Etiology
- Systemic granulomatous vasculitis involving medium to large arteries
- Most commonly the thoracic aorta, cervical arteries, and branches of the external carotid arteries
- Activated dendritic cells attract T-lymphocytes (mainly CD4) infiltration, macrophages exposed to IFN-γ form 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); women account for 65%-75% of patients
- Most common in white people of northern European 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)
- 4% of patients with confirmed GCA had normal ESR and normal CRP at time of diagnosis (Kermani, Semin Arthritis Rheum 2012)
- 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)
- A systematic review and meta-analysis of 20 studies showed sensitivity of 68% (57%–78%; 95% CI) and specificity of 81% (75%–86%; 95% CI) (Rinagel, Autoimmune Rev 2019).
- Can be considered as noninvasive alternative to biopsy
- Temporal artery biopsy (TAB)
- Gold standard for definitive diagnosis of GCA
- Sensitivity 85–95% (Kermani, Ann Rheum Dis 2013)
- 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 significantly
- Breuer (Clin Exp Rheumatol 2009) found increased biopsy length improved positivity rates: ≤ 5 mm (19%), 6–20 mm (79%), > 20 mm (89%)
- Recent systematic review of literature (Buttgereit, JAMA 2016) recommends specimen length of “at least 1 cm.”
- In a recent series of 240 temporal artery biopsies (Grossman, Scand J Rheumatol 2017), the TAB positivity rate was similar among all ranges of biopsy length (<5 mm 70%, 5-9 mm 71%, 10-14 mm 69%, 15-19 mm 69%, 20 mm 73% (p= ns).
- A case-control study of 545 consecutive patients who underwent TA biopsy (Oh, Anz J Surg 2018) found a cut-off point of > 15 mm increased the odds of a positive TAB by 2.25 compared with TAB < 15 mm (P= 0.003)
- Clinical judgment is warranted in the absence of a clear evidence-based minimum TA biopsy length
- 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) but is generally not recommended as a primary approach.
- 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)
- Temporal artery biopsy remains the gold standard for diagnosis of GCA, but significant debate has emerged over whether temporal artery biopsy is necessary
- Clinicians should consider whether a positive or negative biopsy result will alter patient management
- If clinical suspicion is strong, treatment may be indicated regardless of TAB result.
- Temporal artery biopsy may not be required in patients with typical disease features and characteristic ultrasound or MRI findings (Dejaco, Ann Rheum Dis 2018)
- 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