Can a rheumatoid arthritis (RA) flare cause a high-grade fever?

High-Grade Fever in Rheumatoid Arthritis Flares

Yes, rheumatoid arthritis (RA) flares can cause high-grade fever, though this is not the most common presentation and should prompt evaluation for other causes, particularly infection.

Fever in RA: Characteristics and Considerations

Fever as a Systemic Manifestation

• RA is an autoimmune inflammatory disease that can present with systemic manifestations including fever, particularly during disease flares
• While low-grade fever (feberet) is more typical in RA, high-grade fever (≥39°C/102.2°F) can occur in severe flares 1, 2
• Systemic inflammation in RA can trigger the release of pro-inflammatory cytokines that affect the hypothalamic temperature regulation

Differential Diagnosis

When high-grade fever occurs in an RA patient, consider:

1. RA flare with high systemic inflammation

   • More common in severe flares with high disease activity
   • Usually accompanied by multiple joint involvement
   • Elevated inflammatory markers (ESR, CRP)

2. Infection (must be ruled out)

   • Critical to exclude, especially in immunosuppressed patients
   • May present with similar symptoms to RA flare
   • Particularly important to consider in patients on biologics, JAK inhibitors, or other immunosuppressants 3

3. Adult-onset Still's disease

   • Characterized by spiking fevers ≥39°C (102.2°F)
   • Typically accompanied by salmon-pink rash and arthralgia/arthritis 3
   • High ferritin levels are characteristic

4. Other rheumatic conditions

   • Familial Mediterranean fever can coexist with RA 4
   • Systemic vasculitis
   • Macrophage activation syndrome (rare but serious complication)

Diagnostic Approach

Key Clinical Assessment

• Determine fever pattern (continuous vs. intermittent/spiking)
• Assess joint involvement (number, symmetry, severity)
• Look for other symptoms (rash, lymphadenopathy, weight loss)
• Review current medications (some biologics may be associated with drug-induced fever)

Laboratory Evaluation

• Complete blood count with differential
• Inflammatory markers (ESR, CRP, ferritin)
• Blood cultures if infection suspected
• Liver function tests
• Consider specific tests based on clinical suspicion (viral serologies, etc.)

Management Considerations

For RA Flare with Fever

• NSAIDs may help control both fever and joint symptoms in mild-moderate flares
• Glucocorticoids are effective for controlling severe flares with systemic features including fever 3
• Disease-modifying agents may need adjustment if current regimen is inadequate

Special Considerations

• In patients on biologics or JAK inhibitors with high-grade fever, temporarily holding medication may be appropriate until infection is ruled out 3
• Patients with high disease activity may have reduced vaccine response and potentially higher risk of infection 3

Important Caveats

1. High-grade fever (>39°C/102.2°F) is atypical for uncomplicated RA and should prompt thorough investigation for other causes

2. Infection risk is increased in RA patients on immunosuppressive therapy, and infection can mimic an RA flare 5

3. Adult-onset Still's disease should be considered in patients with high spiking fevers, as this condition requires specific management 3

4. Macrophage activation syndrome is a rare but life-threatening complication that can present with high fever and requires prompt recognition and treatment 3

By maintaining a high index of suspicion for alternative diagnoses while acknowledging that RA itself can cause fever, clinicians can ensure appropriate management of patients presenting with high-grade fever in the context of RA.