Makindo Medical Notes

Related Subjects: | Temporal (Giant Cell GCA) Arteritis | Tocilizumab

Giant Cell Arteritis (GCA) is a systemic vasculitis that can lead to preventable blindness if not diagnosed and treated promptly. It often presents in rheumatology, eye clinics, or stroke/TIA clinics. Around 20% of patients may develop vision loss, but this can be prevented with timely diagnosis and corticosteroid treatment.

Tocilizumab is a humanized monoclonal antibody that targets the interleukin-6 receptor (IL-6R), inhibiting the pro-inflammatory effects of interleukin-6 (IL-6). It is used in the treatment of autoimmune conditions and has emerged as an important agent in managing cytokine release syndrome in patients with GCA.

About Giant Cell Arteritis (GCA)

• GCA is a vasculitis that primarily affects the large and medium-sized arteries, typically in the external carotid system.
• It has a predilection for the external carotid, ciliary, and retinal arteries.
• The risk of blindness is due to anterior ischaemic optic neuropathy (AION), often secondary to occlusion of the posterior ciliary arteries.
• About 50% of patients may also present with symptoms of polymyalgia rheumatica (PMR).

Epidemiology

• Mean age of onset is 70 years, and it rarely occurs before age 50.
• More common in Caucasian populations.
• The female-to-male ratio is approximately 3:1.

Phenotypes

• Cranial GCA (cGCA): Involves the cranial arteries, leading to symptoms such as headache, scalp tenderness, and visual disturbances.
• Extracranial GCA (ecGCA): Affects extracranial arteries and may present with features such as claudication and ischemia.
• Mixed GCA (mixGCA): Involves both cranial and extracranial arteries.

Vessels Involved

• Intimal hyperplasia, often with thrombosis, can occur in the short posterior ciliary artery.
• Posterior ciliary arteries, which are branches of the ophthalmic artery, are frequently affected.
• Ischemia of extraocular muscles may lead to diplopia.
• The central retinal artery can also be involved, leading to vision loss.

Aetiology

• The exact cause is unclear, but it is believed to involve an immune response to an unidentified antigen.
• Endovascular damage, coupled with cytokine-mediated inflammation, causes localized ischemia and vascular damage.
• Subacute granulomatous inflammation with giant cells is typical in the affected arteries.
• Th1 cell-mediated immune response with elevated IL-6 levels is a key factor in pathogenesis.
• The gene HLA-DRB1 is associated with a higher risk of developing GCA.

American College of Rheumatology Criteria for GCA

Clinical Presentation

• Fever, weight loss, malaise, and fatigue are common systemic symptoms.
• Monocular visual loss, often transient, may resemble a TIA.
• Abrupt and often unilateral headache, frequently described as severe and localized.
• Temporal artery tenderness or a decreased pulse in the temporal artery.
• Jaw or tongue ache and claudication (due to masseter or lingual artery involvement).
• Ischemic stroke is rare since the internal carotid artery is usually unaffected.
• Blindness can occur due to posterior ciliary artery occlusion.
• Late complications may include aortitis, aortic aneurysm, and aortic dissection.

Investigations

• FBC: Normocytic normochromic anemia is commonly observed.
• ESR: Typically >50 mm/h, CRP elevated; ALP may be elevated in 30% of cases.
• Color Duplex Ultrasound: Hypoechoic halo (vessel edema) and hourglass stenosis are seen, which regress after 2 weeks of steroid treatment.
• Gold Standard: Temporal artery biopsy (TAB) provides definitive diagnosis. A long section is needed to account for skip lesions. Best performed within 2 weeks of diagnosis.
• Fluorescein Angiography: Demonstrates choroidal shutdown, confirming ischemia in the retina.

Management

• If visual symptoms are present, start Prednisolone at 1 mg/kg (often 60 mg/day) immediately. Consult ophthalmology for further management and initiate gastroprotection with a PPI.
• For patients without visual symptoms, refer to Rheumatology or Acute Medicine and start steroid therapy with PPI and bone protection.
• Response to steroids is usually rapid for generalized symptoms, but effectiveness decreases once blindness occurs. Steroid tapering should be done gradually over 18 months to 2 years.
• Tocilizumab, an IL-6 inhibitor, may be used as an adjunct treatment for steroid-sparing effects. Start at 162 mg once weekly subcutaneously.

References

• Hassan N et al. Giant Cell Arteritis. BMJ 2011 May 23;342:d3019.