| disease | Giant Cell Arteritis |
| alias | Granulomatous Arteritis, Cranial Arteritis, Temporal Arteritis, GCA |
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 named giant cell arteritis based on its pathological characteristics.
bubble_chart Etiology
The disease causes of GCA and PMR are unknown. Family disease investigations 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 a genetic predisposition. The inflammatory response in GCA is concentrated in the internal elastic membrane of the stirred pulse, which may be related to certain autoantigens within it. Immunohistochemical studies have also revealed immunoglobulin deposits in the inflamed temporal stirred pulse wall layer, with infiltrating inflammatory cells predominantly being TH cells. Peripheral blood lymphocytes from patients are sensitive to human stirred pulse and muscle antigens in vitro.
bubble_chart Pathological Changes
GCA is a widespread {|###|}stirred pulse{|###|} inflammation, and both medium and large {|###|}stirred pulse{|###|} can be affected. The branches of the cervical {|###|}stirred pulse{|###|} are commonly involved, 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 pulse{|###|}; about 10-15% of large {|###|}stirred pulse{|###|} such as the aortic arch, proximal and distal aorta are affected; while the pulmonary, renal, and splenic {|###|}stirred pulse{|###|} are less commonly involved. The lesions of the affected {|###|}stirred pulse{|###|} are segmentally and skip-distributed, presenting as patchy proliferative granulomas. Tissue sections of the inflamed areas show infiltration of lymphocytes, macrophages, histiocytes, and multinucleated giant cells, with a full-layer {|###|}stirred pulse{|###|} inflammation centered on the elastic membrane, which 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 Clinical Manifestations
GCA is a disease that commonly affects the elderly, with an average onset age of 70 years (ranging from 50 to 90 years). It is more prevalent in women than in men (2:1). The onset of GCA may be sudden, but most patients have had several months of disease course and clinical symptoms before a definitive diagnosis, such as fever (low-grade or high-grade), lack of strength, and weight loss. Some patients present with PMR syndrome. Symptoms related to affected stirred pulse inflammation are typical manifestations of GCA.
⑴ Headache: This is the most common symptom of GCA, characterized by tension pain in one or both temporal regions, forehead, or occipital area, or superficial burning pain, or episodic tearing severe pain. The skin at the pain site may be red and swollen with tenderness, and sometimes scalp nodules or nodular swelling of the superficial temporal stirred pulse can be palpated.
⑵ Other symptoms of cranial stirred pulse insufficiency: When the blood supply to the masticatory muscles, swallowing muscles, and tongue muscles is insufficient, typical intermittent movement pauses occur, such as jaw claudication due to masticatory muscle pain, and pauses in swallowing or speech. Involvement of the posterior ciliary stirred pulse, ophthalmic branch stirred pulse, retinal membrane stirred pulse, or occipital cortical area stirred pulse can cause diplopia, eyelid ptosis, or visual disturbances. About 10-20% of GCA patients experience unilateral or bilateral blindness, or transient visual disturbances, amaurosis, and other precursors. Blindness is one of the serious complications of GCA. If unilateral blindness is not treated promptly, contralateral blindness often occurs within 1-2 weeks, and about 8-15% of GCA patients experience permanent blindness. Therefore, early diagnosis and treatment of GCA are important principles for preventing blindness. Some patients may experience ear pain, vertigo, and hearing loss.
⑶ Other manifestations of stirred pulse involvement: About 10-15% of GCA patients show signs of upper and lower limb stirred pulse insufficiency, presenting with intermittent movement disorders in the upper limbs or intermittent claudication in the lower limbs; when the carotid stirred pulse, subclavian stirred pulse, or axillary stirred pulse is involved, vascular murmurs, weakened or absent pulsations (pulseless disease) may be heard; involvement of the aortic arch or aorta can lead to aortic wall dissection, resulting in stirred pulse aneurysm or dissecting stirred pulse aneurysm, requiring angiography for diagnosis.⑷ Central nervous system manifestations: GCA may present with symptoms such as depression, memory decline, and insomnia.
bubble_chart Auxiliary Examination
Both GCA and PMR lack specific laboratory indicators, with only mild to grade II normochromic normocytic anemia, grade I reduction in serum albumin, elevated α2 globulin in serum protein electrophoresis, and grade I increase in serum transaminase and alkaline phosphatase activity. The more prominent laboratory abnormalities are increased erythrocyte sedimentation rate (ESR) (often as high as 100mm/h during active GCA) and elevated quantitative C-reactive protein.
1. Temporal artery biopsy: Temporal artery or occipital artery biopsy is the most reliable method for diagnosing GCA. The positive rate of temporal artery biopsy ranges between 40-80%, with a specificity of 100%. Since GCA lesions are segmentally and skip distributed, a sufficient length of several centimeters should be taken during biopsy, preferably from tender or nodular areas, and continuous pathological sections should be made to improve the detection rate. Temporal artery biopsy is relatively safe; if one side is negative, the other side can be biopsied or an occipital artery biopsy can be chosen.
2. Temporal artery angiography: It has certain diagnostic value for GCA, can reveal irregular and narrowed temporal artery lumens, and can also serve as an indicator for temporal artery biopsy sites.3. Selective large artery angiography: If large artery involvement is suspected, selective angiography such as aortic arch and its branch artery angiography can be further performed.
For elderly individuals over 50 years old, if unexplained fever, fatigue, weight loss, anemia, or an erythrocyte sedimentation rate (ESR) >50mm/h is observed; or if there are newly occurring headaches, visual disturbances (such as amaurosis, blurred vision, diplopia, or blindness); or other signs of insufficient cranial blood supply, such as intermittent masticatory muscle dysfunction, tinnitus, vertigo, etc.; or if symptoms of PMR syndrome appear, this disease should be suspected. Immediate further examinations, such as temporal artery angiography or temporal artery biopsy, should be conducted to confirm the diagnosis. If conditions do not permit, after ruling out other wind-dampness diseases, a trial of glucocorticoid treatment may be considered.
bubble_chart Treatment Measures
GCA often invades multiple sites of the stirred pulse and can easily lead to serious complications such as blindness. Therefore, once a clear diagnosis is made, glucocorticoid treatment should be initiated immediately. It is generally recommended to use a high-dose continuous therapy, such as prednisone 30-50mg/d, maintained until symptoms are relieved and the erythrocyte sedimentation rate (ESR) drops to normal or near-normal levels before starting to taper the dose. The total treatment course usually takes several months, and it is not advisable to reduce the dose or discontinue the medication too early to avoid a relapse of the condition. After the condition stabilizes, switching to a once-daily morning dose or an alternate-day therapy is a viable and effective option. Although non-steroidal anti-inflammatory drugs (NSAIDs) such as indomethacin can alleviate or control some symptoms, such as fever reduction, pain relief, and improvement of 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 and methotrexate can be used. Additionally, treatment with Root Leaf or Flower of Common Threewingnut glycosides (30-60mg/d) can also be tried.
PMR and GCA are both 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 good prognosis. A small number of mild cases, particularly 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%), abdominal arteries or mesenteric arteries (30-50%), and rarely involves the temporal artery; ② Allergic vasculitis: This disease mainly affects small skin 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 tract, 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 dilation of the arteries, and GCA involving the aorta is rare. In addition, it should be differentiated from malignant tumors, systemic or systemic infections, or other causes of fever, headache, anemia, blindness, etc.
