What is the etiology, diagnosis, and treatment of polymyalgia rheumatica (PMR)?

Polymyalgia Rheumatica: Etiology, Diagnosis, and Treatment

Etiology

Polymyalgia rheumatica (PMR) is an inflammatory condition of unknown etiology that primarily affects individuals over 50 years of age, with peak incidence at 70-75 years, particularly in Western countries 1, 2. While the exact cause remains unclear, the disease demonstrates a strong inflammatory component with elevated inflammatory markers and rapid response to glucocorticoid therapy, suggesting an immune-mediated pathogenesis 3.

Diagnosis

The diagnosis of polymyalgia rheumatica is primarily clinical, with no single diagnostic test available, and requires exclusion of conditions that can mimic its presentation. 3

Clinical Features:

• Bilateral pain and stiffness in the shoulder girdle, neck, and pelvic girdle
• Prolonged morning stiffness (typically >45 minutes)
• Proximal muscle pain without true weakness
• Constitutional symptoms (fatigue, low-grade fever, weight loss)
• Age >50 years (typically >60)

Laboratory Evaluation:

• Complete blood count
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) - typically markedly elevated
• Rheumatoid factor and anti-cyclic citrullinated peptide antibodies (to exclude rheumatoid arthritis)
• Basic biochemistry including liver function tests

Diagnostic Confirmation:

• Rapid response to low-dose glucocorticoids (15-20 mg/day of prednisone) within 24-72 hours is considered confirmatory 3
• Ultrasound imaging may improve diagnostic accuracy by detecting bilateral subdeltoid bursitis, present in approximately 69% of PMR patients 4

Differential Diagnosis:

Must exclude conditions that can mimic PMR, including:

• Rheumatoid arthritis (especially elderly-onset)
• Spondyloarthritis
• Inflammatory myopathies
• Malignancies
• Chronic infections
• Endocrine diseases (particularly hypothyroidism)
• Fibromyalgia
• Polymyositis 3, 5

Treatment

Initial Therapy:

Glucocorticoids are the cornerstone of PMR treatment, with recommended initial doses of 12.5-25 mg prednisone equivalent daily. 3

• Higher initial doses (within the 12.5-25 mg range) for patients with high relapse risk and low adverse event risk
• Lower initial doses for patients with comorbidities such as diabetes, osteoporosis, or glaucoma
• Doses above 30 mg/day are strongly discouraged
• Doses below 7.5 mg/day are conditionally discouraged 3
• Single daily dosing is preferred over divided doses

Alternative Initial Therapies:

• Intramuscular methylprednisolone (120 mg every 3 weeks) may be considered as an alternative to oral glucocorticoids 3

Dose Tapering:

• Initial tapering to 10 mg/day within 4-8 weeks
• Subsequent tapering by 1 mg every 4 weeks, or by 1.25 mg using alternate day schedules, once the patient is stable 3

Steroid-Sparing Agents:

• Methotrexate should be considered in patients with high relapse risk, prolonged therapy requirements, or significant glucocorticoid-related adverse events 3, 4
• Methotrexate can reduce cumulative glucocorticoid dosage by 20-44% and relapses by 36-54% 4
• Leflunomide has shown promising results but requires further study 1
• Biologic agents, particularly IL-6 inhibitors (tocilizumab and sarilumab), have demonstrated efficacy in reducing relapse frequency and lowering cumulative glucocorticoid burden 1
• Anti-TNF agents have failed to show beneficial effects in isolated PMR 1

Monitoring and Follow-up

• Monitor patients every 4-8 weeks during the first year
• Every 8-12 weeks during the second year
• More frequent monitoring during relapse or tapering periods 3

Assessment at Follow-up:

• Clinical response
• Inflammatory markers
• Glucocorticoid-related side effects
• Comorbidities
• Symptoms of giant cell arteritis (GCA)

Relapse Management:

• Up to 60% of PMR patients experience relapse during glucocorticoid tapering 3
• For relapse, temporarily increase prednisone to the pre-relapse dose or to the last effective dose
• Consider adding methotrexate if not already prescribed

Special Considerations

• All PMR patients should be monitored for symptoms of GCA, including headache, jaw claudication, and visual disturbances 3
• If GCA is suspected, immediate treatment with higher glucocorticoid doses (40-60 mg prednisone) is required due to the risk of sight loss 3
• Prolonged glucocorticoid therapy requires monitoring for and management of potential adverse effects, including osteoporosis, diabetes, hypertension, and increased infection risk

PMR management requires balancing effective symptom control with minimizing glucocorticoid-related toxicity, particularly in older adults who are more vulnerable to these adverse effects.