Giant Cell Arteritis

A 70-year journey to unravel a medical mystery

I was always in good health. I never missed work and then all of a sudden it was like my world came undone. I could tell it was something bad.
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Judy Murphy GCA patient and registered nurse from Everett, Massachusetts, USA.

GCA is a formidable enemy. Its complexity, both in terms of how it is caused and the non-specific symptoms it triggers, has been a major challenge for doctors and researchers since it was first described in medical literature in 1890, with the mention of a man with “red streaks” on his forehead.3

A history of giant cell arteritis

1890
The first detailed case of GCA is reported in an elderly man with “red streaks” on his forehead.3

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1950
It is shown GCA responds well to the anti-inflammatory properties of cortisone, a steroid.2,3

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1990
The American College of Rheumatology 1990 criteria for GCA includes elevated levels of erythrocyte sedimentation rate (ESR) as one of the five criteria for the diagnosis of GCA.4

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1997
Researchers find C-reactive protein (CRP) is a more sensitive marker than ESR for the early diagnosis of GCA.5

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2000
Serum levels of interleukin-6 (IL-6) are found to be more sensitive than ESR for indicating disease activity in untreated and treated patients with GCA. This discovery makes IL-6 inhibition of therapeutic interest in GCA.2,6

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2001
Methotrexate, combined with steroids, is investigated as a treatment for GCA and is seen to reduce relapse rate.2

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2006
It is reported that initial treatment of GCA using high doses of intravenous steroids is effective in managing and delaying the recurrence of GCA symptoms, allowing for a more rapid reduction in dosage of oral steroids.7

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2016
The Lancet reports on the results of a phase II trial supporting the role of IL-6 inhibition in GCA.8

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Since then, experts have battled to unravel its complex causes, not just to relieve its debilitating symptoms but to find a cure. What is known about GCA is that it is an inflammatory disease which affects the body’s medium and large arteries.1 It targets mainly the arteries supplying the head, as well as the aorta – the main artery in the human body – and its branches that supply the neck and arms.1

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The term "giant cell" is used because the cells of the immune system known as macrophages can become fused together within the inflamed walls of the artery.

Depending on which arteries are affected, GCA reveals itself in many ways, which is why it is so tough to diagnose. Immune system cells invade the walls of arteries, setting off a chain reaction of inflammation.1,9 Inflammation thickens the artery walls, causing them to narrow and reducing the flow of blood.9 This in turn causes the devastating symptoms suffered by patients - severe headaches, scalp tenderness, jaw pain and sight problems.1 In some cases the blood vessel can close completely and when this happens to the arteries serving the eye, sudden blindness can occur. What is still not known is what triggers this immune attack.1

The most severe and feared symptom is the loss of vision, either temporarily or more serious, irreversible vision loss.
Dr Neil Collinson Senior Clinical Development Scientist at Roche

Steroids have been the mainstay of treatment for GCA for almost 70 years with little progress discovering effective, but less toxic, ways of tackling it.2 Steroids suppress the immune system, and block the inflammatory process, but how exactly they tackle GCA is not known.2 Trying to unravel the mechanism by which steroids treat GCA is leading the way to potentially discover new GCA treatment options. The aim is to find a treatment that could break the devastating inflammatory cascade triggered by the disease to get people into remission quickly without needing to resort to steroids.

Progress is already being made to work out the complex role of all the different immune cells and biological pathways that are implicated in the disease.

As more is understood about the immune system it will hopefully reveal not only why GCA develops, but more importantly how it can be stopped.

References

  • 1. Bhat S, et al. Giant cell arteritis. Midlife and Beyond, GM. Rheumatology. 2010; 071-079.
  • 2. Ponte C, et al. Giant cell arteritis: Current treatment and management. World J Clin Cases, 2015; 3(6): 484-494.
  • 3. Hunder G. History of giant cell arteritis (GCA) polymyalgia rheumatic (PMR). Rheumatology. 2005; 44(suppl 3):iii1.
  • 4. Hunder G et al. The American College of Rheumatology 1990 Criteria for the Classification of Giant Cell Arteritis. Arthritis & Rheum. 1990; 33(8):1122-1128.
  • 5. Salvarani C., et al. Laboratory investigations useful in giant cell arteritis and Takayasu’s arteritis. Clin Exp Rheumatol 2003; 21(Suppl. 32):S23-S28.
  • 6. Chatterjee S., et al. Clinical Diagnosis and Management of Large Vessel Vasculitis: Giant Cell Arteritis. Curr Cardiol Rep (2014) 16:498. DOI 10.1007/s11886-014- 0498-z.
  • 7. Mazlumzadeh M., et al. Treatment of giant cell arteritis using induction therapy with high-dose glucocorticoids: a double-blind, placebo-controlled, randomized prospective clinical trial. Arthritis Rheum. 2006;54(10):3310-8.
  • 8. Villiger P., et al. Tocilizumab for induction and maintenance of remission in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial. The Lancet. Published online 4 March 2016. http://dx.doi.org/10.1016/S0140-6736(16)00560-2.
  • 9. GCA pathophysiology. BMJ best practice. [Internet; cited 2017 Nov 7]. Available at: http://bestpractice.bmj.com/best-practice/monograph/177/basics/pathophysiology.html