Influence of age,sex, and place of residence on clinical expression of giant cell arteritis in northwest Spain

OBJECTIVE: To investigate the epidemiology of giant cell arteritis (GCA), we examined whether differences in clinical and laboratory features exist in patients with biopsy-proven GCA from Northwest Spain according to sex, place of residence, and age at disease onset. METHODS: Retrospective study of biopsy-proven GCA diagnosed from January 1, 1981, to December 31, 2001, at the single hospital for a well defined population of 250,000. A comparative analysis was conducted of clinical and laboratory features according to sex, place of residence (rural or urban), and age at the onset of symptoms (< 70 yrs; >or= 70 yrs). RESULTS: Between 1981 and 2001, 210 patients from the Lugo region were diagnosed with biopsy-proven GCA. In urban areas GCA was significantly more common in women (rate ratio 1.58, 95% CI 1.00-2.53, p = 0.05). Women presented manifestations of polymyalgia rheumatica (PMR) more commonly than men. However, no statistically significant difference in the frequency of visual manifestations or permanent visual loss were observed between the sexes. GCA was slightly more common in rural than in urban areas (annual adjusted incidence rate in rural areas 10.4/100,000 in people age >or= 50 years vs 9.1/100,000 in urban areas; p = 0.34). GCA was more common among men in rural areas (rate ratio 1.73, 95% CI 1.10-2.70, p = 0.02). Patients younger than 70 years at the time of diagnosis (20%) had a trend to a longer delay to diagnosis and a marginal increase in the frequency of PMR compared with those with disease onset at age >or= 70 years. A higher inflammatory response was observed in the patients younger than 70 years. CONCLUSION: In patients with biopsy-proven GCA from Northwest Spain PMR manifestations are more commonly observed in women. The higher inflammatory response and the longer delay to diagnosis in younger patients call for a higher physician awareness of this vasculitis among individuals younger than 70 years.     

Giant cell arteritis without clinically evident vascular involvement in a defined population

OBJECTIVES: To examine the frequency and clinical presentation of biopsy-proven giant cell arteritis (GCA) patients who do not exhibit overt clinical vascular manifestations. To assess whether differences exist between this group of patients and the rest of biopsy-proven GCA patients. METHODS: Retrospective study of biopsy-proven GCA patients diagnosed from 1981 through 2001 at the single hospital for a well-defined population of almost 250,000 people. Patients were considered as having no evident vascular involvement if cranial ischemic manifestations or other vascular complications of GCA were not present at the time of diagnosis or during at least 12 months' followup. RESULTS: Between 1981 and 2001, 210 patients from the Lugo region of northwest Spain were diagnosed with biopsy-proven GCA. Eleven patients did not show overt vascular manifestations of GCA. Nine of them presented with polymyalgia rheumatica (PMR) and another 2 fulfilled criteria for fever of unknown origin. Patients without clinically evident vascular involvement had a significantly longer delay to diagnosis than those with vascular manifestations. Also, PMR manifestations were more frequently observed in this group of patients. CONCLUSIONS: Biopsy-proven GCA without clinically evident vascular involvement is not exceptional. Despite having a longer delay to diagnosis, these patients constitute a more benign subgroup of GCA.     

IL-6 promoter polymorphism at position -174 modulates the phenotypic expression of polymyalgia rheumatica in biopsy-proven giant cell arteritis

OBJECTIVES: Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are related diseases in which diverse genetic and environmental factors are implicated. Both GCA and PMR are characterized by an intense acute phase reaction. In these sYndromes the increased production of IL-6 has been observed. To investigate further the genetic influence of IL-6 in GCA and PMR we have examined the IL-6 promoter polymorphism (G to C) at position -174 in the 5' region in a series of patients from Northwest Spain diagnosed with GCA and/or PMR. METHODS: Sixtxy-two biopsy-proven GCA patients (30 of them with associated PMR) and 84 patients with isolated PMR were studied. Patients and ethnically matched controls (n = 124) were from the Lugo region (Galicia, Northwest Spain). Patients and controls were genotyped for HLA-DRB1 and IL-6 polymorphism at position -174 by molecular methods. RESULTS: IL-6-174 allele C was marginally increased infrequency in GCA patients with PMR manifestations compared with isolated GCA (Pcorr 0.06; OR = 2.3). The increase in the frequency of the CC genotype in GCA patients with PMR versus those with isolated GCA was statistically significant (Pcorr 0.02). The increased frequency of allele C in GCA patients with PMR was more commonly observed in HLA-DRBI *04 negative patients. However, this polymorphism was not associated with a higher risk of ischemic events in GCA or with relapses in PMR. CONCLUSION: Allele C at position -174 in the 5' promoter region of the IL-6 gene may be associated with PMR in biopsy-proven GCA patients not carrying HLA-DRBI *04 alleles.     

Corticotropin releasing hormone promoter polymorphisms in giant cell arteritis and polymyalgia rheumatica

OBJECTIVE: Giant cell (temporal) arteritis (GCA) and polymyalgia rheumatica (PMR) are different but overlapping diseases of unknown etiology affecting the elderly. Corticotropin-releasing hormone (CRH) helps to regulate the immune response and maintain homeostasis during inflammatory stress. CRH promoter region polymorphisms in the 5'regulatory region of the CRH gene have been described. To investigate the possible implications of the CRH promoter polymorphisms in PMR and GCA susceptibility we have examined a series of patients with these conditions. METHODS: Sixty-two patients with biopsy-proven GCA, 86 patients with isolated PMR and 147 ethnically matched controls from the Lugo region of Northwest Spain were included in this study. Patients and controls were genotyped for CRH polymorphism in the 5' regulatory region of the gene at position 1273 (alleles A1 andA2) and at position 225 (alleles B1 and B2) by PCR-restriction fragment length polymorphism. Allele frequencies and genotype distribution were evaluated by the chi-square test. RESULTS: When GCA and PMR patients were examined for alleles and genotypes for each CRH polymorphism no significant differences in frequency were found compared with controls. A higher CRH-A2 allele frequency was observed in GCA patients with visual complications (21.4%) compared with controls (9.2%) and GCA cases without eye involvement [6.3%; p= 0.017, Pcorr = 0.034, O.R: 4.1 (95% CI 1.2- 13.9)], although this was based on a small sample of patients with ischemic visual complications (n = 14) and should be interpreted with caution. No differences in CRH allele or genotype frequencies were observed in isolated PMR patients stratified by relapses and recurrence of disease symptoms. CONCLUSION: Polymorphisms in the CRH gene regulatory region do not appear to be associated with increased susceptibility to PMR or GCA. The CRH-A2 allele may encode risk for the development of visual complications in GCA, although further studies to confirm this will be required.     

Low serum levels of DHEAS in untreated polymyalgia rheumatica/giant cell arteritis

OBJECTIVE: To address a controversy regarding the existence of a relative adrenal hypofunction in patients with untreated polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) we evaluated baseline serum levels of ACTH, cortisol, and DHEAS in a cohort of patients with recent onset PMR/GCA not previously treated with glucocorticoids, in comparison with healthy controls. Possible correlations between baseline DHEAS levels and laboratory measures of disease activity were also explored. METHODS: Basal serum levels of these hormones were prospectively investigated in 25 patients with active untreated disease and compared with those of 25 age- and sex-matched control subjects. RESULTS: Of the 25 patients, 19 had isolated PMR and 6 had biopsy-proven GCA + PMR. Basal levels of cortisol and ACTH in PMR/GCA patients did not differ from control subjects; in relation to inflammatory status, lower than expected basal production of cortisol was observed in active untreated PMR/GCA. Baseline serum DHEAS levels were significantly lower in all patients compared with controls. In these patients, a significant correlation was found between baseline DHEAS values and laboratory measures of disease activity. The percentage of DHEAS reduction and the severity of inflammatory response were higher in women than in men. CONCLUSION: Patients with PMR/GCA with new-onset active disease before steroid treatment have inappropriately normal cortisol levels regarding the ongoing inflammation, and significantly lower levels of DHEAS compared to the age- and sex-matched healthy control subjects. These data support the existence of a relative adrenal hypofunction in PMR and GCA.     

Early large vessel systemic vasculitis in adults

Giant cell arteritis (GCA) is the most common vasculitis in individuals older than 50 years in Western countries. In addition to the typical pattern of cranial ischemic manifestations, large vessel vasculitis (LVV) involvement has emerged as a common feature of GCA. Patients with predominant LVV manifestations differ from those with the cranial pattern. They are usually affected at a younger age and often have nonspecific manifestations such as constitutional syndrome, fever of unknown origin, or refractory/atypical polymyalgia rheumatica (PMR). In these patients, cranial manifestations are often absent. Furthermore, patients with isolated PMR should be followed up because of the potential risk of severe vascular complications in the setting of an underlying GCA. Whereas temporal artery biopsy and/or color duplex ultrasound of the temporal arteries is useful for the diagnosis of cranial GCA, Doppler sonography of the subclavian and axillary arteries, fluorine-18-fluorodeoxyglucose–positron emission tomography/computed tomography, magnetic resonance, and computed tomography-angiography are very useful to identify the presence of LVV, and they may play a potential role in the follow-up of these patients.     

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.     

Fever in biopsy-proven giant cell arteritis: clinical implications in a defined population

OBJECTIVE: To assess the frequency and clinical features of biopsy-proven giant cell arteritis (GCA) patients who had fever at the time of diagnosis of the disease, and the relationship between fever, ischemic complications, and the systemic inflammatory response in GCA. METHODS: A retrospective study of biopsy-proven GCA patients diagnosed between 1981 and 2001 was performed at the single referral hospital for a well-defined population in the Lugo region of northwest Spain. Patients were considered as having fever if the axillary temperature at the time of admission or during the followup prior to the onset of corticosteroid therapy was > or =38 degrees C. RESULTS: During the period of study, 21 (10%) of the 210 biopsy-proven GCA patients had fever. Two of them fulfilled criteria for fever of unknown origin. Patients with fever had a lower frequency of severe ischemic manifestations than the rest of biopsy-proven GCA patients. They also exhibited a more severe inflammatory disease, with significant abnormality in most laboratory variables, including higher elevation of erythrocyte sedimentation rate, lower values of hemoglobin, and higher proportion of patients with increased alkaline phosphatase. By logistic regression analysis, we observed that patients with fever had an increased risk of developing anemia (odds ratio [OR] 12.24). In contrast, a negative association between severe ischemic manifestations and fever was found (OR 0.41). CONCLUSION: Biopsy-proven GCA patients with fever constitute a subgroup of patients with more severe inflammatory response and less ischemic disease.     

Are polymyalgia rheumatica and giant cell arteritis the same disease?

OBJECTIVE: To summarize the evidence about the relationship between polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). METHODS: Review of relevant articles from the English-language literature. RESULTS: Epidemiologic studies suggest that PMR and GCA are closely related conditions affecting people over 50 years and frequently occurring in the same patient. PMR symptoms have been observed in 40 to 60 percent of GCA clinical series. Also, temporal artery biopsy may yield positive results for GCA in patients with isolated PMR. Conflicting HLA-DRB1 genotype results have been reported, and recent studies have shown that PMR and GCA have different expression of RANTES, TNFalpha microsatellite, and IL-6 promoter genetic polymorphisms. Search for a possible common infectious agent have yielded disappointing results. Although parvovirus B19 DNA is present in the artery wall of patients with GCA, this virus may be only an innocent bystander. Cytokine studies on a limited number of temporal artery biopsy specimens have shown that interferon-gamma is produced in GCA and not in PMR, suggesting that this cytokine may be crucial to the development of overt vasculitis. CONCLUSIONS: PMR and GCA frequently occur together but no definitive conclusions can be drawn about the nature of this association.     

Development of ischemic complications in patients with giant cell arteritis presenting with apparently isolated polymyalgia rheumatica: study of a series of 100 patients

Several studies suggest that patients with giant cell arteritis (GCA) presenting with isolated polymyalgia rheumatica (PMR) with no cranial symptoms are at low risk of suffering GCA-related ischemic events. However, the issue remains controversial. In the current study we assessed the development of ischemic events in a large series of GCA patients who suffered from apparently isolated PMR during the main course of their disease. One hundred GCA patients presenting with PMR only for at least 2 months were selected from among 347 individuals with biopsy-proven GCA. Clinical manifestations and their chronologic appearance before diagnosis were recorded. Seventy-three patients presented with isolated PMR for a median of 8 months (range, 2 mo-5 yr) and later developed cranial symptoms for a median of 3 weeks (range, 0 wk-1 yr), which eventually led to GCA diagnosis (Group 1). The remaining 27 patients, after presenting a self-limiting course of dismissed mild cranial symptoms lasting for a median of 2 weeks (range, 1 wk-4 mo), developed PMR, which was their chief complaint for a median of 3 months (range, 2 mo-1.5 yr) and the reason for medical evaluation (Group 2). Twenty (27.4%) patients in Group 1 suffered disease-related ischemic complications at the time of diagnosis. No patient in Group 2 developed ischemic events. Patients with GCA presenting with apparently isolated PMR are not a benign subset and have a significant risk of developing ischemic complications. Among them, the only patients who appear to be at low risk of developing ischemic events are those in whom a self-limiting episode of cranial symptoms can be recorded.     

Aortic aneurysm and dissection in patients with biopsy-proven giant cell arteritis from northwestern Spain: a population-based study

Most classical manifestations of giant cell arteritis (GCA) are the result of occlusive vascular involvement. However, unlike ischemic manifestations, aortic aneurysmal disease in patients with GCA has been less well described. We assessed the incidence and predictors of aortic aneurysm and dissection in patients with biopsy-proven GCA from the Lugo region of northwestern Spain and compared the results with those in a 2003 report from Olmsted County, MN. We performed a retrospective study of biopsy-proven GCA patients diagnosed from 1981 to 2001 at the single hospital for a well-defined population of almost 250,000 people. Twenty (9.5%) of the 210 biopsy-proven GCA patients diagnosed during the study period developed aortic aneurysmal disease. Sixteen of the 20 patients had thoracic aneurysms and 6 had abdominal aneurysms. The incidence of aortic aneurysm and/or dissection in Lugo (18.9 per 1000 person years at risk) was similar to that reported in Olmsted County (18.7 per 1000 person years at risk). Hypertension (hazard ratio: 4.73) and polymyalgia rheumatica with a marked acute inflammatory response at the time of diagnosis of GCA (hazard ratio: 3.71) were the best predictors of aortic aneurysmal disease. Our present observations suggest that a severe inflammatory response associated with hypertension at the time of diagnosis of GCA may promote the development of aortic aneurysmal disease. GCA patients having these features should be monitored for the existence of aortic aneurysm and dissection.     

Audiovestibular manifestations in giant cell arteritis: a prospective study

Giant cell arteritis (GCA) is a multisystemic vasculitis of elderly people that involves large and medium-sized blood vessels with predisposition to the cranial arteries. Some cranial ischemic manifestations, in particular permanent visual loss, have been widely described. Audiovestibular manifestations have been less commonly reported. In the present study we assessed the frequency and outcome of audiovestibular manifestations in a series of GCA and isolated polymyalgia rheumatica (PMR) patients examined prospectively between June 1999 and May 2001 at the single hospital for a defined population. Patients were included in the study if a temporal artery biopsy had been performed and they were examined within a week after beginning corticosteroid treatment. Patients with abnormal otoscopy or tympanogram, history of cerebrovascular complications, syphilis, Ménière and other vestibular syndromes, infections involving the inner ear, barotrauma, or being treated with ototoxic drugs were excluded. During the study period 44 patients with GCA and 10 patients with biopsy-negative isolated PMR were examined. Patients with isolated PMR were younger. Audiovestibular dysfunction was significantly more frequent in GCA patients than in those with isolated PMR and matched controls. Almost 90% of the GCA patients had vestibular dysfunction, which was generally reversible after several days of steroid treatment; after 3 months of treatment, vestibular dysfunction was observed in only 13 (29.6%) of the 44 GCA patients. These patients with persistent vestibular dysfunction were more likely to have persistent head-shaking nystagmus. Twelve (27.3%) of the 44 GCA patients had hearing improvement after 3 months of therapy. After 6 months of therapy, only 1 of the 44 GCA patients had abnormal vestibular tests. However, no additional improvement in hearing function was observed. The present study confirms a high frequency of audiovestibular manifestations in GCA. It also suggests that audiovestibular damage may be reversible in some patients with GCA.     

Polymyalgia rheumatica: a syndrome associated with HLA-DR4 antigen

HLA class II antigens were determined in 65 patients with biopsy-proven giant cell arteritis (GCA). An increase in DR4 antigen frequency was found in the patients (40%) compared with that in 200 healthy controls (20%) (Pcorr less than 0.05). DR4 was significantly more frequent in GCA patients with polymyalgia rheumatica (PMR) than in those without PMR (58.8% versus 19.3%) (P less than 0.005). HLA-DR4 frequency in GCA patients without PMR was similar to that in the control population (20%). Patients with severe, disabling PMR had DR4 more frequently (90%) than did those with moderate symptoms who required medical care because of cranial arteritis manifestations (41.6%) (P less than 0.05). We conclude that, in GCA patients, association with DR4 is mainly related to the manifestation of the disease as PMR. We discuss clinical and immunogenetic similarities between PMR and other DR4-associated rheumatic disorders. Common immunopathogenic mechanisms leading to clinical overlap among them are suggested.     

Genetic markers of disease susceptibility and severity in giant cell arteritis and polymyalgia rheumatica

BACKGROUND AND OBJECTIVES: Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are common and often overlapping diseases that generally occur in elderly patients. In this article, we examine the role of different genes as markers of disease susceptibility and severity in GCA and PMR. METHODS: The influence of human leukocyte antigen (HLA)-DRB1 and tumor necrosis factor alleles, as well as the different allelic polymorphisms, on the susceptibility and severity to GCA and PMR was examined. A review of the literature was conducted. RESULTS: Most studies have described an association of GCA with HLA-DRB1(*)04 alleles. However, HLA-DRB1 association in patients with PMR varies from one population to another. In Northwest Spain, patients with GCA and PMR exhibited different tumor necrosis factor microsatellite polymorphism associations. Studies of intercellular adhesion molecule-1 biallelic polymorphisms have yielded contradictory results. Interleukin 1 cluster and tumor necrosis factor alpha polymorphisms increased susceptibility to GCA and PMR slightly. In Northwest Spain, interleukin 6 promoter polymorphism at position -174 modulated the phenotypic expression of PMR in biopsy-proven GCA. In the same population, regulated upon activation, normal T cell expressed and presumably secreted gene promoter biallelic polymorphism at position -403 was a marker for PMR susceptibility but not for GCA, and corticotropin-releasing hormone polymorphism appeared to be implicated in the risk of severe ischemic complications in patients with GCA. CONCLUSIONS: The present analysis confirms that GCA and PMR are polygenic diseases. The search for additional genes is necessary to better understand the pathogenesis of these conditions.     

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.     

巨细胞动脉炎与风湿性多肌痛临床特征的对比分析

目的:通过比较风湿性多肌痛（PMR）和巨细胞动脉炎（GCA）的临床差异,总结GCA患者的临床特点。方法:收集皖南医学院附属弋矶山医院风湿免疫科2010年8月至2019年9月住院的12例巨细胞动脉炎患者临床资料,并选择同期住院的,与GCA组患者进行2∶1年龄、性别相匹配的PMR患者形成对照组,比较2组患者的临床表现、实验...     

Interleukin-6 promoter polymorphism at position -174 in giant cell arteritis

OBJECTIVE: To investigate potential associations between the -174 G/C interleukin-6 (IL-6) promoter polymorphism and susceptibility to and clinical features of giant cell arteritis (GCA), particularly in patients with or without polymyalgia rheumatica (PMR) and with or without ischemic complications. METHODS: One hundred and twenty-six patients with biopsy-proven GCA who were residents in Reggio Emilia, Italy, and 112 population-based controls from the same geographic area were genotyped for IL-6 polymorphism at position -174 by molecular methods. Patients were divided in subgroups according to presence or absence of PMR and ischemic complications (visual loss, jaw claudication, cerebrovascular accidents, aortic arch syndrome). RESULTS: Distribution of the G/C 174 genotype was similar in patients with GCA and controls. No significant associations with the IL-6 promoter polymorphism at position -174 were found when GCA patients with or without PMR or with or without ischemic complications were compared. Further, IL-6 genotypes did not significantly affect levels of C-reactive protein or other inflammatory markers at diagnosis. CONCLUSION: Our findings show that the 174 G/C promoter IL-6 polymorphism does not seem to be implicated in susceptibility to and clinical expression of GCA.     

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.     

Sex differences in temporal arteritis and polymyalgia rheumatica

OBJECTIVE: Sex-specific differences in treatment outcomes have been observed in polymyalgia rheumatica (PMR) and temporal arteritis (TA), with a significantly longer course of treatment in women than in men. We analyzed whether these sex differences are related to differences in disease presentation and severity of the inflammatory response. METHODS: The records of 163 cases of PMR and/or TA diagnosed over a 15 year period were reviewed. A comparative study of clinical and laboratory features between men and women was performed. RESULTS: Of 163 patients, 90 had isolated PMR and 73 had TA. Among patients with TA, 49 women and 24 men were identified, with a ratio of 2. While there were no differences in the frequency of classic disease manifestations, the presence of constitutional syndrome (malaise, anorexia, and weight loss) and fever were significantly more frequent in women than in men. Of note, evaluation of laboratory measures at time of diagnosis also revealed more marked laboratory abnormalities reflecting inflammation in the female group. Among patients with isolated PMR, 58 women and 32 men were identified, a ratio of 1.8. Comparing the clinical features at presentation, significant sex differences were also found, with a higher frequency of constitutional syndrome and lower values of hemoglobin in women. Moreover, women also had higher erythrocyte sedimentation rate values, and higher prevalence of fever and hepatic involvement, although the difference did not reach statistical significance. CONCLUSION: Modest differences were found in disease expression between women and men with TA and/or PMR. In both conditions, the inflammatory response seemed to be more severe in women. The strong inflammatory response in women could explain the longer duration of treatment reported in this subgroup of patients.     

Biopsy-negative giant cell arteritis: clinical spectrum and predictive factors for positive temporal artery biopsy

OBJECTIVES: To examine the frequency and features of patients with biopsy-negative giant cell arteritis (GCA), establish differences with biopsy-proven GCA, and identify the optimal set of predictors for a positive temporal artery biopsy (TAB) in patients with GCA. METHODS: Retrospective study of an unselected population of patients with GCA diagnosed at the reference hospital for a defined population between 1981 and 1998. Patients were classified into biopsy-proven GCA if a TAB was positive for GCA, or biopsy-negative GCA if they fulfilled the American College of Rheumatology 1990 criteria for the classification of GCA (Hunder GG, et al Arthritis Rheum 1990; 33:1122-8) despite having a negative TAB. RESULTS: One hundred ninety Caucasian patients were diagnosed with GCA. Twenty-nine of them (15.3%) had a negative TAB. In these biopsy-negative patients, headache and polymyalgia rheumatica were frequent presenting symptoms. In contrast, jaw claudication, abnormal temporal artery on physical examination, and constitutional syndrome (asthenia, anorexia, and weight loss of 4 kg or more) were less common. They also had lower biologic markers of inflammation. The best predictive model of biopsy-proven GCA included a history of constitutional syndrome (OR = 6.1), an abnormal temporal artery on physical examination (OR = 3.2), and the presence of visual complications (OR = 4.9). CONCLUSIONS: In GCA, a subset of patients have a high likelihood of having a negative TAB. This subset seems to have less severe ischemic complications than that of biopsy-proven GCA. In patients without visual manifestations, abnormal temporal artery on examination or constitutional syndrome the risk of having an abnormal TAB is low.