This article summarizes the recent elucidations on the immunopathogenic process that leads to giant cell arteritis (GCA) and reviews both the well-known and newly recognized clinical subtypes and manifestations of the disease. The role of various noninvasive imaging techniques that are increasingly used to corroborate a clinical diagnosis of GCA as well as traditional and new treatment strategies are discussed.
Editor's note: This issue, Dr. Kawasaki and Dr. Purvin summarize the clinical features and management of our great nemesis, giant cell arteritis (GCA). In addition, see "GCA focus of regional study".
-Andrew G. Lee, MD
The most common primary vasculitis of adults in the Western world is giant cell arteritis (GCA). Although clinicians are aware that GCA has protean manifestations and can masquerade as any number of clinical disorders, perhaps one of its still under-appreciated aspects is a propensity to attack the aorta.
The pathophysiology of GCA is, in brief, a dual immunologic response. The focal attack on the arterial wall is a T-cell-mediated inflammatory process and results in lumenal occlusion and subsequent tissue ischemia. In addition, a non-specific, generalized inflammatory response leads to symptoms such as fever, night sweats, and myalgias. The focal vascular inflammation and the non-specific systemic inflammation are neither dependent on each other nor mutually exclusive. The patient's clinical manifestations are reflective of whichever inflammatory process-vascular or systemic (or both)-is active at the moment. In fact, depending on which signs and symptoms dominate the patient's clinical picture, three common clinical subtypes have been defined:
1. Systemic inflammatory syndrome. This subtype is characterized by non-specific constitutional symptoms in the absence of focal ischemic symptoms. Such patients have asthenia, arthralgias, myalgias, aching, anorexia, weight loss, and night sweats. A fever of unknown origin, which may be low-grade or spiking up to 40° C (104° F), is common. Serologically, these patients typically have high sedimentation rates; elevated acute phase reactants such as C-reactive protein (CRP), haptoglobin, and fibrinogen; elevated liver function tests; low albumin levels; thrombocytosis; and a normocytic normochromic anemia. The serum level of the inflammatory cytokine interleukin-6, which derives from circulating monocytes, also is a sensitive indicator of active systemic inflammation.
2. Cranial arteritis. This clinical subtype of GCA is dominated by localized vasculitis that primarily involves the branches of the carotid arteries, hence the name "cranial arteritis." Common symptoms of cranial arteritis include headaches or facial pain, even carotidynia, scalp tenderness, jaw claudication, painful dysphagia, and hoarseness. Necrosis of the scalp or tongue is a dramatic but rare manifestation. Patients with this clinical subtype commonly present with (or are at high risk to develop) ophthalmic complications of GCA, namely visual loss and diplopia.
3. Large vessel vasculitis. This form of GCA is a localized vasculitis that primarily involves the subclavian and axillary arteries and/or the aorta. Because the inflammatory process often is so contained to these vascular structures, the temporal artery biopsy results are negative in at least half of patients presenting with large-vessel vasculitis. Although acute aortitis often is asymptomatic, it eventually leads to dilation and aneurysm formation. Acute symptoms are related to local stenosis in the superior branches of the aortic arch, particularly the subclavian artery and axillary artery, leading to complaints of arm claudication, peripheral paresthesias, new-onset Raynaud phenomenon, and even tissue gangrene.
Aortitis also may occur as an isolated complication in patients with the other clinical subtypes of GCA. It remains clinically silent (and undiagnosed) until a complication occurs, either aortic valve insufficiency, aortic rupture, or aortic dissection, heralded by symptoms of acute chest pain, shortness of breath, and hypotension.
Ophthalmologists should be aware that ocular involvement may be the initial or sole manifestation of GCA, emphasizing the need for familiarity with the visual manifestations of the disease. Visual loss is most common and can be transient or permanent. Transient monocular blindness, or amaurosis, in GCA is not a trivial symptom but rather should be considered an ominous sign of possible impending blindness. It occurs as a result of insufficient perfusion of the optic nerve, retina, or choroid and precedes the development of permanent visual loss in more than half of untreated cases. Thus, amaurosis in a patient known or even suspected to have GCA is considered an ophthalmologic emergency, and immediate high-dose steroid treatment is recommended.
By far, the most common cause of permanent visual loss due to GCA is anterior ischemic optic neuropathy (AION). A diagnosis of AION is clinically based on a history of acute visual loss accompanied by optic disc edema. The ophthalmologist, however, must distinguish between the arteritic GCA form of AION and the more common non-arteritic form of AION. The importance lies in the immediate management and prognosis for the other eye. Among patients with arteritic AION, 25% to 50% will suffer similar visual loss in the other eye, typically within 1 to 14 days, if left untreated. In this acute setting, certain historical and examination features favor a diagnosis of arteritic AION: age greater than 70 years, preceding amaurosis, very severe visual loss in range of counting fingers or worse, new headache, and positive systemic review of systems-particularly jaw claudication, "chalky white" disc swelling, a normal or large optic cup in the contralateral eye, and concomitant evidence of retinal ischemia such as cotton-wool spots or cilioretinal artery occlusion.
Diplopia is the second most common visual symptom related to GCA but occurs far less frequently than visual loss. Diplopia may be due to weakness of a single extraocular muscle, an isolated cranial nerve III, IV, or VI palsy (partial or complete), combined cranial nerve palsies, skew deviation, internuclear ophthalmoplegia, or other supranuclear palsies. The more unusual ocular manifestations of GCA include pupil abnormalities (tonic pupil, Horner pupil), acute hypotony, ocular ischemic syndrome, orbital ischemia, and, rarely, orbital infarction syndrome.