Temporal arteritis

Temporal arteritis, also known as giant cell arteritis, is a chronic inflammatory disease that primarily affects medium and large arteries, particularly those in the head and neck region. It represents one of the most common forms of systemic vasculitis in adults over the age of 50 and carries significant risk for visual and neurological complications if not treated promptly.

Definition and Overview

Definition of Temporal Arteritis

Temporal arteritis is defined as an inflammatory vasculitis involving large- and medium-sized arteries, most notably the branches of the external carotid artery such as the superficial temporal artery. The disease leads to granulomatous inflammation of the arterial wall, resulting in narrowing or occlusion of the lumen and subsequent ischemia of affected tissues. It is considered a medical emergency due to its potential to cause irreversible blindness and other ischemic events.

Historical Background

The condition was first described in 1932 by Horton, Magath, and Brown, who detailed cases of arteritis affecting the temporal arteries with associated headache and visual disturbances. Since then, significant progress has been made in understanding its immunopathogenesis and relationship to polymyalgia rheumatica. The introduction of corticosteroid therapy in the mid-20th century markedly improved prognosis and outcomes for affected patients.

Synonyms and Terminology

Temporal arteritis is often referred to by several synonymous terms, each emphasizing different aspects of the disease:

• Giant Cell Arteritis (GCA): Refers to the presence of multinucleated giant cells within the inflamed arterial wall, which is a hallmark histopathological feature.
• Cranial Arteritis: Highlights the predilection of the disease for cranial arteries, including the temporal, ophthalmic, and vertebral arteries.
• Horton Disease: Named after Thomas Horton, one of the first physicians to describe the condition.

Although the term “giant cell arteritis” is more inclusive and often preferred in medical literature, “temporal arteritis” remains widely used in clinical contexts due to the frequent involvement of the temporal artery.

Epidemiology

Incidence and Prevalence

Temporal arteritis is predominantly a disease of older adults, with incidence increasing significantly after the age of 50. The annual incidence rate ranges between 15 and 30 cases per 100,000 persons over 50 years of age. The prevalence is higher in populations of Northern European descent, particularly in Scandinavian countries, compared to Asian or African populations.

Age and Gender Distribution

The condition rarely occurs before the age of 50, with the average age of onset between 70 and 80 years. Women are affected approximately two to three times more frequently than men, indicating a possible hormonal or immunological predisposition.

Geographical Variations

Geographical distribution studies have shown significant variations in the incidence of temporal arteritis. Northern European countries such as Sweden, Norway, and Iceland report the highest rates, whereas Asian and African populations have the lowest. These differences suggest a genetic component, possibly linked to specific HLA class II alleles.

Risk Factors

• Age: The strongest risk factor, with incidence rising sharply after 50 years.
• Gender: Females are at greater risk than males.
• Genetic factors: Associations with HLA-DRB1*04 and other alleles have been reported.
• Ethnicity: Higher prevalence among individuals of Northern European ancestry.
• Environmental triggers: Seasonal variations and viral infections have been proposed as possible triggers, though evidence remains inconclusive.

Etiology and Pathogenesis

Underlying Causes

The exact cause of temporal arteritis remains unknown, but it is widely accepted to be a multifactorial disease involving genetic susceptibility, immune dysregulation, and environmental triggers. The disease is characterized by immune-mediated inflammation targeting arterial walls, primarily involving large elastic arteries and their branches.

• Autoimmune Mechanisms: Temporal arteritis is considered an autoimmune disorder in which autoreactive T-cells and macrophages attack the arterial wall, leading to granulomatous inflammation and tissue damage.
• Genetic Predisposition: Studies have demonstrated strong associations between temporal arteritis and specific human leukocyte antigen (HLA) alleles, such as HLA-DRB1*04, which may influence antigen presentation and immune activation.
• Environmental Triggers: Exposure to certain infectious agents, seasonal factors, and possibly environmental toxins have been proposed to precipitate disease onset in genetically predisposed individuals.
• Infectious Hypotheses: Several infectious agents, including parvovirus B19, Chlamydia pneumoniae, and varicella-zoster virus, have been implicated as potential triggers, though causative links remain inconclusive.

Immunopathogenesis

The immunopathogenesis of temporal arteritis involves a complex cascade of cellular and molecular events leading to arterial wall inflammation, remodeling, and ischemia. The process begins with the activation of dendritic cells in the adventitia, which subsequently stimulate CD4+ T-cells and macrophages.

• Role of T-cells and Macrophages: CD4+ T-helper cells, particularly Th1 and Th17 subsets, secrete pro-inflammatory cytokines that activate macrophages. Activated macrophages release reactive oxygen species and matrix metalloproteinases, causing tissue injury.
• Cytokine-Mediated Inflammation: Key cytokines such as interleukin-6 (IL-6), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) drive the inflammatory response, sustaining vascular damage and systemic symptoms.
• Vascular Remodeling and Intimal Hyperplasia: Chronic inflammation induces smooth muscle proliferation and intimal thickening, leading to luminal narrowing and reduced blood flow. This contributes to ischemic manifestations such as vision loss and jaw claudication.

Pathophysiology

Vascular Inflammation and Damage

Temporal arteritis primarily affects the aorta and its major branches, particularly the superficial temporal, ophthalmic, and vertebral arteries. The hallmark of the disease is granulomatous inflammation involving all layers of the arterial wall. Persistent inflammation leads to destruction of the internal elastic lamina and fibrosis, compromising vascular integrity and elasticity.

Effect on Arterial Wall Layers

The inflammatory process begins in the adventitia, where dendritic cells initiate the immune response. The inflammation extends inward to involve the media and intima, resulting in the following changes:

• Fragmentation of the internal elastic lamina due to enzymatic degradation.
• Proliferation of smooth muscle cells within the intima causing thickening.
• Formation of multinucleated giant cells within granulomatous lesions.
• Occlusion of the arterial lumen leading to ischemia.

Consequences on Blood Flow

Arterial narrowing and occlusion impede blood flow to downstream tissues, resulting in ischemic complications. Involvement of the ophthalmic artery can cause sudden vision loss, while occlusion of the vertebral or carotid branches may lead to cerebral ischemia or stroke. Reduced perfusion in the scalp or jaw contributes to tenderness and claudication symptoms.

Systemic Effects

Beyond localized vascular involvement, temporal arteritis can have systemic manifestations due to the release of inflammatory cytokines into circulation. Elevated IL-6 levels contribute to fever, malaise, and increased hepatic production of acute-phase reactants such as C-reactive protein (CRP) and fibrinogen, leading to markedly elevated erythrocyte sedimentation rate (ESR). These systemic effects explain many of the constitutional symptoms seen in patients.

Histopathology

Gross Pathology

In temporal arteritis, affected arteries may appear thickened, nodular, and tender upon palpation. The temporal artery, when biopsied, often demonstrates segmental involvement, which means the inflammation may be patchy with areas of normal vessel interspersed between affected segments. The luminal narrowing is visible as a result of concentric intimal thickening and fibrosis.

Microscopic Features

Histologically, temporal arteritis is characterized by granulomatous inflammation involving the media and intima of the arterial wall. Key microscopic findings include:

• Granulomatous Inflammation with Giant Cells: The presence of multinucleated giant cells formed by fused macrophages is a hallmark finding, typically situated near the fragmented internal elastic lamina.
• Disruption of Internal Elastic Lamina: The elastic layer is fragmented due to enzymatic degradation by activated macrophages, resulting in structural weakening of the vessel wall.
• Intimal Thickening and Luminal Occlusion: Proliferation of smooth muscle cells and fibroblasts within the intima leads to progressive narrowing of the vascular lumen.
• Perivascular Infiltration: Dense infiltration of lymphocytes, macrophages, and plasma cells surrounds the vessel, reflecting a robust immune-mediated response.

These histological findings are diagnostic when correlated with clinical and laboratory data, and the identification of giant cells confirms the diagnosis in many cases, although their absence does not exclude it.

Clinical Features

General Symptoms

Temporal arteritis often begins with nonspecific systemic symptoms due to the release of inflammatory mediators. These include:

• Fever of unknown origin
• Malaise and fatigue
• Loss of appetite and unintentional weight loss
• Night sweats

These systemic signs may precede localized vascular symptoms by several weeks, contributing to diagnostic delays if not recognized early.

Localized Symptoms

The hallmark clinical manifestation of temporal arteritis is a new-onset headache, typically localized to the temporal or occipital regions. The headache is often described as dull, throbbing, and persistent. Additional localized symptoms include:

• Scalp Tenderness: Patients may experience pain or sensitivity when combing their hair or touching the scalp, due to inflammation of the superficial temporal arteries.
• Jaw Claudication: Pain or fatigue of the jaw muscles during chewing is a characteristic symptom resulting from ischemia of the masseter muscles.
• Temporal Artery Changes: On physical examination, the temporal artery may feel thickened, cord-like, and pulseless.
• Facial or Neck Pain: Due to involvement of nearby arterial branches.

Ocular Manifestations

Ocular involvement is the most feared complication of temporal arteritis, as it can result in permanent visual loss if untreated. The most common manifestation is anterior ischemic optic neuropathy (AION), which occurs due to occlusion of the posterior ciliary arteries supplying the optic nerve head.

• Transient Visual Disturbances: Episodes of blurred vision or amaurosis fugax (temporary vision loss).
• Permanent Visual Loss: Occurs when ischemia causes infarction of the optic nerve.
• Diplopia: Double vision may occur due to involvement of extraocular muscle arteries.

Polymyalgia Rheumatica Association

Temporal arteritis is frequently associated with polymyalgia rheumatica (PMR), a related inflammatory disorder characterized by pain and stiffness in the shoulder and hip girdles. Approximately 40–60% of patients with temporal arteritis exhibit symptoms of PMR, and both conditions may share common immunopathogenic mechanisms. Recognizing this association is crucial, as the presence of PMR symptoms can aid in early diagnosis and treatment initiation.

Complications

Temporal arteritis can lead to several serious complications if diagnosis and treatment are delayed. The most devastating outcomes are related to ischemia of vital tissues caused by arterial occlusion. Early recognition and prompt corticosteroid therapy are essential to prevent irreversible damage.

• Irreversible Blindness: The most feared complication, resulting from occlusion of the posterior ciliary or central retinal arteries. Once vision loss occurs, it is typically permanent, emphasizing the need for urgent intervention at the first sign of visual symptoms.
• Stroke: Involvement of the carotid or vertebral arteries can lead to cerebral ischemia, manifesting as stroke or transient ischemic attacks.
• Aortic Aneurysm and Dissection: Chronic inflammation may extend to the aorta, causing weakening of the vessel wall and increasing the risk of aneurysm formation or dissection, especially in the thoracic region.
• Systemic Vascular Complications: Inflammation of large vessels can lead to claudication of upper or lower limbs, loss of pulses, or bruits over major arteries such as the subclavian or axillary arteries.
• Secondary Effects of Treatment: Long-term corticosteroid therapy may result in complications such as osteoporosis, diabetes, hypertension, and immunosuppression-related infections.

Diagnostic Evaluation

Clinical Assessment

The diagnosis of temporal arteritis is based on a combination of clinical, laboratory, and histological findings. Clinicians should maintain a high index of suspicion in elderly patients presenting with new-onset headache, visual disturbances, or jaw pain. Physical examination findings may include tenderness or thickening of the temporal artery, diminished pulses, and signs of polymyalgia rheumatica.

Laboratory Investigations

Laboratory studies are crucial for supporting the diagnosis and assessing the severity of inflammation:

• Elevated Erythrocyte Sedimentation Rate (ESR): Typically exceeds 50 mm/hour, although a normal ESR does not exclude the diagnosis.
• C-Reactive Protein (CRP): Often markedly elevated and may be a more sensitive indicator of active inflammation than ESR.
• Normocytic Normochromic Anemia: Reflects chronic disease and systemic inflammation.
• Liver Function Abnormalities: Mild elevation in alkaline phosphatase may be seen in some patients.

Imaging Techniques

Advances in vascular imaging have significantly improved the ability to detect inflammation and vessel wall changes in temporal arteritis. Noninvasive imaging modalities are particularly useful when biopsy results are inconclusive or when large-vessel involvement is suspected.

• Ultrasound: The “halo sign,” a dark, hypoechoic area surrounding the arterial lumen, represents mural edema and is a specific finding in active temporal arteritis.
• Magnetic Resonance Imaging (MRI) and Magnetic Resonance Angiography (MRA): Provide detailed visualization of arterial wall thickening, stenosis, or occlusion.
• FDG-PET Scan: Useful for detecting large-vessel involvement by demonstrating increased metabolic activity in inflamed arteries such as the aorta and its branches.

Temporal Artery Biopsy

The temporal artery biopsy remains the gold standard for confirming the diagnosis. It should be performed within one week of initiating corticosteroid therapy to maximize diagnostic yield, though positive findings may persist for several weeks after treatment initiation.

• Indications and Technique: A segment of 2–3 cm of the temporal artery is excised for histological examination. Bilateral biopsies may increase sensitivity due to the segmental nature of the disease.
• Histological Findings: Granulomatous inflammation, multinucleated giant cells, disruption of the internal elastic lamina, and intimal thickening are characteristic. The presence of giant cells confirms the diagnosis, though their absence does not rule it out.

When combined with compatible clinical and laboratory findings, a positive biopsy result provides definitive evidence of temporal arteritis, guiding long-term management decisions.

Differential Diagnosis

Temporal arteritis shares clinical features with several other systemic and localized vasculitic or inflammatory disorders. Differentiating these conditions is essential for accurate diagnosis and appropriate management, as many can present with headache, elevated inflammatory markers, and visual symptoms.

• Polymyalgia Rheumatica (Isolated Form): Although often associated with temporal arteritis, isolated polymyalgia rheumatica presents with proximal muscle stiffness and pain without cranial artery involvement. Inflammatory markers are elevated, but biopsy findings are negative for arteritis.
• Takayasu Arteritis: A large-vessel vasculitis that primarily affects younger women under 40 years of age, involving the aorta and its major branches. It differs in demographic profile and typically lacks temporal artery involvement.
• Systemic Lupus Erythematosus (SLE): May present with headache and vasculitic changes, but laboratory tests reveal positive ANA and anti-dsDNA antibodies, helping to distinguish it from temporal arteritis.
• Polyarteritis Nodosa (PAN): Affects medium-sized arteries and may cause systemic symptoms and neurological deficits, but it typically spares cranial arteries and lacks the granulomatous inflammation seen in temporal arteritis.
• Atherosclerotic Disease: Can cause reduced blood flow and ischemic symptoms but is non-inflammatory in nature and lacks systemic features or elevated ESR/CRP levels.
• Infectious Vasculitides: Secondary to bacterial, viral, or fungal infections; these conditions often demonstrate pathogen-specific markers and systemic infection signs.

Accurate diagnosis requires a comprehensive evaluation combining clinical findings, laboratory tests, imaging, and histological confirmation to distinguish temporal arteritis from these mimicking conditions.

Treatment and Management

Pharmacological Therapy

The cornerstone of treatment for temporal arteritis is prompt initiation of corticosteroid therapy to prevent irreversible ischemic complications, particularly blindness. Treatment should begin as soon as the diagnosis is suspected, even before biopsy results are obtained.

• Corticosteroids:
  • Initial therapy: High-dose oral prednisone (40–60 mg daily) is typically prescribed immediately. In cases with visual symptoms, intravenous methylprednisolone may be used for rapid action.
  • Maintenance therapy: Once symptoms resolve and inflammatory markers normalize, gradual tapering of steroids is initiated to minimize side effects.
• Immunosuppressive Agents:
  • Methotrexate and azathioprine may be used as steroid-sparing agents in patients requiring prolonged therapy or those experiencing corticosteroid-related complications.
  • Leflunomide and mycophenolate mofetil are additional alternatives in refractory cases.
• Biologic Therapy:
  • Tocilizumab, an interleukin-6 (IL-6) receptor inhibitor, has shown efficacy in reducing relapse rates and corticosteroid dependence.
  • Other biologics targeting TNF-α or B-cells are under investigation but are not yet standard therapy.

Monitoring and Tapering

Patients require regular monitoring of ESR, CRP, and clinical symptoms to assess disease activity. The steroid taper should be gradual, often over 12 to 18 months, to prevent relapse. Recurrence is common, particularly during tapering, and may necessitate dose adjustment or the addition of immunosuppressive therapy.

Management of Complications

Preventing and managing treatment-related complications is an integral part of therapy:

• Calcium and vitamin D supplementation, along with bisphosphonates, should be provided to reduce steroid-induced osteoporosis risk.
• Blood glucose and blood pressure should be regularly monitored to detect steroid-related metabolic effects.
• Infections should be promptly treated, and prophylactic measures such as influenza and pneumococcal vaccination are recommended.

Adjunctive Measures

• Antiplatelet Therapy: Low-dose aspirin may reduce the risk of ischemic complications, including vision loss and stroke, by improving microvascular circulation.
• Bone Protection and Infection Prophylaxis: Proactive measures such as osteoporosis prevention, vaccination, and screening for latent infections should accompany long-term immunosuppressive therapy.

With timely and appropriate treatment, the prognosis for temporal arteritis has improved considerably. Corticosteroid therapy remains life- and vision-saving, while newer biologics offer promising alternatives for patients with refractory disease or corticosteroid intolerance.

Prognosis

Factors Influencing Outcome

The prognosis of temporal arteritis largely depends on the timeliness of diagnosis and initiation of corticosteroid therapy. Early treatment can prevent irreversible ischemic complications such as blindness, while delayed intervention is often associated with poor outcomes. Several factors influence the overall disease course:

• Age at Diagnosis: Older patients tend to have a more severe clinical course and slower recovery.
• Severity of Vascular Involvement: Widespread or large-vessel disease is associated with an increased risk of relapse and aortic complications.
• Delay in Treatment: The risk of permanent vision loss increases significantly if therapy is delayed beyond 48 hours after visual symptoms appear.
• Comorbid Conditions: The presence of diabetes, hypertension, or cardiovascular disease may complicate management and recovery.
• Response to Therapy: Patients showing rapid normalization of inflammatory markers and symptom resolution have a better long-term outcome.

Visual Prognosis

Visual impairment in temporal arteritis is often irreversible once established. Prompt corticosteroid therapy can, however, prevent further visual loss and protect the contralateral eye. Approximately 15–20% of untreated patients develop permanent blindness, but this rate has significantly decreased with early intervention. The use of adjunctive therapies such as low-dose aspirin may also improve ocular outcomes by enhancing perfusion and reducing thrombosis risk.

Relapse and Recurrence Rates

Relapses occur in up to 30–50% of patients, often during the tapering phase of corticosteroid therapy. Symptoms such as headache, fatigue, or elevated ESR/CRP indicate recurrence. Patients with large-vessel involvement are particularly prone to repeated flares. Biologic agents like tocilizumab have been shown to reduce relapse frequency in refractory or relapsing cases.

Long-term Follow-up Recommendations

Because temporal arteritis can cause delayed vascular complications, long-term follow-up is essential. Regular clinical evaluations and imaging of the aorta and its branches help detect aneurysm or dissection formation early. Annual monitoring of inflammatory markers and vascular imaging, such as ultrasound or CT angiography, is recommended in patients with persistent or recurrent symptoms.

Prevention and Screening

Early Recognition Strategies

Prevention of complications in temporal arteritis centers on early recognition rather than primary prevention. Clinicians should maintain a high degree of suspicion for the disease in individuals over 50 years presenting with new-onset headache, visual changes, or jaw pain. Education of healthcare providers about the classic clinical triad of headache, jaw claudication, and vision disturbance is crucial for timely diagnosis.

Screening in High-Risk Populations

Routine screening for temporal arteritis in asymptomatic individuals is not recommended. However, patients with polymyalgia rheumatica should be regularly evaluated for signs of cranial arteritis, as the two conditions frequently coexist. Screening strategies may include monitoring ESR, CRP, and clinical symptoms during follow-up visits.

Preventive Use of Steroids or Biologics

There is no role for preventive corticosteroid therapy in individuals without a confirmed diagnosis. However, in patients with polymyalgia rheumatica exhibiting early cranial symptoms or elevated inflammatory markers, a short course of low-dose corticosteroids may be considered while further diagnostic evaluation is underway. Biologic agents are currently reserved for treatment rather than prevention, but ongoing research may expand their role in reducing relapses and long-term vascular damage.

Ultimately, the best prevention of irreversible complications lies in maintaining awareness among clinicians and patients, ensuring rapid recognition of symptoms, and initiating appropriate therapy without delay.

Recent Advances and Research Directions

Advances in Imaging Modalities

Recent years have seen major progress in noninvasive imaging techniques for the diagnosis and monitoring of temporal arteritis. High-resolution vascular ultrasound has become a first-line tool, offering real-time visualization of arterial inflammation through the “halo sign.” In addition, magnetic resonance angiography (MRA) and computed tomography angiography (CTA) allow for detailed assessment of both cranial and extracranial vessel involvement, helping to identify large-vessel vasculitis beyond the temporal arteries. Positron emission tomography with fluorodeoxyglucose (FDG-PET) has also emerged as a valuable modality for detecting metabolic activity in inflamed vessels and assessing systemic disease burden.

Novel Biomarkers and Genetic Studies

Ongoing research is exploring novel biomarkers that may improve diagnostic accuracy and help monitor disease activity. Serum interleukin-6 (IL-6) levels have shown promise as a sensitive indicator of inflammation and treatment response. Other potential biomarkers under investigation include matrix metalloproteinases, vascular adhesion molecules, and endothelial activation markers. Genetic studies have identified associations with HLA-DRB1*04 and other immune-regulatory genes, providing insight into disease susceptibility and potential therapeutic targets.

Emerging Therapeutic Approaches

In addition to corticosteroids, new biologic agents are transforming the management of temporal arteritis. Tocilizumab, an IL-6 receptor antagonist, has demonstrated significant efficacy in inducing remission and reducing steroid dependence. Ongoing clinical trials are evaluating other targeted therapies such as abatacept (T-cell co-stimulation inhibitor), ustekinumab (IL-12/IL-23 inhibitor), and Janus kinase (JAK) inhibitors. These agents offer hope for improved long-term disease control with fewer systemic side effects compared to prolonged corticosteroid use.

Clinical Trials and Future Perspectives

Current clinical trials are focused on refining diagnostic criteria, optimizing steroid tapering regimens, and evaluating the long-term safety and efficacy of biologic therapies. Advances in molecular immunology are paving the way for precision medicine approaches, where treatment can be individualized based on genetic and immunologic profiles. Integration of artificial intelligence into imaging interpretation may further enhance early detection and risk stratification. The future of temporal arteritis management lies in balancing effective disease suppression with minimizing treatment-related toxicity.

References

1. Salvarani C, Cantini F, Hunder GG. Polymyalgia rheumatica and giant-cell arteritis. N Engl J Med. 2002;347(4):261-271.
2. Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, et al. 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013;65(1):1-11.
3. Hellmich B, Agueda A, Monti S, Buttgereit F, de Boysson H, Brouwer E, et al. 2022 EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis. 2022;81(3):446-457.
4. Stone JH, Tuckwell K, Dimonaco S, Klearman M, Aringer M, Blockmans D, et al. Trial of tocilizumab in giant-cell arteritis. N Engl J Med. 2017;377(4):317-328.
5. Weyand CM, Goronzy JJ. Giant-cell arteritis and polymyalgia rheumatica. N Engl J Med. 2014;371(1):50-57.
6. Hunder GG, Bloch DA, Michel BA, Stevens MB, Arend WP, Calabrese LH, et al. The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum. 1990;33(8):1122-1128.
7. Dasgupta B, Borg FA, Hassan N, Alexander L, Barraclough K, Bourke B, et al. BSR and BHPR guidelines for the management of giant cell arteritis. Rheumatology (Oxford). 2010;49(8):1594-1597.
8. Grossman C, Ben-Zvi I. Giant cell arteritis: diagnosis and classification. Autoimmun Rev. 2017;16(6):655-659.
9. Cid MC, Prieto-González S, Arguis P, Espigol-Frigolé G, Butjosa M, Hernández-Rodríguez J. The spectrum of vascular involvement in giant-cell arteritis: clinical, imaging, and pathophysiological implications. Autoimmun Rev. 2017;16(7):744-755.
10. Firestein GS, Budd RC, Gabriel SE, McInnes IB, O’Dell JR, editors. Kelley and Firestein’s Textbook of Rheumatology. 11th ed. Philadelphia: Elsevier; 2024.