creation date: 2025-12-21 22:40
tags: Pathologies
Giant Cell Arteritis
Background
Definitions
Giant cell arteritis (GCA) is a chronic inflammatory vasculitis that affects large- and medium-sized arteries in individuals older than 50. This condition typically involves cranial branches of the carotid arteries.
Temporal arteritis refers to the same condition but is not preferred over GCA despite the temporal arteries being the most common occurrence as GCA can occur in arteries within the body.
Etiology
The exact cause of GCA is incompletely understood. Current models suggest polymorphisms to major histocompatability complex with contribution from senescence, sex, and genetic background.
Triggering agents have not been identified with certainty. However, studies have suggested environmental factors such as microbes and viruses may cause inciting event.
Pathogenesis
Pathogen or damage sensing receptors activate dendritic cells present in the adventitia of normal arteries. This produce chemokines that promote attraction of leukocytes.
Excessive T-cell activation and differentiation, whether due to deficient immune checkpoints or other factors, results in the development of transmural inflammation. Macrophages in particular play a major role through production of cytokines which alter disease manifestation.
Invasion of inflammatory cells into the medial layer of arteries results in substantial loss of vascular small muscle cells. Further reactive oxygen species generation contribute to vessel wall injury.
Chronic injury causes myofibroblast differentiation resulting in remodelling and occlusion. Many symptoms of GCA occurs as a result of widespread stenosis and aneurysm of affected vessels.
Ischemia due to stenosis of the posterior ciliary artery (branch of opthalmic artery from the internal carotid) or central retinal artery can result in vision loss.
Of note, macrophages fuse to form multinucleated giant cells within granulomas, of which the condition is named.
Clinical Presentation
Signs & Symptoms
Symptoms often present with subacute onset but presentations over a few days can occur as well.
Constitutional symptoms may be the only manifestations (~15%).
- Fever
- Fatigue
- Weight loss
Headache is common (2/3 of patients) with varying descriptions. The classic presentation is:
- Located over the temples
- Progressively worsen
- Waxes and wanes
- Tenderness of scalp
Jaw claudication occurs in half of GCA patients which involves mandibular pain or fatigue from mastication.
Ocular involvement may occur due to ischemia of the optic blood supply:
- Transient visual loss (amaurosis fugax) - typically monocular, described as partial field defect or curtain effect
- Permanent vision loss - often irreversible unilateral or bilateral
Vision changes may initially manifest as diplopia which is highly specific in the presence of other GCA symptoms.
Large vessel involvement includes manifestations relating to the aorta and the major proximal branches. This is typically not symptomatic but manifestations include:
- Aortic aneurysm
- Aortic dissection
- Arterial bruits, absent blood pressures, and arm claudication of the upper extremities
MSK involvement may present with symptoms of polymyalgia rheumatica.
Less common manifestations include:
- CNS involvement (eg. stroke)
- Upper respiratory tract symptoms (particularly, nonproductive cough)
- Head and neck involvement (eg. maxillary/dental pain, facial swelling)
Physical exam signs include:
- Abnormal pulses
- Temporal artery abnormalities (thickened, nodular, tender, erythematous, absent pulse; enlarged occipital arteries)
- Bruits heard over carotid or supraclavicular areas, over axillary, brachial, or femoral arteries, and over abdominal aorta
- Heart murmur (aortic regurgitation if aortic aneurysm)
History & Physical Exam
Physical should include complete cardiovascular exam. For patients with visual changes, fundoscopy is indicated.
In patients with polymyalgia rheumatica, MSK exam may find limited ROM.
Fundoscopy findings
Transient monocular visual loss:
- May be normal
- Cotton wool spots in retina if local, retinal ischemia
Acute visual loss from arteritic anterior ischemic optic neuropathy: - Swollen, pale disc and blurred margins
Permanent visual loss: - Optic disc pallor
Posterior ischemic optic neuropathy: - Normal in acute phase (ischemia occurs behind optic disc)
Risk factors
The greatest risk factor is age, with the disease almost never occurring prior to age 50. Incidence increases with age, peaking between 70-79.
Other risk factors include:
- Ethnicity (greatest in Scandinavians)
- Female sex (3:1 to male in Scandinavians)
- Concurrent polymyalgia rheumatica (found in 10% of PMR patients)
Diagnosis
Criteria
The diagnosis of GCA requires histopathologic and/or imaging findings. It should be noted that a diagnosis is not required and should not delay treatment, especially as false negatives are possible.
In such cases, clinicians can choose to pursue alternative diagnoses or make a clinical diagnosis to treat accordingly.
Temporal artery biopsy
Unilateral biopsy with in vivo length of ≥1 cm. This is typically ordered within 2-4 weeks of initiation of treatment (which is started at suspicion of GCA).
Pathologic features include:
- Transmural inflammatory infiltrate with lymphocytes, macrophages, and giant cells
- Concentric rings appearance of lesion
- Other structural changes such as mediointimal scar, medial attenuation, intimal hyperplasia etc.
Temporal artery colour doppler ultrasound
Consist of ultrasonography of the head, neck, and upper extremities to visualize arteries.
Findings include:
- Homogenous, hypoechoic wall thickening that is well delineated towards the luminal side
- Mural edema seen as the “halo sign” which, if persistent with compression of the vessel, is highly specific for diagnosis (“compression sign”)
Work-up
If GCA is suspected from history and physical:
- CBC - may find normochromic anemia
- ESR and CRP - may be elevated
- Liver enzymes - ALP may be elevated
- Serum creatinine
- Glucose
- Urine dipstick
- Serum protein electrophoresis
- Bone profile panel (calcium, phosphorous, albumin, total protein, ALP, 25-hydroxyvitamin D)
Further workup is indicated if a patient is over than age 50 with signs/symptoms, especially in presence of elevated ESR/CRP and/or with prior diagnosis of PMR.
This typically consist of temporal artery biopsy. If a skilled clinician is available for diagnostic colour doppler ultrasound of the temporal artery, it may be used as a surrogate for biopsy.
It should be noted that diagnostic evaluation is not required for and should not delay treatment.
In patients with negative initial evaluation but clinical suspicion remains high, additional testing may be warranted. Evalulation of large vessel GCA can be done with:
- CT or CTA
- MRI and MR angiography
- Fluorodeoxyglucose (FDG) PET
- PET with CT of aorta and branches
- Colour doppler US of large vessels
Differential
Several conditions may overlap in presentation of GCA.
Other systemic vasculitides
Takayasu arteritis
- Indistinguishable histopathology and radiographic findings
- Differentiate: occurs before age 50 and different clinical manifestations
Small and medium vessel vasculitides - Systemic symptoms but different on histology
Primary angiitis of CNS - Cranial ischemic events (eg. stroke)
Others
Idiopathic aortitis
- Affects ascending aorta with similar histology of GCA
- No characteristic clinical findings of GCA
VEXAS syndrome - Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic syndrome
- Older males with biopsy-negative GCA symptoms
Nonarteritic anterior ischemic optic neuropathy - Monocular visual loss in older adult
- RFs: hypertension, diabetes, use of drugs such as sildenafil
- Small, crowded optic nerve head and small physiologic cup (small cup-to-disc ratio)
- Absent clinical and laboratory features of GCA
Infection - Symptoms and elevation of inflammatory markers
- Consider blood culture
Red Flags / Complications
Complications of GCA include the possible sequelae of untreated vessel stenosis:
- Vision loss
- Aortic aneurysm and dissection
- Stroke
- Tongue necrosis
Other complications include:
- Higher risk of comorbid CAD
- Higher risk of MI and cerebrovascular disease
- Adverse effects to treatment with glucocorticoids/alternative medications
Management
Management should be initiated promptly on suspicion of GCA.
Initial Treatment
Initial treatment depends on the presence of visual manifestations or cerebrovascular events potentially attributable to GCA.
No visual loss or cerebrovascular events
Glucocorticoids with goal of relieving symptoms and preventing vision loss:
- Prednisone 40-60 mg PO once daily
- Increase to maximum of 80 mg per day until symptom managed
In patients at risk of developing glucocorticoid toxicity, do not use lower doses. Instead, add glucocorticoid-sparing agent to facilitate tapering:
- Tocilizumab 162 mg subcutaneous weekly injection or IV infusion monthly
Possible visual loss or cerebrovascular events
Patients with signs of ischemic organ damage require a higher initial dose of glucocorticoids. Refer to opthalmology.
- Methylprednisolone 500-1000 mg IV daily for three days
- Followed by: prednisone 40-60 mg (or 1 mg/kg) PO once daily
Large-vessel involvement
In addition to glucocorticoid treatment, consider:
- Antiplatelet therapy (low-dose aspirin) if patient has critical or flow-limiting involvement of cerebral or carotid arteries
- Surgical intervention for vascular complications (eg. aortic aneurysm)
Subsequent Management
Tapering
Glucocorticoids should be tapered followed 2-4 weeks of therapy. For glucocorticoid monotherapy:
- Reduce to 50 mg/day after 2 weeks, then 40 mg/day at end of week 4, assuming ESR/CRP has declined to normal or near-normal
- Reduce by 5 mg q2wks to 20 mg/day, then 2.5 mg q2wks to 10mg/day
- Taper remaining 10 mg/day over next 6-12 months (eg. 1 mg decrements each month)
In patients with glucocorticoid-sparing agent therapy, an accelerated regimen can be used.
Follow-up monitoring
In the first six months of treatment, monthly follow-ups are recommended with interval increasing once stable. Visits should include:
- Monitoring symptoms through history and physical
- ESR and CRP for monitoring monotherapy glucocorticoid treatment
- Imaging surveillance for patients with large-vessel involvement
- Monitoring of glucocorticoid-associated toxicity (eg. infection risk, osteoporosis, vaccination, screening of latent TB)
Treatment of relapse
Relapses may be treated as above, based on presentation with or without vision and cerebrovascular events. It is recommended to initiate a glucocorticoid-sparing agent for relapse if patient was not previously treated with one.