Ophthalmology – Polymyalgia Rheumatica

Basics

Description

Polymyalgia rheumatica (PMR) is an inflammatory disorder of adults aged ≥50 years characterized by:

• Bilateral shoulder pain
• Marked morning stiffness
• Hip-girdle pain or stiffness
• Elevated inflammatory markers in most patients
• Rapid symptomatic response to glucocorticoids

Despite the name, PMR is primarily a disorder of:

• Bursae
• Synovial structures
• Periarticular tissues

rather than a primary inflammatory myopathy.

The most important ophthalmic association is:

Giant cell arteritis (GCA)

because GCA can cause sudden, irreversible blindness.

PMR and Giant Cell Arteritis

PMR and GCA are closely related inflammatory diseases occurring in the same age group.

Approximately:

• 10–20% of patients with PMR develop clinically apparent GCA
• Roughly 40–60% of patients with GCA have PMR-type symptoms

Therefore every patient with PMR should be questioned about symptoms of GCA.

Ophthalmic Importance

The key clinical priority is identifying GCA before permanent visual loss occurs.

Ask specifically about:

• New headache
• Scalp tenderness
• Jaw claudication
• Transient monocular visual loss
• Diplopia
• Sudden visual loss
• Constitutional symptoms

Any of these should prompt:

Urgent evaluation for GCA

Epidemiology

PMR occurs almost exclusively in people:

Older than 50 years

Incidence rises substantially with age.

It is more common in:

• Women
• People of Northern European ancestry

but can occur in all ethnic groups.

Risk Factors

Established associations include:

• Age >50 years
• Female sex
• Northern European ancestry

Genetic susceptibility has been associated with:

• HLA-DRB1
• Other immune-regulatory loci

There is no simple Mendelian inheritance pattern.

Pathophysiology

PMR is characterized by systemic inflammation involving:

• Subacromial-subdeltoid bursae
• Trochanteric bursae
• Glenohumeral synovium
• Hip synovium
• Periarticular structures

A major inflammatory mediator is:

Interleukin-6 (IL-6)

which helps explain the effectiveness of IL-6 pathway inhibition in selected patients.

Etiology

The precise cause is unknown.

Likely contributors include:

• Genetic susceptibility
• Immune dysregulation
• Environmental triggers

No single infectious agent has been established as the cause.

Clinical Presentation

The classic patient is:

An adult over 50 with new bilateral shoulder aching and prolonged morning stiffness

Symptoms often develop:

• Over days to weeks
• Occasionally quite abruptly

Pain Distribution

Typical areas include:

• Shoulders
• Neck
• Upper arms
• Hips
• Buttocks
• Thighs

Pain is usually:

• Bilateral
• Symmetric
• Worse after inactivity

Morning Stiffness

A characteristic feature is:

Morning stiffness lasting >45 minutes

Patients may report difficulty:

• Getting out of bed
• Dressing
• Raising the arms
• Combing hair
• Rising from a chair

Muscle Strength

Despite severe subjective weakness:

True muscle strength is usually normal

when pain is overcome.

True objective weakness should prompt consideration of:

• Inflammatory myopathy
• Neuromuscular disease
• Neurologic disorders

Constitutional Symptoms

Patients may also have:

• Fatigue
• Malaise
• Low-grade fever
• Anorexia
• Weight loss
• Depression

Prominent constitutional symptoms should also raise consideration of:

• GCA
• Infection
• Malignancy

Peripheral Manifestations

Some patients develop:

• Wrist or knee synovitis
• Distal extremity edema
• Carpal tunnel syndrome

A syndrome of remitting seronegative symmetrical synovitis with pitting edema may overlap clinically.

Diagnosis

PMR remains a:

Clinical diagnosis supported by inflammatory markers and exclusion of mimics

There is no single confirmatory test.

Typical Diagnostic Features

Features supporting PMR include:

• Age ≥50 years
• Bilateral shoulder pain
• Morning stiffness >45 minutes
• Hip pain or restricted movement
• Elevated ESR and/or CRP
• Negative RF and anti-CCP
• Rapid improvement with low-to-moderate-dose glucocorticoid

Inflammatory Markers

Typical laboratory abnormalities include:

• Elevated CRP
• Elevated ESR
• Thrombocytosis
• Mild normocytic anemia

ESR may exceed:

• 40 mm/h
• Occasionally >100 mm/h

However:

A normal ESR does not exclude PMR

and a small minority can have relatively normal inflammatory markers.

CRP

CRP is often especially useful because it:

• Responds rapidly to inflammatory activity
• Is less affected by age or anemia than ESR

Both ESR and CRP should be interpreted with the clinical picture.

Creatine Kinase

CK is generally:

Normal

This helps distinguish PMR from:

• Polymyositis
• Dermatomyositis
• Some drug-induced myopathies

Rheumatoid Factor and Anti-CCP

RF and anti-CCP are usually:

Negative

Positive anti-CCP, especially with peripheral synovitis, raises concern for:

Elderly-onset rheumatoid arthritis

rather than pure PMR.

Ultrasound

Musculoskeletal ultrasound may support the diagnosis.

Typical findings include:

• Subacromial-subdeltoid bursitis
• Biceps tenosynovitis
• Glenohumeral synovitis
• Trochanteric bursitis
• Hip synovitis

Ultrasound is particularly helpful when:

• Diagnosis is uncertain
• Inflammatory markers are equivocal
• RA is in the differential

PET/CT

FDG-PET/CT is not routinely required for uncomplicated PMR.

It may be useful when evaluating:

• Large-vessel GCA
• Atypical systemic inflammation
• Persistent unexplained inflammatory markers

Giant Cell Arteritis – Symptoms

Ask every PMR patient about:

• New headache
• Temporal or occipital scalp tenderness
• Jaw claudication
• Tongue pain or claudication
• Transient visual obscurations
• Amaurosis fugax
• Diplopia
• Sudden vision loss

Jaw claudication is particularly suggestive of GCA.

Giant Cell Arteritis – Ocular Manifestations

Ocular ischemia may produce:

• Arteritic anterior ischemic optic neuropathy (AAION)
• Central retinal artery occlusion
• Cilioretinal artery occlusion
• Ocular ischemic syndrome
• Diplopia from ischemic cranial neuropathy
• Rare posterior ischemic optic neuropathy
• Choroidal ischemia

The most common cause of permanent visual loss is:

AAION

AAION Appearance

Typical optic disc findings include:

• Profound visual loss
• RAPD if unilateral/asymmetric
• Chalky-white or pale disc edema
• Occasionally peripapillary hemorrhages

This contrasts with the more hyperemic disc often seen in NAION.

Visual Symptoms Are an Emergency

In a patient over 50 with suspected GCA:

Transient or permanent visual symptoms require immediate treatment.

Do not wait for:

• Temporal artery biopsy
• Ultrasound
• Imaging results

before starting glucocorticoids when clinical suspicion is high.

GCA Laboratory Testing

Order urgently:

• ESR
• CRP
• CBC with platelet count

Possible findings include:

• High ESR
• High CRP
• Thrombocytosis
• Normocytic anemia

Normal inflammatory markers reduce the likelihood but do not absolutely exclude GCA.

Temporal Artery Examination

Look for:

• Tenderness
• Nodularity
• Reduced pulsation
• Thickened artery

However:

A normal temporal artery examination does not exclude GCA.

Temporal Artery Ultrasound

High-resolution vascular ultrasound is increasingly important.

The classic finding is:

Halo sign

representing circumferential arterial wall edema.

Ultrasound can assess:

• Temporal arteries
• Axillary arteries in selected protocols

In experienced centers it may be the preferred initial diagnostic test.

Temporal Artery Biopsy

Temporal artery biopsy remains useful when:

• Diagnosis remains uncertain
• Imaging is unavailable or equivocal
• Histologic confirmation is desired

Classic histology may show:

• Granulomatous arteritis
• Multinucleated giant cells
• Fragmentation of internal elastic lamina

Giant cells are not required for a positive diagnosis.

Biopsy Timing

Treatment should never be delayed for biopsy.

Biopsy is ideally performed promptly, but diagnostic histologic abnormalities may persist for:

At least 1–2 weeks and often longer after starting glucocorticoids.

Large-Vessel GCA

GCA may involve:

• Aorta
• Subclavian arteries
• Axillary arteries
• Other large vessels

Large-vessel disease may occur without classic temporal artery symptoms.

Imaging options include:

• Ultrasound
• CTA
• MRA
• FDG-PET/CT

depending on presentation.

Differential Diagnosis of PMR

Important mimics include:

• Elderly-onset rheumatoid arthritis
• Fibromyalgia
• Polymyositis
• Dermatomyositis
• Hypothyroidism
• Rotator cuff disease
• Osteoarthritis
• Cervical spondylosis
• Statin-associated myopathy
• Infection
• Endocarditis
• Malignancy
• Multiple myeloma

PMR vs Polymyositis

PMR

• Pain and stiffness
• True strength usually preserved
• CK normal

Polymyositis

• True proximal muscle weakness
• CK elevated
• Less prominent shoulder-girdle stiffness

PMR vs Rheumatoid Arthritis

RA is more likely with:

• Persistent peripheral joint synovitis
• MCP/PIP involvement
• Positive anti-CCP
• Erosive changes

PMR more strongly favors:

• Shoulder/hip girdle stiffness
• Bursitis
• Dramatic response to low-dose prednisone

Treatment

First-Line – Glucocorticoids

Initial treatment for uncomplicated PMR is typically:

Prednisone approximately 12.5–25 mg/day

The exact dose depends on:

• Body size
• Symptom severity
• Relapse risk
• Comorbidities

Most patients improve dramatically within:

Several days

Response to Prednisone

A strong clinical response supports the diagnosis.

However:

Steroid response is not specific for PMR

and should not be used as the sole diagnostic test.

Failure to improve substantially should prompt reconsideration of the diagnosis.

Steroid Taper

Once symptoms and inflammatory markers improve:

• Gradually reduce prednisone
• Avoid rapid tapering

A common approach is to taper toward:

10 mg/day over several weeks

then reduce more slowly, often by approximately:

1 mg every 1–2 months

depending on relapse and tolerance.

There is no single taper suitable for every patient.

Duration of Treatment

Older teaching suggested a short self-limited course.

In practice:

Many patients require glucocorticoids for 1–2 years or longer.

Relapses are common.

Relapse

Relapse usually presents with recurrence of:

• Shoulder/hip stiffness
• Pain
• Constitutional symptoms

often accompanied by increased:

• CRP
• ESR

Treatment generally involves:

• Returning temporarily to the previous effective steroid dose
• Then tapering more slowly

Methotrexate

Methotrexate may be added when there is:

• Recurrent relapse
• High glucocorticoid requirement
• High risk of steroid toxicity

Typical weekly doses are approximately:

10–15 mg or more depending on regimen

with:

Folic acid supplementation

IL-6 Inhibition

IL-6 blockade is an increasingly important steroid-sparing strategy.

Sarilumab is approved for adults with PMR who:

• Have inadequate response to corticosteroids
• Cannot adequately tolerate a corticosteroid taper

It can reduce glucocorticoid exposure in selected patients.

Tocilizumab

Tocilizumab has strong evidence and regulatory approval for:

Giant cell arteritis

and may also have efficacy in PMR, although its routine role in isolated PMR depends on local practice and regulatory approval.

Giant Cell Arteritis Treatment

Suspected GCA requires:

Immediate high-dose systemic glucocorticoids

Treatment should begin before diagnostic confirmation if clinical suspicion is substantial.

GCA Without Visual Loss

A typical regimen is approximately:

Prednisone 40–60 mg/day

or about:

1 mg/kg/day up to approximately 60 mg

followed by a prolonged taper.

GCA With Visual Loss or Amaurosis Fugax

When there is:

• Acute visual loss
• Amaurosis fugax
• Strongly threatened vision

many specialists use:

IV methylprednisolone 500–1000 mg/day for 3 days

followed by high-dose oral glucocorticoids.

The goal is primarily to:

Protect the fellow eye

because established ischemic visual loss is often irreversible.

Tocilizumab in GCA

Tocilizumab is an important steroid-sparing treatment for GCA.

It can:

• Reduce relapse
• Reduce cumulative glucocorticoid exposure

Management is coordinated with rheumatology.

Glucocorticoid Toxicity Prevention

Long-term steroid therapy requires monitoring for:

• Hypertension
• Diabetes
• Osteoporosis
• Infection
• Cataract
• Glaucoma
• Weight gain
• Adrenal suppression

Bone Protection

Assess:

• Calcium intake
• Vitamin D
• Fracture risk
• Bone density

Bisphosphonate therapy may be indicated depending on:

• Steroid dose
• Duration
• Baseline fracture risk

Ophthalmic Steroid Monitoring

Patients on prolonged systemic corticosteroids may develop:

• Steroid-induced ocular hypertension/glaucoma
• Posterior subcapsular cataract

Periodic ophthalmic evaluation is appropriate, especially with prolonged treatment.

Follow-Up

Monitor:

• Clinical symptoms
• ESR/CRP when clinically useful
• Glucocorticoid adverse effects
• Signs of relapse
• New symptoms of GCA

Inflammatory markers should support, not replace:

Clinical assessment

Important Monitoring Point With IL-6 Inhibitors

IL-6 inhibitors can markedly suppress:

• CRP
• ESR

Therefore these laboratory markers become less reliable indicators of active disease during therapy.

Clinical evaluation becomes especially important.

Prognosis

PMR generally has a:

Good overall prognosis

but the course is often longer than older descriptions suggested.

Many patients experience:

• Relapses
• Prolonged steroid requirements

The major serious concern is:

Development of GCA

Visual Prognosis in GCA

Once profound visual loss from arteritic ischemic optic neuropathy occurs:

Recovery is usually limited

Therefore treatment is aimed at:

• Preventing additional visual loss
• Protecting the fellow eye
• Preventing systemic vascular complications

Complications

Complications of PMR itself include:

• Recurrent symptoms
• Functional disability
• Development of GCA

Complications of treatment include:

• Osteoporosis
• Diabetes
• Hypertension
• Infection
• Cataract
• Glaucoma
• Adrenal suppression

GCA complications include:

• Permanent blindness
• Stroke
• Aortic aneurysm
• Aortic dissection

Ophthalmology Pearls

• PMR causes bilateral shoulder/hip girdle pain and prolonged morning stiffness in patients aged ≥50 years; true muscle weakness is usually absent.
• ESR and CRP are usually elevated, but normal inflammatory markers do not completely exclude PMR or GCA.
• CK is generally normal, helping distinguish PMR from inflammatory myopathy.
• The most important ophthalmic association is giant cell arteritis.
• Every PMR patient should be asked about new headache, scalp tenderness, jaw claudication, diplopia, amaurosis fugax, and visual loss.
• Jaw claudication and transient visual loss are major red flags for GCA.
• The classic ocular emergency is arteritic anterior ischemic optic neuropathy with profound vision loss and chalky-pale disc edema.
• If GCA is strongly suspected, start glucocorticoids immediately—do not wait for temporal artery biopsy or imaging.
• Temporal artery ultrasound showing a halo sign is increasingly important; biopsy remains useful when diagnosis is uncertain.
• Uncomplicated PMR usually responds to prednisone about 12.5–25 mg/day, whereas GCA requires much higher doses.
• Visual symptoms from GCA often prompt IV methylprednisolone followed by high-dose oral therapy.
• Tocilizumab is an established steroid-sparing treatment for GCA; sarilumab is an option for relapsing or glucocorticoid-refractory PMR.
• PMR commonly requires treatment for 1–2 years or longer, and relapse is frequent.
• The ophthalmologist’s critical role is recognizing GCA early enough to prevent irreversible bilateral visual loss.