints to exclude metastases and evaluate for erosions 2, 1
• Wrist radiographs specifically in suspected AOSD 1
• Echocardiography mandatory if ARF suspected to evaluate for carditis and valvular involvement 2, 1
• Ultrasound or MRI of affected joints if persistent arthritis unresponsive to treatment or suspicion for septic arthritis 2

Treatment Approach Based on Diagnosis

If Infection Suspected or Confirmed

• Hold all immunosuppression immediately 2
• Initiate empiric antibiotics after cultures obtained if septic arthritis suspected 1
• Urgent orthopedic consultation for joint drainage if septic arthritis 1
• Supportive care for viral infections: hydration, antipyretics, analgesics 2
• Oseltamivir 75 mg twice daily for 5 days if influenza confirmed, initiated within 48 hours of symptom onset 5

If AOSD Diagnosed

• NSAIDs first-line for mild disease (e.g., naproxen 500 mg twice daily or indomethacin 50 mg three times daily) 1
• Prednisone 0.5-1 mg/kg daily for moderate-severe disease 1
• If unable to taper corticosteroids below 10 mg/day after 3 months, consider DMARDs (methotrexate, leflunomide) or biologics (IL-1 or IL-6 inhibitors) 2, 1

If ARF Diagnosed

• Aspirin or NSAIDs for arthritis (highly responsive to anti-inflammatory therapy) 2, 1
• Penicillin prophylaxis for secondary prevention (penicillin G benzathine 1.2 million units IM every 3-4 weeks or oral penicillin V 250 mg twice daily) 1

Common Pitfalls to Avoid

• Do not administer NSAIDs or corticosteroids before establishing diagnosis, as these mask the classic migratory pattern of ARF polyarthritis and may delay diagnosis 2
• Do not use first-generation antihistamines (diphenhydramine) or vasopressors for minor infusion reactions, as these can convert minor reactions into hemodynamically significant events 2
• Do not obtain routine radiographic imaging unless complications or alternative diagnoses are suspected, to avoid unnecessary radiation exposure and cost 2
• Polyarthralgia alone (without objective joint swelling) is a minor manifestation in low-risk populations for ARF and should not be overweighted diagnostically 2
• Do not delay joint aspiration if septic arthritis is possible, as this is a true medical emergency requiring urgent drainage 1