Giant Cell Arteritis

Dost Jarbakhyl

Introduction

Giant cell arteritis (GCA), also known as temporal arteritis, is the most common primary vasculitis in adults, primarily affecting individuals over 50 years of age. It is characterised by granulomatous inflammation of medium- to large-sized vessels, particularly the extracranial branches of the carotid artery, such as the temporal artery. GCA leads to the degradation of vascular smooth muscle cells and elastic fibres, resulting in vascular remodelling, aneurysm formation, and ischemic complications due to intimal thickening and vessel occlusion. The association between blindness and temporal arteritis was recognised as early as the 10th century by Ali-ibn-Isa of Baghdad (1). In 1890, Hutchinson first described the clinical characteristics of GCA, and in 1930, Horton and his colleagues provided a detailed account of its histopathological features (2).

Epidemiology and Risk Factors

GCA has a higher prevalence in individuals of Northern European descent and is more common in women (3). The incidence increases with age, peaking between the ages of 70 and 80 years. Several genetic and environmental factors have been implicated in its pathogenesis, including associations with the HLA-DRB1*04 allele and possible infectious triggers (4).

Pathophysiology

Giant cell arteritis (GCA) is an immune-mediated vasculitis affecting medium- and large-sized arteries, primarily the extracranial branches of the carotid artery, though the aorta and its major branches may also be involved. Granulomatous inflammation in the arterial walls leads to lesions composed of T cells and macrophages. While multinucleated giant cells are present in about half of cases, they are not essential for diagnosis (5).

The disease process is believed to start in the outermost layer of the artery, the adventitia, where dendritic cells become highly activated and initiate an immune response. Once activated, these T cells secrete interferon-gamma (IFN-γ), stimulating macrophages and promoting multinucleated giant cell formation, often near the fragmented internal elastic lamina (6). Macrophages contribute to vascular damage by releasing reactive oxygen species and matrix metalloproteinases, leading to oxidative stress and breakdown of the internal elastic lamina (6).

Meanwhile, interleukin-1 (IL-1) and interleukin-6 (IL-6) production drives systemic inflammation and raises inflammatory markers (5). To counteract the damage, the artery releases growth factors such as platelet-derived growth factor and vascular endothelial growth factor, triggering myofibroblast proliferation, neovascularisation, and intimal thickening. These changes result in vessel narrowing and occlusion, increasing the risk of ischemic complications (6).

Clinical Manifestations

The clinical presentation of GCA is variable, with symptoms often overlapping with those of polymyalgia rheumatica (PMR). Common symptoms include:

  • Headache: Often temporal and new in onset.
  • Scalp tenderness: Particularly over the temporal arteries.
  • Jaw claudication: Pain or fatigue in the jaw muscles during chewing, highly specific for GCA.
  • Visual symptoms: Transient or permanent vision loss due to anterior ischemic optic neuropathy (AION) or central retinal artery occlusion.
  • Systemic symptoms: Fatigue, weight loss, fever, and night sweats.
  • Large-vessel involvement: Can present with limb claudication, aortic aneurysms, and dissection.

Diagnosis

Blood tests that should be performed include Full blood count, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). These should be obtained before initiating high-dose glucocorticoids. Elevated CRP and ESR are commonly observed, with platelet counts often increased. However, inflammatory markers tend to decrease once glucocorticoid therapy is initiated. CRP is considered a more specific and reliable marker than ESR in diagnosing GCA. However, despite the importance of laboratory tests, treatment with high-dose glucocorticoids should not be delayed in patients with a strong clinical suspicion of GCA (7).

The definitive diagnosis of GCA is through imaging studies or temporal artery biopsy should be performed, depending on availability.  Vascular ultrasonography of the temporal and axillary arteries is the preferred first-line diagnostic tool when available. In patients with GCA, ultrasonography may reveal arterial wall thickening (halo sign), stenosis, or occlusion. The non-compressible halo sign is the most specific finding (8). A positive ultrasonography result in a patient with high clinical suspicion of GCA is sufficient to confirm the diagnosis, eliminating the need for further testing.

When ultrasonography is unavailable or when clinical suspicion is high despite a normal ultrasound result then Temporal artery biopsy (TAB) remains as an important diagnostic tool. The biopsy is taken from the side showing abnormal clinical findings by an experienced clinician. A positive biopsy confirms GCA if it demonstrates characteristic intramural inflammation, including giant cells or pan-arteritis (9).

Management

Corticosteroid therapy is the main treatment for GCA, with high-dose prednisone (40–60 mg/day) initiated immediately upon suspicion. In cases of acute vision loss, intravenous methylprednisolone (1 g/day for 3 days) is recommended. Referral to rheumatology is necessary and treatment is gradually tapered over 12–24 months, guided by symptom resolution and inflammatory markers. To minimise long-term steroid exposure and reduce relapse rates, tocilizumab (an IL-6 inhibitor) is commonly used as a steroid-sparing agent, while methotrexate and azathioprine may be considered in refractory cases (10).

Low-dose aspirin (75mg daily) may help lower the risk of ischemic complications. Long-term management includes regular ESR and CRP monitoring, screening for glucocorticoid-related complications such as osteoporosis, diabetes, hypertension, and infections, and imaging surveillance for aortic aneurysms in patients with large-vessel involvement(10).

Conclusion

Giant cell arteritis (GCA) is a systemic vasculitis that can lead to life threatening complications if not promptly treated and discussed with a rheumatologist. Advances in diagnostic imaging and the introduction of biologic therapies have improved disease management, enhancing control while minimising steroid-related adverse effects.

References

(1)          Holden WA. Memorandum Book of a Tenth-Century Oculist. A Translation of the Tadhkirat of Ali ibn Isa of Baghdad (cir. 940-1010 A. D.), the Most Complete, Practical and Original of All the Early Textbooks on the Eye and Its Diseases. Archives of Ophthalmology 1936;16:541–3. https://doi.org/10.1001/archopht.1936.00840210215020.

(2)          Hunder GG. Giant Cell (Temporal) Arteritis. Rheumatic Disease Clinics of North America 1990;16:399–409. https://doi.org/10.1016/S0889-857X(21)01065-6.

(3)          Hunder GG. Epidemiology of giant-cell arteritis. Cleve Clin J Med 2002;69 Suppl 2:SII79-82. https://doi.org/10.3949/ccjm.69.suppl_2.sii79.

(4)          Mackie SL, Taylor JC, Haroon-Rashid L, Martin S, Dasgupta B, Gough A, et al. Association of HLA-DRB1 amino acid residues with giant cell arteritis: genetic association study, meta-analysis and geo-epidemiological investigation. Arthritis Res Ther 2015;17:195. https://doi.org/10.1186/s13075-015-0692-4.

(5)          Lyons HS, Quick V, Sinclair AJ, Nagaraju S, Mollan SP. A new era for giant cell arteritis. Eye (Lond) 2020;34:1013–26. https://doi.org/10.1038/s41433-019-0608-7.

(6)          Dinkin M, Johnson E. One Giant Step for Giant Cell Arteritis: Updates in Diagnosis and Treatment. Curr Treat Options Neurol 2021;23:6. https://doi.org/10.1007/s11940-020-00660-2.

(7)          Mackie SL, Dejaco C, Appenzeller S, Camellino D, Duftner C, Gonzalez-Chiappe S, et al. British Society for Rheumatology guideline on diagnosis and treatment of giant cell arteritis. Rheumatology (Oxford) 2020;59:e1–23. https://doi.org/10.1093/rheumatology/kez672.

(8)          Pouncey AL, Yeldham G, Magan T, Lucenteforte E, Jaffer U, Virgili G. Halo sign on temporal artery ultrasound versus temporal artery biopsy for giant cell arteritis. Cochrane Database Syst Rev 2024;2:CD013199. https://doi.org/10.1002/14651858.CD013199.pub2.

(9)          Rubenstein E, Maldini C, Gonzalez-Chiappe S, Chevret S, Mahr A. Sensitivity of temporal artery biopsy in the diagnosis of giant cell arteritis: a systematic literature review and meta-analysis. Rheumatology (Oxford) 2020;59:1011–20. https://doi.org/10.1093/rheumatology/kez385.

(10)       Maz M, Chung SA, Abril A, Langford CA, Gorelik M, Guyatt G, et al. 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Giant Cell Arteritis and Takayasu Arteritis. Arthritis Rheumatol 2021;73:1349–65. https://doi.org/10.1002/art.41774.

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