| disease | Giant Cell Arteritis |
GCA was previously referred to as cranial arteritis, temporal arteritis, or granulomatous arteritis. It was later recognized that any large artery in the body could be affected, and it was renamed giant cell arteritis based on its pathological characteristics.
bubble_chart Etiology
The disease cause of
GCA and PMR is unknown. Family disease surveys have found that first-degree relatives of GCA and PMR patients have a higher incidence of the disease, and most carry HLA-DR4 and CW3, suggesting genetic susceptibility. The inflammatory response in GCA is concentrated in the internal elastic membrane of the stirred pulse, possibly related to certain autoantigens. Immunohistochemical studies have also revealed immunoglobulin deposits in the inflamed temporal stirred pulse wall, with TH cells being the predominant infiltrating inflammatory cells. Peripheral blood lymphocytes from patients show sensitivity in vitro to human stirred pulse and muscle antigens.
Pathological changes
GCA is a widespread stirred pulse inflammation that can affect medium and large stirred pulses. Common sites include branches of the cervical stirred pulse, such as the superficial temporal stirred pulse, vertebral stirred pulse, ophthalmic stirred pulse, and posterior ciliary stirred pulse, followed by the internal and external carotid stirred pulses. Approximately 10–15% of large stirred pulses, such as the aortic arch and proximal and distal aorta, are affected, while pulmonary, renal, and splenic stirred pulses are less commonly involved. The lesions in affected stirred pulses exhibit segmental and skip distribution, presenting as patchy proliferative granulomas. Tissue sections from inflamed areas show infiltration of lymphocytes, macrophages, histiocytes, and multinucleated giant cells, with pan-stirred pulse inflammation centered around the elastic membrane. This can lead to vascular wall rupture, intimal thickening, and luminal stenosis or occlusion [5, 6]. Among the infiltrating cells, multinucleated giant cells are the most characteristic, with occasional eosinophils and neutrophils. Fibrinoid deposits are rare.
bubble_chart DiagnosisGCA is a disease commonly seen in the elderly, with an average onset age of 70 (ranging from 50 to 90 years). It is more prevalent in women than in men (2:1 ratio). The onset of GCA may be sudden, but most patients have already experienced several months of disease course and clinical symptoms before a definitive diagnosis is made, such as fever (low-grade or high-grade), lack of strength, and weight loss. Some patients present with PMR syndrome. Symptoms related to affected {|###|}arteritis are typical manifestations of GCA.
(1) Headache: This is the most common symptom of GCA, characterized by tension-like pain on one or both sides of the temples, forehead, or occipital region, or superficial burning pain, or episodic tearing severe pain. The skin over the painful area may appear red and swollen, with tenderness upon touch, and sometimes palpable scalp nodules or nodular swelling of the superficial temporal {|###|}artery can be detected.
(2) Other symptoms of cranial {|###|}artery insufficiency: When the blood supply to the masticatory muscles, swallowing muscles, or tongue muscles is insufficient, typical intermittent movement pauses may occur, such as jaw claudication due to masticatory muscle pain, or pauses in swallowing or speech. Involvement of the posterior ciliary {|###|}artery, ophthalmic branch {|###|}artery, retinal {|###|}artery, or occipital cortical {|###|}artery can cause diplopia, eyelid ptosis, or visual disturbances. Approximately 10–20% of GCA patients experience unilateral or bilateral blindness, or transient visual disturbances, amaurosis, or other precursors. Blindness is one of the severe complications of GCA. If unilateral blindness is not treated promptly, contralateral blindness often occurs within 1–2 weeks. About 8–15% of GCA patients suffer permanent blindness, making early diagnosis and treatment of GCA a critical principle in preventing blindness. Some patients may also experience ear pain, vertigo, and hearing loss.
(3) Other manifestations of {|###|}artery involvement: About 10–15% of GCA patients exhibit signs of upper or lower limb {|###|}artery insufficiency, such as intermittent upper limb movement disorders or lower limb claudication. When the carotid {|###|}artery, subclavian {|###|}artery, or axillary {|###|}artery is affected, vascular murmurs, weakened or absent pulses (pulseless disease) may be heard. Involvement of the aortic arch or aorta can lead to aortic wall dissection, resulting in aneurysms or dissecting aneurysms, which require angiography for diagnosis.(4) Central nervous system manifestations: GCA may present with symptoms such as depression, memory decline, and insomnia.
For individuals over 50 years old who present with unexplained fever, fatigue, weight loss, anemia, and an ESR >50 mm/h; recent-onset headache, visual disturbances (amaurosis, blurred vision, diplopia, blindness); or other signs of cranial {|###|}artery insufficiency, such as intermittent masticatory muscle {|###|}artery dysfunction, tinnitus, vertigo, etc.; or PMR syndrome, GCA should be suspected. Prompt further examinations, such as temporal {|###|}artery angiography or temporal {|###|}artery biopsy, should be performed to confirm the diagnosis. If such tests are not feasible, a trial of glucocorticoid therapy may be initiated after excluding other rheumatic diseases.
[Auxiliary Examinations]
Neither GCA nor PMR has specific laboratory markers. Findings may include mild to moderate normochromic normocytic anemia, slight reduction in serum albumin, elevated α2-globulin on serum protein electrophoresis, and mild increases in serum transaminase and alkaline phosphatase activity. The most notable laboratory abnormalities are elevated ESR (often as high as 100 mm/h during active GCA) and increased C-reactive protein levels.
1. {|###|}Artery biopsy: Biopsy of the superficial temporal {|###|}artery or occipital {|###|}artery is the most reliable method for diagnosing GCA. The positive rate of superficial temporal {|###|}artery biopsy ranges from 40–80%, with 100% specificity. Since GCA lesions are segmental and skip in distribution, the biopsy should include a sufficient length (several centimeters), preferably from tender or nodular areas, and serial pathological sections should be examined to improve detection rates. Temporal {|###|}artery biopsy is relatively safe; if one side yields a negative result, the other side or the occipital {|###|}artery may be biopsied.2. Temporal {|###|}artery angiography: This has some diagnostic value for GCA, as it can reveal irregular lumens and stenosis in the temporal {|###|}artery. It can also guide the selection of biopsy sites for temporal {|###|}artery biopsy.
3. Selective angiography When large vessel involvement is suspected, selective angiography can be further performed, such as aortic arch angiography and branch vessel angiography.
bubble_chart Treatment Measures
GCA often affects multiple pulse sites and can lead to severe complications such as blindness. Therefore, once diagnosed, glucocorticoid treatment should be initiated immediately. High-dose continuous therapy is generally recommended, such as prednisone 30–50 mg/day, maintained until symptoms improve and the erythrocyte sedimentation rate (ESR) returns to normal or near-normal before tapering. The total treatment course typically lasts several months, and premature dose reduction or discontinuation should be avoided to prevent relapse. After the condition stabilizes, switching to a once-daily morning dose or an alternate-day regimen is a viable and effective approach. Although nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin can alleviate or control some symptoms—such as fever, pain, and general discomfort—they cannot prevent ischemic complications like blindness. For patients with contraindications to glucocorticoids, a combination of NSAIDs and cytotoxic immunosuppressants such as cyclophosphamide or methotrexate may be used. Alternatively, Root Leaf or Flower of Common Threewingnut glycosides (30–60 mg/day) can also be tried.
Both PMR and GCA are vasculitic diseases that respond well to glucocorticoids, which can quickly control the condition, reduce and prevent serious complications such as blindness, and generally have a favorable prognosis. A few mild cases, especially PMR, have a certain degree of self-limiting nature.
GCA should be differentiated from other vasculitic diseases: (1) Polyarteritis nodosa: This disease mainly affects small and medium-sized arteries, such as renal arteries (10-80%), mesenteric arteries, or intestinal submucosal arteries (30-50%), and rarely involves the temporal artery; (2) Allergic vasculitis: This disease primarily affects small cutaneous vessels, venules, or capillaries, with obvious skin lesions such as macules, papules, purpura, ecchymosis, nodules, ulcers, etc.; (3) Wegener's granulomatosis: Characterized by necrotizing granulomas of the upper and lower respiratory tracts, generalized small and medium-sized vasculitis, and focal necrotizing glomerulonephritis (80%); (4) Aortic arch arteritis: Aortic arch arteritis has extensive lesions, often causing segmental stenosis, occlusion, or pre- and post-stenotic arterial dilation, while GCA rarely involves the aorta. Additionally, it should be differentiated from malignant tumors, systemic or local infections, or other causes of fever, headache, anemia, blindness, etc.
