Can Polymyalgia Rheumatica (PMR) occur in patients over 50 with normal Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP) levels?

Can PMR Occur with Normal ESR and CRP?

Yes, polymyalgia rheumatica (PMR) can occur with normal ESR and CRP levels, occurring in approximately 20% of cases, though this represents an atypical presentation that warrants careful evaluation and specialist referral. 1, 2

Epidemiology and Clinical Characteristics

PMR with normal inflammatory markers is not uncommon:

• Approximately 20% of PMR patients present with ESR <40 mm/h at diagnosis 2
• These patients tend to be younger, more frequently male, and have a clinically less severe syndrome compared to classic PMR 2
• They experience lower frequency of constitutional symptoms including fever and weight loss 2
• Laboratory abnormalities such as anemia and abnormal protein electrophoresis are less common in this subset 2

Diagnostic Approach

Clinical presentation takes precedence over laboratory values in PMR diagnosis, and normal inflammatory markers do not exclude the diagnosis. 1

Essential Clinical Features to Assess:

• Age ≥50 years (though <60 years is considered atypical) 1, 3
• Bilateral shoulder and/or pelvic girdle pain and stiffness lasting >1 month 3, 2
• Morning stiffness duration and severity 4
• Functional impairment in daily activities 4
• Rapid response to low-dose glucocorticoids (12.5-25 mg prednisone) 4, 2

Comprehensive Laboratory Workup Required:

• Repeat ESR and CRP (single normal values may not reflect disease activity) 1
• Rheumatoid factor and anti-CCP antibodies (exclude rheumatoid arthritis) 4, 1
• Creatine kinase (should be normal; elevated suggests myositis) 4, 1
• Complete blood count (assess for anemia, other inflammatory conditions) 4, 1
• Metabolic panel including glucose, creatinine, liver function tests 4, 1
• Thyroid stimulating hormone (exclude thyroid disorders) 4, 1
• Protein electrophoresis (exclude paraproteinemia) 4, 1
• Vitamin D level 4, 1

Critical Differential Diagnoses

Failure to respond to glucocorticoids or persistently elevated inflammatory markers despite treatment should trigger immediate reassessment for alternative diagnoses. 3, 5

High-Priority Mimickers to Exclude:

• Malignancies (most common alternative diagnosis in PMR-like presentations) 3
• Other rheumatic diseases: rheumatoid arthritis, RS3PE syndrome, spondyloarthropathy, vasculitis 3, 5
• Infections: particularly infective endocarditis 3
• Endocrine disorders: hypothyroidism, vitamin D deficiency 3
• Giant cell arteritis: requires urgent evaluation if headaches or visual symptoms present 1
• Fibromyalgia in obese patients: obesity itself can elevate inflammatory markers, creating diagnostic confusion 6

Treatment Considerations

For PMR with normal inflammatory markers, initiate moderate-dose glucocorticoids (prednisone 10-20 mg/day) and monitor response closely. 1

Key Management Points:

• PMR with normal inflammatory markers responds similarly to glucocorticoids as classic PMR 2
• These patients have similar relapse rates and treatment duration as those with elevated markers 2
• Lack of response to steroids within 1-2 weeks mandates diagnostic reconsideration 3, 5
• The average time to diagnosis change in PMR mimickers is 4.5 months, emphasizing need for vigilant follow-up 3

Indications for Specialist Referral

PMR with normal inflammatory markers is explicitly considered an atypical presentation requiring rheumatology referral. 1, 7

Additional Referral Triggers:

• Age <60 years 1
• Peripheral inflammatory arthritis 1
• Inability to taper prednisone below 10 mg/day after 3 months 1
• Relapses or refractory disease 1
• Lack of response to appropriate glucocorticoid therapy 3, 5

Clinical Pitfalls to Avoid

• Do not exclude PMR diagnosis based solely on normal inflammatory markers - clinical syndrome is paramount 1, 2
• Beware of obesity-related inflammatory marker elevation creating false diagnostic confidence in young patients with fibromyalgia 6
• Remember that glucocorticoid therapy suppresses ESR/CRP - low markers during treatment do not indicate disease absence 7
• High baseline ESR (>40 mm/h) predicts higher relapse risk when present, but absence does not predict benign course 7, 2