Pathophysiology and Treatment of Polymyalgia Rheumatica (PMR)
Pathophysiology
Polymyalgia rheumatica (PMR) is an inflammatory rheumatic condition primarily affecting older adults, characterized by pain and stiffness in the shoulders, neck, and pelvic girdle, with elevated inflammatory markers and a robust response to glucocorticoid therapy. While the exact pathophysiology remains incompletely understood, it involves systemic inflammation with potential overlap with giant cell arteritis (GCA) 1, 2.
Key pathophysiological features include:
- Inflammatory involvement of the connective vascular tissue, particularly affecting proximal muscle groups 2
- Systemic inflammatory response with elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) 3, 1
- Possible shared pathophysiological mechanisms with giant cell arteritis 4, 1
- Predominantly affects individuals over 50 years of age, with peak incidence in the eighth decade 4, 1
Diagnosis
Diagnostic workup should include:
Laboratory assessment to exclude mimicking conditions 3:
- Rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies (ACPA) to exclude rheumatoid arthritis 3
- Inflammatory markers: C-reactive protein (CRP) and/or erythrocyte sedimentation rate (ESR) - typically elevated in PMR 3
- Complete blood count, glucose, creatinine, liver function tests, bone profile 5
- Consider protein electrophoresis, thyroid stimulating hormone (TSH), creatine kinase and vitamin D 5
Additional investigations based on clinical presentation:
Treatment
Initial Glucocorticoid Therapy
The panel strongly recommends using glucocorticoids (GC) instead of NSAIDs in patients with PMR, with the minimum effective GC dose within a range of 12.5–25 mg prednisone equivalent daily as the initial treatment. 5
- Higher initial prednisone doses (within 12.5-25 mg range) for patients with high relapse risk and low adverse event risk 5, 3
- Lower initial doses for patients with comorbidities (diabetes, osteoporosis, glaucoma) 5
- The panel discourages initial doses ≤7.5 mg/day and strongly recommends against initial doses >30 mg/day 5
Glucocorticoid Tapering
Individualized tapering schedule based on regular monitoring of disease activity, laboratory markers, and adverse events 5:
- Initial tapering: Taper to 10 mg/day prednisone equivalent within 4–8 weeks 5
- Relapse therapy: Increase to pre-relapse dose and decrease gradually (within 4–8 weeks) to the dose at which relapse occurred 5
- Once remission achieved: Taper daily oral prednisone by 1 mg every 4 weeks (or by 1.25 mg using alternate day schedules) until discontinuation 5
Alternative Treatment Options
- Intramuscular methylprednisolone as an alternative to oral GCs (120 mg i.m. injection every 3 weeks) 5
- Single rather than divided daily doses of oral GCs, except for prominent night pain while tapering below 5 mg daily 5
- Consider early introduction of methotrexate as a steroid-sparing agent in patients at high risk for relapse or GC-related adverse events 5, 6
- Tocilizumab has shown promise in recent studies for patients with refractory disease 6
Monitoring and Follow-up
- Follow-up visits every 4–8 weeks in the first year, every 8–12 weeks in the second year, and as indicated for relapses or during tapering 5, 3
- Monitor for steroid-related side effects, comorbidities, other relevant medications, and risk factors for relapse/prolonged therapy 5
- Document a minimal clinical and laboratory dataset while prescribing GCs 5
- Ensure patients have rapid access to medical advice for reporting flares and adverse events 5
Risk Factors for Relapse/Prolonged Therapy
Special Considerations
- Consider specialist referral for atypical presentations (peripheral arthritis, systemic symptoms, low inflammatory markers, age <60 years) 5, 3
- Female sex may be associated with higher risk of glucocorticoid side effects 5
- Assess and monitor for comorbidities that might be exacerbated by PMR or GC therapy (hypertension, diabetes, osteoporosis, etc.) 5, 3