Giant cell arteritis: an updated review

Giant cell arteritis (GCA) is the most common primary vasculitis of adults. The incidence of this disease is practically nil in the population under the age of 50 years, then rises dramatically with each passing decade. The median age of onset of the disease is about 75 years. As the ageing population expands, it is increasingly important for ophthalmologists to be familiar with GCA and its various manifestations, ophthalmic and non‐ophthalmic. A heightened awareness of this condition can avoid delays in diagnosis and treatment. It is well known that prompt initiation of steroids remains the most effective means for preventing potentially devastating ischaemic complications. This review summarizes the current concepts regarding the immunopathogenetic pathways that lead to arteritis and the major phenotypic subtypes of GCA with emphasis on large vessel vasculitis, novel modalities for disease detection and investigative trials using alternative, non‐steroid therapies.     

Giant cell arteritis

Giant cell arteritis has been considered an enigmatic disease. It is characterised by chronic granulomatous inflammation of the walls of large and medium‐sized arteries. The process has a predilection for the extradural cranial arteries, which include the ophthalmic and the posterior ciliary arteries. It is a multi‐symptom disease of older individuals and patients often present with challenging issues and diagnostic dilemmas. We review the literature and latest protocols for the diagnosis and management of giant cell arteritis.     

A case of biopsy-negative temporal arteritis--diagnostic challenges

A patient with systemic symptoms but no visual loss was investigated for suspected giant cell arteritis. Initial temporal artery biopsy was reported as negative; however, she returned with visual loss 2 months later, and the diagnosis of giant cell arteritis was confirmed with a subsequent biopsy. In hindsight, signs suggestive of the disease were present in the original biopsy, although the usual diagnostic features were absent.     

Giant-Cell Arteritis: Signs and Symptoms

Giant-cell arteritis is a polysymptomatic disease of the elderly. Systemic symptomatology includes headaches, arthralgias, myalgias, tender temporal arteries, jaw claudication, low-grade fever, anemia, anorexia, malaise, and weight loss. Visual loss from anterior ischemic optic neuropathy and diplopia resulting from ischemia of the ocular muscles represents the major ocular manifestations of giant cell arteritis. When the diagnosis is suspected, blood for a sedimentation rate should be drawn, and, if it confirms the clinical impression, high dose prednisone should be started immediately and a temporal artery biopsy performed at a later date. Only by asking the proper questions and suspecting the diagnosis will this preventable form of blindness receive the prompt attention it deserves.     

An occult case of giant cell arteritis presenting with combined anterior ischemic optic neuropathy and cilioretinal artery occlusion

A 61-year-old female presented with a moderate decrease in vision in the left eye. The patient denied any other ocular or systemic symptoms related to giant cell arteritis. Visual acuity was 20/50 in the left eye with a 2+ relative afferent pupillary defect and markedly abnormal color vision. Dilated fundus examination and flourescein angiography revealed optic disc edema as well as a cilioretinal artery occlusion. Erythrocyte sedimentation rate was only slightly elevated. Subsequent biopsy of the superficial temporal artery confirmed the diagnosis of giant cell arteritis. Cilioretinal arteries are anatomical variants derived from the short posterior ciliary arteries. Arteritic anterior ischemic optic neuropathy typically results from thrombotic occlusion of the short posterior ciliary arteries. Consequently, arteritic occlusion of the short posterior ciliary arteries can result in concomitant occlusion of the cilioretinal artery. This case highlights the situation where clinical symptoms were not suspicious for giant cell arteritis but the presence of an anterior ischemic optic neuropathy and a cilioretinal artery occlusion was virtually pathognomonic for giant cell arteritis.     

缺血性视神经病变的研究进展

缺血性视神经病变(ION)是一种常见的中老年人致盲眼病。根据是否存在视盘水肿,ION可分为前部缺血性视神经病变(AION)和后部缺血性视神经病变(PION),其中AION更为常见(90%); 根据是否患有血管炎,又可分为非动脉炎性ION和动脉炎性ION。几种类型ION的临床表现相似,但致病原因、治疗方法和预后却明显不同,动脉炎性ION可快速致盲、致残甚至致死。所以,对于ION,需早期识别是否伴有动脉炎,确定皮质类固醇药物使用的必要性。识别并尽可能控制ION潜在的可改变的危险因素对于防止患眼复发和对侧眼发作有一定的积极意义。文章就几种类型ION的病因、危险因素、诊断和管理做一综述,以期降低此类疾病的漏诊误治,改善其总体预后。     

Optic disc structure in anterior ischemic optic neuropathy

The etiology of anterior ischemic optic neuropathy (AION), when not associated with giant cell arteritis, is usually unknown. Clinical, pathologic, and experimental studies have not determined a cause. The optic disc appearance in both the involved and normal fellow eye was studied in 51 patients with acute nonarteritic AION. The number of discs (both involved and fellow) without a physiologic cup was significantly greater than would be expected from normal population studies. The etiology of nonarteritic AION may be related to the anatomic configuration of the optic nerve.     

Intravitreal triamcinolone acetonide injection for acute non‐arteritic anterior ischaemic optic neuropathy*

Non‐arteritic anterior ischaemic optic neuropathy is the most common optic neuropathy of the elderly, characterised by unilateral, sudden, painless visual loss. No effective treatment has been proven to reverse or limit the course of this disease. We evaluated the role of intravitreal triamcinolone acetonide injection in eyes with non‐arteritic anterior ischaemic optic neuropathy (NAION). Four eyes of four patients with acute NAION received a single intravitreal injection of triamcinolone acetonide (4 mg). The time between visual loss and intravitreal injection varied between four and 10 days. Mean age of patients was 57.25 years (range, 44 to 77 years). All patients experienced some visual gain. No complications related to the injection were observed during the following three months. Intravitreal triamcinolone injection may offer help in limiting the damage in this small group of patients with a relatively short history of visual loss due to NAION.     

Optic Disc Cupping in Arteritic Anterior Ischemic Optic Neuropathy Resembles Glaucomatous Cupping

Five cases of anterior ischemic optic neuropathy secondary to biopsy-proven giant cell arteritis are presented. In each case, cupping of the optic disc, which closely resembled glaucomatous cupping, was observed in the affected eye. The presence of glaucoma was ruled out on the basis of normal intraocular pressures and normal tonographic measurements of facility of outflow. These cases indicate that arteritic ischemic optic neuropathy can result in optic disc cupping, which closely resembles glaucomatous cupping. The similarities in the appearance of cupping of these discs with that seen in eyes with glaucoma suggest that the pathogenesis of cupping in glaucoma and in arteritic ischemic optic neuropathy may share some common mechanisms.     

Optical Coherence Tomography Angiography of Macula in Chronic Anterior Ischaemic Optic Neuropathy Associated with Giant Cell Arteritis

A 74-year-old man presented with bilateral optic nerve atrophy related to arteritic anterior ischaemic optic neuropathy (AION) which started 22 years ago. Atrophic papilla was noted in both eyes and optical coherence tomography showed thinning of the retinal nerve fibres layer as well as the macular ganglion cell complex. Optical coherence tomography angiography of the macula found a decreased density of the superficial capillary complex, whereas deep capillary complex was well-preserved. Inner retinal layer atrophy in chronic arteritic AION is followed by a loss of vascularisation in these layers as a consequence of the neurodegeneration.     

Quantitative analysis of temporal artery contraction after biopsy for evaluation of giant cell arteritis

BACKGROUND: Although the degree of contraction of temporal artery biopsy specimens after formalin fixation has been previously reported to range from 6% to 13%, the degree of contraction before fixation has not been previously studied. The aim of this study was to quantify the postexcision (prefixation) contraction of temporal artery biopsy specimens and to determine the relationship between contraction and the result of the biopsy. METHODS: All patients undergoing temporal artery biopsies from February 2003 through May 2004 were retrospectively reviewed. Contraction was determined by subtracting the in vivo and ex vivo lengths, then dividing the difference by the in vivo length to obtain a percentage of contraction. Statistical analysis was performed with the unpaired t test and Fisher exact test. RESULTS: We reviewed 37 negative and 7 positive biopsies for giant cell arteritis (GCA). For specimens positive for GCA, the mean contraction was 12%, whereas for negative specimens, mean contraction was 22%. There was a significant difference in the contraction between the specimens positive and negative for GCA (p = 0.009). The Fisher exact test revealed that GCA was positively associated with arterial contraction of less than 15% (p = 0.002). INTERPRETATION: The temporal artery can contract substantially after excision and before tissue fixation. GCA-positive specimens exhibit statistically less contractility than negative specimens.     

Giant Cell Arteritis: Oral Versus Intravenous Corticosteroids

This review summarizes the current literature on the use of oral versus intravenous steroids for giant cell arteritis. Giant cell arteritis is an immune-mediated vasculitis of medium to large sized arteries that affects individuals older than the age of fifty. Patients typically present with signs of vascular insufficiency of the extracranial arteries of the head and systemic inflammation. Steroids remain the backbone of therapy, but the dose, maintenance and route of administration remain debatable.     

Treatment of anterior ischemic optic neuropathy: Clues from the bench

Anterior ischemic optic neuropathy (AION) is due to optic nerve head ischemia, and there is currently no effective treatment. Age is a significant risk factor for both arteritic and nonarteritic AION (NAION), although we do not fully understand the changes that occur in aging that lead to selective vulnerability of the optic nerve head. Arteritic AION, which is most often seen in the setting of giant cell arteritis, is caused by vasculitis and thromboembolism of the ophthalmic circulation leading to impaired perfusion of the short posterior ciliary artery and infarction of the optic nerve head. More commonly, AION is nonarteritic, and vision loss is typically altitudinal and noted most commonly upon awakening. NAION has been associated with a variety of risk factors, including disc-at-risk, vascular risk factors including diabetes, vasospasm and impaired autoregulation, nocturnal hypotension, and sleep apnea. This review summarizes the clinical presentation of non-arteritic AION and arteritic AION associated with giant cell arteritis and the current and future treatment approaches for human NAION based on lessons from photochemical thrombosis models of NAION.     

Ischemic Optic Neuropathy: Still the Ophthalmologist's Dilemma

Ischemic optic neuropathy, in its arteritic and idiopathic varieties, presents both diagnostic and therapeutic challenges to the clinician, specificially: the role of temporal artery biopsy in management of giant cell arteritis; the preferred treatment regimen for giant cell arteritis, including decisions to begin tapering therapy and stopping therapy; action to take if major steroid complications arise while the disease is still active; distinguishing anterior ischemic optic neuropathy from idiopathic optic neuritis; whether cerebral arteriography is indicated in the assessment of idiopathic ischemic optic neuropathy; and whether steroid therapy is of any value in the treatment of idiopathic ischemic optic neuropathy.     

Giant cell arteritis presenting with scalp necrosis – the timing of temporal artery biopsy?

Scalp necrosis in patients presenting with clinical features suggestive of giant cell arteritis is rare. The immediate concern is that temporal artery biopsy might further compromise scalp circulation. We report a case of extensive scalp necrosis caused by giant cell arteritis. Temporal artery biopsy performed after 14 days was not associated with any significant damage and still provided florid evidence of the disease. Rapid and complete scalp healing was achieved with aggressive treatment.     

Subtleties in the Histopathology of Giant Cell Arteritis

A temporal artery biopsy is typically obtained in cases of suspected giant cell arteritis (GCA). The differentiation between a “positive” versus a “negative” biopsy is sometimes not simple. Degrees of inflammation can vary from obvious, florid accumulations of giant cells to subtle pockets of non-granulomatous inflammation. Areas of normal pathology, or “skip lesions,” may be interspersed within inflamed sections of the artery, resulting in a false negative diagnosis. Other features of the biopsy, such as the state of the internal elastic lamina and inflammation of the adjacent, smaller vessels, must also be evaluated and considered as possible signs of disease. Finally, some biopsies have an intermediate histopathologic appearance with mild inflammation and scarring, which may indicate prior treatment with corticosteroids, or “healed” arteritis. Careful examination and clinical correlation is therefore essential to evaluate for these subtleties, which can affect the final diagnosis.     

Giant cell (temporal) arteritis. The differential diagnosis

A patient was referred to the neuro-ophthalmology unit with a diagnosis of Foster-Kennedy syndrome; “papilledema” had been noted in the right eye and optic atrophy in the left. Results of radiographic examinations and lumbar puncture had been normal. The considerations and procedures leading to a correct diagnosis of giant cell arteritis are discussed.     

Nonarteritic anterior ischemic optic neuropathy associated with coexisting factor V Leiden and methylenetetrahydrofolate reductase mutations

We present a case of bilateral, not simultaneous, nonarteritic anterior ischemic optic neuropathy in a 53-year-old man with thrombophilic tendency. The investigation included determination of protein C, free protein S, antithrombin III, activated protein C resistance, and antiphospholipid syndrome study. Polymerase chain reaction and hybridization to allele-specific oligonucleotide probes were performed to determine the presence of thrombophilic polymorphisms. The patient was found to be heterozygous for factor V G1691A (Leiden) mutation and homozygous for methylenetetrahydrofolate reductase (MTHFR) C677T mutation.This case serves to demonstrate that the additive effect of two mild thrombophilic mutations may contribute to the occurrence of nonarteritic anterior ischemic optic neuropathy.