Decoding Giant Cell Arteritis: Unravelling The Mysteries Of A Silent Threat

Introduction

Giant Cell Arteritis (GCA) is a potentially debilitating vascular disease. Characterised by inflammation of the blood vessels, particularly the temporal arteries, GCA can lead to severe complications if left untreated, including irreversible vision loss. Often referred to as a "silent threat," GCA can develop gradually and subtly, making early detection and intervention critical.

Despite its severity, GCA remains a relatively under-recognised condition. Because of the limited awareness, diagnosing GCA can be significantly delayed, worsening its adverse effects on patients' lives. This article will prompt better understanding about giant cell arteritis, its presentations and its management.

What is Giant Cell Arteritis?

Giant cell arteritis is an autoimmune disease in which large and medium-sized arteries become inflamed. It mostly affects individuals older than 50, is more common in women, and rarely presents in young adults. GCA has two commonly known forms, differentiated by the location and presenting symptoms. 

Why does it occur?

To begin with, the immune system is triggered by injury to the vessels. The injury is mostly due to autoimmune processes, infections, or ageing processes. In GCA, the body’s immune system has an abnormal response to the injury, causing sustained inflammation. 

Researchers have yet to identify the exact cause of the abnormal response, but a strong association has been found with genetic abnormalities. Abnormalities in specific genes predispose a person to developing giant cell arteritis. These genes, including HLA (human leukocyte antigen) genes and T cell genes, are crucial for the normal functioning of the immune system. A fault in these genes will naturally cause a fault in our immune system.¹ 

What is the mechanism of GCA?

In GCA, the body’s immune system persistently attacks arteries, causing inflammation and narrowing of the affected arteries over time. To understand the underlying mechanism, we must learn about granulomatous inflammation. Granulomatous inflammation is a hallmark of Giant Cell Arteritis.

It is a distinct type of chronic inflammation characterised by the formation of granulomas, which are small, organised collections of immune cells (mostly macrophages and T cells). These cells combine to form giant cells within the granuloma, hence the name giant cell arteritis.² The granulomas serve to isolate and contain the offending agents, but their presence can disrupt normal tissue structure and function. 

So, in GCA the body’s immune cells attack the arteries and form granulomas. These granulomas narrow the arteries over time and disrupt normal blood flow.

What are the risk factors?

Not everyone with faulty genes will develop GCA. Some of the well-known risk factors of GCA are advancing age, female gender, and polymyalgia rheumatica.

1. Advancing age: Giant cell arteritis commonly develops in adults above the age of 50. The highest incidence is recorded in those between 70-79. This may be attributed to the decline of bodily functions with advancing age²
2. Females: Overall, women are more likely to develop GCA. However, interestingly men are more prone to blindness caused by GCA. The role of gender in the development of GCA is not completely understood
3. Polymyalgia Rheumatica (PMR): PMR is an autoimmune disease of the muscles. It causes stiffness in movement and pain in muscles. Generally, any autoimmune disease can increase the risk of developing another; but PMR and GCA have a special relationship. Around 10% of patients with PMR also have GCA, and 50% of patients with GCA have PMR

What are the types of GCA?

GCA can be classified into two types by the location of inflammation. The presentation of GCA can differ according to the type, and it will be discussed in later sections. Many patients with GCA may have features of both types, and the inflammation can extend from the cranial arteries to larger vessels over time.

1. Cranial GCA: This is the more common form of GCA. It primarily affects medium-sized arteries located around the head, particularly the temporal artery – this is why GCA is also known as temporal arteritis
2. Extracranial GCA: The inflammation is not confined to the cranial arteries. Large arteries like the aorta are involved in this form of GCA³ 

Signs and symptoms

As mentioned above, a patient with GCA can present with overlapping symptoms. The exact presentation may vary from case to case.

Cranial GCA

Symptoms include:

1. Headache
2. Scalp tenderness
3. Jaw pain
4. Visual disturbances
5. Temporal artery abnormalities

One of the first symptoms to present is a severe, persistent headache. The headache will be felt in the temples. The pain can be bilateral or unilateral. Next is scalp tenderness, which is more specific to GCA than a normal headache. Patients complain of pain while combing their hair, or wearing hats. This is because the scalp becomes more sensitive to pain in GCA. The inflammation also causes jaw pain, especially when chewing. 

Perhaps the most alarming symptom of cranial GCA is visual disturbance. Since inflammation narrows the arteries, blood flow to the eyes is compromised. Visual disturbance in GCA can range from transient blurring or double vision, to sudden vision loss. Unfortunately, vision loss can be permanent. Any changes in vision should be reported to the doctor. 

Lastly, there might be external abnormalities of the temporal artery. Various case studies have noted the presence of a thickened and tender temporal artery. It appears as an elongated bulge on the temples.⁴ 

Extracranial GCA

Symptoms include: 

1. Systemic symptoms (symptoms that affect the entire body)
2. Arm or leg claudication
3. Asymmetrical blood pressure
4. Aortic aneurysms and dissections

Inflammation of large arteries in extracranial GCA contributes to the presence of systemic symptoms. Systemic symptoms include fatigue, fever, weight loss, and general malaise (discomfort or unease). Systemic symptoms are common in both types of GCA but may be more pronounced in extracranial GCA.

The aorta is one of the most important arteries, impacting the entire body’s blood flow. Involvement of the aorta results in alarming symptoms. First of all, blood flow to the limbs is disrupted due to narrowing of the aorta (arm or leg claudication). You may feel pain, cramping and fatigue in your limbs. Exercising often makes these symptoms more prominent. 

Secondly, aortic involvement can result in significant differences in blood pressure readings between the arms. Next is the development of aortic aneurysms or dissections. It is by far the most alarming development of extracranial GCA. The wall of the aorta becomes weaker as GCA progresses. The weakening of the aortic wall results in aneurysms or life-threatening dissections.³

Diagnosing GCA

Initially, the doctor will investigate your symptoms. You will be asked about relevant risk factors and your past medical history. Next, the doctor will ask for the relevant tests that can be used to diagnose GCA to be conducted. These will include blood tests, ultrasound, and biopsy. 

Blood tests are useful to rule out other diseases, and to determine the severity of inflammation. However, blood tests are not enough to confirm GCA. Ultrasounds are the preferred method of initial investigation for giant cell arteritis. Early changes in the arteries can be detected by ultrasound, like narrowing of arteries and thickening of the arterial wall due to inflammation.²

But alas, ultrasounds are not enough to confirm the diagnosis either. The only test that can confirm the diagnosis of giant cell arteritis is a biopsy.⁵ A small sample of the arterial wall is taken to examine under a microscope. GCA is confirmed by the presence of inflammation, giant cells and granulomas in the arterial wall.

Treatment

To treat GCA, the priority is to control inflammation in the arteries. Thus, the treatment of GCA revolves around glucocorticoids/steroids.⁶ Steroids decrease inflammation, slowing the progression of the disease and preventing complications. Regardless of severity and complications, the initial therapy is high-dose steroids, typically prednisone. Steroids are taken until remission of GCA and then tapered off with a doctor’s advice. 

Patients with a high risk of developing complications from steroids may be prescribed steroid-sparing agents to reduce the long-term side effects. Tocilizumab is one such effective steroid-sparing agent that has been able to maintain steroid-free remission (disappearance of symptoms of a disease) with no relapses.^2,7 In the event of visual disturbances, a combination of intravenous steroids and oral steroids is used. Intravenous delivery of high-dose steroids can control inflammation more rapidly.

Apart from medications, long-term follow-up is a crucial part of managing GCA. Patients need to be monitored for relapse, and development of complications so that medication can be adjusted accordingly. With medication and consistent monitoring, there are some hopes for successfully treating giant cell arteritis.⁷ 

Summary

Although a potentially debilitating form of vascular disease, early detection and treatment can play a significant role in minimising the dangers of giant cell arteritis. Its cranial form presents with headaches, scalp and jaw tenderness, and visual disturbances; however, extracranial GCA is harder to detect by symptoms alone. Thus, readers are suggested to look out for any predisposing risk factors, such as age above 50 years, female gender, and autoimmune diseases like polymyalgia rheumatica.