Etiology

• Systemic granulomatous vasculitis involving medium to large arteries
• Most commonly the thoracic aorta, cervical arteries, and branches of the external carotid arteries
• T-lymphocyte (mainly CD4) infiltration, macrophages, multinucleated giant cells
• Cytokine production including IFN‑γ, IL‑1b, IL‑6, matrix metalloproteinases (MMP)
• Exact etiology unclear
• Some genetic predisposition, associated w/ HLA‑DR4 haplotype
• Suggestion of infectious origin (mycoplasma, chlamydia, parvovirus B19, burkholderia)
• Age-related changes in the immune system and affected arteries might be important in disease pathogenesis.

Figure 1. H&E photomicrograph of a medium sized artery with giant cell arteritis; note the multinucleated giant cells (arrow).

Epidemiology

• Incidence 18 per 100,000 in individuals over 50 years old (Salvarani, Ann Intern Med 1995)
• Elderly (mean age at presentation 71 years)
• Female > male (2–6 times greater)
• Most common in white people of Scandinavian descent
• Unusual in Hispanic, Asian, and African-American populations

History

• Headache (present in 67%)
• Jaw claudication (present in 50%)
• Tongue claudication
• Scalp tenderness
• Systemic weakness, malaise, weight loss, fever
• Polymyalgia rheumatica (present in 40%–50%)
• Throat pain
• Nonspecific neck/shoulder/muscle pain
• Loss of vision
• Diplopia
• Eye pain

Clinical features

• Ophthalmic: Ischemic complications in 25% of giant cell arteritis (GCA) patients
• Anterior ischemic optic neuropathy (AION): Accounts for about 80% of vision loss attributable to GCA
• Decreased vision: Often worse than 20/200, 21% NLP
• Can be preceded by transient vision loss
• Visual field defect: Typically central or altitudinal
• Afferent pupillary defect
• Swollen optic nerve head with pallor
• Optic atrophy usually evident after 3–6 weeks
• Posterior ischemic optic neuropathy (PION)
• Same as above, but optic nerve head initially appears normal
• Central retinal artery occlusion (CRAO) or cilioretinal artery occlusion
• Vision loss, afferent pupillary defect, cherry red spot
• Choroidal infarction
• Ischemic cranial nerve palsy
• Oculomotor nerve (nerve III) typically pupil-sparing
• Extraocular muscle infarction
• Ocular ischemic syndrome
• Hypotony due to decreased aqueous production
• Amaurosis fugax
• Horner syndrome
• Neurologic
• Ischemic stroke, transient ischemic attack (TIA), spinal cord infarction, mono/polyneuropathies, sensorineural hearing loss
• GCA can be “occult” (isolated ocular complications without other neurological findings) in 21%–38% of cases (Hayreh, Am J Ophthalmol 1997)
• Vascular
• Superficial temporal artery tenderness, lack of pulsation
• Thoracic/abdominal aortic aneurysm, coronary ischemia, intestinal infarction, pulmonary artery thrombosis, renal failure
• Upper or lower extremity claudication

Testing

• Erythrocyte sedimentation rate (ESR)
• Nonspecific marker of inflammation
• Usually elevated (> 50 mm/hr in 85%–95% of patients)
• "Normal" ESR level subject of debate
• Miller formula (Miller, Br Med J 1983)
• Men: Age divided by 2
• Women: Age plus 10 divided by 2
• C-reactive protein (CRP)
• Usually elevated (> 2.45 mg/dL)
• When combined with elevated ESR, specificity is 97% (Hayreh, Am J Ophthalmol 1997)
• Thrombocytosis
• 65% of patients with permanent vision loss have thrombocytosis (Liozon, Am J Med 2001)
• Fluorescein angiogram
• AION: Delayed filling of optic disc or peripapillary choroid, choroidal nonperfusion
• CRAO: Delayed filling of CRA
• Duplex ultrasound of temporal artery
• Arterial edema represented by hypoechoic haloes immediately adjacent to arterial wall
• Sensitivity 75%, specificity 83% (Ball, Br J Surg 2010)
• Can be considered as noninvasive alternative to biopsy
• Temporal artery biopsy (TAB)
• Gold standard for definitive diagnosis of GCA
• Sensitivity 60%–80%
• Positive predictive value 90%–100%
• Histopathologic findings
• T-lymphocyte and macrophage infiltrates of the vessel media and internal elastic lamina
• Giant cells might or might not be present
• Intimal thickening with disruption of internal elastic lamina
• Areas of unaffected tissue (skip lesions) in 21%–28% of cases
• Recommendations for biopsy length vary from 15 mm to 3–6 cm
• Breuer (Clin Exp Rheumatol 2009) found increased biopsy length improved positivity rates: ≤ 5 mm (19%), 6–20 mm (79%), > 20 mm (89%)
• Contralateral biopsy might be required if first biopsy negative (controversial).
• Positivity rate of second biopsy 9% (Hayreh, Am J Ophthalmol 1997)
• Bilateral biopsy can increase diagnostic sensitivity by up to 12.7% (Breuer, J Rheumatol 2009)
• Systemic steroids can affect histopathologic findings, but should not be withheld prior to biopsy due to risks associated with treatment delay.
• Biopsy within 1–2 weeks of initiating steroid treatment might optimize diagnostic yield.
• Histopathologic evidence of GCA can still be seen after 6 months or more of steroid treatment (Narváez, Semin Arthritis Rheum 2007).
• Complications of procedure
• Bleeding, infection, pain, scarring, alopecia
• Scalp necrosis
• Damage to temporal branch of facial nerve (brow paralysis)
• Significant debate over whether temporal artery biopsy is necessary to establish diagnosis of GCA
• Clinicians should consider whether a positive or negative biopsy result will alter patient management
• If clinical suspicion is strong, treatment is indicated regardless of TAB result.
• In paucity of signs and symptoms consistent with GCA, diagnostic yield of TAB is extremely low.
• Medico-legal ramifications: Positive TAB can justify risks of long-term steroid use

Figure 2. Temporal artery biopsy. (A) Scalp incision aided by preoperative doppler testing. (B) blunt dissection in subcutaneous fat and superficial temporal fascia to identify artery. (C) 2-cm arterial specimen to be obtained. (D) Deeper dissection demonstrates deep temporal fascia under the correct arterial plane.

American College of Rheumatology criteria

(Hunder, Arthritis Rheum 1990)

3 out of 5 of the following (sensitivity/specificity 93.5%/91.2%):

• Age at onset > 50 years
• New headache
• Temporal artery abnormalities (on exam or ultrasound)
• ESR > 50 mm/hr
• Positive temporal artery biopsy

• Increasing age
• Smoking and atherosclerosis: Increases risk in women but not men
• Low body mass index
• Early menopause
• Relative adrenal hypofunction
• Genetic susceptibility suggested by several studies

• Nonarteritic ischemic optic neuropathy
• Other optic neuropathies (infectious, inflammatory, infiltrative, compressive, toxic)
• Nonarteritic central artery occlusion
• Central retinal vein occlusion
• Other causes of headache/jaw pain (trigeminal neuralgia, dental conditions)

Natural history

• Disease course is chronic
• Visual prognosis depends on vision at presentation
• Incidence of blindness 7%–25%
• Vision loss due to AION or CRAO usually irreversible
• Features associated with poor visual prognosis: Older age, fever, weight loss, amaurosis, diplopia, jaw claudication
• 65% of untreated patients develop bilateral ischemic optic neuropathy.
• Vision loss in second eye typically occurs within 10 days of first.
• Failure to diagnose GCA is a significant cause of litigation against ophthalmologists.

Medical therapy

• Systemic corticosteroids: First line therapy
• Administration:
• Oral prednisone, typically 1 mg/kg/day
• IV administration for severe vision loss or amaurosis: Methylprednisolone 250 mg IV Q6 h for 3 days, then oral prednisone 80–100 mg/day
• Initiate steroids while awaiting biopsy results to avoid delay in treatment
• Follow ESR and clinical symptoms
• Symptoms typically respond within days
• Several weeks of steroids usually required before ESR/CRP normalize
• Visual improvement unusual, especially in AION and if delayed
• Decision to treat or stop treatment should be based on the complete clinical picture
• Taper corticosteroids slowly: A 1–2 year course typical
• Other medications
• Aspirin is often prescribed to prevent thrombotic complications.
• Efficacy in preventing blindness unproven
• Steroid-sparing agents: investigative
• Methotrexate, infliximab, other immunobiologics

Steroid-related complications

• Inability to taper drug without flare of disease
• Hyperglycemia
• Aseptic necrosis of the hip
• Hypertension
• Osteoporosis
• GI bleeding
• Weight gain
• Cushingoid facies
• Depression

Prevention

• Limit long-term use
• Discuss side effects with patient before use
• Monitor for side effects (hyperglycemia, hypertension, osteoporosis, etc.) and treat as appropriate

• Ocular
• Permanent loss of vision
• Diplopia
• Neurologic
• Transient ischemic attack, stroke
• Vertigo
• Hearing loss
• Mononeuritis multiplex
• Coronary ischemia
• Aortic aneurysm or dissection
• Renal failure
• Mesenteric ischemia
• Tongue claudication/ischemia

Temporal artery biopsy technique

• Mark frontal branch of superficial temporal artery (STA) on symptomatic side, starting in preauricular region and extending toward forehead/brow:
• Locate artery by palpation or Doppler ultrasound.
• Incision should be at least as long as planned length of biopsy segment.
• Stay as distal to main STA trunk as possible.
• Shave scalp overlying STA if necessary.
• Infiltrate with local anesthetic, avoiding direct intravascular injection.
• Prep and drape surgical site in standard sterile fashion.
• Create skin incision parallel to artery, either directly overlying or slightly to either side.
• Bluntly dissect through subcutaneous fat to expose superficial temporalis fascia, also known as temporoparietal fascia.
• Superficial fascia is loose and areolar, as contrasted with underlying deep temporalis fascia, which is fibrous and glistening.
• Identify artery lying within superficial temporalis fascia.
• Spreading fascia with blunt-tipped instrument parallel to artery can assist in locating artery.
• Open fascia overlying the artery and dissect the artery from surrounding tissues:
• Avoid undue penetrating or crushing trauma to the specimen (e.g., with toothed forceps).
• Ligate and divide arterial branches as necessary.
• Double-ligate the artery both proximally and distally with braided nonabsorbable suture (for example, 4‑0 or 5‑0 silk), leaving adequate specimen length between ligation points.
• Ligating the artery early during procedure can limit intraoperative bleeding.
• Excise specimen and send in standard tissue fixative for pathologic examination.
• Obtain meticulous hemostasis.
• Close incision with deep and/or superficial skin sutures.
• Apply topical antibiotic ointment and dressing as desired.
• Instruct patient on proper wound care and precautions.

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