Case 26.3 – Polymyalgia Rheumatica & Temporal Arteritis

Most likely diagnosis: Giant cell arteritis (GCA, also known as temporal arteritis) with visual loss, in a patient with polymyalgia rheumatica (PMR).

Medical emergency: This is a rheumatological emergency due to visual loss from anterior ischemic optic neuropathy (AION). Without immediate treatment, there is high risk of:

• Permanent bilateral blindness (the contralateral eye is at very high risk within days)
• Other vascular complications (stroke, aortic dissection)

Immediate investigation:

• Urgent blood tests: ESR and CRP (typically markedly elevated - ESR often >50 mm/hr, frequently >100 mm/hr), FBC (may show normochromic normocytic anaemia, thrombocytosis), U&Es, LFTs (alkaline phosphatase may be elevated)
• Do NOT delay treatment waiting for results - if clinical suspicion is high, treat immediately
• Temporal artery biopsy: Should be arranged urgently (ideally within 7 days of starting steroids, but can still be diagnostic up to 2 weeks) - but do NOT delay treatment to arrange biopsy
• Urgent ophthalmology review for full assessment of visual loss

Immediate management:

• High-dose intravenous methylprednisolone 500mg-1g daily for 3 days (for patients with visual symptoms), OR
• High-dose oral prednisolone 40-60mg daily immediately (if no visual symptoms, or if IV not available but start oral immediately)
• Do NOT wait for biopsy or test results - treatment should be started on clinical suspicion alone
• Aspirin 75mg daily (antiplatelet effect may reduce risk of further ischemic events)
• Gastroprotection (PPI)
• Bone protection (calcium/vitamin D, consider bisphosphonate)
• Arrange temporal artery biopsy urgently but do not delay steroid treatment

Key point: GCA with visual symptoms is a "treat first, investigate later" emergency. Visual loss may be irreversible, but immediate high-dose steroids can prevent bilateral blindness.

Relationship between PMR and GCA:

• PMR and GCA are closely related conditions, considered part of the same disease spectrum
• They share similar demographics (age >50, peak 70-80 years, more common in women, Northern European ancestry)
• 15-20% of PMR patients develop GCA
• 40-60% of GCA patients have PMR symptoms
• Both have similar inflammatory markers (elevated ESR/CRP) and respond to corticosteroids
• Temporal artery biopsies in PMR patients without GCA symptoms sometimes show subclinical arteritis
• Consider them as overlapping conditions: isolated PMR, PMR + GCA, or isolated GCA

Polymyalgia Rheumatica (PMR) - typical features:

• Age: Almost always >50 years (mean age 70 years)
• Pain and stiffness: Bilateral shoulder and pelvic girdle (neck, shoulders, upper arms, hips, thighs)
• Morning stiffness: Marked, lasting >45 minutes (typically several hours)
• Functional impairment: Difficulty with activities - rising from chair, lifting arms above head, getting dressed
• Systemic symptoms: Fatigue, malaise, low-grade fever, weight loss, depression
• Onset: Usually subacute (over weeks), can be acute
• Important negative findings: No muscle weakness on testing (pain limits movement, not weakness), peripheral joints generally spared

Giant Cell Arteritis (GCA/Temporal Arteritis) - typical features:

Cranial symptoms (most common):

• Headache (70%): New onset, severe, temporal or occipital, may be continuous
• Scalp tenderness: Pain when combing hair or resting head on pillow
• Jaw claudication (40%): Pain in jaw/tongue with chewing, pathognomonic when present
• Visual symptoms (25-50%):
  • Amaurosis fugax (transient visual loss - warning symptom)
  • Diplopia (extraocular muscle ischemia)
  • Permanent visual loss (AION - anterior ischemic optic neuropathy, central retinal artery occlusion)
• Temporal artery abnormalities: Prominent, tender, reduced/absent pulsation, may be nodular

Systemic symptoms:

• Fever, malaise, weight loss, night sweats (constitutional symptoms in 50%)
• PMR symptoms (in 40-60%)

Large vessel involvement (less common but important):

• Aortic aneurysm/dissection
• Limb claudication (subclavian, axillary, brachial arteries)
• Asymmetric blood pressures/pulses in arms
• Stroke (carotid/vertebral involvement)

Key distinguishing features: Headache, jaw claudication, visual symptoms, and temporal artery abnormalities suggest GCA. PMR alone has predominantly musculoskeletal symptoms without cranial features.

Blood tests (both PMR and GCA):

• ESR and CRP: Typically markedly elevated
  • PMR: ESR usually >40 mm/hr (often 40-100)
  • GCA: ESR often >50 mm/hr (frequently >100, can be >100)
  • However, ~20% of GCA patients have ESR <50
  • CRP usually elevated in parallel with ESR
  • Normal inflammatory markers do NOT exclude GCA if clinical suspicion is high
• FBC:
  • Normochromic normocytic anaemia (anaemia of chronic disease)
  • Thrombocytosis (reactive)
• LFTs: Alkaline phosphatase may be elevated (particularly in GCA)
• Other tests to exclude differential diagnoses: Rheumatoid factor, anti-CCP, CK (normal in PMR - excludes myositis), thyroid function, protein electrophoresis, urinalysis

Temporal artery biopsy (gold standard for GCA):

Indications:

• Suspected GCA (cranial symptoms, visual symptoms, or PMR with high inflammatory markers)
• To confirm diagnosis, especially if long-term steroids anticipated

Procedure and findings:

• Sample at least 1-2cm length (skip lesions can be missed with short samples)
• Unilateral biopsy is usually sufficient; if negative but high clinical suspicion, consider contralateral biopsy
• Histology shows: Granulomatous inflammation, multinucleated giant cells, disruption of internal elastic lamina, intimal hyperplasia

Timing:

• Should NOT delay treatment - start steroids immediately on clinical suspicion
• Biopsy should ideally be performed within 7 days of starting steroids (remains positive up to 2-4 weeks in many cases)
• Changes on biopsy may disappear after prolonged steroid treatment

Limitations:

• Sensitivity only 60-90% (due to skip lesions - patchy arterial involvement)
• False negatives occur - negative biopsy does NOT exclude GCA if clinical suspicion is high
• Positive biopsy confirms diagnosis, but treatment decisions are clinical

Imaging (increasingly used, especially if biopsy not available/contraindicated):

• Temporal artery ultrasound:
  • Non-invasive, can be performed quickly
  • Characteristic "halo sign" (hypoechoic wall thickening due to edema)
  • Operator-dependent, requires experienced sonographer
  • Sensitivity ~75%, specificity ~83%
  • Can be used to guide biopsy site
• MRI/MRA, CT angiography, PET-CT:
  • Useful for detecting large vessel involvement (aorta, subclavian, carotid arteries)
  • PET-CT shows increased FDG uptake in inflamed vessel walls
  • Can identify aortic aneurysms/complications

Diagnostic criteria for PMR (BSR/BHPR 2010 provisional criteria include):

• Age ≥50 years
• Bilateral shoulder and/or pelvic girdle aching
• Morning stiffness >45 minutes
• Elevated ESR/CRP
• Rapid response to prednisolone (≤20mg/day)
• Exclusion of other diagnoses

Clinical diagnosis: Both PMR and GCA remain largely clinical diagnoses. Investigations support the diagnosis but should not delay treatment in GCA. A dramatic response to corticosteroids is characteristic and supports the diagnosis.

Corticosteroid treatment for GCA:

Acute phase:

• With visual symptoms (emergency):
  • IV methylprednisolone 500mg-1g daily for 3 days
  • Then oral prednisolone 40-60mg daily
• Without visual symptoms:
  • Oral prednisolone 40-60mg daily (some use up to 1mg/kg)
• Expected response: Dramatic improvement in symptoms within 24-72 hours (if no response, reconsider diagnosis)

Tapering regimen (BSR guidelines):

• Weeks 0-4: High dose (40-60mg)
• Weeks 4-8: Reduce to 20mg daily (if symptoms controlled and CRP normalizing)
• Weeks 8-12: Reduce to 15mg daily
• Months 3-6: Reduce by 2.5mg every 2-4 weeks to 10mg
• Months 6-12: Reduce by 1mg every 1-2 months
• After month 12: Continue slow taper by 0.5-1mg every 1-2 months
• Total duration: Typically 1-2 years, but many patients need longer (individualized)

Corticosteroid treatment for PMR (without GCA):

Initial dose:

• Prednisolone 15mg daily (range 12.5-25mg, but avoid >25mg - suggests alternative diagnosis)
• Expected response: Marked improvement within days (70% respond within 1 week); lack of response should prompt reconsideration of diagnosis

Tapering regimen (BSR guidelines):

• Weeks 0-3: 15mg daily
• Weeks 3-6: Reduce to 12.5mg daily
• Weeks 6-12: Reduce to 10mg daily
• Months 3-6: Reduce by 1mg every 4-8 weeks (slow taper)
• After 10mg reached: Reduce by 1mg every 4-8 weeks or 0.5mg every 4-8 weeks below 5mg
• Total duration: Typically 1-2 years (range 6 months to several years)

Monitoring during treatment:

• Clinical symptoms: Most important - recurrence of symptoms indicates active disease
• ESR/CRP: Monitor regularly (every 4-8 weeks during tapering, more frequently if concerns)
  • Should normalize on treatment
  • Rising ESR/CRP may indicate relapse (but can also be due to infection or other causes)
  • Some patients have persistently elevated ESR without clinical relapse
• Watch for GCA symptoms in PMR patients: Headache, visual symptoms, jaw claudication (requires immediate increase in steroids)

Managing relapses:

• Relapse definition: Recurrence of symptoms (with or without rising inflammatory markers)
• Management:
  • Increase prednisolone to last effective dose (or higher if symptoms severe)
  • If GCA symptoms: treat as initial presentation (40-60mg)
  • Resume tapering once remission re-achieved (slower taper may be needed)
• ~50% of PMR patients and higher proportion of GCA patients experience relapse during tapering

Steroid-sparing agents (consider if):

• Relapsing disease requiring high steroid doses
• Unable to taper below 7.5-10mg prednisolone
• Significant steroid-related side effects

Options:

• Methotrexate: 7.5-25mg weekly (modest steroid-sparing effect, limited evidence)
• Tocilizumab (IL-6 inhibitor): Licensed for GCA (particularly refractory/relapsing cases); 162mg SC weekly or fortnightly
  • Proven to increase remission rates and reduce cumulative steroid dose
  • Expensive, usually reserved for difficult cases
• Azathioprine, leflunomide: limited evidence, occasionally used

Co-prescribing with steroids:

• Bone protection: Calcium + vitamin D, bisphosphonate (if high fracture risk or prolonged steroids anticipated)
• Gastroprotection: PPI (especially if other GI risk factors)
• Monitoring: Blood glucose, BP, bone density (DEXA scan), eye checks (cataracts, glaucoma)
• Lifestyle: Advise regular weight-bearing exercise, smoking cessation, falls prevention

Key principles: Tailored tapering based on clinical response (not just ESR/CRP); slow taper reduces relapse risk; never abruptly stop steroids after prolonged use (adrenal suppression).

Complications of untreated/inadequately treated GCA:

Ophthalmic complications (most feared):

• Permanent visual loss (15-20% if untreated):
  • Anterior ischemic optic neuropathy (AION) - most common cause
  • Central retinal artery occlusion
  • Posterior ischemic optic neuropathy
  • Cortical blindness (occipital lobe infarction)
• Bilateral involvement: High risk of second eye being affected within days if not treated (30-50% become bilateral)
• Diplopia (extraocular muscle ischemia)
• Prevention: Immediate high-dose steroids dramatically reduce risk of visual loss

Neurological complications:

• Stroke (3-7%): Carotid or vertebral artery involvement
• Transient ischemic attacks
• Cranial nerve palsies
• Peripheral neuropathy (less common)

Large vessel complications:

• Thoracic aortic aneurysm: 17x increased risk (may present years after initial diagnosis)
• Aortic dissection
• Limb ischemia (subclavian, axillary artery stenosis/occlusion)
• Long-term monitoring: Annual chest X-ray or periodic imaging of thoracic aorta recommended by some experts

Other complications:

• Jaw/tongue necrosis (rare, from severe ischemia)
• Scalp necrosis (rare)
• Myocardial infarction

Side effects of long-term corticosteroid therapy (very common - almost all patients on long-term steroids experience some):

Endocrine/metabolic:

• Weight gain and central obesity (very common): Increased appetite, fat redistribution (Cushingoid appearance)
• Diabetes/impaired glucose tolerance: Monitor blood glucose regularly; may need oral hypoglycemics or insulin
• Adrenal suppression: After prolonged use (\>3 weeks); risk of adrenal crisis if steroids stopped abruptly or during acute illness
  • Patients need steroid alert card/bracelet
  • May need temporary increase during illness/surgery
• Dyslipidemia

Musculoskeletal:

• Osteoporosis and fragility fractures (common):
  • Bone loss most rapid in first 3-6 months of therapy
  • Vertebral fractures particularly common
  • Prevention essential: Calcium, vitamin D, bisphosphonates, DEXA monitoring
• Myopathy: Proximal muscle weakness (distinguish from PMR symptoms - myopathy causes true weakness)
• Avascular necrosis (osteonecrosis), especially femoral head
• Tendon rupture (Achilles particularly)

Cardiovascular:

• Hypertension (common): Monitor BP regularly; may need antihypertensives
• Increased cardiovascular risk (MI, heart failure)
• Peripheral edema

Gastrointestinal:

• Peptic ulceration and GI bleeding: Risk increased, especially with NSAIDs; consider PPI prophylaxis
• Dyspepsia
• Pancreatitis (rare)

Ophthalmic:

• Cataracts (common with prolonged use): Posterior subcapsular cataracts typical
• Glaucoma: Increased intraocular pressure
• Regular ophthalmology screening recommended

Dermatological:

• Skin thinning and easy bruising (very common)
• Striae
• Delayed wound healing
• Acne

Immunological:

• Increased infection risk: Particularly opportunistic infections at higher doses
  • Consider pneumococcal and annual flu vaccination
  • Avoid live vaccines while on immunosuppression
  • Be vigilant for atypical presentations of infection (steroids may mask fever)

Neuropsychiatric:

• Mood changes (euphoria, depression, irritability)
• Insomnia (advise taking morning dose)
• Psychosis (rare but serious)
• Cognitive impairment

Patient counseling and monitoring strategy:

• Explain the risk-benefit balance: Serious complications of untreated GCA (blindness, stroke) far outweigh steroid risks, but long-term side effects are almost inevitable and need proactive management
• Provide steroid alert card
• Advise NOT to stop abruptly
• Regular monitoring: BP, blood glucose, bone density, weight, mood, infections
• Lifestyle measures: Healthy diet, exercise, smoking cessation, falls prevention, adequate calcium/vitamin D intake
• Report warning symptoms: Visual changes, severe headache (disease relapse); signs of infection or new symptoms (steroid complications)
• Long-term follow-up essential

Key message: While steroids carry significant long-term risks, they are life- and sight-saving in GCA. The goal is to use the minimum effective dose for the shortest necessary duration while implementing measures to mitigate steroid-related complications.