Horton's giant cell arteritis

Giant cell arteritis (GCA) is a spontaneous vasculitic syndrome specifically involving the walls of medium and large arteries. While involvement of other arterial beds is occasionally identified, this syndrome is most frequently recognized when symptomatic involvement of the temporal arteries occurs. Vascular lesions are characterized by patchy granulomatous infiltrates composed of T cells, macrophages, histiocytes, and giant cells. A better prognosis depends on early recognition of the clinical symptoms and prompt treatment. Diagnosis was based on the 5 clinical criteria previously used by the American College of Rheumatology (1990): 1) age 50 years or older; 2) new localized headache; 3) temporal artery tenderness or decrease in temporal artery pulse; 4) erythrocyte sedimentation over 50 mm/ hour; 5) abnormal result on artery biopsy. Giant cell arteritis was considered a rare disease under age 50; however, it is now known to be an important and significant cause of morbidity and mortality in elderly people. Therefore early recognition and treatment with corticosteroid are very important. There is no general agreement concerning the initial dosage, 40-65 mg/day are commonly recommended. After a few months the majority of patients can be treated with a low maintenance dosage of prednisolone (5 to 7.5 mg/day). The mean duration of treatment is about 5 years. The literature is reviewed and the clinical implications of this disease are discussed.     

Choroidal nonperfusion in giant cell arteritis

A 68-year-old man had visual loss secondary to isolated choroidal nonperfusion as a clinical manifestation of giant cell arteritis. Ophthalmoscopy disclosed scattered yellow-white lesions at the level of the retinal pigment epithelium in the posterior pole of the right eye. Intravenous fluorescein angiography demonstrated marked delay in choroidal filling of the macula in the right eye. There was no ophthalmoscopic or angiographic evidence of anterior ischemic optic neuropathy or central retinal artery occlusion. After approximately 72 hours of intravenous corticosteroid therapy, the patient's visual acuity improved and repeat intravenous fluorescein angiography showed normal choroidal circulation. Isolated choroidal ischemia is a potential cause of reversible visual loss in patients with giant cell arteritis.     

Polymyalgia rheumatica and giant cell arteritis

Giant cell (temporal) arteritis and polymyalgia rheumatica are related conditions that primarily affect older persons. They are among the most common chronic inflammatory disorders in this age group. In recent years, several new insights have been gained about the clinical features of these illnesses as well as their underlying pathophysiology. In addition, a great deal of study is underway to find better ways of detecting, monitoring, and treating them. This article provides a general review of these conditions, including their diagnosis and treatment.     

Carotid occlusion mimicking giant cell arteritis

Hybrids of a ligand protein crosslinked to a DNA binding protein have been developed as gene delivery vehicles mediated by receptors. To identify the effect of the crosslinks between the ligand and DNA binding protein on gene expression caused by an internalized hybrid-DNA complex, we prepared two kinds of transferrin-poly-L-lysine (TF-PL) hybrids: one was crosslinked by probably cleavable disulfide bonds (TF-ss-PL) and the other was linked by a probably uncleavable Schiff's base (TF-Schiff-PL). The binding affinity of the hybrids to HeLa cells was not different. However, the expression of a reporter gene (for luciferase) bound to these hybrids in HeLa cells transfected with TF-Schiff-PL was greater than that of TF-ss-PL.     

Large vessel vasculitis (giant cell arteritis, Takayasu arteritis)

Giant cell arteritis and Takayasu arteritis are separate but similar idiopathic diseases clinically characterized by constitutional symptoms, shared surrogate markers of systemic inflammation and indistinguishable granulomatous pan-arteritis of large vessels. This review emphasizes and analyses changing perceptions about the diseases. Recent series suggest that aortic involvement in giant cell arteritis may be more common than was previously appreciated. The case for and against inflammatory arthritis in giant cell arteritis is discussed. Ethnic new geographical variation in Takayasu arteritis-disease expression is reviewed. New philosophies of treatment are presented for both diseases. Prognosis in giant cell arteritis and its relationship to treatment is analysed. The utility of the laboratory for diagnosis and monitoring disease activity is appraised for each.     

Current concepts in giant cell (temporal) arteritis

Giant cell (temporal) arteritis continues to be a sight-threatening, systemic vasculitis with a poorly understood pathogenesis. The characteristic granulomatous inflammation of the vessel wall commonly leads to local ischemia. Recent advances in immunological investigations have characterized the cellular components of the disease process, but the etiology has so far remained unresolved. A reappraisal of the clinical features of giant cell (temporal) arteritis demonstrates the heterogeneity of the manifestations of the disease, including ischemic optic neuropathy. A range of new laboratory investigations and blood flow studies with color Doppler imaging have demonstrated promising roles, with respect to diagnosis and long-term follow-up. Prompt diagnosis and expeditious treatment require a high index of clinical suspicion, particularly for atypical cases. Corticosteroids remain the treatment of choice, other immuno-suppressive agents being used as second line steroid-sparing agents. Giant cell (temporal) arteritis leads to increased vascular and visual morbidity and, if untreated, may prove fatal. To maintain high standards of management of this enigmatic disorder, ophthalmologists need to be aware of the clinical spectrum of giant cell (temporal) arteritis and currently available diagnostic tests and treatment strategies.     

Refractory giant cell arteritis with spinal cord infarction

We report an elderly patient with aggressive steroid-refractory giant cell arteritis manifesting as myelopathy and bilateral visual loss while on treatment. Pathologically, spinal cord infarction was observed and was due to extensive necrotizing granulomatous arteritis of spinal arteries. Spinal cord damage in giant cell arteritis is rare. One prior autopsy report of spinal cord infarction in giant cell arteritis did not identify vasculitic changes in the spinal arteries.     

Seropositive rheumatoid arthritis with interstitial lung disease in giant cell arteritis

Unusually high mortality rates have been recorded among HIV-infected tuberculosis patients in urban Africa 6 and 12 months after initiation of tuberculosis treatment--a trend that impedes efforts to achieve the 85% cure rate target set by the World Health Organization. This study investigated tuberculosis treatment outcomes in relation to HIV serostatus in a rural district of Malawi (Ntcheu). All 205 smear-positive pulmonary tuberculosis patients newly diagnosed in the district in 1995 received 2 months of daily supervised streptomycin, rifampicin, isoniazid, and pyrazinamide in the hospital followed by 6 months of isoniazid and thiacetazone at home. HIV testing, offered to all tuberculosis patients, was accepted by 110 (54%), 73 (66%) of whom were HIV-positive. By the end of treatment, 126 patients (61%) had been cured and 56 (27%) had died. Significantly fewer HIV-positive patients or patients who declined HIV testing were cured (59% and 55%, respectively) than those who agreed to testing and were HIV-negative (84%). The mortality rate was 29% among patients who tested HIV-positive, 8% among those with a negative test result, and 34% among patients who declined HIV testing. Acceptance of HIV testing improved over the course of the study period in response to changes in counseling techniques, especially clarification that blood taken for HIV testing would not be used for transfusions. Overall, these findings suggest that, in areas where HIV infection is prevalent, an 85% tuberculosis cure rate may be unrealistic.     

HLA antigens in patients with giant cell arteritis and polymyalgia rheumatica

The frequency of 24 HLA antigens was determined in 43 patients with giant cell arteritis (25 of whom had polymyalgia rheumatica) and 12 others with polymyalgia rheumatica without evident arteritis. No haplotype was present in significantly increased frequency above controls in the total group nor when the patients were separated according to the presence or absence of polymyalgia rheumatica.     

Cotton-wool spots and the early diagnosis of giant cell arteritis

BACKGROUND: Giant cell arteritis is a common cause of severe visual loss in older individuals. Patients often present to the ophthalmologist having already lost vision in one eye. Detection of early ophthalmoscopic signs that precede irreversible visual loss in giant cell arteritis would allow preventative treatment in an otherwise frequently blinding disease. METHODS: Case presentations. RESULTS: Seven patients with mild visual symptoms and results of an ophthalmologic examination significant for cotton-wool spots were found to have giant cell arteritis. On specific questioning, six of seven patients described constitutional symptoms consistent with giant cell arteritis. Six patients had an abnormally elevated Westergren erythrocyte sedimentation rate. Temporal artery biopsy confirmed giant cell arteritis in six patients. The seventh patient received a diagnosis of polymyalgia rheumatica. Prompt treatment with corticosteroids led to preservation of vision and uneventful resolution of the cotton-wool spots in all seven patients. CONCLUSION: Cotton-wool spots are an early ophthalmoscopic finding in giant cell arteritis and can precede severe visual loss. Recognition of the significance of cotton-wool spots, use of laboratory studies, and prompt treatment may preserve vision in an otherwise frequently blinding disease.     

Risk factors for thrombotic events in giant cell arteritis and polymyalgia rheumatica

BACKGROUND: FOLFOX2, a bimonthly regimen of high-dose leucovorin (LV), 48-hour continuous infusion of 5-fluorouracil (5-FU) (LV-5-FU) and oxaliplatin (100 mg/m2) produced a high response rate (46%; 95% confidence interval (95% CI): 31%-60%) in 5-FU pre-treated patients with metastatic colorectal cancer. In this phase II study, pre-treated patients were given a lower dose of oxaliplatin to reduce the toxic effects of the regimen. PATIENTS AND METHODS: Thirty patients with advanced colorectal adenocarcinoma and progression while receiving bimonthly LV-5-FU (LV: 500 mg/m2, 5-FU: 1.5-2 g/m2/22 hours, days 1-2, every two weeks), were given the same LV-5-FU schedule with the addition of oxaliplatin (85 mg/m2) every two weeks (FOLFOX3). RESULTS: The main toxic effects were peripheral neuropathy (90%) with four severe sensitive neuropathies (WHO grade 2: 13%). The response rate was 20% (95% CI: 8%-39%). Median progression-free survival was 26 weeks, median survival was 57 weeks from the start of FOLFOX3 and median duration of the response was 37 weeks. CONCLUSIONS: Results obtained with FOLFOX3 confirmed the synergy between oxaliplatin and 5-FU in 5-FU-resistant metastatic colorectal cancer. However, the response rate seems to be lower than that obtained with FOLFOX2. Further studies to determine the best oxaliplatin dose intensity are in progress.     

Elastase derived elastin peptides: putative autoimmune targets in giant cell arteritis

OBJECTIVE: Histological analysis of giant cell arteritis (GCA) reveals a granulomatous reaction around the internal elastic lamina. Elastolysis by multinucleated giant cells has also been reported. We investigated elastin derived peptides as putative recall antigens for peripheral blood mononuclear cells (PBMC) from patients with GCA. METHODS: PBMC were collected from 17 patients with GCA (Group 1), 17 patients with vascular diseases, connective tissue diseases, or polymyalgia rheumatica without GCA (Group 2), and 17 healthy controls (Group 3). Cultures of PBMC with different elastin derived peptides or elastase were analyzed. RESULTS: A proliferative response was obtained only with elastate derived elastin peptides in 12/13 untreated patients with GCA. Steroid treatment was believed to abolish this proliferative response in 4 patients with GCA. PBMC from only 3/34 non-GCA subjects responded to these antigens. No proliferative response was obtained for other elastin derived peptides or elastase in any subject. CONCLUSION: Degradation of native elastin by leukocyte elastase can provide elastin derived peptides that act as autoimmune targets for T cells in GCA.     

Progressive visual loss from giant cell arteritis despite high-dose intravenous methylprednisolone

BACKGROUND: Giant cell arteritis (GCA) often presents with devastating visual loss in the elderly, yet the ideal treatment is unknown. The disease most often has been treated with oral prednisone, although recently the use of the high-dose intravenous methylprednisolone (IVMP) has been reported to enhance visual recovery. METHODS: The authors reviewed patient charts from two university-based neuroophthalmology services and reviewed all previously reported cases of GCA treated with IVMP. RESULTS: Four patients with GCA exhibited severe, progressive visual loss after at least 48 hours of high-dose IVMP. A fifth patient had further visual loss in one eye and improvement in the other eye after 24 hours of IVMP. In previous reports of IVMP treatment in GCA, four patients lost vision and 14 patients recovered vision. The authors review the details of these reports. CONCLUSIONS: The results of IVMP treatment of patients with visual loss from GCA are similar to the results of treatment with oral corticosteroids, with IVMP treatment being more costly and having a small risk of sudden death. The optimal dosage and route of corticosteroid treatment for GCA with visual loss remain elusive and warrant a treatment trial.