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Arteritis, Temporal
Cynthia M. Waickus, MD, PhD
image BASICS
DESCRIPTION
  • Technically termed giant cell arteritis (GCA)
  • A chronic, generalized, cellular, and humoral immune-mediated vasculitis of large- and mediumsized vessels, predominantly affecting the cranial arteries originating from the aortic arch, although vascular involvement may be widespread. Inflammation of the aorta is observed in 50% of cases (1,2).
  • Frequent features include fatigue, headaches, jaw claudication, loss of vision, scalp tenderness, polymyalgia rheumatica (PMR), and aortic arch syndrome (decreased or absent peripheral pulses, discrepancies of blood pressure, arterial bruits) (3).
EPIDEMIOLOGY
  • The mean age of onset is approximately 75 years; rare <50 years.
  • Women are affected about 2 times as often as men.
  • Most common vasculitis in individuals of Northern European decent (Scandinavain countries)
  • Rare in Asians and African Americans
Incidence
  • Prevalence in individuals > 50 years: 1 in 500 (1,4,5)
  • Cyclic incidence: peaking every 5 to 7 years
ETIOLOGY AND PATHOPHYSIOLOGY
  • The exact etiology of GCA remains unknown, although current theory suggests that advanced age, ethnicity, and specific genetic predisposition lead to a maladaptive response to endothelial injury, intimal hyperplasia, and ultimately vascular stenosis.
  • Temporal arteritis (TA) is a chronic, systemic vasculitis primarily affecting the elastic lamina of medium- and large-sized arteries. Histopathology of affected arteries is marked by transmural inflammation of the intima, media, and adventitia, as well as patchy infiltration by lymphocytes, macrophages, and multinucleated giant cells. Mural hyperplasia can result in arterial luminal narrowing, resulting in subsequent distal ischemia (1,4,5).
  • Current theory regarding the etiology of TA is that a maladaptive response to endothelial injury leads to an inappropriate activation of T cell-mediated immunity via immature antigen-presenting cells. The subsequent release of cytokines within the arterial vessel wall can attract macrophages and multinucleated giant cells, which form granulomatous infiltrates and give diseased vessels their characteristic histology. This also leads to an oligoclonal expansion of T cells directed against antigens in or near the elastic lamina. Ultimately, this cascade results in vessel wall damage, intimal hyperplasia, and eventual stenotic occlusion (5,6).
  • In recent years, GCA and polymyalgia rheumatica (PMR) have increasingly been considered to be closely related conditions (3,4).
Genetics
The gene for HLA-DRB1-04 has been identified as a risk factor for TA, and polymorphisms of ICAM-1 have also been implicated (2).
RISK FACTORS
  • Increasing age >70 years is the greatest risk factor.
  • Genetic predisposition
  • Environmental factors influence susceptibility (6,7,8).
  • Heavy smoking and atherosclerotic disease are risk factors for females but not for males.
COMMONLY ASSOCIATED CONDITIONS
Polymyalgia rheumatica (PMR) may develop either before or after the arteritis (4,6).
image DIAGNOSIS
PHYSICAL EXAM
  • Temporal artery abnormalities (beading, prominence, tenderness)
  • Typically appear “ill”
  • Decreased peripheral pulses in the presence of large vessel diseases
  • Funduscopic exam shows pale and edema of the optic disk, scattered cotton wool patches, and small hemorrhages.
  • Unlike other forms of vasculitis, GCA rarely involves the skin, kidneys, and lungs.
DIFFERENTIAL DIAGNOSIS
  • Classification criteria are as follows:
    • Age >70 years
    • New localized headache
    • Temporal artery abnormality (tenderness to palpation, decreased or absent pulses)
    • ESR >50 mm/hr
    • Abnormal temporal artery biopsy showing vasculitis with predominance of mononuclear cell infiltration or granulomatous inflammation
  • Three or more of the above symptoms: 95% sensitivity/91% specificity for GCA diagnosis (The American College of Rheumatology criteria for the classification of GCA)
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • ESR >50 mm/hr (86% sensitivity), although nonspecific (27%); infrequently, may be normal (3,7)[A]
  • C-reactive protein (CRP) >2.45 mg/dL is a more sensitive marker of inflammation (97% sensitivity) and is associated with increased odds of a positive biopsy result.
  • A normal ESR and/or CRP renders the diagnosis of GCA unlikely.
  • Platelet count >400 × 103
  • Acute-phase reactants (fibrinogen, interleukin-6) are frequently elevated, but very nonspecific, and reserved for diagnostically difficult cases.
  • Mild anemia: very nonspecific but may be associated with a lower rate of ischemic complications.
  • Color Doppler US of the temporal artery may identify vascular occlusion, stenosis, or edema (“halo sign”); it is low cost and noninvasive but also very operator dependent and does not significantly improve on the clinical exam. It may aid in the diagnosis of larger vessel involvement (9).
  • MRI and MRA allow for noninvasive evaluation of both the vessel lumen and the vessel wall and assess mural thickness (edema) and lumen diameter (occlusion). The information may aid in diagnosis, but results are affected by prior glucocorticoid treatment, perhaps indicating more value in assessing the disease course or relapse. Cost, logistics, and lack of validity data preclude its routine usefulness.
  • Positron emission tomography (PET), like MRI/MRA and color Doppler, may be useful in diagnostically difficult cases to quantify the inflammatory burden and early in the course of disease, as the metabolic changes occur prior to structural vascular damage, but it also lacks studies to support its use (10).
Follow-Up Tests & Special Considerations
  • Development of aortic aneurysms (late and potentially serious complication of GCA) can lead to aortic dissection.
  • Due to the risk of irreversible vision loss, treatment with high-dose steroids should be started on strong clinical suspicion of temporal arteritis, prior to the temporal biopsy being done.
Diagnostic Procedures/Other
  • Gold standard diagnostic study: histopalogic examination of the temporal artery biopsy specimen
  • Overall sensitivity is 87%.
  • The temporal artery is chosen because of its accessibility in the systemic disease, but any accessible cranial artery may be chosen.
  • Length of biopsy specimen should be at least 2 cm to avoid false-negative results, as skip lesions may occur.
  • Diagnostic yield of biopsy may be increased if procedure is coupled with imaging (high-resolution MRI or color Doppler US).
  • Bilateral temporal artery biopsy should not be performed unless the initial histopathology is negative and the suspicion for GCA remains high.
  • May be negative in up to 42% of patients, especially in large vessel disease
  • Biopsy results are not affected by prior glucocorticoids, so treatment should not be delayed.
Test Interpretation
  • Inflammation of the arterial wall, with fragmentation and disruption of the internal elastic lamina
  • Multinucleated giant cells are found in <50% of cases and are not specific for the disease.
  • Temporal arteritis occurs in three histologic patterns: classic, atypical, and healed.
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image TREATMENT
MEDICATION
First Line
Glucocorticoids:
  • Prolonged treatment with glucocorticoids has been the mainstay of treatment and should be initiated immediately when the diagnostic suspicion for GCA is high (3)[A],(11)[B].
  • Because of the risk of irreversible vision loss, treatment with high-dose steroids should be started on strong clinical suspicion of temporal arteritis, prior to the temporal biopsy being done.
  • The typical dose of prednisone is 60 mg/day (or 1 mg/kg/day). Steroids should not be in the form of alternate day therapy, as this is more likely to lead to a relapse of vasculitis.
  • The initial dose of steroids is continued for 2 to 4 weeks and slowly tapered over 9 to 12 months. Tapering may require ≥2 years.
  • Oral steroids are at least as effective as IV steroids, except in the treatment of acute visual loss where IV steroids appear to offer significant benefit over oral steroids.
  • It has been suggested that low-dose aspirin might be effective for patients with GCA (12)[B].
  • Patients on corticosteroids should be placed on therapy to minimize osteoporosis unless there are contraindications.
Second Line
  • Methotrexate as an adjunct to glucocorticoid therapy may have a modest effect in decreasing the relapse rate of temporal arteritis (13)[B],(14,15)[A].
  • Therapies directed at TNF as adjunct to steroids have not shown significant benefit (15,16)[B]. Therapies directed at IL-6 blockade (tocilizumab - TCZ), and cyclophosphamide, have shown some benefit in patients who have not adequately responded to glucocorticoids (17,18)[A].
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Sun avoidance and protection of the head and the face from photodamage may eventually prove to be important preventive measures for TA.
Patient Monitoring
  • TA is typically self-limited and lasts several months or years.
  • Overall, TA does not seem to decrease longevity. Nevertheless, it may lead to serious complications such as visual loss, which occurs in about 15-20% of patients.
  • Another complication of GCA is the development of aortic aneurysms, usually affecting the ascending aorta. Yearly chest x-rays may be useful to identify this problem (19).
  • About 50% of the patients with GCA will eventually develop polymyalgia rheumatica (stiffness of shoulder and hip girdle).
DIET
Calcium and vitamin D supplementation
PATIENT EDUCATION
  • Consequences of discontinuing steroids abruptly (adrenal insufficiency, disease relapse)
  • Risks of long-term steroid use (infection, hyperglycemia, weight gain, impaired wound healing, osteoporosis, hypertension)
  • Possibility of relapse and importance of reporting new headaches and vision changes to provider immediately
PROGNOSIS
  • Life expectancy is not affected by the disease unless severe aortitis is present.
  • Once vision loss has occurred, it is unlikely to be recovered, but treatment resolves the other symptoms and prevents future vision loss and stroke.
  • In most patients, glucocorticoid therapy can eventually be discontinued without complications. In a few patients, however, the disease is chronic and prednisone must be continued for years.
  • Disease relapse is a distinct possibility.
REFERENCES
1. Ezeonyeji AN, Borg FA, Dasgupta B. Delays in recognition and management of giant cell arteritis: results from a retrospective audit. Clin Rheumatol. 2011;30(2):259-262.
2. Cantini F, Niccoli L, Storri L, et al. Are polymyalgia rheumatica and giant cell arteritis the same disease? Semin Arthritis Rheum. 2004;33(5):294-301.
3. Gonzalez-Gay MA, Vazquez-Rodriguez TR, Lopez-Diaz MJ, et al. Epidemiology of giant cell arteritis and polymyalgia rheumatica. Arthritis Rheum. 2009;61(10):1454-1461.
4. Robson JC, Kiran A, Maskell J, et al. The relative risk of aortic aneurysm in patients with giant cell arteritis compared with the general population of the UK. Ann Rheum Dis. 2015;(74)1:129-135.
5. Waldman CW, Waldman SD, Waldman RA. Giant cell arteritis. Med Clin North Am. 2013;97(2):329-335.
6. Weyand CM, Goronzy JJ. Immune mechanisms in medium and large-vessel vasculitis. Nat Rev Rheumatol. 2013;9(12):731-740.
7. Kermani TA, Warrington KJ. Recent advances in diagnostic strategies for giant cell arteritis. Curr Neurol Neurosci Rep. 2012;12(2):138-144.
8. Crowson CS, Matteson EL, Myasoedova E, et al. The lifetime risk of adult-onset rheumatoid arthritis and other inflammatory autoimmune diseases. Arthritis Rheum. 2011;63(3):633-639.
9. Arida A, Kyprianou M, Kanakis M, et al. The diagnostic value of ultrasonography-derived edema of the temporal artery wall in giant cell arteritis: a second meta-analysis. BMC Musculoskelet Disord. 2010;11:44.
10. Besson FL, Parienti JJ, Bienvenu B, et al. Diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography in giant cell arteritis: a systematic review and meta-analysis. Eur J Nucl Med Mol Imaging. 2011;38(9):1764-1772.
11. Villa-Forte A. Giant cell arteritis: suspect it, treat it promptly. Cleve Clin J Med. 2011;78(4):265-270.
12. Lee MS, Smith SD, Galor A, et al. Antiplatelet and anticoagulant therapy in patients with giant cell arteritis. Arthritis Rheum. 2006;54(10):3306-3309.
13. Mahr AD, Jover JA, Spiera RF, et al. Adjunctive methotrexate for treatment of giant cell arteritis: an individual patient data meta-analysis. Arthritis Rheum. 2007;56(8):2789-2797.
14. Kötter I, Henes JC, Wagner AD, et al. Does glucocorticoid-resistant large-vessel vasculitis (giant cell arteritis and Takayasu arteritis) exist and how can remission be achieved? A critical review of the literature. Clin Exp Rheumatol. 2012;30(1 Suppl 70):S114-S129.
15. Borchers AT, Gershwin ME. Giant cell arteritis: a review of classification, pathophysiology, geo-epidemiology and treatment. Autoimmun Rev. 2012;11(6-7):A544-A554.
16. Yates M, Loke YK, Watts RA, et al. Prednisolone combined with adjunctive immunosuppression is not superior to prednisolone alone in terms of efficacy and safety in giant cell arteritis: metaanalysis. Clin Rheumatol. 2014;33(2):227-236.
17. Salvarani C, Magnani L, Catanoso M, et al. Tocilizumab: a novel therapy for patients with large-vessel vasculitis. Rheumatology (Oxford). 2012;(51)1:151-156.
18. Quartuccio L, Masset M, De Maglio G, et al. Role of oral cyclophosphamide in the treatment of giant cell arteritis. Rheumatology (Oxford). 2012;51(9):1677-1686.
19. Tomasson G, Peloquin C, Mohammad A, et al. Risk for cardiovascular disease early and late after a diagnosis of giant-cell arteritis: a cohort study. Ann Intern Med. 2014;160(2):73-80.
Additional Reading
Mukhtyar C, Guillevin L, Cid MC, et al. EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis. 2009;68(3):318-323.
See Also
Depression; Fibromyalgia; Headache, Cluster; Headache, Tension; Polymyalgia Rheumatica; Polymyositis/Dermatomyositis
Codes
ICD10
  • M31.6 Other giant cell arteritis
  • M31.5 Giant cell arteritis with polymyalgia rheumatica
Clinical Pearls
  • Due to the risk of irreversible vision loss, treatment with high-dose steroids (prednisone 60 mg/day) should be started immediately in patients suspected of temporal arteritis.
  • Temporal artery biopsy is the gold standard for diagnosis. Temporal artery biopsy is not likely to be affected by a few weeks of treatment.
  • Treatment consists of a very slow steroid taper. Bone protection therapy and low-dose aspirin should be considered.
  • Normal ESR level = value of age/2 for men and age + 10/2 for women