Giant Cell Arteritis

Neuro-OphthalmologyCombinationHigh YieldAlso: Temporal Arteritis, GCA, Cranial Arteritis, Horton Disease

Key Points

•GCA is an ophthalmological emergency — treatment with high-dose steroids must begin immediately upon clinical suspicion, without waiting for biopsy results.
•Arteritic AION causes sudden, severe, and usually irreversible vision loss; without treatment, the fellow eye is at 50-75% risk of involvement within days to weeks.
•Jaw claudication is the most specific clinical symptom for GCA (LR+ ~4.2, odds ratio ~9 for positive biopsy); amaurosis fugax is the critical warning sign preceding permanent visual loss.
•Combined ESR and CRP provides 97% specificity for diagnosis; however, normal ESR does not exclude GCA (4-5% of biopsy-proven cases have normal ESR).
•Tocilizumab (IL-6 receptor inhibitor) is now FDA-approved for GCA and significantly reduces relapse rate and cumulative steroid dose.

Hallmark Features(Combination)

Arteritic anterior ischaemic optic neuropathy (A-AION) — sudden, severe vision loss

Jaw claudication

Scalp tenderness (temporal artery region)

Elevated ESR and CRP

Positive temporal artery biopsy (granulomatous vasculitis)

Finder Clues

Sudden severe vision loss (arteritic AION)Jaw claudication (pain on chewing)Scalp tenderness (over temporal arteries)New-onset headache (temporal, unilateral or bilateral)Amaurosis fugax (transient visual loss — warning sign)Diplopia (cranial nerve palsies, especially CN VI)Constitutional symptoms (fever, weight loss, malaise)Polymyalgia rheumatica symptoms (shoulder/hip girdle stiffness)

1. Definition

Giant cell arteritis (GCA) is a chronic, granulomatous vasculitis of medium-to-large arteries, predominantly affecting branches of the external carotid artery (especially the temporal and ophthalmic arteries). It is the most common primary systemic vasculitis in adults over 50, with a mean age of onset of 70-75 years. The most feared complication is arteritic anterior ischaemic optic neuropathy (A-AION), causing sudden, severe, and often irreversible vision loss. GCA is an ophthalmological emergency because prompt treatment can prevent bilateral blindness.

3. Pathogenesis

GCA involves granulomatous inflammation targeting the arterial wall, particularly the media-intima junction.

Immunopathogenesis:

Dendritic cells in the adventitial vasa vasorum become activated (possibly by an unknown antigen)
Activated dendritic cells recruit CD4+ T cells and macrophages into the arterial wall
T cells produce IFN-gamma and IL-17, driving Th1 and Th17 inflammatory responses
Macrophages differentiate into multinucleated giant cells (the hallmark histological finding)
Giant cells and macrophages produce matrix metalloproteinases that destroy the internal elastic lamina
Intimal hyperplasia — reactive smooth muscle proliferation narrows the lumen → vessel occlusion
Ischaemia of end-organ tissues (optic nerve, retina, extraocular muscles, brain)

Why the ophthalmic artery is vulnerable:

The posterior ciliary arteries (branches of the ophthalmic artery) supply the optic nerve head
These are end-arteries without significant collateral circulation
Occlusion produces anterior ischaemic optic neuropathy (A-AION)
The central retinal artery may also be involved, causing CRAO

Association with polymyalgia rheumatica (PMR):

40-60% of GCA patients have PMR symptoms
15-20% of PMR patients will develop GCA
Shared immunopathogenic pathways but PMR lacks granulomatous arteritis

4. Clinical Features

Age criterion: Virtually always age >50 years (mean 70-75 years); GCA below age 50 is exceedingly rare.

Cranial symptoms (classic phenotype):

New-onset headache — the most common symptom (~75%); temporal, unilateral or bilateral
Scalp tenderness — particularly over temporal arteries; patients may report pain when combing hair
Jaw claudication — pain/fatigue of masseter muscles during chewing; most specific symptom for GCA (positive likelihood ratio ~4.2)
Temporal artery abnormality — tender, thickened, nodular, non-pulsatile artery on palpation
Tongue claudication — rare but highly specific

Visual symptoms (the ophthalmological emergency):

Amaurosis fugax — transient monocular visual loss; critical warning sign preceding permanent visual loss
A-AION — sudden, severe, painless visual loss; the most common cause of permanent visual loss
CRAO — sudden complete visual loss
Diplopia — from ischaemia of cranial nerves or extraocular muscles

Constitutional symptoms:

Low-grade fever, fatigue, malaise, anorexia, weight loss
Polymyalgia rheumatica — proximal muscle pain and morning stiffness (shoulders, hips)

Large-vessel phenotype:

Aortitis, subclavian/axillary artery stenosis — may present with arm claudication
Thoracic aortic aneurysm — a late complication requiring long-term surveillance

5. Ocular Manifestations

Arteritic anterior ischaemic optic neuropathy (A-AION):

The most common and most feared ophthalmic complication
Sudden, painless, severe visual loss — typically worse than non-arteritic AION
Visual acuity often counting fingers or worse at presentation
Disc appearance — chalky white, pallid oedema of the optic disc (unlike the hyperaemic swelling in non-arteritic AION)
Visual field — altitudinal defect (classically inferior), but any pattern possible
RAPD present in unilateral cases
Fellow eye at risk — without treatment, 50-75% risk of bilateral involvement, often within days to 2 weeks

Central retinal artery occlusion (CRAO):

Cherry-red spot at the macula with diffuse retinal whitening
Accounts for ~10% of GCA-related visual loss
Box-carring of retinal arterioles on examination

Posterior ischaemic optic neuropathy (PION):

Visual loss with initially normal-appearing disc (retrobulbar ischaemia)
Less common than A-AION

Diplopia:

Occurs in 5-10% of GCA patients
Cranial nerve palsies (CN VI most common, followed by CN III)
Ischaemia of extraocular muscles can also cause diplopia
May be a presenting or warning symptom before visual loss

Ocular ischaemic syndrome:

From involvement of the ophthalmic artery or its branches
Anterior segment ischaemia — hypotony, anterior chamber inflammation, rubeosis iridis

Cotton wool spots:

May be seen on fundoscopy in both eyes — a sign of retinal ischaemia
Should prompt urgent GCA workup in a patient >50 with headache

6. Systemic Manifestations

Polymyalgia rheumatica (PMR):

40-60% of GCA patients have concurrent PMR
Proximal muscle pain and morning stiffness affecting shoulders, neck, and hips
Dramatic response to low-dose steroids (15-20 mg prednisone)

Constitutional:

Fever (low-grade, sometimes fever of unknown origin)
Weight loss, anorexia, malaise
May be the only presentation ("occult GCA")

Neurological:

Stroke — from vertebral or carotid artery involvement
Transient ischaemic attack
Peripheral neuropathy (rare)

Cardiovascular:

Aortitis — thoracic aorta involvement in 15-20%
Thoracic aortic aneurysm — 17-fold increased risk; may develop years after initial diagnosis
Aortic dissection or rupture (rare but fatal)
Subclavian/axillary artery stenosis — upper limb claudication, blood pressure discrepancy

Other:

Scalp necrosis — rare, from superficial temporal artery occlusion
Tongue necrosis — rare, from lingual artery involvement
Cough — dry cough may be a presenting feature

7. Diagnosis

Laboratory investigations:

ESR (erythrocyte sedimentation rate) — typically markedly elevated (>50 mm/hr; often >100 mm/hr)
CRP (C-reactive protein) — more sensitive than ESR; elevated in >95% of cases
Combined ESR + CRP — 97% specificity for GCA diagnosis
Platelets — thrombocytosis (reactive)
FBC — normochromic normocytic anaemia
LFTs — elevated alkaline phosphatase in some cases
Normal ESR does not exclude GCA — 4-5% of biopsy-proven GCA have normal ESR

Temporal artery biopsy (gold standard):

The definitive diagnostic test
Specimen should be at least 2-3 cm in length (to account for skip lesions)
Histology: granulomatous inflammation with multinucleated giant cells, intimal hyperplasia, destruction of internal elastic lamina
Skip lesions — inflammation may be segmental; negative biopsy does not exclude GCA (false-negative rate 5-13%)
Contralateral biopsy should be considered if initial biopsy is negative with high clinical suspicion
Biopsy can remain positive for up to 2-6 weeks after starting steroids

Imaging:

Temporal artery ultrasound — halo sign (hypoechoic periluminal thickening) has good specificity
MRI — wall enhancement and mural thickening of temporal arteries
PET-CT — for large-vessel vasculitis assessment (aortitis)
CTA/MRA — aortic and branch vessel assessment

ACR 1990 Classification Criteria (3/5 required):

Age ≥50
New headache
Temporal artery tenderness or decreased pulsation
ESR ≥50 mm/hr
Abnormal artery biopsy (granulomatous inflammation)

8. Differential Diagnosis

Differential of acute vision loss in elderly:

Non-arteritic AION (NA-AION) — hyperaemic disc swelling (not pallid), moderate VA loss, small cup-to-disc ratio ("disc at risk"), age 40-60, no systemic inflammatory markers
CRAO (non-arteritic) — cherry-red spot, cardiac embolic source, normal ESR
Optic neuritis — pain with eye movement, younger patient, MS association
Compressive optic neuropathy — gradual onset, proptosis

Differential of headache + elevated ESR in elderly:

Polymyalgia rheumatica without GCA — proximal stiffness, no visual symptoms or cranial findings
Malignancy — elevated ESR, weight loss, but no temporal artery abnormality
Infection — fever, elevated CRP/ESR, but localising features present
Other vasculitis — Takayasu (younger patients, large vessel), polyarteritis nodosa

Other causes of painful ophthalmoplegia in elderly:

Diabetic cranial neuropathy — pupil-sparing CN III palsy, self-limiting
Tolosa-Hunt syndrome — cavernous sinus granulomatous inflammation, no elevated ESR
Posterior communicating artery aneurysm — CN III with pupil involvement, urgent CTA

9. Management

IMMEDIATE treatment (do not wait for biopsy results):

Treatment must begin immediately upon clinical suspicion — delay risks permanent bilateral blindness.

Without visual loss:

Prednisone 1 mg/kg/day (typically 60-80 mg/day) orally
Continue high dose for 2-4 weeks, then gradual taper over 12-24 months

With visual loss or impending visual loss (amaurosis fugax):

IV methylprednisolone 1g/day for 3 days followed by oral prednisone 1 mg/kg/day
This is an ophthalmological emergency — immediate IV steroids to protect the fellow eye

Headache/systemic symptoms typically improve within 24-72 hours; visual loss is usually irreversible.

Steroid-sparing agents:

Tocilizumab (IL-6 receptor inhibitor) — FDA-approved for GCA (2017); significantly reduces relapse rate and cumulative steroid dose
Methotrexate — modest steroid-sparing benefit

Aspirin:

Low-dose aspirin (75-100 mg/day) — may reduce risk of ischaemic events

Bone protection:

Calcium + Vitamin D supplementation
Bisphosphonates — for patients on long-term steroids

Monitoring:

ESR + CRP to track disease activity and guide steroid taper
Long-term aortic imaging surveillance — for aortic aneurysm (US, CTA, or MRA)
Regular ophthalmological review
Monitor for steroid complications (diabetes, osteoporosis, cataracts, infection)

10. Prognosis

Visual prognosis:

A-AION visual loss is usually permanent and irreversible
Only 15% of patients show any visual improvement after treatment
Fellow eye protection is the primary goal — without treatment, 50-75% develop bilateral visual loss
With prompt steroid treatment, fellow eye involvement drops to <10%

Systemic prognosis:

Excellent response to steroids — headache and systemic symptoms improve within 24-72 hours
Most patients require 12-24 months of steroid therapy with gradual taper
Relapse rate: 40-60% during steroid taper; tocilizumab significantly reduces this
Thoracic aortic aneurysm — 17-fold increased risk; requires long-term surveillance
Overall mortality is similar to the general population with appropriate treatment

Key prognostic factors:

Jaw claudication is the most specific predictor of positive biopsy (odds ratio ~9)
Amaurosis fugax is a critical warning sign — immediate treatment can prevent permanent visual loss
Bilateral visual loss at presentation carries the worst visual prognosis

Clinical Pearls

Any patient over 50 with new-onset headache, jaw claudication, or sudden visual loss should be considered GCA until proven otherwise — empiric steroids should be started immediately while arranging biopsy.

The chalky-white pallid disc oedema of arteritic AION is distinctly different from the hyperaemic disc swelling of non-arteritic AION — this fundoscopic finding should immediately raise suspicion for GCA.

Temporal artery biopsy can remain diagnostic for up to 2-6 weeks after starting steroids — never delay steroid treatment to obtain a biopsy.

Diplopia or amaurosis fugax in an elderly patient may be the only warning sign before irreversible A-AION — always check ESR and CRP urgently in this clinical context.

Mnemonics

GCA Red Flags — JAW-HEADS

J—Jaw claudication

A—Amaurosis fugax (transient visual loss)

W—Weight loss / constitutional

H—Headache (new-onset)

E—ESR/CRP elevated

A—Artery (temporal) tender/non-pulsatile

D—Disc pallor (chalky-white swelling)

S—Scalp tenderness

Key clinical features prompting urgent GCA investigation

ACR Criteria — HAT-BE

H—Headache (new-onset)

A—Age ≥50

T—Temporal artery abnormality

B—Biopsy abnormal (granulomatous)

E—ESR ≥50 mm/hr

(3 of 5 required)

ACR 1990 classification criteria for GCA

A-AION vs NA-AION — Key Differences

Arteritic: Chalky-white disc, severe VA (CF or worse), giant cell vasculitis, age >70

Non-arteritic: Hyperaemic disc, moderate VA loss (20/60), small cup-to-disc ratio, age 40-60

Distinguishing arteritic from non-arteritic AION at the bedside