Introduction

Vasculitis is a general term for vessel wall inflammation and damage to blood vessels. The vessel lumen is
usually compromised because of ischemia of the tissues supplied by the involved vessel. A broad and
heterogeneous group of syndromes may occur, since any type, size, and location of blood vessel may be
involved. Vasculitis and its consequences may be the primary manifestation of a disease, and can also be a
secondary component of another primary disease. Vasculitis may be confined to a single organ, or may involve
several organs. A major feature of the vasculitis syndromes that there major heterogeneity at the same time as
there is considerable overlap among them which caused difficulties for the development of a fitting
classification system for these diseases. [2]

One of common vasculitis syndromes is the Giant cell arteritis (GCA), also referred to as cranial arteritis or
temporal arteritis, a chronic inflammatory disorder, typically presented with granulomatous inflammation, that
principally affects large and middle arteries in the head. Vertebral and ophthalmic arteries, as well as the aorta
(giant cell aortitis), are other common sites of involvement. Giant cell arteritis is often associated with
polymyalgia rheumatica (that manifest muscle and joint pain). GCA occurs almost exclusively in individuals
who are older than 50 years with peak incidence between 70 and 80 years, two to three times more common in
women than in men, and high incidence in Scandinavian populations while rare in blacks. Signature features
include presence of giant cells, and overgrowth of intima, while signature symptoms include vision loss
(blindness), and jaw claudication. [1]
Pathogenesis
GCA is a complex systematic disorder and it is believed to represent the result of the breakdown of
immunologic tolerance, resulting from interactions between the immune system and poorly defined components
of the arterial wall. Recent studies suggested that both the innate and the adaptive branches of immune system
are activated and may lead to vessel wall injury. Although the temporal artery is most frequently involved in
giant cell arteritis, patients often have a systemic vasculitis of multiple medium and large sized arteries, which
may go undetected during diagnosis. Histopathologically, the disease is a panarteritis type (Inflammation
involving all the layers of an artery) with inflammatory mononuclear cells that infiltrate within the vessel wall
with frequent giant cell formation. There is proliferation of the tunica intima and fragmentation of the internal
elastic lamina. Experimental data support that giant cell arteritis is an antigen-driven disease in which activated
T-lymphocytes, macrophages, and dendritic cells play a critical role in the disease pathogenesis. Sequence
analysis of the T-cell receptor (TCR) of tissue-infiltrating T-cells in lesions of giant cell arteritis indicates
restricted clonal expansion, suggesting the presence of an antigen residing in the arterial wall. Giant cell arteritis
is believed to be initiated in the adventitia where CD4+ T-cells enter through the vasa vasorum, become
activated, and orchestrate macrophage differentiation. T-cells recruited to vasculitic lesions in patients with
giant cell arteritis produce predominantly pro-inflammatory cytokines (IL-2, IL-6, and IFN-γ) where their
functions include mediation the recruitment of inflammatory cells, inhibition of cell migration, enhancement of
T cell proliferation and stimulation of T and B cells. The net result is further amplification of the immune
response, through positive feedback loops. [1]&[3]
A summary [3]:
1. An antigen is sensed by dendritic cells in the adventitia → recruits more dendritic cells, lymphocytes, and
macrophages.
2. Dendritic cells process and present the antigens → cluster of differentiation 4 (CD4+) T cell activation.
3. CD4+ T cells proliferate → vascular inflammation via activation of macrophages.
4. Medial layer is invaded by inflammatory cells → macrophages undergo granulomatous organization (giant
cells) → growth factors and metalloproteinases produced → loss of vascular smooth muscle cells and
destruction of the internal elastic lamina.
5. Injured smooth muscle cells respond to this damage → myofibroblasts differentiate, migrate toward the
intimal layer, and produce extracellular matrix proteins → intimal hyperplasia and arterial occlusion →
ischemic complications of the disease.
Causes of Giant Cell Arteritis (GCA)
Giant Cell Arteritis (GCA), commonly known as temporal arteritis, is an inflammatory illness that mostly
affects the head and neck. A number of variables are thought to have a role in the development of GCA, despite
the fact that its precise etiology is still unclear.
1. Immune System Dysfunction: It is believed that a dysfunctional immune response is one of the main causes
of GCA. The immune system, which typically guards the body against diseases, has
the potential to target healthy tissues—including artery walls—by accident. This
immune-mediated process injures the blood vessels and causes inflammation. [4]
2. Genetic Predisposition: The emergence of GCA may be influenced by genetics.
Some people may inherit particular genetic characteristics that increase their risk of
developing autoimmune diseases like GCA. However, it is still unclear which
individual genes are at play. [4]
3. Age and Gender: adults over the age of 50 are most commonly impacted by GCA, with adults over the age of
70 having the greatest frequency. Women are also more likely to be impacted than males, however it's unclear
why this difference exists.
4. Environmental Triggers: In people who are genetically susceptible to developing GCA, environmental
variables may play a role. There have been certain infections mentioned as probable causes, although there is
little proof to support this. [4]
5. Blood Vessel Structure: GCA may be brought on by structural alterations in blood vessels. The immune
system's onslaught may be more likely to affect arteries that are already prone to inflammation or have specific
weaknesses. [4]
6. Immunosuppressive Drugs: It's interesting to note that GCA instances have been
recorded following immunosuppressive cancer therapy with immune checkpoint
inhibitors. These drugs may change how the immune system functions, which might
result in autoimmune diseases like GCA.
7. The Relationship Between Giant Cell Arteritis and Polymyalgia Rheumatica: Polymyalgia rheumatica
(PMR), a disorder that causes muscular discomfort and stiffness, is frequently linked to GCA. Although there
are some parallels between these two illnesses in terms of immune system participation and inflammatory
processes, their link is not entirely understood. [4]
8. Geographic Variations: The incidence of GCA varies by region, indicating
potential environmental or genetic variables. In comparison to other places of the
world, it is more prevalent in Northern Europe and North America.
Giant Cell Arteritis is a complicated and multifaceted illness with a number of
probable causes, to put it succinctly. The development of GCA may be influenced
by a number of variables, including immune system malfunction, genetic predisposition, age, gender,
environmental triggers, blood vessel structure, and certain drugs. To completely comprehend how these
elements, interact and to provide more efficient therapies for this illness, additional study is required. It is
crucial to seek immediate medical assistance if you or someone you know exhibits symptoms that point to GCA
in order to enable an accurate diagnosis and effective treatment. [4]
Clinical features:
The cardinal symptom of giant cell arteritis is a new headache which is often
localized to the temporal or occipital region but it can occur anywhere and may be
accompanied by scalp tenderness. Jaw pain develops in some patients brought on
by chewing or talking. Jaw claudication if present is more specific than sensitive
and a “chewing gum test” can be performed to bring this out. [5]

It’s really important that any patient with active or inactive GCA should report any new headaches changes in
vision or jaw pain to their doctor. If GCA is spread to the blood supply of the eye, visual disturbances can occur
(most specifically amaurosis) and a catastrophic presentation is with irreversible blindness in one of the eyes
due to occlusion of the posterior ciliary artery. Permanent vision loss can occur if diagnosis and treatment is
delayed but with proper treatment this can be prevented. on fundoscopy, the optic disc may appear pale and
swollen with hemorrhages, but these changes may take 24-36 hours, and the fundi may initially appear
normal. [6]

Rarely, neurological involvement may occur, with transient ischemic attacks, brainstem infarcts and
hemiparesis. In GCA, constitutional symptoms such as fever, loss of appetite, unintended weight loss, fatigue,
malaise, flue-like symptoms and night sweats, are common. There may also be stiffness and painful restriction
of active shoulder movements on waking. Additionally, there may be joint involvement causing arthralgia and
myalgia (Polymyalgia). [1]
The disease however could present with nonspecific symptoms causing delay in diagnosis or confusion with
other diseases such as other types of vasculitis (Takayasu's arteritis), infections, or local causes.
Diagnosis:
The type of vasculitis syndrome must be diagnosed based on a thorough history and physical examination
because there are so many different signs, symptoms, and body systems that can be affected. Blood tests are
performed, and an x-ray or biopsy may be necessary in some circumstances and some other physical
examination to give the appropriate treatment, a precise diagnosis is required. [7]
Blood tests:
These examinations search for indicators of inflammation, such as elevated C-
reactive protein levels. You can determine if you have enough red blood cells by
getting a complete blood count. Vasculitis can be identified using blood tests that
check for specific antibodies, such as the anti-neutrophil cytoplasmic antibody (ANCA) test. [8]
Imaging tests:
Where blood vessels and organs are impacted can be ascertained with the aid of
noninvasive imaging techniques. The doctor can use them to track how well you are
responding to treatment. X-rays, ultrasound, computed tomography (CT), magnetic
resonance imaging (MRI), and positron emission tomography (PET) are imaging
procedures used to diagnose GCA.[7]
X-rays of your blood vessels:
Angiograms are X-rays of your blood vessels. A flexible catheter, similar to a thin straw, is placed during this
surgery into a major artery or vein. After injecting a particular dye into the catheter, the artery or vein is filled
with the dye while X-rays are being taken. The ensuing X-rays show the contours of your blood vessels.[7]
Biopsy:
During this surgical process, your doctor will take a small sample of tissue from
the area of your body that is injured. The tissue is then examined by your doctor
for indicators of vasculitis.[8]
Additional targeted testing: Additional tests may be carried out depending on the
organs affected and the suspected form of vasculitis. For instance, if lung involvement is suspected, lung
function tests may be carried out. [8]
Depending on the precise symptoms of the disorder, the diagnosis of vasculitis can be challenging and may call
for involvement from numerous specialists, including rheumatologists, dermatologists, nephrologists, and
pulmonologists. To effectively manage vasculitis and avoid complications, early diagnosis and adequate therapy
are crucial. You must consult a doctor right away if you think you or someone else may have vasculitis or if
you're exhibiting alarming symptoms. [9]
Treatment
Corticosteroids are the cornerstone of treatment for GCA since they can reduce inflammation and stop
additional damage. However, prolonged corticosteroid use may have negative consequences.
Since many years ago, corticosteroids have been the first-line treatment for GCA. These medications
successfully treat inflammation and relieve symptoms like headache, soreness in the scalp, jaw claudication,
and vision abnormalities. The corticosteroid most frequently used in the treatment of GCA is prednisone. The
first dose is often high—between 40 and 60 mg per day—and is gradually reduced over a period of months.
Based on the patient's reaction to therapy and the presence of any side effects, the tapering timetable should be
customized.
Although long-term usage of corticosteroids can have a number of negative effects, such as osteoporosis,
diabetes, hypertension, and an increased risk of infections, they are helpful in managing GCA. Alternative
treatment approaches have been researched in an effort to reduce the dosage and duration of corticosteroid
medication. [4]
Methotrexate, an immunosuppressive medication frequently prescribed for rheumatoid arthritis, is one such
strategy. In GCA patients, methotrexate may facilitate a quicker tapering of corticosteroid dosage, potentially
lowering the risk of steroid-related problems. It frequently works best when combined with corticosteroids and
has occasionally been successful in bringing about remission or at least disease management. [4]
Tocilizumab, a monoclonal antibody that targets the interleukin-6 receptor, is another immunosuppressive
substance that has been investigated in GCA. Tocilizumab can increase the likelihood of attaining a prolonged
remission and decrease the cumulative corticosteroid dose when taken as an adjuvant to corticosteroids,
according to clinical trials. [4]
Other immunomodulatory treatments, such as azathioprine and mycophenolate mofetil, have also been
investigated in the management of GCA. These drugs function by calming inflammation and inhibiting the
immune system. They may be taken into account in situations where corticosteroids and other medications are
ineffective or poorly tolerated. [4]
The treatment strategy for GCA should be individualized for each patient, taking into account their unique
features, the severity of their condition, and any potential comorbidities, it is crucial to understand. To control
side effects, track treatment response, and modify the course of treatment as necessary, it is essential to follow
up often with medical specialists. [4]
Lifestyle adjustments can help manage GCA in addition to
pharmaceutical therapy. Patients' general well-being and
prospective treatment results may be enhanced by encouraging
them to lead healthy lifestyles that include frequent exercise, a
balanced diet, and quitting smoking. [4]
To sum it up, Corticosteroids are typically used to treat giant cell
arteritis in order to decrease inflammation and manage symptoms.
Alternative treatments and immunosuppressive drugs, such as
methotrexate and tocilizumab, have been studied due to the
possibility of negative consequences linked to long-term corticosteroid usage. To get the best results and
improve the patient's quality of life, individualized treatment programs, routine monitoring, and lifestyle
changes are crucial aspects of GCA care. Always seek the advice of a medical expert when choosing the best
course of therapy for GCA based on unique requirements and circumstances.
References:-
[1] Robbins basic pathology 10th edition; Vinay Kumar, Abul K. Abbas, Jon C. Aster.
[2] Harrison’s rheumatology 3rd Edition; Anthony S. Fauci, Carol A. Langford.
[3] www.intechopen.com; Immunopathophysiology of Large Vessel Involvement in Giant Cell Arteritis —
Implications on Disease Phenotype and Response to Treatment; Panagiota Boura, Konstantinos Tselios, Ioannis
Gkougkourelas and Alexandros Sarantopoulos; from the book: Updates in the Diagnosis and Treatment of
Vasculitis.
[4] Giant-Cell Arteritis; Imtiaz A. Chaudhry.
[5] Davidson’s principles and practice of medicine textbook, by Stanley Davidson.
[6] www.mayoclinic.com; Giant cell arteritis – Symptoms and causes.
[7] Allergy.org.au ASCIA_PCC_Vasculitis_disorders_2019.pdf ()
[8] Rheumatology; Volume 39; Issue 3; March 2000; Pages 245–252.
[9] Openaccessjournals.com; article on Diagnosis and treatment of cutaneous leukocytoclastic vasculitis;
Carmen E Gota & Leonard H Calabrese. diagnosis-and-treatment-of-cutaneous-leukocytoclastic-vasculitis.pdf
(openaccessjournals.com)