Ophthalmic Emergency Series: Giant Cell Arteritis

Giant cell arteritis (GCA), also known as temporal arteritis, is an autoimmune disease that causes inflammation of medium and large-sized arteries and is the most common systemic arteritis. Any acute ophthalmic symptoms of GCA constitute true ophthalmic emergencies due to the risk of permanent vision loss. Ophthalmic manifestations of GCA result from inflammation and occlusion of the ophthalmic artery and its branches, causing arteritic anterior ischemic optic neuropathy (AAION). These symptoms include amaurosis fugax, visual hallucinations, diplopia, and irreversible blindness. Vision loss is generally painless and may be monocular or binocular. Thus, prompt recognition and treatment with high-dose glucocorticoids is crucial to preserve vision.

Epidemiology and Presentation

GCA most commonly affects women over the age of 50 of Northern European descent. Peak incidence occurs in age 70-79. About half of patients with GCA also have polymyalgia rheumatica (PMR) and any patient with PMR should be considered for GCA.

The typical clinical picture of GCA includes a prodrome of constitutional symptoms followed by a new onset headache in a Caucasian woman over the age of 50. The patient may say that they have never had a history of headaches or that these headaches somehow feel different from previous headaches they have had. The headache is usually throbbing and continuous, and there is usually focal tenderness on direct palpation. Patients may also complain of jaw fatigue and discomfort with use, which is highly predictive of temporal arteritis. Elderly females with new complaints of headaches are often referred to ophthalmology for GCA workup, so it is important to be aware of how to recognize and manage the disease.

However, GCA can be difficult to diagnose as the clinical presentation can vary from patient to patient and symptom onset may occur precipitously or insidiously. Symptoms may fluctuate or be transient. Due to its potentially subtle clinical presentation and possible devastating consequences, clinicians should be on high alert for GCA and have a low threshold for working up patients for suspected GCA. Any patient should be considered for GCA if they are 50 or older and have one of the following signs or symptoms: new-onset headache, amaurosis fugax, jaw claudication (pain with chewing), elevated erythrocyte sedimentation rate (ESR) or C-Reactive Protein (CRP), or unexplained constitutional symptoms including fever, fatigue, malaise, and night sweats.

Because of its potentially indistinct presentation, patients should be carefully questioned regarding a history of any of these symptoms as they could suggest a diagnosis of GCA. Laboratory tests usually show an elevated ESR, CRP, and thrombocytosis, reflecting inflammation.

Diagnosis

The diagnosis of GCA can be difficult as there is no single laboratory testor physical exam finding that is consistently positive in the disease. If GCA is highly suspected clinically, then high-dose glucocorticoids should be given prior to diagnostic testing to reduce the risk of vision loss. The American College of Rheumatology 1990 criteria for the classification of GCA require three or more of the following:

age onset of 50 or older
new onset headache
tenderness to palpation over the temporal artery or decreased temporal artery pulsation
abnormal temporal artery biopsy
ESR >= 50 mm/hour

Laboratory studies customarily exhibit increased inflammatory markers, including an elevated ESR and CRP. That said, the definitive diagnosis of GCA requires histopathologic or imaging evidence. Temporal artery biopsy is the gold standard for the diagnosis of GCA. A positive biopsy result generally demonstrates panarteritis, most prominent in the media, with lymphocytes and macrophages and fragmentation of the internal elastic lamina. Giant cells are often present but are not necessary for diagnosis.

Recently, color Doppler ultrasound (CDUS) of the head, neck and upper extremities has been implemented as an alternative to temporal artery biopsy. Advantages of CDUS include that it is non-invasive and provides immediate imaging results with no radiation exposure, but it does require an experienced operator. In a patient with suspected GCA, a negative temporal artery biopsy and/or CDUS should be followed-up with advanced imaging of the vascular tree in the thorax.

Any patient with suspected GCA should receive a full ophthalmological examination for visual acuity, color vision, pupillary function, ocular motility, intraocular pressures, and anterior and posterior segment examinations. Fundoscopic findings can include signs of AAION, such as optic nerve swelling, optic nerve pallor, and cotton wool spots. Fluorescein angiography (FA) may demonstrate a delay of perfusion or hypoperfusion of the choroid. FA often demonstrates evidence of posterior ciliary artery occlusion.

Differential Diagnosis

Migraine
Temporomandibular joint dysfunction
Orbital mass
Other vasculitides, including Takayasu arteritis, granulomatosis with polyangiitis, and polyarteritis nodosa
Non-arteritic anterior ischemic optic neuropathy (NAION)
Endocarditis

Treatment

Glucocorticoids are the mainstay of GCA treatment and are effective at preventing vision loss. For patients with a high index of suspicion for GCA, especially those with vision loss, oral steroids should be started immediately, prior to performing other diagnostic studies.

Patients with no visual symptoms at presentation should receive high-dose prednisone 1mg/kg, up to 60mg once. Patients with visual complaints at presentation should receive high-dose systemic methylprednisolone for three days. Patients should then be tapered on oral prednisone slowly over 2-4 weeks and maintained on lower dose corticosteroids for 18-24 months. However, some patients may need low-dose corticosteroid treatment for up to five years.

Patients should also be evaluated by a rheumatologist. During the maintenance phase, patients should be monitored regularly for GCA, as relapse is common when the corticosteroid dosage is reduced. Routine follow-up with laboratory studies for inflammatory markers is important to monitor the progression of the disease.

Antiplatelet therapy may also be considered, but there is no consensus on its efficacy in GCA. Long-term corticosteroid side effects, such as osteoporosis and risk of opportunistic infections, should be monitored closely. Because of the many side effects associated with corticosteroid use and the frequency of disease relapse during steroid taper, some have proposed the addition of steroid-sparing therapies, such as tocilizumab (anti-IL-6) and methotrexate. These agents may help establish lasting remission. That said, there is no specific scientifically agreed upon GCA treatment protocol or optimal protocol for glucocorticoid withdrawal.

Summary

GCA is a vision-threatening inflammatory vasculitis that often presents with new-onset headaches, systemic symptoms and visual disturbance. Prompt diagnosis and treatment with steroids are critical in the prevention of permanent blindness—in the affected and unaffected eye. If there is a high index of suspicion for GCA, high-dose steroids should be initiated prior to further workup. Patients with visual symptoms should receive intravenous methylprednisolone. Temporal artery biopsy is the established gold standard in diagnosis, but CDUS is emerging as an alternative, less invasive diagnostic modality.

Steroids are the primary therapy for acute treatment and maintenance management of GCA. During maintenance, steroids should be tapered slowly, patients should be frequently monitored for evidence of disease relapse, and steroid side effects should be closely monitored. There is emerging evidence that tocilizumab and methotrexate may serve as alternatives or adjunct treatments.

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