Can a Polymyalgia Rheumatica (PMR) flare occur if C-Reactive Protein (CRP) is negative?

PMR Flares Can Occur with Normal CRP Values

Yes, polymyalgia rheumatica (PMR) flares can definitely occur even when C-reactive protein (CRP) is negative or normal. While inflammatory markers like CRP are typically elevated in PMR, their normal values do not rule out disease activity or relapse 1.

Evidence for PMR Flares with Normal Inflammatory Markers

Guidelines and Recommendations

• The 2024 EULAR treat-to-target recommendations for PMR explicitly acknowledge that "relapses may also be present despite normal erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)" 1
• This phenomenon is particularly noted in patients receiving interleukin-6 receptor (IL-6R) blocking agents, but is not limited to this population 1

Research Evidence

• A 2018 case report documented PMR in a centenarian man with completely normal ESR and CRP values at diagnosis, who responded well to glucocorticoid therapy 2
• A 1989 study found that during PMR relapses, ESR was normal in 48% of cases and CRP was normal in 56% of cases 3

Clinical Implications for Monitoring PMR

Recognizing Flares Without Elevated Inflammatory Markers

• Patient-reported symptoms remain crucial in identifying PMR flares
• Characteristic symptoms include:
  • Return of shoulder and hip girdle pain
  • Morning stiffness lasting >45 minutes
  • Difficulty raising arms above shoulder level
  • Functional limitations in daily activities

Monitoring Approaches

1. Regular clinical assessment of symptoms is essential, regardless of laboratory values
2. Patient education about distinguishing disease-related symptoms from unrelated conditions (e.g., osteoarthritis, adhesive capsulitis) 1
3. Consider imaging when clinical symptoms suggest flare despite normal inflammatory markers:
   • Ultrasound
   • MRI
   • PET-CT in selected cases 1

Management of PMR Flares with Normal CRP

Treatment Recommendations

• For minor relapses: increase glucocorticoid dose to at least the last effective dose 1
• For major relapses: reinstitute or escalate glucocorticoid therapy as recommended for new-onset disease 1
• Consider adding or modifying adjunctive therapy (e.g., methotrexate) particularly after recurrent relapses 1, 4

Important Considerations

• Normal inflammatory markers should not delay treatment if clinical symptoms strongly suggest PMR flare
• When evaluating a patient with normal CRP but PMR symptoms:
  • Rule out other causes of symptoms (e.g., mechanical joint problems)
  • Consider alternative biomarkers like serum amyloid A (SAA) which may remain elevated when CRP normalizes 5
  • Evaluate response to a therapeutic trial of glucocorticoids

Risk Factors and Predictors of Flares

• Female sex is associated with lower likelihood of achieving complete remission and higher risk of flares 6
• Higher baseline prednisone dosage is a negative predictor of complete remission 6
• Patients who do not achieve sustained complete remission experience flares more frequently and earlier 6

Pitfalls and Caveats

• Don't rely exclusively on inflammatory markers to diagnose or rule out PMR flares
• Don't delay treatment of clinically evident flares while waiting for biomarker confirmation
• Don't confuse PMR symptoms with other conditions that can cause similar pain patterns
• Don't overlook the possibility that normal inflammatory markers might reflect partial suppression from current therapy rather than absence of disease activity

In clinical practice, the diagnosis and management of PMR flares should be guided primarily by characteristic symptoms and clinical findings, with inflammatory markers serving as supportive but not definitive evidence.