Giant cell (temporal) arteritis: an overview and update

Giant cell arteritis is a systemic disease that continues to be a sight-threatening medical emergency requiring prompt recognition and treatment in order to avoid devastating ophthalmic consequences. Although there have been advances in the genetic and immunologic understanding of the underlying pathogenesis of the disease, the exact etiology of the condition, to date, remains unclear. Visual manifestations of giant cell arteritis are the common mode of presentation, making the ophthalmologist critically responsible for early diagnosis and treatment. Although temporal artery biopsy remains the only confirmatory procedure, newer laboratory investigations and blood flow studies with fundus fluorescein angiography have aided in the diagnosis of temporal giant cell arteritis. Maintenance of a high index of clinical suspicion is essential to institute prompt adequate treatment, especially in atypical cases. Corticosteroids remain the mainstay of treatment of giant cell arteritis. Recently, immunosuppressive agents as secondary steroid-sparing drugs have been used, particularly in some steroid-resistant cases. A wider recognition of the disease will minimize the prevalence of irreversible visual loss among patients with giant cell arteritis.     

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 in Alaska Natives

Objective: To investigate the incidence of biopsy-proven giant cell arteritis in the Native population of Alaska.Design: Retrospective review of medical diagnostic and Current Procedural Terminology (CPT) codes.Participants: 110 000 Alaska Native patients.Methods: We conducted a retrospective review of medical diagnostic codes for temporal arteritis, giant cell arteritis, and anterior ischemic optic neuropathy in the medical records of 110 000 Alaska Native patients seen between 1983 and 2003. We examined this same database in search of the CPT code for the temporal artery biopsy procedure. We also re-examined all temporal artery biopsy specimens that had been reported as positive.Results: We identified 122 patients whose diagnostic codes matched those of giant cell arteritis, temporal arteritis, or anterior ischemic optic neuropathy. We found that of 20 temporal artery biopsies that had been performed on this group, only 4 were reported to have had positive results. On re-examination of pathologic specimens, 1 of the 4 was found not to meet the latest pathologic criteria for this disease, leaving only 3 cases of biopsy-proven giant cell arteritis. The calculated incidence of giant cell arteritis in the Alaska Native population is approximately 1/100 000 in those over 50 years old.Conclusions: Compared with previous epidemiologic studies performed worldwide, our review suggests a very low incidence of biopsy-proven giant cell arteritis among Alaska Natives.     

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.     

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 arteritis presenting with aortic aneurysm, normal erythrocyte sedimentation rate, and normal C-reactive protein

CASE REPORT: We report on an extremely rare case of giant cell arteritis (GCA) presenting without elevated erythrocyte sedimentation rate or C-reactive protein level, with aortic root involvement, and in the absence of typical clinical findings. COMMENTS: The clinical signs and symptoms as well as the laboratory investigations involved in the diagnosis of GCA are discussed.     

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.     

Factors associated to temporal artery biopsy result in suspects of giant cell arteritis: a retrospective,multicenter, case–control study

Purpose: To evaluate the positivity rate of temporal artery biopsies (TAB) performed in suspects of giant cell arteritis (GCA) and to study the epidemiological and clinical factors associated to the biopsy result. Methods: A retrospective, multicenter, case–control study was performed, including three hundred and thirty‐five patients who underwent TAB for a suspicion of GCA from 2001 to 2010. Clinical, epidemiological and pathology data were recovered from the patients’ clinical records. Histologic diagnosis of GCA was made when active inflammation or giant cells were found in the arterial wall. Results: Eighty‐one biopsies (24.2%) were considered positive for GCA. Clinical factors independently associated to TAB result in a logistic regression analysis were temporal cutaneous hyperalgesia (OR = 10.8; p < 0.001), jaw claudication (OR = 4.6; p = 0.001), recent‐onset headache (OR = 4.4; p = 0.001), decreased temporal pulse (OR = 2.8; p = 0.02), pain and stiffness in neck and shoulders (OR = 2.3; p = 0.05), unintentional weight loss (OR = 1.33; p = 0.003) and age (OR = 1.085; p = 0.004). Other factors such as length of the surgical specimen (OR = 1.079; p = 0.028) and erythrocyte sedimentation rate (OR = 1.042; p < 0.001) were also statistically significant. The model was accurate (C‐index = 0.921), reliable (p_{Hosmer–Lemeshow} = 0.733) and consistent in the bootstrap sensitivity analysis. No significant association was detected between TAB result and number of days of previous systemic corticosteroid treatment (p = 0.146). However, an association was observed between TAB result and the total accumulated dose of previous systemic corticotherapy (p = 0.043). Conclusions: Exhaustive anamnesis and clinical examination remain of paramount importance in the diagnosis of GCA. To improve the yield of TAB, it should be performed specially in older patients with GCA‐compatible clinic. TAB could be avoided in patients with an isolated elevation of acute phase reactants, without GCA‐compatible clinic.     

Oral and intravenous steroids in giant cell arteritis

Giant cell arteritis can result in devastating visual loss. Treatment with steroids does result in visual recovery in some patients but the exact percentage is unknown. Intravenous megadose steroids appear to offer some advantage over oral steroids presumably through non-genomic effects, which manifest at doses of 500 mg or more. Side-effects are more likely in the elderly especially those with renal and cardiac co-morbidities. The authors' current recommendation is that intravenous steroids should be given to patients with established visual loss or amaurosis fugax.     

Review of Giant cell arteritis

Giant-cell arteritis (GCA) is a systemic autoimmune disease affecting primarily the elderly. Giant cell arteritis can cause sudden and potentially bilateral sequential vision loss in the elderly. Therefore, it is considered a medical emergency in ophthalmology and a significant cause of morbidity in an increasingly aging population. Ophthalmologists need to be able to recognize the classic symptoms and signs of this disease, and then be able to work-up and treat these patients in an efficient manner. An in-depth review of GCA from the literature as well as personal clinical experience follows.     

Suspected giant cell arteritis: a study of referrals for temporal artery biopsy

Background: The purpose of this study is to describe the nature of cases undergoing temporal artery biopsy (TAB) for suspected giant cell arteritis (GCA). Methods: A retrospective review of case notes was undertaken for all patients on whom ophthalmologists had performed TAB in 2 teaching hospitals between 1995 and 2001. Presenting symptoms, referring specialty, TAB result, treatment, and discharge diagnosis were recorded.Results: Ophthalmologists performed TAB on 110 patients for suspected GCA. A variety of specialties referred patients to ophthalmology for TAB; presenting symptoms varied with referral source. Of the 110 TABs, 21 (19%) were reported as positive for GCA, 84 (76%) were negative, and 5 (4.5%) were reported as inadequate. The symptoms most commonly associated with a positive TAB were visual disturbance (15/21) and headache (15/21). The odds ratios for having a positive TAB result rather than a negative result were 1.0 for the presence of headache, 4.1 for visual disturbance, and 6.7 for jaw claudication. Interpretation: Physicians were faced with a different population of GCA suspects than ophthalmologists. While physicians should be alert to the significance of visual symptoms or jaw claudication, ophthalmologists should be ready to facilitate prompt TABs when appropriate. TAB should be performed promptly and an adequate length of artery taken for biopsy. An argument can be made that TAB is not needed in cases of suspected GCA. However, a positive result provides firm justification for the use of steroids. We feel that TAB has a useful role and we make reference to methods to maximize its usefulness.     

Giant Cell Arteritis and Angiogenesis: A Review

Giant cell arteritis is a vasculitis of large and medium sized arteries with variable clinical presentations. Arteritic anterior ischemic optic neuropathy is the most common cause of visual loss from giant cell arteritis and the ischemia related to this process is presumed to be secondary to luminal stenosis from intimal hyperplasia. This process has been found to be initiated and promoted by various inflammatory and pro-angiogenic factors.     

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.     

Giant cell arteritis in a neuro-ophthalmology clinic in Saskatoon, 1998-2003

Background: We present a retrospective review of all biopsy-positive cases of giant cell arteritis (GCA) presenting to a neuro-ophthalmology practice in Saskatoon, Saskatchewan.Methods: Records of 141 consecutive patients who underwent temporal artery biopsy at the Saskatoon Eye Centre from July 1998 through June 2003 were reviewed. Patients that were biopsy-positive for GCA were studied and an estimated regional incidence was calculated. Study variables included age at diagnosis, sex, ethnicity, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) level.Results: Of 141 patients, 37 (26%) had a positive biopsy result for GCA; 11 underwent a second biopsy for a total of 152 biopsies. The average age of the biopsy-positive patients was 76.5 (SD 8.2) years, and the female-to-male ratio was 2.4:1. There were 35 patients (95%) of European descent and 2 patients (5%) of Aboriginal descent. Twenty-three patients had both ESR and CRP testing done before starting steroids. The ESR was elevated in 19 (83%) and the CRP in 22 (96%). The estimated incidence of GCA for Saskatoon and area was 9.4 per 100 000 for people over the age of 50 years.Interpretation: GCA occurs primarily in people of European descent; however, it can affect North American people of Aboriginal descent. Sensitivity for the detection of GCA is higher in CRP than in ESR. The estimated incidence of GCA in Saskatoon and surrounding referral area is moderate compared with other northern areas.     

Bilateral internuclear ophthalmoplegia—an unusual initial presenting sign of giant cell arteritis

A 63-year-old man presented six days after the sudden onset of horizontal double vision. His left eye became divergent two days later. On initial examination he had bilateral internuclear ophthalmoplegia with weakness of adduction and abducting nystagmus. Convergence was weak but there were no other neuro-ophthalmic signs. Constitutional signs included confusion and unsteadiness on his feet. A provisional diagnosis of arteritis was made. His ESR was 92 mm/h and a superficial temporal artery biopsy confirmed the diagnosis of giant cell arteritis. After two weeks or oral prednisolone his eye movements returned to normal. There have been no further relapses.
This would appear to be a unique presentation of giant cell arteritis. The causes of internuclear ophthalmoplegia are discussed along with a review of the ocular and neuro-ophthalmic signs of giant cell arteritis.     

Visual system involvement in giant cell (temporal) arteritis

A case of giant cell arteritis is reported. The presenting complaint was referable to the vertebral-basilar system. Visual symptoms and signs of vertebral-basilar, carotid, posterior ciliary, and branch central retinal arterial involvement are described. Blindness occurred on steroid therapy. Death resulted from steroid complications. The wide clinical spectrum and management of this condition are dicussed.     

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.     

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.