Does Polymyalgia Rheumatica (PMR) always present with elevated Erythrocyte Sedimentation Rate (ESR) or C-Reactive Protein (CRP) levels?

Polymyalgia Rheumatica Can Present with Normal Inflammatory Markers

No, polymyalgia rheumatica (PMR) does not always present with elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) levels, although this is the typical presentation in the majority of cases. While elevated inflammatory markers are characteristic of PMR, a subset of patients can have normal ESR and/or CRP values at diagnosis.

Prevalence of Normal Inflammatory Markers in PMR

• Approximately 6-22% of patients with PMR may have normal or only slightly increased ESR at the time of diagnosis 1, 2
• In a recent study (2023), 14% of PMR patients had both normal ESR and CRP values at diagnosis 3
• CRP is generally more sensitive than ESR for detecting disease activity in PMR, with only about 1% of patients having normal CRP values at diagnosis compared to 6% with normal ESR 2

Clinical Characteristics of PMR with Normal Inflammatory Markers

• Patients with normal ESR tend to be younger and have a less marked female predominance 1
• These patients often experience longer diagnostic delays due to the absence of the classic laboratory findings 1, 4
• They typically have fewer constitutional symptoms such as fever or weight loss 1
• Despite normal ESR/CRP, these patients respond similarly to glucocorticoid therapy as those with elevated markers 4

Diagnostic Approach for Suspected PMR with Normal Inflammatory Markers

• The EULAR/ACR guidelines recognize that PMR with normal inflammatory markers is an atypical presentation that warrants specialist referral 5, 6
• Additional inflammatory markers like serum amyloid A (SAA) may be elevated even when ESR and CRP are normal 3
• Imaging studies can be particularly valuable in these cases:
  • Ultrasound may demonstrate characteristic bursitis even in patients with normal ESR and CRP 3
  • MRI or FDG-PET/CT can be considered as second-line investigations when there is diagnostic uncertainty 7

Monitoring and Management Considerations

• Even in patients who initially present with normal inflammatory markers, ESR and CRP should still be monitored during follow-up as they may become elevated during disease flares 5
• Some patients may experience relapses with normal ESR but elevated CRP (62% of relapse episodes with normal ESR had elevated CRP in one study) 2
• The treatment approach remains the same regardless of baseline inflammatory marker status - glucocorticoids are the cornerstone of therapy 7

Predictive Value of Inflammatory Markers

• High baseline ESR (>40 mm/1st hour) is associated with higher relapse rates and need for prolonged therapy 5, 6
• ESR appears to be a better predictor of relapse risk than CRP, with a relative risk approximately twice as high (4.9 vs 2.1) 2
• However, CRP is generally more sensitive for detecting current disease activity 2

Clinical Pitfalls to Avoid

• Do not rule out PMR solely based on normal inflammatory markers, especially if the clinical presentation is otherwise typical 1, 4
• Consider alternative diagnoses more carefully in patients with normal inflammatory markers, as this is an atypical presentation 5
• Remember that glucocorticoid response can be delayed in PMR, taking 3-4 weeks in up to 45% of cases, regardless of baseline inflammatory marker status 7