Polymyalgia rheumatica and giant cell arteritis
Description
- Two ends of one disease spectrum in people over 50
| PMR | GCA | |
|---|---|---|
| Lesion | Bursitis + synovitis of shoulder and hip girdles | Granulomatous panarteritis of large and medium arteries |
| Core symptom | Bilateral shoulder and hip girdle pain + stiffness | Headache, jaw claudication, visual loss |
| Risk | Disability, steroid toxicity | Irreversible blindness, aortic aneurysm |
- ~40-50% of GCA patients have PMR symptoms
- ~15-20% of PMR patients develop GCA
- *Always ask a PMR patient about headache, jaw claudication and visual symptoms - at every visit*
GCA phenotypes
- Cranial GCA - temporal/occipital headache, scalp tenderness, jaw claudication, visual loss
- Large-vessel GCA (LV-GCA) - aorta, subclavian, axillary; fever of unknown origin, limb claudication, absent pulses, constitutional symptoms without headache
- Younger, more female, more likely to be biopsy-negative, more aortic complications
Epidemiology
- Age >50 is an absolute requirement for both (GCA under 50 is essentially never GCA - think Takayasu)
- PMR: peak 70-80; F:M ~2:1; incidence ~50-100/100,000 over 50
- Second commonest inflammatory rheumatic disease of older adults after RA
- GCA: peak >70; F:M ~3:1; incidence ~15-25/100,000 over 50
- The commonest primary systemic vasculitis in adults
- Strong Northern European, particularly Scandinavian, ancestry gradient; rare in Asian and African populations
Aetiopathogenesis
- Adventitial dendritic cell activation -> CD4 T cells -> Th1 (IFN-gamma) and Th17 (IL-17) responses
- Granuloma with multinucleate giant cells at the internal elastic lamina
- Intimal hyperplasia -> luminal occlusion -> ischaemia (the vessel narrows from the inside; the artery is not simply inflamed)
- IL-6 drives the systemic features - fever, weight loss, anaemia, high ESR/CRP
- This is why tocilizumab works and why it abolishes the inflammatory markers
- Skip lesions - inflammation is segmental (hence a 1-2 cm biopsy segment and false-negative biopsies)
Visual loss mechanism
- Arteritic anterior ischaemic optic neuropathy (A-AION)
- Granulomatous occlusion of the posterior ciliary arteries supplying the optic nerve head
- Not the retinal artery in most cases - hence a pale, swollen ("chalky white") disc
- Also: central retinal artery occlusion, posterior ION, cortical blindness, diplopia from ocular motor ischaemia
- *Once established, visual loss is irreversible, and the second eye is at risk within days*
Diagnosis
PMR - clinical features
- Rapid onset (days-weeks) bilateral shoulder pain and restricted movement
- Upper arms, neck, pelvic girdle, hips, thighs
- Worse in the morning, improves with movement; morning stiffness >45 min
- Constitutional symptoms: fatigue, weight loss, low-grade fever, depression
- Difficulty rising from a chair, turning in bed, raising arms
- True weakness is absent - the limitation is pain. Weakness with a normal CK-negative pattern means myositis or myopathy, not PMR**
2012 ACR/EULAR PMR classification criteria
- Required: age >=50, new bilateral shoulder aching, abnormal CRP and/or ESR
- Then score:
| Item | Points |
|---|---|
| Morning stiffness >45 min | 2 |
| Absence of RF AND anti-CCP | 2 |
| Hip pain or restricted range of movement | 1 |
| Absence of other joint involvement | 1 |
| (with US) Bilateral shoulder bursitis/synovitis, or shoulder + hip findings | 1 |
| (with US) Both shoulders involved | 1 |
- >=4 points without ultrasound; >=5 with ultrasound
PMR investigations
- ESR >30 mm/h, CRP >6 mg/L (~7-20% have a normal ESR - CRP is more sensitive)
- RF and anti-CCP negative - a positive result should make you reconsider (elderly-onset seronegative RA)
- FBE (normocytic anaemia, thrombocytosis), LFT (raised ALP), CK NORMAL, TSH, calcium, protein electrophoresis, urinalysis
- US or MRI: bilateral subacromial/subdeltoid bursitis, long head of biceps tenosynovitis, hip trochanteric bursitis
- PET-CT: large-vessel uptake (occult GCA) plus cervical and lumbar interspinous bursitis - characteristic of PMR
PMR - what it is NOT
Consider before committing to long-term steroid:
- Elderly-onset RA (positive serology, small-joint synovitis, erosions)
- Late-onset spondyloarthritis / RS3PE
- Inflammatory myopathy (weakness, high CK)
- Hypothyroidism, osteomalacia, statin myopathy
- Malignancy (myeloma, lymphoma, solid tumour), infection (endocarditis, osteomyelitis)
- Bilateral rotator cuff disease, fibromyalgia (normal inflammatory markers)
- Parkinson disease
- *An incomplete response to 15 mg prednisolone within a week argues strongly against PMR*
GCA - clinical features
- Headache - new, ~2/3 temporal, ~1/3 occipital
- Jaw claudication - the most specific symptom (LR+ ~4-6)
- Scalp tenderness (combing hair, wearing glasses); temporal artery thickened, tender, pulseless, nodular
- Visual disturbance in 25-50% - amaurosis fugax, diplopia, blurring, then permanent loss
- Constitutional symptoms; PMR in ~40-50%
- Extracranial large-vessel involvement in 30-80% on imaging - limb claudication, pulse or BP asymmetry, bruits
- Skin, lung and kidney involvement are rare - their presence suggests ANCA vasculitis instead
- Tongue or scalp necrosis (rare, severe)
GCA investigations
- inc CRP and ESR (ESR often >100; but ~4% have both normal), normocytic anaemia, thrombocytosis, raised ALP
- Temporal artery biopsy - the gold standard
- Take >=1-2 cm (skip lesions)
- Remains positive for up to ~2 weeks after starting steroid - never delay treatment for the biopsy
- Histology: panarteritis, granulomatous infiltrate with giant cells, fragmentation of the internal elastic lamina, intimal hyperplasia
- A negative biopsy does not exclude GCA - sensitivity ~70-90%
- Temporal artery ultrasound - increasingly first-line
- "Halo sign" (hypoechoic circumferential wall thickening), non-compressible artery
- Sensitivity ~88%, specificity ~97% in experienced hands; do within 3-7 days of starting steroid before the halo resolves
- High-resolution MRI of temporal arteries - similar performance
- CT angiography, MR angiography or PET-CT for large-vessel disease - do in everyone with suspected LV-GCA or fever of unknown origin
- Urgent ophthalmology if any visual symptom
2022 ACR/EULAR GCA classification criteria
- Absolute requirement: age >=50
- Weighted items: positive temporal artery biopsy or halo sign (+5), ESR >=50 or CRP >=10 (+3), sudden visual loss (+3), morning stiffness/PMR, jaw or tongue claudication, new temporal headache, scalp tenderness, abnormal temporal artery examination, bilateral axillary involvement, FDG-PET uptake throughout the aorta
- Score >=6 classifies GCA
Management
Axis: disease phase - immediate control, then taper with steroid-sparing therapy, then relapse surveillance. GCA is a medical emergency; PMR is not.
A. GCA - immediate
- *Start glucocorticoid on clinical suspicion. Do not wait for biopsy, ultrasound or bloods.*
- No visual symptoms: prednisolone 40-60 mg daily (~1 mg/kg)
- Visual symptoms or amaurosis fugax: IV methylprednisolone 500-1000 mg daily for 3 days, then oral
- Low-dose aspirin - reduces ischaemic events (weigh bleeding risk)
- Arrange biopsy or US within 1-2 weeks - do not let treatment erase the diagnosis entirely
- Urgent ophthalmology review
B. GCA - maintenance and tapering
- Continue the initial dose ~2-4 weeks until symptoms and inflammatory markers normalise, then taper
- To ~20 mg by ~2-3 months, ~10 mg by ~6 months, then 1 mg reductions
- Total course typically 1-2 years; ~50% need longer
- Tocilizumab (anti-IL-6R) for relapsing or refractory GCA, and to spare glucocorticoid
- GiACTA: markedly higher sustained steroid-free remission and roughly halved cumulative steroid dose
- *Abolishes CRP and ESR - relapse must be judged clinically and on imaging*
- PBS-restricted in Australia
- Methotrexate - modest steroid-sparing effect; an alternative where tocilizumab is unavailable
C. PMR
- Prednisolone 12.5-25 mg daily, commonly 15 mg - the lowest effective dose within this range
- A dramatic response within 3-7 days is expected and is itself diagnostic
- No response -> the diagnosis is wrong. Do not simply escalate the dose
- Taper slowly
- To 10 mg over ~4-8 weeks, then reduce by ~1 mg every 4 weeks
- Typical total duration 1-2 years; up to 50% relapse during tapering
- Methotrexate (oral or SC) as a steroid-sparing agent if relapsing, steroid-dependent, or high risk of steroid toxicity (diabetes, osteoporosis, glaucoma)
- Tocilizumab and sarilumab have evidence in relapsing PMR
D. Steroid-toxicity prophylaxis - mandatory in both
- Calcium, vitamin D, and a bisphosphonate (prednisolone >=7.5 mg for >=3 months in this age group)
- Baseline DXA
- Monitor BP, glucose/HbA1c, weight, lipids
- Gastroprotection if NSAIDs or high steroid dose
- PJP prophylaxis if prednisolone >=20 mg for >4 weeks with a second immunosuppressant
- Vaccination; falls and cataract review; steroid card and sick-day rules
E. Relapse
- Judge on symptoms, not on ESR/CRP alone (and not at all on markers if on tocilizumab)
- Relapse -> return to the last effective dose (or higher for visual/ischaemic symptoms), then re-taper more slowly, and add or escalate a steroid-sparing agent
- New visual symptoms at any dose -> pulse methylprednisolone
F. Long-term surveillance in GCA
- Aortic aneurysm and dissection risk persists for years - periodic imaging (CT/MR aorta) or at least clinical review and CXR
- Cardiovascular risk factor management
Associations
- PMR and GCA with each other
- Aortic aneurysm and dissection (thoracic > abdominal) - ~17x risk of thoracic aortic aneurysm in GCA
- Large-vessel stenosis - subclavian, axillary, vertebral -> limb claudication, subclavian steal
- Stroke (vertebrobasilar territory over-represented)
- Cardiovascular disease and myocardial infarction
- Steroid-related: osteoporosis and fragility fracture, diabetes, cataract, glaucoma, hypertension, infection, skin fragility, myopathy, adrenal suppression
- Depression, sleep disturbance
- RS3PE (remitting seronegative symmetrical synovitis with pitting oedema) - overlaps PMR
- A weak association with malignancy exists but routine cancer screening beyond age-appropriate care is not indicated
Natural history & complications
PMR
- Excellent response to steroid, but long course - median 1-2 years, ~1/3 need >2 years
- Relapse in up to 50%, usually during taper below 10 mg
- Normal life expectancy; morbidity is dominated by cumulative glucocorticoid toxicity
- Watch for evolution into GCA or into seronegative RA
GCA
- Visual loss occurs in ~15-20% overall; ~1-2% once treatment has started
- Irreversible - the goal of urgent treatment is to save the other eye
- Highest risk in the first 1-2 weeks; preceded by amaurosis fugax or diplopia in many
- Relapse in ~30-50%, usually in the first year of tapering
- Mortality approaches that of the general population, except for aortic complications
- Aortic aneurysm and dissection can occur years after apparent remission - persistent surveillance
- Cumulative steroid morbidity is substantial: ~85% experience at least one glucocorticoid adverse effect
Poor prognostic features
- Visual loss at presentation
- Large-vessel involvement (aneurysm risk)
- Frequent relapse and high cumulative steroid exposure
- Very high inflammatory markers at diagnosis
- Age and comorbidity burden
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