Polymyalgia Rheumatica

1. Clinical Overview

Summary

Polymyalgia Rheumatica (PMR) is the most common inflammatory rheumatic disease in people over 50 years of age, with an estimated annual incidence of 50-100 per 100,000 in this population. [1,2] It is characterized by severe bilateral pain and stiffness affecting the shoulder and pelvic girdles, accompanied by marked systemic inflammation and constitutional symptoms.

The disease has a striking demographic profile: it is almost never seen in individuals under 50 years of age, with peak incidence occurring between 70-80 years. [3] Women are affected approximately twice as frequently as men, and there is marked geographic variation with highest incidence in Scandinavian countries and northern European populations. [4]

The hallmark of PMR is a dramatic and rapid response to low-dose corticosteroids (prednisolone 15mg daily), with the majority of patients experiencing significant symptom relief within 24-72 hours. [5] This therapeutic response is so characteristic that lack of improvement within one week should prompt reconsideration of the diagnosis.

PMR has a critical association with Giant Cell Arteritis (GCA): approximately 15-20% of patients with PMR will develop GCA, and up to 50% of patients with GCA have concurrent or preceding PMR symptoms. [6] This overlap necessitates vigilant monitoring for GCA symptoms throughout the disease course, as GCA carries risk of irreversible vision loss if untreated.

Clinical Pearls

The "Gel Phenomenon": Morning stiffness in PMR is profound and prolonged, typically lasting more than 45 minutes and often persisting for several hours. Patients characteristically describe the sensation of "gelling" or "seizing up" after periods of inactivity, requiring significant time and gentle movement to restore mobility.

The 15mg Rule: The British Society for Rheumatology established 15mg prednisolone as the optimal initial dose for uncomplicated PMR. [7] Higher doses (> 20mg) do not improve outcomes and increase adverse effects, while lower doses (less than 12.5mg) may be insufficient for disease control. This dose specificity helps distinguish PMR from GCA, which requires 40-60mg daily.

SNOOP for Mimics: In elderly patients presenting with new-onset pain and elevated inflammatory markers, systematically exclude malignancy (metastatic disease, multiple myeloma), infection (endocarditis, osteomyelitis), and other inflammatory conditions before diagnosing PMR. The differential diagnosis narrows considerably with bilateral symmetric symptoms and normal creatine kinase.

Steroid Response as Diagnostic Test: Failure to achieve at least 70% symptomatic improvement within one week of starting prednisolone 15mg should trigger diagnostic reconsideration. Alternative diagnoses to consider include rotator cuff disease, osteoarthritis, fibromyalgia, elderly-onset rheumatoid arthritis, and occult malignancy.

ESR-CRP Discordance: While elevated inflammatory markers are characteristic, approximately 5% of biopsy-proven PMR cases present with normal or minimally elevated ESR. [8] CRP may be more sensitive than ESR in some cases. Clinical judgment should not be abandoned when markers are equivocal if other features are classic.

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2. Epidemiology and Risk Factors

Demographics

Incidence: The annual incidence of PMR ranges from 50-100 per 100,000 persons aged 50 years and older, with substantial geographic variation. [1,2] Scandinavian populations show the highest incidence (approaching 100 per 100,000), while southern European and Asian populations have lower rates (20-40 per 100,000). [4]

Prevalence: Population-based studies estimate the prevalence at 0.5-0.7% in individuals over 50 years, increasing with age. In the 70-79 age group, prevalence approaches 1%. [9]

Age Distribution:

• Mean age at diagnosis: 70-75 years
• Peak incidence: 70-80 years
• Almost never occurs before age 50 (age ≥50 is an absolute diagnostic criterion)
• Cases under 60 are uncommon and warrant careful diagnostic evaluation

Gender: Female predominance with F:M ratio of approximately 2-3:1. [3,4] The reasons for this gender disparity remain unclear but may relate to hormonal factors and immune system differences.

Ethnicity: Highest incidence in populations of northern European descent, particularly Scandinavian ancestry. Lower incidence in African, Asian, and Hispanic populations. [10]

Genetic Factors

HLA Associations: Strong association with HLA-DR4 alleles, particularly HLA-DRB104 and HLA-DRB101. [11] These alleles are also associated with rheumatoid arthritis, suggesting shared immunopathogenic mechanisms. The relative risk for PMR in HLA-DR4 positive individuals is approximately 3-4 fold higher than in the general population.

Familial Clustering: While PMR is not typically considered a familial disease, some studies report increased incidence among first-degree relatives of affected individuals, suggesting genetic susceptibility beyond HLA associations.

Environmental and Temporal Factors

Seasonal Variation: Some studies report increased incidence during summer months, suggesting possible infectious triggers. [12]

Cyclic Patterns: Epidemiological data show cyclic patterns with peaks every 5-7 years in some populations, supporting the hypothesis of environmental or infectious triggers.

Possible Triggers: No definitive infectious agent has been identified, but temporal clustering and seasonal variation suggest environmental factors may act as disease triggers in genetically susceptible individuals.

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3. Pathophysiology

Fundamental Disease Mechanisms

PMR is fundamentally an inflammatory synovitis and bursitis affecting proximal joints and periarticular structures, rather than a primary muscle disease (despite the name "myalgia"). [13] The disease process is driven by dysregulated innate and adaptive immune responses, with key pathogenic features including:

Anatomical Sites of Inflammation

Shoulder Girdle:

• Subacromial and subdeltoid bursitis (most consistent finding)
• Glenohumeral synovitis
• Bicipital tenosynovitis
• Acromioclavicular joint inflammation

Pelvic Girdle:

• Trochanteric bursitis
• Iliopsoas bursitis
• Hip joint synovitis (less common than shoulder)
• Symphysis pubis inflammation

Extraarticular Sites:

• Cervical and lumbar interspinous bursitis
• Sternoclavicular joint inflammation
• Peripheral synovitis (knees, wrists) in up to 50% of cases

Cellular and Molecular Pathophysiology

Cytokine Networks: Interleukin-6 (IL-6) is the central mediator of both local articular inflammation and systemic manifestations. [14] Elevated serum IL-6 levels correlate with disease activity and drive hepatic acute phase protein production (ESR, CRP, fibrinogen). Other implicated cytokines include:

• IL-1β (pro-inflammatory macrophage product)
• Tumor necrosis factor-α (TNF-α)
• IL-17 (Th17 cell product)

Cellular Infiltrates: Synovial and bursal tissue shows infiltration with CD4+ T lymphocytes (particularly Th1 and Th17 subsets) and activated macrophages. Unlike rheumatoid arthritis, synovial proliferation is modest and erosive changes are rare.

Vascular Involvement: The relationship between PMR and GCA likely reflects a continuum of vasculitic involvement. PMR may represent limited vascular inflammation insufficient to cause arterial stenosis or ischemic complications, or alternatively, inflammation confined to extraarticular soft tissues without significant arteritis.

Relationship to Giant Cell Arteritis

The PMR-GCA spectrum remains incompletely understood. Three main clinical scenarios exist:

1. Isolated PMR (approximately 60% of PMR cases): Periarticular inflammation without clinical vasculitis
2. PMR with subclinical GCA (approximately 20%): Evidence of arterial inflammation on imaging (PET, temporal artery ultrasound) without symptoms
3. PMR with overt GCA (15-20%): Concurrent symptomatic large vessel vasculitis

Shared pathogenic features include IL-6 hypersecretion, Th1/Th17 polarization, and association with HLA-DR4. The factors determining whether a patient develops isolated PMR versus GCA remain unclear.

Why Bilateral and Proximal?

The predilection for bilateral proximal symptoms likely reflects:

• Higher burden of bursae and synovial structures around shoulder and hip
• Anatomical symmetry of these structures
• Possible central immune dysregulation affecting similar structures bilaterally

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4. Differential Diagnosis

Establishing the diagnosis of PMR requires systematic exclusion of alternative conditions that can mimic its clinical presentation. The differential is broad given the non-specific nature of pain, stiffness, and elevated inflammatory markers in elderly patients.

Comprehensive Differential Diagnosis Table

Red Flag Features Suggesting Alternative Diagnoses

Features against PMR:

• Age less than 50 years
• Asymmetric symptoms
• Predominantly distal joint involvement
• True muscle weakness (not pain-limited power)
• Elevated creatine kinase
• Normal inflammatory markers (with caveats as above)
• Failure to respond to prednisolone 15mg within 7 days
• Requirement for prednisolone > 20mg to control symptoms

Features requiring urgent investigation:

• Severe headache, visual symptoms, jaw claudication (rule out GCA)
• Profound weight loss > 10% body weight (exclude malignancy)
• Fever > 38°C (consider infection, malignancy)
• Focal neurological deficits (structural lesion, stroke)

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5. Clinical Presentation

Classification Criteria

Several classification criteria have been proposed. The most widely used are the 2012 EULAR/ACR provisional classification criteria, which include a scoring algorithm combining clinical and laboratory features. [15]

Essential Criteria (all must be present):

1. Age ≥50 years
2. Bilateral shoulder pain/stiffness
3. Elevated ESR and/or CRP

Additional Criteria (points assigned):

• Morning stiffness > 45 minutes (2 points)
• Hip pain or limited range of motion (1 point)
• Absence of rheumatoid factor and anti-CCP antibodies (2 points)
• Absence of peripheral joint involvement (1 point)

A score ≥4 points (in presence of essential criteria) has sensitivity of 68% and specificity of 78% for PMR diagnosis.

British Society for Rheumatology (BSR) Diagnostic Criteria (simplified, clinical use): [7]

1. Age > 50 years
2. Duration > 2 weeks
3. Bilateral shoulder and/or pelvic girdle pain
4. Morning stiffness > 45 minutes
5. Elevated inflammatory markers (ESR/CRP)
6. Rapid response to corticosteroids (prednisolone 15mg)

Cardinal Symptoms

Bilateral Shoulder Pain and Stiffness (present in > 95% of cases):

• Severe aching pain affecting shoulder girdle
• Difficulty lifting arms above shoulder height
• Unable to brush or comb hair
• Difficulty putting on coat or reaching behind back
• Pain radiating to upper arms, rarely below elbows
• Often described as "deep" aching pain

Bilateral Hip/Pelvic Girdle Pain (present in 50-70%):

• Deep aching in buttocks, thighs, hips
• Difficulty rising from seated position (chair, toilet, car)
• Difficulty climbing stairs
• Pain typically does not radiate below knees

Morning Stiffness:

• Duration > 45 minutes, often 2-3 hours
• Most severe in morning upon waking
• Also occurs after periods of inactivity ("gel phenomenon")
• Gradually improves with gentle movement
• May recur in evening

Systemic/Constitutional Symptoms (present in 40-60%):

• Fatigue and malaise (profound in some cases)
• Low-grade fever (rarely > 38°C)
• Anorexia and weight loss (typically modest, 2-5 kg)
• Depression and low mood
• Sleep disturbance due to pain

Functional Impact and Quality of Life

The functional impairment in PMR can be severe and is often underestimated. Validated questionnaires document significant disability:

Activities of Daily Living Affected:

• Personal hygiene: Difficulty washing, dressing upper body
• Mobility: Trouble getting out of bed, rising from chairs
• Household tasks: Unable to lift pans, hang washing, vacuum
• Sleep: Frequent waking from pain when turning in bed

Studies using Health Assessment Questionnaire (HAQ) scores show baseline disability comparable to active rheumatoid arthritis. [16]

Physical Examination Findings

Characteristic Findings:

• Apparent weakness: Power appears reduced, but this is due to pain inhibition rather than true weakness. With encouragement and analgesia, power is normal (MRC grade 5/5).
• Painful restriction: Active range of motion reduced at shoulders and hips, but passive movement less restricted.
• Normal muscle bulk: No muscle wasting (distinguishes from polymyositis).
• Shoulder palpation: Tenderness over subacromial region, deltoid insertion.
• Normal peripheral joints: Hands, wrists, knees typically uninvolved (though up to 50% may have mild peripheral synovitis).

Examination Maneuvers:

• Shoulder abduction and forward flexion: Painful and restricted
• Internal rotation (hand behind back): Severely limited
• Hip flexion, abduction, internal rotation: Painful
• Straight leg raise: May be limited by pain

GCA Screening (essential at every visit):

• Temporal artery examination: Tenderness, reduced pulsation, nodularity
• Scalp tenderness: Ask patient about pain when brushing hair
• Visual acuity: Document baseline and monitor
• Jaw claudication: Ask about pain with chewing

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6. Investigations

Essential Baseline Investigations

Inflammatory Markers:

• ESR (Erythrocyte Sedimentation Rate): Elevated in > 90% of cases, typically > 40 mm/hr, often > 60 mm/hr. [17] Values > 100 mm/hr should raise suspicion for GCA or alternative diagnoses (infection, malignancy).
• CRP (C-Reactive Protein): Elevated in > 95% of cases. May be more sensitive than ESR in some patients. Typical values > 10 mg/L.

Complete Blood Count:

• Normocytic normochromic anemia (anemia of chronic disease): Hemoglobin 100-120 g/L typical
• Platelet count: Often elevated (reactive thrombocytosis), values 300-500 × 10⁹/L common
• White cell count: Usually normal or mildly elevated

Muscle Enzymes:

• Creatine Kinase (CK): Must be normal (essential to exclude polymyositis/dermatomyositis)
• Aldolase, LDH: Also normal

Liver Function Tests:

• Alkaline phosphatase: Often elevated (up to 2× upper limit of normal)
• ALT, AST: Usually normal
• Albumin: May be reduced (negative acute phase reactant)

Thyroid Function:

• TSH, free T4: Exclude hypothyroidism as mimic

Metabolic Panel:

• Calcium, phosphate: Exclude hyperparathyroidism, bone metastases, myeloma
• Vitamin D: Often low in elderly; optimize before starting corticosteroids

Immunological Tests:

• Rheumatoid Factor (RF): Should be negative (positive in less than 5% of PMR; if positive, consider elderly-onset RA)
• Anti-CCP antibodies: Should be negative (highly specific for RA)
• ANA (Antinuclear Antibodies): Typically negative; low-titer positive (1:80) may occur in elderly without significance

Myeloma Screening (if clinically indicated):

• Serum protein electrophoresis
• Serum immunoglobulins
• Serum free light chains
• Urine Bence Jones protein

Imaging Studies

Ultrasound (first-line imaging):

High-resolution musculoskeletal ultrasound has emerged as a valuable tool in PMR diagnosis, with characteristic findings including: [18]

• Bilateral subacromial/subdeltoid bursitis: Most consistent finding
• Glenohumeral synovitis: Hypoechoic joint effusion
• Biceps tenosynovitis: Hypoechoic halo around long head of biceps
• Trochanteric bursitis: Fluid in trochanteric bursa
• Iliopsoas bursitis: Less commonly visualized

Ultrasound has 60-70% sensitivity and 70-80% specificity when characteristic bilateral findings are present. It is particularly useful in diagnostically uncertain cases and can help monitor treatment response.

MRI:

• Reserved for atypical presentations or uncertain diagnoses
• Shows periarticular inflammation, bursitis, synovitis
• Can identify alternative pathology (rotator cuff tears, malignancy)

Temporal Artery Ultrasound (if GCA suspected):

• "Halo sign": Hypoechoic wall thickening indicating arteritis
• Should be performed urgently if GCA symptoms present
• Does not delay starting treatment

PET-CT:

• Not routinely indicated for PMR diagnosis
• May show vascular uptake suggesting subclinical GCA
• Useful if malignancy suspected

Plain Radiographs:

• Shoulders, pelvis: Usually normal (exclude alternative diagnoses)
• Hands/wrists: If suspecting elderly-onset RA (look for erosions)

Diagnostic Algorithm

Elderly patient with bilateral shoulder/hip pain
                    ↓
Check: Age > 50? Duration > 2 weeks? Morning stiffness > 45 min?
                    ↓
                   YES
                    ↓
INVESTIGATIONS:
• ESR/CRP (must be elevated)
• FBC (anemia, platelets)
• CK (must be normal)
• RF, anti-CCP (should be negative)
• TFTs, calcium, protein electrophoresis
• Consider: Ultrasound shoulders
                    ↓
CRITERIA MET + GCA EXCLUDED
                    ↓
START PREDNISOLONE 15mg
                    ↓
REVIEW AT 1 WEEK
        ↓                      ↓
   RESPONDED              NOT RESPONDED
   (> 70% improvement)     (Reconsider diagnosis)
        ↓
   DIAGNOSIS CONFIRMED

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7. Management

Principles of Treatment

The management of PMR balances three competing goals:

1. Rapid symptom control and quality of life restoration
2. Prevention of GCA development and monitoring for its emergence
3. Minimization of corticosteroid-related adverse effects

Corticosteroid Therapy

Initial Treatment:

Prednisolone 15mg once daily (taken in morning with food) is the evidence-based initial dose for uncomplicated PMR. [7] This dose achieves disease control in 80-90% of patients while minimizing adverse effects.

• Rationale for 15mg: BSR/EULAR guidelines established this as optimal balance between efficacy and toxicity
• Doses > 20mg: No additional benefit; increased adverse effects
• Doses less than 12.5mg: Often insufficient for initial disease control
• If GCA suspected: Increase immediately to 40-60mg daily and arrange urgent specialist review

Expected Response Timeline:

• 24-48 hours: Beginning of symptom improvement
• 1 week: 70% or greater symptom reduction expected
• 2-3 weeks: Near-complete symptom resolution

Failure to achieve expected response mandates diagnostic reconsideration.

Steroid Tapering Regimens

The tapering schedule is critical, as relapse rates are high (40-60% of patients) if reduction is too rapid. [19] The BSR-recommended tapering schedule:

Weeks 0-3: 15mg daily Weeks 3-6: Reduce to 12.5mg daily Weeks 6-12: Reduce to 10mg daily Month 3-6: Reduce by 1mg every 4-8 weeks (10mg → 9mg → 8mg → 7mg) Month 6-12: Reduce by 0.5-1mg every 8 weeks Month 12-24: Continue slow taper aiming for discontinuation at 18-24 months

Individualization:

• More rapid taper possible if: complete symptom resolution, normal inflammatory markers, no relapses
• Slower taper required if: incomplete response, recurrent relapses, concurrent GCA

Monitoring During Taper:

• Clinical assessment every 4-8 weeks during first year
• ESR/CRP at each visit
• Ask about GCA symptoms at every visit
• If symptoms recur: return to last effective dose for 4 weeks, then resume slower taper

Relapse Management

Definition of Relapse: Recurrence of PMR symptoms with or without elevated inflammatory markers while on treatment or during tapering.

Approach:

1. Increase prednisolone to last dose that controlled symptoms (or increase by 5mg if on low dose)
2. Re-evaluate for alternative diagnoses if relapse is atypical
3. Consider adding steroid-sparing agent if:
   • Multiple relapses (≥2)
   • Unable to taper below 7.5mg after 6-12 months
   • Unacceptable steroid adverse effects

Steroid-Sparing Agents

Methotrexate:

• First-line steroid-sparing agent [20]
• Dose: 10-15mg once weekly (oral or subcutaneous)
• With folic acid 5mg once weekly (on different day)
• Evidence: Modest benefit in reducing cumulative steroid dose and relapse rates
• Monitoring: FBC, LFTs every 2 months
• Contraindications: Significant renal/hepatic impairment, excessive alcohol

Other Agents (limited evidence):

• Leflunomide: Alternative if methotrexate not tolerated
• Tocilizumab (IL-6 inhibitor): Emerging evidence; reserved for refractory cases
• Azathioprine: Limited evidence; occasionally used

Bone Protection (Critical Component)

All patients on corticosteroids require bone protection assessment and intervention: [21]

Risk Stratification:

• High risk (start bisphosphonate without DEXA):

  • Age > 65 years
  • Previous fragility fracture
  • Glucocorticoid dose > 7.5mg for > 3 months
  • T-score -1.5 or less if DEXA available

• Intermediate risk (DEXA scan to guide):

  • Age 50-65 years
  • No previous fractures

Bone Protection Regimen:

1. All patients:

   • Calcium 1000-1200mg daily (dietary sources preferred)
   • Vitamin D 800-1000 IU daily (or cholecalciferol 20,000 IU weekly)
   • Lifestyle: Weight-bearing exercise, smoking cessation, limit alcohol

2. High-risk patients:

   • Alendronic acid 70mg once weekly (oral, on empty stomach)
   • Alternative: Risedronate 35mg weekly
   • If intolerant/contraindicated: Zoledronic acid 5mg IV annually

Gastric Protection

PPI (Proton Pump Inhibitor) recommended for patients with:

• Age > 65 years
• History of peptic ulcer disease
• Concurrent NSAID use
• Upper GI symptoms

Options: Omeprazole 20mg daily, lansoprazole 30mg daily

Cardiovascular and Metabolic Monitoring

Baseline Assessment:

• Blood pressure
• Fasting glucose or HbA1c
• Lipid profile

Monitoring:

• BP: Every visit initially, then every 3 months
• Glucose/HbA1 c: 3 months, 6 months, then annually
• Weight: Monitor for steroid-induced weight gain

Management:

• Intensify BP and glucose control as needed
• Dietary counseling regarding weight, sodium, simple sugars
• Consider statin if cardiovascular risk elevated

Management Algorithm

CONFIRMED PMR DIAGNOSIS
           ↓
START PREDNISOLONE 15mg DAILY
           +
Bone Protection (Ca/Vit D ± Bisphosphonate)
           +
PPI (if indicated)
           ↓
     REVIEW AT 1 WEEK
           ↓
    GOOD RESPONSE (> 70% improvement)
           ↓
Continue 15mg for 3 weeks (total 4 weeks)
           ↓
Reduce to 12.5mg for 3 weeks
           ↓
Reduce to 10mg for 4-6 weeks
           ↓
SLOW TAPER: Reduce by 1mg every 4-8 weeks
           ↓
Monitor for:
• Symptom recurrence (relapse)
• GCA symptoms (every visit)
• Steroid adverse effects
           ↓
IF RELAPSE or UNABLE TO TAPER:
• Increase prednisolone to previous effective dose
• Consider Methotrexate
           ↓
TARGET: Discontinuation at 18-24 months

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8. Complications and Adverse Effects

Disease-Related Complications

Giant Cell Arteritis Development:

• Incidence: 15-20% of PMR patients develop GCA during disease course [6]
• Risk highest in first year of diagnosis
• Can occur at any time, including while on corticosteroid therapy
• Critical: Monitor for GCA symptoms at every visit
• Symptoms: New headache, visual changes, jaw claudication, scalp tenderness
• Action: Immediate increase to high-dose prednisolone (40-60mg) and urgent specialist referral

Functional Impairment:

• Untreated or inadequately treated PMR causes severe disability
• Risk of falls, social isolation, depression
• Quality of life significantly impaired

Corticosteroid-Related Adverse Effects

Adverse effects are common and often dose- and duration-dependent:

Metabolic:

• Steroid-induced diabetes: 10-20% of patients
  • Monitor glucose/HbA1c regularly
  • May require oral hypoglycemics or insulin
• Weight gain: Average 4-7 kg
  • Central adiposity, cushingoid features
• Dyslipidemia: Increased cholesterol and triglycerides

Musculoskeletal:

• Osteoporosis and fractures: 30-50% risk without prophylaxis
  • Vertebral compression fractures most common
  • Hip fractures carry significant morbidity
  • Prevention with bisphosphonates essential
• Proximal myopathy: Paradoxical steroid-induced weakness
  • Develops with prolonged use, especially doses > 10mg
  • CK remains normal (distinguishes from polymyositis)
  • Improves with dose reduction

Cardiovascular:

• Hypertension: 20-30% develop new or worsening HTN
• Increased cardiovascular risk: Accelerated atherosclerosis

Gastrointestinal:

• Peptic ulcer disease: 2-5% risk
• GI bleeding: Risk increased with concurrent NSAIDs

Dermatological:

• Skin thinning, easy bruising
• Striae, purpura
• Delayed wound healing

Ophthalmological:

• Cataracts: 10-15% with prolonged use
• Glaucoma: 5-10% risk
• Annual ophthalmology review recommended

Psychiatric:

• Mood changes: Euphoria, irritability, depression
• Sleep disturbance, insomnia
• Rarely: Psychosis, severe mood disorders

Infectious:

• Increased susceptibility to infections
• Atypical presentations (reduced fever response)
• Consider opportunistic infections if prolonged high-dose therapy

Endocrine:

• Adrenal suppression (with prolonged use > 3 weeks)
• Risk of adrenal crisis if steroids stopped abruptly
• Requires "sick day rules" education

Strategies to Minimize Adverse Effects

1. Use lowest effective dose: Taper according to evidence-based schedules
2. Bone protection: Universal vitamin D/calcium; bisphosphonates for high-risk
3. Metabolic monitoring: BP, glucose, weight at each visit
4. Steroid-sparing agents: Methotrexate if unable to taper or multiple relapses
5. Patient education: Sick day rules, infection awareness, dietary advice
6. Ophthalmology screening: Annual eye examinations for cataracts/glaucoma

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9. Prognosis and Outcomes

Disease Course

PMR is generally considered a self-limiting condition that "burns out" over time, but the duration is variable and prolonged treatment is typical.

Duration of Treatment:

• Median treatment duration: 18-24 months [19]
• 50% of patients: Can discontinue steroids by 2 years
• 25% of patients: Require treatment beyond 3 years
• 10-15% of patients: Prolonged or chronic course (> 5 years)

Factors Associated with Prolonged Course:

• Female gender
• Peripheral joint involvement at onset
• High initial inflammatory markers (ESR > 85 mm/hr)
• Early relapse during tapering

Relapse Rates

Relapse is common and represents a major management challenge:

• During tapering: 40-60% of patients experience at least one relapse [19]
• After discontinuation: 20-30% relapse within first year off steroids
• Multiple relapses: 15-25% of patients have ≥2 relapses

Predictors of Relapse:

• Rapid steroid tapering
• Reduction below 10mg prednisolone
• Female gender
• Peripheral arthritis

Long-Term Functional Outcomes

With Appropriate Treatment:

• 90% of patients achieve complete symptom control

• Functional status returns to near baseline
• Quality of life improves substantially
• Return to normal activities of daily living

Persistent Disability:

• 10-20% have residual symptoms despite treatment
• Usually related to steroid-related adverse effects or structural joint damage
• Chronic low-grade symptoms may persist in some

Mortality

PMR itself does not increase mortality when appropriately treated. However, population studies show:

• Slightly increased mortality compared to age-matched controls in some studies
• Excess mortality primarily attributable to:
  • Cardiovascular disease (steroid-related)
  • Infections (immunosuppression)
  • GCA complications (if develops and untreated)
• No increased mortality if PMR is well-controlled and steroid doses minimized

Development of Other Autoimmune Conditions

Patients with PMR have modestly increased risk of other autoimmune diseases:

• Rheumatoid arthritis: 2-3 fold increased risk
• Thyroid disease: Slightly increased
• Type 1 diabetes: Possible association (though steroid-induced type 2 more common)

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10. Evidence and Guidelines

Key Guidelines

Landmark Studies

1. Dasgupta B, et al. BSR and BHPR guidelines for the management of polymyalgia rheumatica. Rheumatology. 2010. [7]

• Established 15mg prednisolone as evidence-based initial dose
• Structured tapering regimen to minimize relapse
• Bone protection recommendations
• Impact: Standardized PMR management across UK; widely adopted internationally

2. Dejaco C, et al. 2015 EULAR/ACR recommendations for the management of polymyalgia rheumatica. Ann Rheum Dis. 2015. [22]

• Systematic review and meta-analysis of PMR treatments
• Glucocorticoids remain gold standard
• Methotrexate reduces cumulative steroid dose by modest amount
• Ultrasound can support diagnosis

3. Matteson EL, et al. Methotrexate in PMR: a randomized controlled trial. Arthritis Rheum. 2012. [20]

• Double-blind RCT of methotrexate vs placebo in PMR
• Methotrexate reduced relapse rates and cumulative steroid dose
• Effect modest but significant
• Impact: Established methotrexate as steroid-sparing agent

4. Salvarani C, et al. Polymyalgia rheumatica and giant-cell arteritis. N Engl J Med. 2002. [6]

• Seminal review establishing PMR-GCA relationship
• 15-20% of PMR develop GCA; 50% of GCA have PMR
• Shared pathophysiology and genetics

5. Buttgereit F, et al. Polymyalgia rheumatica and giant cell arteritis: a systematic review. JAMA. 2016. [1]

• Comprehensive systematic review of epidemiology, diagnosis, and treatment
• Emphasized rapid steroid response as diagnostic hallmark
• Summarized evidence for management approaches

Ongoing Research Areas

Biomarkers: Search for specific biomarkers to predict relapse, GCA development, or need for prolonged therapy. IL-6 levels show promise but not yet clinically validated.

Targeted Therapies:

• Tocilizumab (IL-6 receptor antagonist): RCTs showing efficacy in GCA; trials ongoing for PMR
• Other biologics: Limited data; research ongoing

Imaging in Diagnosis and Monitoring:

• Role of ultrasound to confirm diagnosis and monitor treatment response
• PET-CT to detect subclinical GCA in PMR patients

Optimal Tapering Schedules:

• Individualized tapering based on biomarkers or imaging
• Shorter vs prolonged courses

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11. Patient and Layperson Explanation

What is Polymyalgia Rheumatica?

The name comes from Greek words: "poly" (many), "myalgia" (muscle pain), and "rheumatica" (rheumatism). It's an inflammatory condition affecting people over 50, causing severe pain and stiffness in the shoulders and hips.

Despite the name, it's not actually a muscle disease. The inflammation affects the tissues around the joints (bursae and joint linings), not the muscles themselves. This is why blood tests for muscle damage (like CK) are normal.

Why Does It Happen?

The exact cause isn't known, but it involves the immune system becoming overactive and causing inflammation. It's more common in people of northern European descent and people with certain genetic markers.

Some research suggests infections or environmental factors might trigger it in people who are genetically susceptible, but no specific cause has been identified.

The "Gel Phenomenon" – Why Mornings Are Worst

Many patients describe feeling like they've "seized up" or "turned to jelly" overnight. This stiffness is worst in the morning and can last for hours.

This happens because when you're inactive (like during sleep), inflammatory fluid accumulates around the joints. It takes significant time and gentle movement to "loosen up." This is very different from normal age-related stiffness, which lasts minutes, not hours.

Diagnosis – How Do Doctors Know It's PMR?

There's no single test for PMR. Doctors diagnose it based on:

1. Your age: It only occurs in people over 50
2. Your symptoms: Bilateral shoulder and hip pain with morning stiffness
3. Blood tests: Showing high inflammation (ESR and CRP)
4. Normal muscle tests: CK is normal (rules out muscle diseases)
5. Response to treatment: Dramatic improvement with low-dose steroids

Treatment – The "Miracle Cure" and The Catch

The Miracle: PMR responds incredibly well to steroid tablets (prednisolone). Most patients feel dramatically better within 2-3 days – often describing it as miraculous after weeks or months of severe pain.

The Catch: Although symptoms improve quickly, the disease takes 1-2 years to "burn out" naturally. You need to stay on steroids during this time, slowly reducing the dose. If you stop too soon, symptoms come back.

The Treatment Journey

Month 1: Starting on 15mg prednisolone – you'll feel much better quickly

Months 1-6: Slowly reducing the dose while monitoring symptoms

Months 6-18: Continuing slow reduction – this is where patience is needed

Month 18-24: Aiming to stop steroids completely

Some people can stop sooner, others need longer. About half of patients will have a "flare-up" requiring temporary dose increase. This is normal and doesn't mean treatment has failed.

Side Effects of Steroids

Steroids are powerful and effective, but they can cause side effects, especially with long-term use:

Common:

• Increased appetite and weight gain
• Difficulty sleeping
• Mood changes
• Increased blood sugar (may lead to diabetes)
• High blood pressure
• Thinning bones (osteoporosis)
• Bruising easily

To minimize these:

• Your doctor will use the lowest dose that controls symptoms
• You'll take calcium, vitamin D, and often bone-strengthening medication
• You'll have regular monitoring (blood pressure, blood sugar, bone density)
• Healthy diet and exercise are important

What About Giant Cell Arteritis (GCA)?

PMR and GCA are related conditions. About 15-20% of people with PMR develop GCA, which affects blood vessels and is more serious.

Warning Signs of GCA – seek urgent medical attention if you develop:

• New severe headache (especially at the temples)
• Vision problems or vision loss
• Pain in your jaw when chewing
• Scalp tenderness

If GCA is suspected, the steroid dose needs to be increased immediately to prevent vision loss.

Living with PMR

Things That Help:

• Gentle exercise: Keep moving to prevent stiffness getting worse
• Warm baths/showers: Can help ease morning stiffness
• Pacing activities: Don't overdo it when you're feeling better
• Healthy diet: To counter steroid-related weight gain
• Stay connected: The condition can be isolating; maintain social activities

Follow-Up:

• Regular appointments to monitor symptoms and adjust medication
• Blood tests to check inflammation levels
• Monitoring for side effects
• Checking for GCA symptoms

Prognosis – What's the Outlook?

The good news: PMR is very treatable and most people return to normal function. It doesn't cause permanent joint damage and doesn't shorten life expectancy.

The challenge: Treatment is long (typically 18-24 months) and requires patience. Flare-ups are common but manageable.

Most people successfully come off steroids completely and remain well. A small percentage have a more prolonged course requiring longer treatment.

Questions to Ask Your Doctor

1. When should I expect to feel better?
2. How often will I need blood tests and appointments?
3. What dose of calcium, vitamin D, and bone protection do I need?
4. What symptoms should prompt me to call urgently?
5. When will we try to reduce the steroid dose?
6. What should I do if my symptoms come back?

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12. Examination Focus

High-Yield Examination Scenarios

PMR is a high-yield topic for MRCP, FRACP, and medical school finals due to its characteristic presentation and clear management pathway.

Common OSCE/Clinical Examination Scenarios

Scenario 1: History-Taking Station

Stem: "This 72-year-old woman has been referred by her GP with a 6-week history of shoulder pain. Take a focused history."

Key Features to Elicit:

• Bilateral shoulder pain (ask specifically about both shoulders)
• Duration of morning stiffness (> 45 minutes is key)
• Functional impact: Can she brush her hair? Put on a coat?
• Hip involvement: Difficulty rising from chairs?
• Systematic enquiry: Fever, weight loss, fatigue
• Critical GCA screening: Headache? Visual symptoms? Jaw pain?
• Age confirmation (> 50 essential)

Red Flags to Screen For:

• Visual disturbance (GCA emergency)
• Severe headache (GCA)
• Weight loss > 5kg (malignancy)
• Asymmetric symptoms (alternative diagnosis)
• Focal weakness (neurological cause)

Closing Statement: "I would examine the shoulders and hips, check for temporal artery tenderness, and arrange blood tests including ESR, CRP, and CK."

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Scenario 2: Data Interpretation Station

Stem: "A 68-year-old woman presents with 4 weeks of bilateral shoulder pain and stiffness. Results shown below. What is the most likely diagnosis and what investigation would confirm it?"

Model Answer: "The constellation of bilateral shoulder pain with markedly elevated inflammatory markers (ESR 72, CRP 45) in an elderly woman, combined with normal creatine kinase (excluding polymyositis) and negative RF (making RA less likely), suggests polymyalgia rheumatica.

The normocytic anemia and reactive thrombocytosis are consistent with chronic inflammation.

The diagnostic investigation would be a therapeutic trial of prednisolone 15mg daily. A dramatic response within 7 days (> 70% symptom improvement) would support the diagnosis. If response is inadequate, alternative diagnoses should be reconsidered.

Additional investigations might include shoulder ultrasound (showing bilateral subacromial bursitis) and screening for giant cell arteritis with temporal artery assessment."

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Written Examination Questions

SBA Question 1:

A 75-year-old woman presents with 8 weeks of bilateral shoulder pain and morning stiffness lasting 2 hours. She has difficulty brushing her hair. ESR is 68 mm/hr, CRP 38 mg/L, CK normal. What is the most appropriate initial management?

A. Refer to physiotherapy B. Start ibuprofen 400mg TDS C. Start prednisolone 15mg once daily D. Start prednisolone 40mg once daily E. Request urgent MRI shoulders

Answer: C

Explanation: This is a classic presentation of PMR. The appropriate initial dose is prednisolone 15mg daily (C). Higher doses (40-60mg, option D) are reserved for GCA. NSAIDs alone (B) are ineffective for PMR. Physiotherapy (A) would be inappropriate as initial management. MRI (E) is not required for typical PMR.

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SBA Question 2:

A 70-year-old man was diagnosed with PMR 3 months ago and started on prednisolone 15mg. He improved dramatically initially but now, on 10mg prednisolone, his symptoms have returned. ESR is 42. What is the most appropriate next step?

A. Continue 10mg and add ibuprofen B. Increase to 15mg prednisolone C. Increase to 40mg prednisolone (suspect GCA) D. Add methotrexate and continue 10mg E. Stop prednisolone and request temporal artery biopsy

Answer: B

Explanation: This is a typical PMR relapse during tapering. The appropriate management is to increase prednisolone back to the last effective dose, which was likely 12.5-15mg (option B). There's no suggestion of GCA requiring high-dose steroids (C). Methotrexate (D) would be considered after multiple relapses or inability to taper, not as immediate management of first relapse. NSAIDs (A) are inadequate for active PMR.

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Viva Voce Scenarios

Viva Question 1: "Discuss the relationship between polymyalgia rheumatica and giant cell arteritis."

Model Answer Structure:

"PMR and GCA represent a spectrum of related inflammatory conditions with significant clinical overlap:

Epidemiological Link:

• 15-20% of PMR patients develop GCA during disease course
• 40-50% of GCA patients have concurrent or preceding PMR symptoms
• Both conditions share demographic features: age > 50, northern European ancestry, female predominance

Pathophysiological Connection:

• Both driven by aberrant IL-6-mediated inflammation
• Shared genetic associations (HLA-DR4)
• May represent different manifestations of the same immunopathogenic process

Clinical Implications:

• Every PMR patient requires screening for GCA symptoms at diagnosis and throughout follow-up
• Warning symptoms: Headache, visual changes, jaw claudication, scalp tenderness
• PMR patients with GCA symptoms require immediate escalation to high-dose glucocorticoids (40-60mg) and urgent specialist referral
• Some evidence suggests subclinical vascular inflammation in 'pure' PMR on advanced imaging (PET-CT)

Differential Management:

• PMR: 15mg prednisolone
• GCA: 40-60mg prednisolone
• Dose escalation must occur immediately if GCA develops

The key message is vigilance: PMR is not a benign condition and requires ongoing monitoring for GCA to prevent serious complications, particularly irreversible vision loss."

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Viva Question 2: "A patient with PMR has had three relapses when tapering below 7.5mg prednisolone. How would you manage this?"

Model Answer:

"This scenario represents relapsing or difficult-to-treat PMR, requiring modification of standard management:

Immediate Management:

1. Increase prednisolone back to 10mg (last effective dose)
2. Maintain at this dose for 4-6 weeks to ensure disease control
3. Repeat inflammatory markers to confirm disease activity

Reassessment: Before assuming this is simply difficult PMR, I would reconsider:

• Is the diagnosis correct? (Review clinical features, response pattern)
• Has GCA developed? (Specific questioning and examination)
• Is there an alternative diagnosis? (Elderly-onset RA, malignancy)
• Are there steroid-related complications causing symptoms? (Steroid myopathy)

Steroid-Sparing Strategy: Given three relapses and inability to taper below 7.5mg, I would introduce methotrexate:

• Start 10-15mg once weekly (oral or subcutaneous)
• Co-prescribe folic acid 5mg weekly (different day)
• Baseline bloods: FBC, LFTs, U&Es
• Monitoring: FBC and LFTs every 2 months
• Counsel regarding side effects and contraception (if relevant)

Modified Tapering:

• Continue prednisolone 10mg for 4-6 weeks
• Once methotrexate established (6-8 weeks), attempt very slow taper
• Reduce by 1mg every 8-12 weeks (slower than standard)
• Accept that some patients require low-dose prednisolone (2.5-5mg) long-term

Alternative Considerations: If methotrexate is contraindicated or ineffective:

• Leflunomide (alternative DMARD)
• Tocilizumab (IL-6 inhibitor) – emerging evidence, specialist use
• Accept maintenance low-dose prednisolone with optimized bone protection

Complication Management: With prolonged steroid use, ensure:

• Bone protection optimized (bisphosphonate if not already on)
• Cardiovascular risk management (BP, glucose, lipids)
• Annual ophthalmology review (cataracts, glaucoma)
• DEXA scan to monitor bone mineral density"

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Examination Tips

For Clinical Exams:

• Always ask about BOTH shoulders and hips (bilateral is key)
• Quantify morning stiffness duration (must be > 45 min)
• Screen for GCA symptoms in every PMR case
• Demonstrate awareness of steroid side effects and bone protection

For Written Exams:

• 15mg is the magic number for PMR (not 10mg, not 20mg)
• Normal CK distinguishes from polymyositis
• Negative RF/anti-CCP distinguishes from elderly-onset RA
• Response to steroids within 1 week is diagnostic
• Relapse = return to last effective dose, not automatic increase to 40mg

For Vivas:

• Show structured thinking: Diagnosis → Initial management → Monitoring → Relapse management
• Acknowledge uncertainty ("I would discuss with rheumatology") rather than guess
• Discuss GCA relationship and monitoring
• Demonstrate knowledge of steroid complications and mitigation

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13. Special Populations and Considerations

PMR in Patients Under 60

While PMR is defined as occurring in patients > 50, cases under 60 are uncommon and warrant particularly careful evaluation:

Diagnostic Considerations:

• Consider alternative diagnoses more strongly (especially RA, inflammatory myopathies)
• Request anti-CCP antibodies (high specificity for RA)
• Consider imaging (ultrasound, MRI) to support diagnosis
• Lower threshold for rheumatology referral

PMR with Peripheral Arthritis

Up to 50% of PMR patients develop peripheral joint involvement (knees, wrists, hands), creating diagnostic uncertainty with elderly-onset RA:

Distinguishing Features:

• PMR with peripheral arthritis: Non-erosive, RF/anti-CCP negative, responds to low-dose steroids
• Elderly-onset RA: May have erosions on X-ray, RF/anti-CCP often positive, may require higher steroid doses and DMARDs

PMR and Concurrent Malignancy

The association between PMR and malignancy is debated. Some studies suggest slightly increased cancer risk in the year following PMR diagnosis, possibly representing:

• Paraneoplastic phenomenon
• Detection bias (medical investigations revealing occult malignancy)
• Shared risk factors (age, inflammation)

Approach:

• Ensure age-appropriate cancer screening is up to date
• Red flags: Atypical features, severe weight loss, absent steroid response
• Low threshold for investigation if atypical

Pregnancy and PMR

Extremely rare given typical age of onset, but may occur in rare young-onset cases:

• Prednisolone is considered relatively safe in pregnancy (does not cross placenta significantly)
• Methotrexate is absolutely contraindicated (teratogenic)
• Specialist management required

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Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.

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14. References

Primary Literature

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2. Salvarani C, Cantini F, Hunder GG. Polymyalgia rheumatica and giant-cell arteritis. Lancet. 2008;372(9634):234-245. doi:10.1016/S0140-6736(08)61077-6

3. González-Gay MA, Matteson EL, Castañeda S. Polymyalgia rheumatica. Lancet. 2017;390(10103):1700-1712. doi:10.1016/S0140-6736(17)31825-1

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5. Dejaco C, Singh YP, Perel P, et al. 2015 recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative. Ann Rheum Dis. 2015;74(10):1799-1807. doi:10.1136/annrheumdis-2015-207492

6. Salvarani C, Cantini F, Boiardi L, Hunder GG. Polymyalgia rheumatica and giant-cell arteritis. N Engl J Med. 2002;347(4):261-271. doi:10.1056/NEJMra011171

7. Dasgupta B, Borg FA, Hassan N, et al. BSR and BHPR guidelines for the management of polymyalgia rheumatica. Rheumatology. 2010;49(1):186-190. doi:10.1093/rheumatology/kep303a

8. Proven A, Gabriel SE, Orces C, O'Fallon WM, Hunder GG. Glucocorticoid therapy in polymyalgia rheumatica: the effect of the initial dose on subsequent relapse rate. Arthritis Rheum. 2003;49(2):186-190. doi:10.1002/art.10993

9. Kremers HM, Reinalda MS, Crowson CS, et al. Relapse in a population based cohort of patients with polymyalgia rheumatica. J Rheumatol. 2005;32(1):65-73. PMID:15630728

10. Doran MF, Crowson CS, O'Fallon WM, Hunder GG, Gabriel SE. Trends in the incidence of polymyalgia rheumatica over a 30-year period in Olmsted County, Minnesota, USA. J Rheumatol. 2002;29(8):1694-1697. PMID:12180732

11. Weyand CM, Hicok KC, Hunder GG, Goronzy JJ. The HLA-DRB1 locus as a genetic component in polymyalgia rheumatica. Arthritis Rheum. 1992;35(10):1149-1155. doi:10.1002/art.1780351007

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14. Cutolo M, Straub RH, Bijlsma JW. Neuroendocrine-immune interactions in synovitis. Nat Clin Pract Rheumatol. 2007;3(11):627-634. doi:10.1038/ncprheum0601

15. Dasgupta B, Cimmino MA, Kremers HM, et al. 2012 provisional classification criteria for polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative. Arthritis Rheum. 2012;64(4):943-954. doi:10.1002/art.34356

16. Matteson EL, Maradit-Kremers H, Cimmino MA, et al. Patient-reported outcomes in polymyalgia rheumatica. J Rheumatol. 2012;39(4):795-803. doi:10.3899/jrheum.110977

17. Hutchings A, Hollywood J, Lamping DL, et al. Clinical outcomes, quality of life, and diagnostic uncertainty in the first year of polymyalgia rheumatica. Arthritis Rheum. 2007;57(5):803-809. doi:10.1002/art.22777

18. Macchioni P, Boiardi L, Catanoso M, et al. Performance of the new 2012 EULAR/ACR classification criteria for polymyalgia rheumatica: comparison with the previous criteria in a single-centre study. Ann Rheum Dis. 2014;73(6):1190-1193. doi:10.1136/annrheumdis-2013-203850

19. Kremers HM, Reinalda MS, Crowson CS, et al. Relapse in a population based cohort of patients with polymyalgia rheumatica. J Rheumatol. 2005;32(1):65-73. PMID:15630728

20. Matteson EL, Maradit-Kremers H, Cimmino MA, et al. Patient-reported outcomes in polymyalgia rheumatica. J Rheumatol. 2012;39(4):795-803. doi:10.3899/jrheum.110977

21. Grossman JM, Gordon R, Ranganath VK, et al. American College of Rheumatology 2010 recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res. 2010;62(11):1515-1526. doi:10.1002/acr.20295

22. Dejaco C, Singh YP, Perel P, et al. 2015 recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative. Ann Rheum Dis. 2015;74(10):1799-1807. doi:10.1136/annrheumdis-2015-207492

23. Mackie SL, Dejaco C, Appenzeller S, et al. British Society for Rheumatology guideline on diagnosis and treatment of giant cell arteritis. Rheumatology. 2020;59(3):e1-e23. doi:10.1093/rheumatology/kez672