Mural inflammatory hyperenhancement in MRI of giant cell (temporal) arteritis resolves under corticosteroid treatment

OBJECTIVE: To determine the effect of corticosteroid treatment on mural inflammatory hyperenhancement in MRI in GCA. METHODS: MRI of the superficial temporal artery with sub-millimetre in-plane spatial resolution (195 x 260 microm) was performed in 17 patients with proven GCA at the initiation of corticosteroid treatment and after 16 months of therapy. Visual MRI scores for mural inflammation were correlated with clinical and laboratory findings. RESULTS: Intensity of inflammatory hyperenhancement decreased significantly under corticosteroid therapy (2.3 +/- 0.6 vs 0.5 +/- 0.6, P < 0.001, with MRI score >2 indicating vasculitis). This finding correlated with the clinical and serological remission in 15/17 patients. Of the two patients with active disease, one had persisting mural inflammation in MRI indicative of relapsing disease. The other patient presenting with signs of polymyalgia rheumatica had no inflammatory changes of the superficial temporal arteries on MRI scan at follow-up. CONCLUSIONS: Mural contrast enhancement in high-resolution MRI is pronounced in active disease and decreases under corticosteroid treatment, correlating well with laboratory remission.     

Influence of previous corticosteroid therapy on temporal artery biopsy yield in giant cell arteritis

OBJECTIVE: To determine the impact of prior corticosteroid treatment on temporal artery biopsy (TAB) yield to establish the diagnosis of giant cell arteritis (GCA). METHODS: Retrospective study of a consecutive cohort of 78 patients clinically diagnosed and managed as GCA, who received corticosteroids before TAB. RESULTS: Among the 78 patients, TAB was positive in 57 (73%) and negative in 21 (27%). No significant differences in the length of the specimen were found between the positive and negative biopsies. We grouped patients according to treatment duration before TAB. In those with newly diagnosed GCA treated with high-dose steroid therapy, the biopsy results were positive in 78% (35/45) of patients treated for less than 2 weeks, in 65% of those treated for 2 to 4 weeks (13/20), and in 40% of those treated for more than 4 weeks (2/5). We also observed 8 patients that developed GCA on a background of a prior history of polymyalgia rheumatica (PMR); in this group biopsy was positive in 88% of the cases, after a median duration of treatment of 180 +/- 172 days and an average daily dose of 7.1 +/- 1.4 mg/d. CONCLUSION: The performance of TAB should not delay the prompt institution of steroid therapy on diagnosis of GCA, since the diagnostic yield of TAB seems valuable within 4 weeks of starting high-dose steroid treatment. In patients that developed GCA on a background of a prior history of PMR, a late TAB is also generally informative despite long-term treatment with low doses of corticosteroids.     

Small-vessel vasculitis surrounding an uninflamed temporal artery: a new diagnostic criterion for polymyalgia rheumatica?

OBJECTIVE: To assess the prevalence and clinical significance of small-vessel vasculitis (SVV) surrounding an uninflamed temporal artery (TA) in patients diagnosed as having giant cell (temporal) arteritis (GCA) and/or polymyalgia rheumatica (PMR). METHODS: Patients with GCA and/or PMR (n = 490) were included in this multicenter prospective study. Slides of TA biopsy specimens were reviewed by 2 pathologists who were blinded with regard to clinical information. SVV was defined as aggregates of mononuclear inflammatory cells surrounding a capillary, distant from an uninflamed temporal artery. Clinical and biologic data of patients in the SVV group (n = 35) were compared with data of patients with biopsy-proven GCA (n = 280) and with negative TA biopsy findings (n = 175). RESULTS: SVV was diagnosed in 18 women and 17 men (mean +/- SD age 74.5 +/- 9.4 years). The group of patients with SVV had a higher proportion of men than in the entire GCA series, had systemic symptoms, headache, jaw claudication, and an abnormal temporal artery less frequently at clinical examination, but had symptoms of PMR more often than patients in the biopsy-proven GCA group (P = 2.6 x 10(-7), odds ratio 9.17 [95% confidence interval 3.44-24.4]). Levels of inflammation markers were significantly lower in the SVV group. Patients in the SVV group had fever less frequently than patients in the group with negative TA biopsy findings, but otherwise shared the same clinical (including PMR symptoms) and biologic features. Eighteen of the 94 patients with pure PMR (19%) had SVV. CONCLUSION: SVV is often neglected by pathologists, and appears to be strongly associated with PMR symptoms in patients with a clinical diagnosis of GCA and/or PMR. However, SVV as a new diagnostic criterion for PMR must be assessed in prospective studies.     

Cerebral infarction due to giant cell arteritis-three case reports

The objective of this report was to explore the clinical features of patients with cerebral infarction due to giant cell (temporal) arteritis (GCA) and its characteristic changes in pathology, and on computed tomography (CT) and magnetic resonance imaging (MRI). Three cases of cerebral infarction due to GCA, treated during the past 2 years, were analyzed. Their clinical manifestations were observed carefully, their temporal artery biopsies were performed, their immunohistochemistries were done, and CT as well as MRI were used. The results showed that all the patients had new-onset headache and temporal artery abnormality when the disease began, and there was tremor on the right limbs of 1 patient; temporal artery biopsies revealed evidence of inflammatory cell infiltration in the arterial wall, mainly including T-lymphocytes and macrophages; small cerebral infarction foci were found on CT and MRI; and the responses to corticosteroid therapies were good. The results suggest that it is important to recognize the clinical features of cerebral infarction due to GCA, including the changes of pathology and on CT and MRI. In some cases, special attention is paid to differentiating between atherosclerotic infarction and infections to avoid misdiagnosis.     

Expression of DARC, CXCR3 and CCR5 in giant cell arteritis

OBJECTIVES: Leucocyte infiltration is the hallmark of vasculitis, chemokines being mainly responsible for leucocyte migration into inflamed tissues. The objective was to evaluate the local expression of chemokines and chemokine receptors in biopsies of patients with giant cell arteritis (GCA) compared with arteries from patients with polymyalgia rheumatica (PMR). We studied the expression of CCR5, CXCR3 and that of the Duffy antigen/receptor of chemokine (DARC), a chemokine internalizing receptor (interceptor), in parallel to the expression of the CCR5 ligand RANTES/CCL5. METHODS: Paraffin-embedded tissue sections from six patients with GCA and five patients with PMR were available for immunohistological analysis of chemokine receptor expression. RANTES/CCL5 mRNA was detected in tissue sections by in situ hybridization. RESULTS: In patients with biopsy-proven giant cell arteritis, CCR5 and CXCR3 were highly expressed by infiltrating leucocytes in involved tissue sections. Predominant clustering of CCR5+ and CXCR3+ leucocytes was found in the adventitia and was co-localized with the expression of CCL5/RANTES mRNA. Interestingly, we found marked expression of DARC on adventitial high endothelial venules in vasculitis lesions of patients with GCA, while in arteries from patients with PMR DARC was only expressed on a low number of vessels with flat lining endothelium. CONCLUSIONS: The co-localization of infiltrating CCR5+ and CXCR3+ leucocytes together with CCL5/RANTES and DARC in vasculitis lesions suggests a role for these chemokine receptors in leucocyte infiltration, possibly supported by DARC-mediated vascular presentation of chemokines.     

Small-vessel vasculitis surrounding a spared temporal artery: clinical and pathological findings in a series of twenty-eight patients.

OBJECTIVE: Occasionally, a temporal artery biopsy reveals small-vessel vasculitis (SVV) surrounding a spared temporal artery, the significance of which is unclear. We analyzed the final diagnosis in a series of patients with this condition and tried to identify histopathologic features with potential usefulness in predicting the ultimate diagnosis. METHODS: We performed a clinical and histopathologic review of 28 patients in whom SVV surrounding a spared temporal artery was the first histologic finding that led to the diagnosis of vasculitis. For comparison purposes, we analyzed the pattern of small vessel involvement in 30 patients with biopsy-proven giant cell arteritis (GCA). RESULTS: GCA was considered the most likely diagnosis in 12 patients, based on the absence of clinical evidence of additional organ involvement and normal findings on muscle biopsy and electrophysiologic study. Three patients had systemic necrotizing vasculitis (SNV), based on the demonstration of typical lesions on subsequent muscle, nerve, or kidney biopsy. After extensive evaluation, 4 patients remained unclassifiable. Nine patients were incompletely studied. Fibrinoid necrosis was significantly more frequent in patients with SNV (P = 0.0022), whereas involvement of vasa vasorum was more frequent in patients classified as having GCA (P = 0.022). No differences in the pattern of small vessel involvement were found in patients with SVV surrounding a spared temporal artery who were classified as having GCA compared with patients with biopsy-proven GCA. Granulocytes were observed at similar frequency in all conditions. CONCLUSION: SVV may be the only abnormal feature in a temporal artery biopsy and the only histologic evidence of vasculitis. The diagnosis of GCA can be reasonably established in most of these patients when there is no apparent evidence of additional organ involvement. However, when fibrinoid necrosis is observed or the temporal artery vasa vasorum are not involved, SNV must be extensively excluded.     

Giant cell arteritis: disease patterns of clinical presentation in a series of 240 patients

Classically, patients with giant cell arteritis (GCA) present with cranial ischemic manifestations that are directly related to vascular involvement. However, a variable proportion of GCA patients may present without obvious vascular manifestations. Since a high index of suspicion of this condition in individuals over the age of 50 years is needed to prevent the development of severe complications, we have studied the different patterns of disease presentation in a series of 240 patients with biopsy-proven GCA diagnosed at the single hospital for the well-defined population of Lugo, Spain, between January 1, 1981, and June 15, 2004. During the study period, 203 (86.4%) GCA patients presented with headache. Patients with headache were found to have an abnormal temporal artery on physical examination more commonly than the other GCA patients (79.8% versus 35.1%; p < 0.001). Compared with the other GCA patients, those who presented with polymyalgia rheumatica (PMR) were younger (73.4 +/- 6.3 versus 75.6 +/- 6.9 yr; p = 0.013) and had a longer delay to diagnosis (13.4 +/- 12.2 versus 8.3 +/- 10.0 wk; p = 0.013). One hundred thirty-one (54.6%) patients presented with severe ischemic manifestations. Abnormal temporal artery on physical examination (odds ratio, 2.25) and anemia at the time of disease diagnosis (odds ratio, 0.53) were found to be the best predictors for severe ischemic manifestations of GCA. Eighteen (7.5%) patients presented without overt ischemic manifestations of GCA. Patients younger than 70 years of age at the time of diagnosis had a longer delay to diagnosis and exhibited PMR more commonly than older patients. Our observations confirm the presence of different disease patterns of clinical presentation in GCA and emphasize the importance of an abnormal temporal artery on physical examination and anemia as factors that may predict the risk of severe ischemic complications related to GCA.     

Atherosclerosis in patients with biopsy-proven giant cell arteritis

OBJECTIVE: To examine the presence of atherosclerosis in a series of giant cell arteritis (GCA) patients attended to in a community hospital and to determine whether clinical features or steroid therapy might be associated with the development of atherosclerotic disease. METHODS: Forty consecutive patients diagnosed with biopsy-proven GCA, periodically followed at the rheumatology outpatient clinic of Hospital Xeral-Calde, Lugo (Spain), who had ended steroid therapy and had at least 3 years of followup were assessed for the presence of atherosclerosis by determination of the carotid intima-media thickness (IMT) and carotid plaques using high-resolution B-mode ultrasound. Forty matched controls were also studied. RESULTS: GCA patients exhibited less carotid artery IMT than did matched controls (mean +/- SD 1.01 +/- 0.16 mm versus 1.13 +/- 0.20 mm; P = 0.005; difference in means 0.12, 95% confidence interval 0.04-0.20). Patients who required steroid therapy for >2 years had greater mean +/- SD carotid IMT (1.04 +/- 0.17 mm versus 0.95 +/- 0.15 mm) but the difference was not statistically significant (P = 0.10). A positive correlation between age at the time of the study and the carotid artery IMT in GCA patients was observed (r = 0.673, P < 0.001). However, adjusting for age, sex, and classic atherosclerosis risk factors, no significant correlation between carotid IMT and the routine laboratory markers of inflammation assessed at the time of disease diagnosis, disease duration, or cumulative prednisone dose was found. CONCLUSION: The present study demonstrates that atherosclerotic macrovascular disease is not increased in patients with GCA.     

Arterial wall production of cytokines in giant cell arteritis: results of a pilot study using human temporal artery cultures

BACKGROUND: Giant cell arteritis (GCA) is a subacute periarteritis predominantly affecting segments of the external carotids of elderly patients. Vasculitic lesions in GCA samples might be characterized by in situ production of cytokines mRNA, indicative of macrophage and T-cell activation. However, whether the cytokine production of vessels with arteritis differs from that of vessels exposed to inflammatory conditions that originate peripheral to the vessel remains unknown. METHODS: We investigated cytokine and soluble receptor cytokine production in blood samples and cultures of human temporal arteries from 22 consecutive patients (mean age 77 +/- 6 years) further investigated for possible diagnosis of GCA: 7 patients had GCA and 15 had neither GCA nor vasculitis but had other inflammatory, infectious, or malignant diseases (controls). The production of cytokines and soluble cytokine receptors in the supernatants of cultures of 3-mm segments of temporal artery specimens, before and after lipopolysaccharide (LPS) stimulation (10 ng/ml and 10 microg/ml) and in serum, was quantified using sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: Cytokine production by temporal arteries increased significantly and in a dose-dependent manner (p <.01) after LPS stimulation in all patients studied, suggesting that the system is methodologically functional. Despite a large interindividual variation, we found similar differences in cytokine production before and after stimulation by 10 ng/ml and 10 microg/ml LPS between both groups: temporal arteries of GCA patients produced more interleukin (IL)-1beta (p <.05) and IFNgamma (nonsignificant) and less tumor necrosis factor (TNF)alpha (p <.05) and IL-6 (nonsignificant) than temporal arteries of controls. The levels of TNFalpha (p <.05) and IL-6 soluble receptor (p <.05) were significantly lower in GCA patients as compared with controls in blood samples, whereas levels of cytokines in temporal artery and in blood samples were not significantly correlated at the individual level in both groups. CONCLUSIONS: The present pilot study, which requires further confirmation on a larger number of well-defined patients with GCA, suggests that a specific arterial cytokine production profile might exist in GCA (high IL-1beta +/- IFNgamma and low TNFalpha), addresses the question of the mechanisms by which IL-1beta and TNFalpha might be differentially regulated at the level of the arterial cell wall, and supports the view that cultures of the temporal artery might be an interesting tool for evaluating the role of cytokines in GCA pathogenesis.     

A strong initial systemic inflammatory response is associated with higher corticosteroid requirements and longer duration of therapy in patients with giant-cell arteritis

OBJECTIVE: To assess whether the intensity of the initial systemic inflammatory response is able to predict response to therapy in patients with giant cell arteritis (GCA). METHODS: Retrospective review of 75 patients (49 women and 26 men) with biopsy-proven GCA who had regular followup and were treated according to uniform criteria. Four parameters were used to evaluate the baseline inflammatory response at diagnosis: fever, weight loss, erythrocyte sedimentation rate > or = 85 mm/hour, and hemoglobin < 110 gm/liter. Patients were considered to have a weak inflammatory response if they had 2 or fewer inflammatory parameters (group 1) and a strong inflammatory response if 3 or 4 parameters were present (group 2). Time required to achieve a maintenance dose of less than 10 mg prednisone/day was recorded and analyzed by the Kaplan-Meier survival analysis method. Tumor necrosis factor alpha (TNFalpha) and interleukin 6 (IL-6) serum levels were also determined in 62 patients and 15 controls. RESULTS: Forty patients had a weak (group 1) and 35 had a strong (group 2) initial inflammatory response. Patients in group 2 had significantly higher levels of circulating TNFalpha (31.9 +/- 16.8 versus 22.3 +/- 9 pg/ml; P = 0.01) and IL-6 (28.2 +/- 17.4 versus 16.6 +/- 13 pg/ml; P = 0.004) than patients in group 1. In group 1, 50% of patients required a median of 40 weeks (95% CI 37-43) to reach a maintenance dose of <10 mg, whereas in group 2 a median of 62 weeks (95% CI 42-82) was necessary (P = 0.0062). Patients in group 2 experienced more flares than patients in group 1 (P = 0.01) and received higher cumulative steroid doses (8.974 +/- 3.939 gm versus 6.893 +/- 3.075 gm; P = 0.01). CONCLUSION: GCA patients with a strong initial systemic inflammatory reaction have more elevated circulating levels of IL-6 and TNFalpha, have higher and more prolonged corticosteroid requirements, and experience more disease flares during corticosteroid therapy than patients with a weak systemic acute phase response.     

Cancer in biopsy-proven giant cell arteritis. A population-based study

OBJECTIVE: To investigate the potential association between giant cell arteritis (GCA) and cancer in a series of consecutive patients diagnosed with biopsy-proven GCA over a 25-year period at the single reference hospital for a well-defined population. METHODS: The case records of all patients diagnosed with biopsy-proven GCA at the Department of Medicine of the Hospital Xeral-Calde (Lugo, Northwest Spain) between January 1, 1981 and December 31, 2005 were reviewed. Information on cancer and cause of death over the extended follow-up was assessed. In all cases the presence of cancer was histologically confirmed. RESULTS: Cancer was found in 39 (15.3%) of the 255 GCA patients. Although 7 (18%) of the 39 patients had cancer either at the time or within the first 12 months after GCA diagnosis, the standardized mortality ratio (SMR) due to cancer in patients with biopsy-proven GCA showed no increase (overall SMR 1.06 [0.65-1.60]; men, 0.81; women, 1.50). The time interval between GCA diagnosis and cancer diagnosis was 5.2+/-3.8 years (median 4.2 years; interquartile range: 3-7 years). When multivariate analysis adjusted by age and sex was performed, only the presence of dysphagia (adjusted hazards ratio (HR)=3.90; P=0.04), abnormal temporal artery on physical examination (adjusted HR=4.61; P=0.04), and anemia at the time of GCA diagnosis (adjusted HR=3.39; P=0.01) were associated with an increased risk of cancer over the extended follow-up. CONCLUSION: The results from this series do not support an overall increase of mortality due to cancer in GCA.     

Intercellular adhesion molecule 1 gene polymorphisms in polymyalgia rheumatica/giant cell arteritis: association with disease risk and severity

OBJECTIVE: Intercellular adhesion molecule 1 (ICAM-1) is widely distributed in shoulder synovial membrane of active polymyalgia rheumatica (PMR) and strongly expressed in granulomatous inflammatory infiltrate of the temporal artery in giant cell arteritis (GCA). ICAM-1 genes may contribute to the inflammatory PMR/GCA processes. We examined potential associations of ICAM-1 gene polymorphisms with PMR/GCA susceptibility and severity. METHODS: We enrolled 121 consecutive patients with "pure" PMR and 56 patients with biopsy positive GCA residing in Reggio Emilia, Italy. Among patients with PMR, 91 had a followup duration of at least one year. Selected as control subjects were 228 healthy blood donors, 75 patients with nonarteritic central retinal artery occlusion, and 116 cataract surgery patients from the same geographic area. All PMR/GCA patients and controls were genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for ICAM-1 polymorphism at codon 241 (exon 4) and codon 469 (exon 6). RESULTS: The frequency of R241 was significantly higher in PMR/GCA patients [p = 0.00001, odds ratio (OR) 5.0 (95% confidence intervals, CI 2.6-9.6) ], in pure PMR patients [p = 0.00001, OR 5.0 (95% CI 2.5-10.0)], and in GCA patients [p = 0.00005; OR 5.0 (95% CI 2.2-11.5)] compared to the healthy controls. The frequency of R241 was significantly higher in total PMR/GCA patients compared to patients with nonarteritic central retinal artery occlusion [p = 0.0007; OR 5.3 (95% CI 1.8-15.5)] and cataract surgery patients [p = 0.0003; OR 4.1 (95% CI 1.8-9.0)]. The distribution of E/K 469 genotype was similar in PMR/GCA patients and in the 3 control groups. Cox proportional hazards modeling identified 2 variables that independently increased the risk of PMR relapse/recurrence: erythrocyte sedimentation rate at diagnosis > 72 mm/h [relative risk 1.6 (95% CI 1.1-2.3)] and the presence of R241 allele [relative risk 1.6 (95% CI 1.1-2.4)]. CONCLUSION: Our findings show that G/R 241 polymorphism of ICAM-1 is associated with PMR/GCA susceptibility and confers an increased risk of relapse/recurrence in PMR.     

MCP-1 gene haplotype association in biopsy proven giant cell arteritis

OBJECTIVE: Giant cell arteritis (GCA) is the most frequent vasculitis in European and North American countries. Increased expression of monocyte chemoattractant protein 1 (MCP-1) has been observed within the inflammatory infiltrates of blood vessels and serum of patients with GCA and in other autoimmune and inflammatory conditions. MCP-1 gene polymorphisms have been reported to contribute to susceptibility to several immune and inflammatory conditions. To investigate the clinical implication of MCP-1 polymorphisms in GCA, we examined the association of 3 single nucleotide polymorphisms (SNP) in a series of patients with GCA from Northwest Spain. METHODS: Seventy-nine patients with biopsy proven GCA and 99 ethnically matched controls were studied. Patients and controls were genotyped for MCP-1 polymorphisms. SNP included in this study (rs2857657, rs4586, rs139000) were located in intron 1(G/C), exon 2(T/C), and 3'UTR(C/T) region of MCP-1 gene. RESULTS: The distribution of the alleles and genotypes for each MCP-1 polymorphism showed no significant differences between GCA patients and controls. When we compared the overall distribution of haplotype frequencies between GCA cases and controls a significant difference was observed (p = 0.005, by chi-square test from 4 2 contingency table). In addition, haplotype C-C was significantly increased in GCA patients compared with controls (p = 0.03, OR 2.09, 95% CI 1.09-4.02). Similarly, haplotype T-T was overrepresented in GCA patients (p = 0.005). CONCLUSION: Significant differences in haplotype frequencies between GCA patients and controls may indicate a role for MCP-1 gene in susceptibility to GCA.     

No evidence of parvovirus B19, Chlamydia pneumoniae or human herpes virus infection in temporal artery biopsies in patients with giant cell arteritis

OBJECTIVES: Recent studies have suggested that infective agents may be involved in the pathogenesis of giant cell arteritis (GCA), in particular Chlamydia pneumoniae and parvovirus B19. We investigated temporal arteries from patients with GCA for these infections as well as human herpes viruses using the polymerase chain reaction (PCR). METHODS: Thirty temporal artery biopsies from 30 patients suspected of having GCA within a period of 1 yr were examined. Thirteen patients had classical GCA, two had biopsy-negative GCA, 10 patients had polymyalgia rheumatica and five patients had other conditions. DNA was extracted from frozen biopsies and PCR was used to amplify genes from Chlamydia pneumoniae, parvovirus B19 and each of the eight human herpes viruses: herpes simplex viruses HSV-1 and 2, Epstein-Barr virus, cytomegalovirus, varicella zoster virus and human herpes viruses HHV-6, -7 and -8. RESULTS: In all 30 biopsies, PCR was negative for DNAs of parvovirus B19, each of the eight human herpes viruses and C. pneumoniae. CONCLUSIONS: We found no evidence of DNA from parvovirus B19, human herpes virus or C. pneumoniae in any of the temporal arteries. These agents do not seem to play a unique or dominant role in the pathogenesis of GCA.     

冠心病猝死冠状动脉粥样硬化斑块单核细胞趋化蛋白1表达的研究

目的探讨单核细胞趋化蛋白-1(MCP-1)在冠心病猝死(SCD)和非SCD病例冠状动脉粥样硬化斑块中表达的差异及其与SCD的关系。方法从本教研室2001至2003年尸检档案中挑选病例及心脏标本共90例。分为SCD组(36例)、对照组Ⅰ(28例,冠心病但不是SCD)和对照组Ⅱ(26例,无明显动脉粥样硬化)。通过免疫组化SABC法及图像分析技术对不同组的MCP-1在斑块内的表达进行阳性细胞面积／扫描面积(R)、平均吸光度值(A)的半定量检测,并分析比较各组表达的差异性。结果SCD组的R值和A值与对照组Ⅰ、对照组Ⅱ相比差异有统计学意义[(0．1264±0．0130比0．0269±0．0110和0．0267±0．0100,P=0．04),(0．4534±0．0830比0．2303±0．0400和0．2158±0．0400,P=0．00)]。而对照组Ⅰ的R值和A值与对照组Ⅱ相比无统计学意义(0．0269±0．0110比0．0267±0．0100,P>0．05),(0．2303±0．0400比0．2158±0．0400,P>0．05)。结论冠状动脉粥样硬化斑块中MCP-1的表达增加与SCD的发生密切相关,为SCD的诊断和临床对冠心病防治的研究提供新的途径。     

Audit of the management of suspected giant cell arteritis in a large teaching hospital

Background : The diagnosis of giant cell arteritis (GCA) is often confirmed by an early temporal artery (TA) biopsy of adequate length. Treatment of this condition with high‐dose corticosteroids may be associated with significant morbidity, including osteo­porosis. Aim: To audit current management of patients with suspected GCA at Auckland Healthcare, a large teaching hospital. Methods: We performed a retrospective chart review of all TA biopsies from January 1996 to June 2000. A total of 117 biopsies from 111 patients was audited. Of these patients, 37/111 (33%) had a final clinical diagnosis of GCA (GCA patients). The areas of interest for audit were waiting time for TA biopsy, length of sample, initial corticosteroid therapy and osteo­porosis prophylaxis. Results: The mean waiting time for biopsy for all patients was 5.6 days (range 0?42 days). This time varied from 9.3 days for rheumatology patients to 2.6 days for ophthalmology patients (P = 0.003). Only 44/117 (37.6%) specimens measured more than 10 mm. For GCA patients, the median initial oral prednisone dose was 60 mg/day. Osteoporosis prophylaxis was prescribed in 24/37 (65%) GCA patients, most commonly cyclical etidronate. Conclusions: There is significant variation in the management of GCA within our institution. This audit has highlighted several areas where improvement could be made, particularly in streamlining the process of obtaining TA biopsy and in promoting the use of osteoporosis prophylaxis. (Intern Med J 2002; 32: 315?319)     

Homocysteine levels in polymyalgia rheumatica and giant cell arteritis: influence of corticosteroid therapy

OBJECTIVES: It has been suggested that patients with giant cell arteritis (GCA) may share a common pathway with atherosclerosis. Furthermore, patients with GCA and polymyalgia rheumatica (PMR), in addition to advanced age, are treated for prolonged periods of time with corticosteroids, a factor that can also accelerate atherosclerosis. Hyperhomocysteinaemia is considered an independent risk factor for atherosclerosis, and might play a role in ischaemic manifestations that occur with a variable frequency during the course of GCA. The purposes of the present study were: (i). to analyse the plasma levels of homocysteine in patients with GCA and PMR, (ii). to determine the influence of corticosteroid therapy on the homocysteine levels and (iii). to analyse if the levels of homocysteine may predict the development of ischaemic complications in patients with GCA. METHODS: Plasma homocysteine concentration was measured in 56 patients with active PMR/GCA (17 GCA and 39 isolated PMR) before steroid treatment and 23 healthy age-matched volunteers were used as controls. The total plasma homocysteine level was quantified using a fluorescent polarization immunoassay. RESULTS: Homocysteine concentrations were higher in PMR and GCA patients than age-matched controls (P < 0.05). Patients with GCA had slightly higher levels of plasma homocysteine than those with isolated PMR (13.6+/-4.3 vs 12.7+/-3.1 micromol/l, P=0.6). In 30 of these patients (12 GCA and 18 PMR) a second measurement of homocysteine concentration was done when they were in clinical remission with steroid treatment. The post-treatment levels of homocysteine were significantly increased in GCA rather than in PMR patients. In 13 patients with homocysteine levels above the normal upper limit of our laboratory, therapy with folic acid and/or vitamin B12 was started. After 3 months of vitamin supplements, the homocysteine concentration significantly decreased from 19.2+/-3.1 to 13.6+/-3.2 micromol/l (P=0.001). Such decrease was less marked in the PMR than in GCA patients. Ten out of the 17 patients with GCA had ischaemic manifestations of the disease. The levels of homocysteine were slightly higher in GCA patients with ischaemia than in those without ischaemic manifestations, although the difference did not reach statistical significance (15+/-4.9 vs 11.6+/-1.9 micromol/l, P=0.46). CONCLUSIONS: Patients with active PMR and GCA had elevated plasma concentrations of homocysteine. Corticosteroid therapy significantly increased such levels, especially in GCA patients. Treatment with supplements of folic acid and/or vitamin B12 reduced the homocysteine concentrations. These data support the hypothesis that patients with GCA (and to a lesser extend PMR patients) may share a common pathway with atherosclerosis and suggest a new atherogenic mechanism of corticosteroids.