Introduction

Temporal arteritis (also known as giant cell arteritis: GCA) is a vasculitis of unknown cause that affects the medium and large sized vessels, typically the branches of the external carotid artery. It occurs in those over 50 years old, with peak incidence in patients who are in their 70s.

It is a medical emergency that required early recognition and treatment to minimize further risk of complication such as permanent loss of vision. Hence, when temporal arteritis is suspected, treatment must be started promptly with high dose prednisolone as well as urgent referral for assessment by specialist.

About 50% of temporal arteritis coexist with polymyalgia rheumatica (PMR) in which some proposed that they might be different clinical presentations of the same underlying condition.

Epidemiology

  • Incidence: 20.00 cases per 100,000 person-years
  • Peak incidence: 70+ years
  • Sex ratio: more common in females 3:1
Condition Relative
incidence
Migraine250.00
Polymyalgia rheumatica4.20
Temporal arteritis1
Fibromuscular dysplasia0.50
Takayasu's arteritis0.01
<1 1-5 6+ 16+ 30+ 40+ 50+ 60+ 70+ 80+

Aetiology

It is unknown of what causes the inflammation of artery. But genetic and environments factors do play a role to the development of the disease.
  • Old age: temporal arteritis is a disease of elderly and it rarely affect those under 50-year-old
  • Sex: women are twice more likely to develop the condition.
  • Race: it is more common among Caucasians and Northern European descent.
  • Polymyalgia rheumatica: about 10% of patient with PMR also diagnosed with temporal arteritis
  • Family history: studies have shown that certain people are genetically predisposition to development of temporal arteritis

Pathophysiology

Temporal arteritis: a disease of cell-mediated immune response
  • Temporal arteritis is believed to be caused by cell-mediated immune response to large and medium- sized vessels with the adventitial layer as the primary site of immunologic injury as it is the only layer that contains vasa vasorum which allows the access of T cell and macrophages to initial and regular vascular inflammation.

Activation of dendritic cell: the beginning of temporal arteritis
  • It is not fully understood of what factors that lead to the activation of dendritic cell in adventitia. But once activated, dendritic cells will trigger the recruitment of CD4+ T cells which then polarize into T helper 1 cells (Th1) and T helper 17 cells (Th17) through their co-stimulatory molecules (CD80 and CD86).
  • Th1 cells will then produce interferon-γ (IFN-γ) while Th17 cells produce interleukin-17 (IL-17). On exposure to IFN-γ, vascular smooth muscle cells produce chemokines that leads to recruitment of more Th1 cells, CD8+ T cells and monocytes to amplify the inflammatory process.
  • Later, monocytes differentiate into macrophage in the arterial wall and fuse to form multinucleated giant cells, the histological hallmark of temporal arteritis.

Intimal hyperplasia: the contributor of temporal arteritis’ ischemic symptoms
  • Activated macrophage also produces IL-1, IL-6 and tumor necrosis factor-α (TNF-α) to augment the inflammation and releases harmful substance such as reactive oxygen species (ROS), matrix metalloproteinase-2 (MMP-2), MMP-9 and platelet-derived growth factor (PDGF) that leads to destruction of internal elastic lamina and abnormal vascular remodelling.
  • During the healing process, the proliferation of myofibroblasts and deposition of extra cellular matrix protein may eventually results in intimal hyperplasia, leading to stenosis and occlusion of arterial wall.

Clinical features

Patients with temporal arteritis can present with variety of symptoms and it is often due to occlusion of vessels and hence ischaemic manifestation of the affected organs. These include:
  • Headache (80%): either new-onset or worsening of pre-existing headache. The pain is continuous in nature which may or may not response to standard dose of analgesics and is usually localized to the temporal/occipital region.
  • Jaw/tongue claudication (50%): typically occurs during chewing or prolonged talking. It is due to the inflammation and occlusion of maxillary artery leading to ischaemia of masseter muscles.
  • Scalp tenderness: simple activity like combing the hair or sleeping on a pillow might trigger the pain
  • Visual symptoms: amaurosis fugax, diplopia, blurring of vision, blindness (due to occlusion of posterior ciliary artery of ophthalmic artery)
  • Polymyalgia rheumatica (PMR): It is seen in 50% of the patients with temporal arteritis. PMR is characterized by pain associated with morning stiffness that affecting the shoulder and pelvic girdle
  • Constitutional symptoms: fever, malaise, weight loss, lethargic

Examination may reveal:
  • Prominent and tenderness of temporal artery with or without pulsation upon palpation
  • Fundoscopy examination shows evidence of ischaemic complication in patients presented with vision disturbance (eg. Pale, swollen optic disc, haemorrhage)
  • Auscultation of carotid, axillary or brachial arteries may reveal bruits which could suggest a possibility of large vessel giant cell arteritis involvement

According to the American College of Rheumatology classification criteria, if 3 or more of the criteria are present below, the patient is highly suspected to have temporal arteritis
  • Age of onset≥50 years
  • New onset of headache
  • Temporal artery abnormality: tenderness, thickening or reduced pulsation of temporal artery
  • ESR>50mm/h
  • Abnormal artery biopsy

***NICE guideline only considers the first 3 criteria when suspecting a diagnosis of temporal arteritis because patients rarely present with the remaining criteria to primary care.

Investigations

Temporal arteritis is usually suspected based on presentations, laboratory test and imaging with confirmation of diagnosis be made via temporal artery biopsy (TAB). The British Society for Rheumatology (BSR) guideline updated on March 2020 recommends the following assessments to be carried out to identify patient’s prognostic factors. These include:
  • Measurement of height, weight and body temperature
  • Assessment for ischaemic manifestation: jaw and tongue claudication, visual loss
  • Assessment for possibility of extracranial arteries involvement: bruits, limb claudication, different blood pressure between arms
  • Identify for comorbidities relevant to treatment: diabetes, hypertension, bone fracture risk, peptic ulcer, infection
  • Full Blood Count (FBC), CRP and ESR: taken before or immediately after initiation of high dose prednisolone. Notes that platelet count and the inflammatory markers usually elevated in temporal arteritis. They are useful in monitoring patient’s response on prednisolone therapy

In previous BRS guideline dated in 2010, it was recommended that temporal artery biopsy be done in all patient with suspected temporal arteritis. The recent BRS guideline, however, advise on the selection of the appropriate test based on estimation of pre-test probability.
  • For a low clinical probability of temporal arteritis (<20%): order a temporal and axillary artery ultrasound scan.
    • If ultrasound result is positive (eg. Detection of halo sign, stenosis/occluded vessel), arrange for a TAB to confirm the diagnosis. It should be carried out within 14 days after commencing steroid therapy.
    • If ultrasound result is negative, consider alternative diagnoses
  • For a medium clinical probability of temporal arteritis (20–50%): ultrasound may be performed prior to biopsy to aids in diagnostic certainty in case the biopsy is negative
  • For a high clinical probability of temporal arteritis (>50%): a positive ultrasound alone may be sufficient to make a diagnosis of temporal arteritis
  • If ultrasound scan is unavailable, patients should still have a temporal artery biopsy.

Note that initiation of treatment should not be delayed while carry out all these investigation.

Differential diagnosis

As a general rule, we should always rule out common conditions and diseases that require urgent treatment before thinking of the rare diagnosis. Here, we should consider causes of sudden loss of vision as well as conditions that may present with worrying symptoms such as fever, weight loss and pain.

Possible differential diagnoses include:
  • Migraine:
    • Similarities: severe headache
    • Differences: No visual loss but only temporary visual disturbance experience such as photophobia, scotoma in the shape of a jagged crescent, hemianopia or jumbling of lines and dots, no muscle stiffness
  • Central retinal artery occlusion:
    • Similarities: sudden onset, loss of vision
    • Differences: fundoscopy may reveal presence of cherry red spot with retinal whitening, no muscle stiffness
  • Acute glaucoma
    • Similarities: sudden onset, severe pain within/around the eye,associated headache, blurring of vision, loss of vision
    • Differences: redness of eye, hazy cornea, nausea and vomiting
  • Transient ischaemic attack:
    • Similarities: temporary loss of vision, diplopia
    • Differences: unilateral body weakness, dysarthria, abnormal gait
  • Trigeminal neuralgia:
    • Similarities: sudden onset, jaw pain
    • Differences: No vision impairment
  • Multiple sclerosis
    • Similarities: sudden onset, loss of vision, diplopia, blurring of vision
    • Differences: there is pain on eye movements, facial weakness, weakness of lower limb and autonomic dysfunction (eg. Urine incontinence)
  • Polymyositis
    • Similarities: fatigue, myalgia
    • Differences: proximal muscle weakness in polymyositis which is not a feature of PMR, raised creatinine kinase, no visual impairment
  • Systemic lupus erythematosus
    • Similarities: fever, myalgia, fatigue, weight loss, headache
    • Differences: No visual impairment

Management

The following notes will give an overview on the initial and long term management of temporal arteritis. It aims to achieve a good control of symptoms, minimize further complication and risk of long-term prednisolone therapy as well as to improve quality of life.

Initial management for suspected temporal arteritis

As mentioned earlier, temporal arteritis is a medical emergency. Patient should be promptly treated with high-dose prednisolone which should then give a good respond ideally within 24-48h of starting treatment. Patient’s clinical presentation and level of function should also be recorded before and after the onset of condition to evaluate the response to treatment. The starting dose of steroid varies depending on absence or presence of visual symptoms:
  • Without visual symptoms: prescribe 40-60mg oral prednisolone daily (minimum 0.75mg/kg)
  • With visual symptoms: prescribe IV methylprednisolone 500mg to 1000mg daily for 3 days followed by oral prednisolone. If IV drug is unavailable, then start 60-100mg oral prednisolone daily for 3 days

In addition, primary care providers should make an urgent referral to
  • The local GCA pathway for specialist evaluation (usually by a rheumatologist), on the same working day if possible and in all cases within 3 working days.
  • Ophthalmologist if patient presents with visual impairment (eg. Visual loss, diplopia), ideally on the same day.

Ongoing management for confirmed temporal arteritis

Upon confirmation of diagnoses of temporal arteritis, patients usually would be on steroid treatment for at least 1-2 years to control their symptoms. This also means they are at risk of long-term complication from steroid treatment such as weight gain, osteoporosis and increased susceptibility to infection. Hence, clinician should consider:
  • Prescription of calcium and vitamin D supplementation for bone protection and proton pump inhibitor (omeprazole/lansoprazole) for patient at high risk of gastrointestinal bleeding or dyspepsia
  • Giving advice on diet, exercise and smoking cessation (if applicable) to reduce any potential adverse effect upon starting prednisolone therapy.
  • Advice patients without immunity to chicken pox to avoid close contact with people who have chickenpox or shingles and to seek urgent medical advice if they have been exposed

BRS guideline does not recommends routine use of antiplatelet, anticoagulant or statin unless they are indicated for other medical conditions (eg. Coronary heart disease or stroke).

Follow up

As patient may takes year(s) to achieve remission, clinician should regularly monitor on patient's condition. At each visit, take a full history and conduct a targeted physical examination. Do blood test (eg. FBC, ESR /CRP, glucose level) and monitor for any signs of relapse and steroid-related side effects.
  • Patients should be seen at least every 2-8 weeks during the first 6 months
  • Then every 12 weeks during the second 6 months
  • Then every 12-24 weeks during the second year
  • Additional appointments should be arranged for cases of relapse and during dose adjustment

Patient with temporal arteritis are at risk of developing aortic aneurysm. However, BSR advice using clinical judgement when selecting people for aortic imaging as currently there is uncertain cost-effectiveness in carrying out routine aortic imaging.

Tapering down dose of steroid

While steroid is mainstay of treatment for temporal arteritis, long term and high dose intake of steroid can cause complications. We should, however, only consider steroid reduction when patient has been in remission for 4-8 weeks. This is achieved by
  • Reducing dose by 10mg every 2 weeks to 20mg
  • Then reduce by 2.5mg every 2-4 weeks to 10mg
  • After this, steroid shall be tapered down slowly by 1mg every 1-2 months if patient's condition allows

When dose adjustment has been made, provide patient with information on warning signs of relapse, how to alter their steroid dose during intercurrent illness and who to contact for medical advice. After one week of dose adjustment, follow up with patient to exclude signs of relapse. Bear in mind that relapse commonly happen at dose less than 20mg/day and if relapse occur, patients should be treated with high dose steroid which initially control the symptoms.

Treatment when relapse

Suspect relapse if there is recurrence of symptoms and signs that are not explained by other causes. Note that relapse can occur with normal level of inflammatory markers. Furthermore, in the absence of clinical symptoms, an alteration of steroid dose based solely on elevation of inflammatory markers is not routinely recommended as it may be due to other causes rather than relapse. Doses and type of treatment varies according the symptoms present at time of relapse (see below).
  • If present with headache or PMR feature only, then treat with previous higher steroid dose
  • If present with headache and jaw claudication, then treat with 40-60mg daily prednisolone
  • If present with new onset eye symptoms, then treat with either 60mg prednisolone or intravenous methylprednisolone and refer for urgent assessment by ophthalmologist
  • If present with large vessel temporal arteritis such as limb claudication, abdominal pain or back pain, then investigate patients with PET/MRI/CT scan
  • Discuss with specialist to start methotrexate or tocilizumab while tapering down steroid dose in patients who are at high risk of drug toxicity or relapse

Complications

  • Early complication: anterior ischemic optic neuropathy (AION), stroke
  • Irreversible bilateral visual loss
    • 35% of patients are at high risk of bilateral vision loss if one eye is affected at initial presentation. This can be make worse if further delay of treatment
  • Steroid-related side effect: cataracts, fractures, infections, hypertension, diabetes mellitus, osteonecrosis, weight gain, bruising, glaucoma
  • Late complication: aortic aneurysms and dissection