Giant Cell Arteritis and Polymyalgia Rheumatica

Definitions

Epidemiology

Pathogenesis

Clinical manifestations

Visual Manifestations

Clinical Manifestations

Diagnosis

Treatment

Prognosis

Definitions

· Vasculitis of large-medium vessels – mostly branches of proximal aorta

· PMR

Epidemiology

· Most common primary vasculitis in older people

· Very rare in patients <50yrs old

· Avg age of onset ~70years

· Incidence:

o 2.3/100,000 in pts in 60’s

o 50/100,000 in pts in 90’s

· Mostly white, northern Europeans (but can occur in many other ethnic groups)

· F>M

· Some familial aggregation

· Association with HLA-DRB1*04

o Increased incidence, severity and risk of visual complications

· PMR

o Occurs in same patient population

o 40-50% of patients have PMR

Pathogenesis

· Dendritic cells in vascular walls

· Acctivated by TLR-ligand

· Release chemokines

· Hyperplasia and vessel occlusion

· Inflammatory infiltrate of lymphocytes, macrophages and multinucleated giant cells.

o CD4+ T cells predominate and are central to pathogenesis

Clinical manifestations

· Accounts for ~15% of PUO in patients >65 years

· Occult malignancy can mimic symptoms

· 25% can present with only visual symptoms

Pain

· Headache

o Most common symptom (50-70% at onset, 90% over course of disease)

o Begins early

o Severe – usu localised to the temples

o May be occipital

o May be precipitated by brushing hair

o Can subside even though disease still active

· Scalp tenderness or pain (~15%)

· Jaw pain

· Jaw claudication

o Relatively specific but not sensitive

· Tongue claudication

Systemic symptoms

· Weight loss (50%)

· Malaise (35%)

· Anorexia

· Fever

Symptoms of PMR

· Occur in ~40%

Neurological manifestations

· CNS ischaemia

o Vertebral or basilar artery stenosis

· Peripheral neuropathy

Other arterial involvement

· Coronaries (MI, AR, CCF)

· Aortic arch

o Limb claudication/ischaemia

o Dissection

· Signs

o Arteries can be thickened, tneder and nodular with reduced or absent pulsation

Visual Manifestations

· Occur in 30-40%

· The only symptom in 25%

· Visual disturbances

o 35-50%

o Visual loss 6-10%

o Usually sudden, painless and permanent

Types

· Ischaemic optic neuropathy

o AION

o PION

· Cillio-retinal artery occlusion

· Choroidal ischaemia

· Ocular ischaemia

· Cerebral ischaemia

· CRAO – 1-2%

Diplopia ~15%

· Ischaemia to

o Muscles

o Nerves

o Brainstem

Diagnosis

Criteria (ACR 1990)

· Age >50

· Headache

· Tenderness or reduced pulsation of TA

· ESR >50

· Histological changes on biopsy

· Requires 3/5 criteria

Inflammatory markers

· ESR may be normal in 8-25% of patients

· Combing ESR and CRP more sensitive as both low in only 1.2%

· CRP may be more sensitive for diagnosis and detection of relapses

· WCC usually normal

· Use ESR normal range:

o Men Age/2

o Women (Age+10)/2

Other laboratory tests

· Anaemia can occur

· Non-specific increase in globulins

· Anti-cardiolipin AB can be positive

· Liver and thyroid abnormalities can be seen

· High platelets

Imaging

· Doppler US of cranial arteries or MRI

o Can give some information if unable to biopsy, can also help guide biopsy

· Plain radiography usually normal

· MRI and ultrasound may demonstrate bursitis

Temporal artery biopsy

· Bilateral biopsy with 3cm on each side gives best sensitivity

· Biopsy remains positive despite steroids for at least 7 days.

· Highly specific but not sensitive

o Sensitivity 87% (i.e. misses 13%)

· Histology

o Panarteritis

o Giant cell granulomas may be seen

o Disruption of internal elastic lamina

o Patchy and skip lesions

In patients with pure PMR

Probably not necessary, low yield (and treatment is the same)

Treatment

Steroids

Mainstay of Rx
Rapid response
Reduces complications including blindness
Best if can be started after biopsy if practical
Higher dose may be used if visual symptoms
Otherwise 40-60mg daily
Slow taper once symptoms controlled (~1month)
Gradual reduction at lower doses
Usually require steroids for 2 years

Prognosis

PMR

Pathogenesis

Similar inflammatory response but without arteritis

Clinical Manifestations

PMR

Chronic or subacute onset
Aching and morning stiffness in shoulders, hip girdle, neck, torso
Usually symmetric
Systemic symptoms can occur but these are more severe (particularly fever) is patients with co-existent GCA
Swelling of hands and feet can occur.
Associated with carpal tunnel syndrome
Synovitis and bursitis may lead to pain around joints on palpation.
Pain often worse with movement and at night/early morning
Can be similar presentation to late onset RA, myositis, paraneoplastic myalgia, connective tissue diseases.

Diagnosis

Treatment

PMR

Steroids
Usually good response to lower doses
Start with 10-20mg/day
Taper by 10% every 2-4 weeks or 1mg/month
NSAIDs may allow lower prednisone doses to be used. (but caution with ulcers with combination)
Patients with ESR <50 are more likely to respond rapidly to lower steroid doses.
Methotrexate etc. can be used if needed

Prognosis

PMR

Self-limited course over months or years at which point steroids can be ceased.
Need to be vigilant for development of GCA with its worse prognosis