Difficulties in the development of histological scoring of the inflamed temporal arteries in giant cell arteritis.
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Biopsy↗
Biomedical subjects
E Nordborg
Publications and source records attributed to E Nordborg.
Early menopause, low body mass index, and smoking are independent risk factors for developing giant cell arteritis.
OBJECTIVE: To assess female sex hormone related variables in a group of women with biopsy positive giant cell arteritis and a control group. METHODS: 49 women with biopsy positive giant cell arteritis, aged 50 to 69 years at the time of diagnosis, answered a questionnaire on hormonal and reproductive factors. The same questions were answered by a large population of women from the same geographical area in connection with routine mammograms. The results were tested statistically, using logistic regression analysis of each variable adjusted for age, and a multivariate logistic regression analysis including age and the variables which differed significantly between giant cell arteritis and controls. RESULTS: From the multivariate logistic regression analysis, three independent variables were associated with an increased risk of having giant cell arteritis: smoking and being an ex-smoker (odds ratio (OR) = 6.324 (95% confidence interval (CI), 3.503 to 11.418), p<0.0001); body mass index (a reduction of 1.0 kg/m2 increased the risk by 10% (OR = 0.898 (0.846 to 0.952), p = 0.0003); and menopause before the age of 43 (OR = 3.521 (1.717 to 7.220), p = 0.0006). CONCLUSIONS: There was a significant association between hormonal and reproduction related factors and the risk of developing giant cell arteritis in women given the diagnosis before the age of 70. The results suggest a possible role of oestrogen deficiency in the pathogenesis of giant cell arteritis. To confirm the results, an extended study will be needed, including women older than 70.
Aged↗
Cell-type-specific expression of p53 and p21 in giant cell arteritis.
The aim of the present study was to investigate the expression of TP53 (p53) and CDKN1A (CIP1; p21) in the arterial wall in giant cell arteritis (GCA). Cross-sections from 18 temporal artery biopsies displaying GCA and 8 control arteries were double-stained with monoclonal antibody directed at p53 or p21 on the one hand and alpha-smooth muscle actin, CD68 (macrophage) or CD3 (T-cell) on the other. Nuclear p53 was expressed in CD68-positive cells and smooth muscle cells in 16 of the 18 inflamed arteries. P21-positive nuclei were found in CD68-positive cells in 14 biopsies and in smooth muscle cells in all the specimens. All p53-positive giant cells also contained p21-positive nuclei. In the giant cells, immunopositive nuclei were mixed with negative ones. CD3-positive T-cells did not express p53 or p21. Only one p53-positive smooth muscle cell nucleus was found in the non-GCA controls and, compared with GCA, p21 expression was noted in few smooth muscle nuclei. The presence of p53 and p21 in the same types of cell in GCA indicates that the former protein is functional; p21 expression is induced by wild-type, functional p53 but not by its mutant form. The current observations suggest cellular stress in GCA, the nature of which requires further investigation.
Aged↗
Giant cell arteritis: epidemiological clues to its pathogenesis and an update on its treatment.
Giant cell arteritis (GCA) is a chronic systemic vasculitis with a marked female predominance and restriction to old age. The disease process distinctly targets large and medium sized arteries, preferentially the aorta and its extracranial branches. Morphological observations indicate that the age and sex distribution of GCA is related to the occurrence of degenerative changes in the arterial wall. GCA is not a truly infectious vasculitis. However, an infection might be a triggering factor. Different centres report an increase in GCA incidence, but annual fluctuations have not been shown to be statistically significant. However, significant seasonal variations have been observed by several groups. The mortality is not increased in adequately treated patients. Although, alternative steroid-sparing agents have been proposed, corticosteroids are still the first treatment choice.
Age Factors↗
The epidemiology of biopsy-positive giant cell arteritis: special reference to changes in the age of the population.
OBJECTIVE: The incidence of giant cell arteritis (GCA) increases with age. The aim of the present study was to investigate whether the increasing incidence of biopsy-proven GCA in Göteborg, Sweden, could be explained in terms of a change in the age composition of the general population. METHODS: All cases of biopsy-verified GCA between 1976 and 1995 were recorded. The annual incidence was calculated for women and men aged 50 yr or older and its relationship with the age composition of the general population was tested statistically. RESULTS: There was a significant positive correlation between age and the risk of developing GCA. In the general population, there was a shift towards higher age; in 1976, the mean age of people 50 yr or older was 63.2 (men) and 65.0 (women), whereas in 1995 it was 65.0 (men) and 68.1 (women). After compensating for this, the incidence of biopsy-proven GCA still increased significantly. Moreover, for women aged 50 yr or older, the risk of developing the disease increased more among younger subjects than older ones. CONCLUSIONS: The increase in the incidence of biopsy-proven GCA between 1976 and 1995 could not be explained merely in terms of the increasing age of the general population. It is most probably related to an increase in the influence of other factors.
Age Distribution↗
Radiographic joint destruction in postmenopausal rheumatoid arthritis is strongly associated with generalised osteoporosis.
OBJECTIVES: To investigate determinants of joint destruction and reduced bone mineral density (BMD) in postmenopausal women with active rheumatoid arthritis (RA) not treated with bisphosphonates or hormone replacement therapy and to evaluate if there are common markers of erosive disease and bone loss. METHODS: BMD was measured using dual x ray absorptiometry and joint damage was examined by x ray examination according to the Larsen method in 88 patients with RA. Associations between BMD and Larsen score, and between demographic and disease related variables, including proinflammatory cytokines, HLA-DR4 epitopes, and markers of bone and cartilage turnover, were examined bivariately by simple and multiple linear regression analyses. RESULTS: 49/88 (56%) patients had osteoporosis in at least one site. Reduced BMD and increased joint destruction were associated with: at the forearm and femoral neck, high Larsen score, low weight, and old age (R(2)=0.381, p<0.001; R(2)=0.372, p<0.001, respectively); at the total hip, low weight, high Larsen score, and dose of injected glucocorticosteroids (R(2)=0.435, p<0.001); at the lumbar spine, low weight, reduced cartilage oligomeric matrix protein, and increased carboxyterminal propeptide of type I procollagen (R(2)=0.248, p<0.001). Larsen score was associated with long disease duration and increased C reactive protein (CRP) (R(2)=0.545, p<0.001). CONCLUSIONS: Osteoporosis is common in postmenopausal patients with RA. Low weight and high Larsen score were strongly associated with BMD reduction. Increased CRP and long disease duration were determinants of erosive disease in postmenopausal women with RA. These findings indicate common mechanisms of local and generalised bone loss in RA.
Age Factors↗
Lower level of education in young adults with arthritis starting in the early adulthood.
An appropriate education may lead to less work disability in patients with arthritis. The aim of the study was to determine the educational level in two groups of young adults with arthritis. Patients with juvenile arthritis ( JA, n=32) and patients with early adult onset of arthritis (EA, n=47) were examined with the Quality of Life Scale (QOLS) and a questionnaire concerning education and profession counselling. Comparisons with a reference group (n=95) from the general population were made. The EA group had lower level of education (p<0.01), compared to the reference group. Among the EA patients, 62% had not discussed their choice of occupation with anybody, compared to 19% in the JA group. The educational level was lower in patients with rheumatic disease starting in early adulthood. Educational issues and counselling should be focused on the care of young adults with arthritis.
Adolescent↗
Giant cell arteritis. Epidemiology, etiology and pathogenesis.
Giant cell arteritis (GCA) is a chronic inflammatory disorder targeting large and medium-sized arteries, which predominantly affects postmenopausal women. Its high incidence in populations with Scandinavian lineage, some familial accumulation, and the association with the HLA-DR4 haplotype indicate a genetic predisposition. Epidemiological observations, as well as the symptomatology, may indicate an infectious origin, but so far GCA has not been shown to be a truly infectious form of vasculitis. Immunological research indicates an antigen-driven disease with local T-cell and macrophage activation in the vessel wall. Morphologically, the inflammatory process appears to be initiated by a foreign-body giant-cell attack on calcified internal elastic membrane in arteries and on calcified atrophic parts of the aortic media. The ensuing diffuse chronic inflammation leads to vessel dilatation and extensive intimal thickening. The latter, which relates to the production of promoting factors by the inflammatory cells, causes arterial stenosis and ischemic complications. The possible role of female sex hormones in GCA requires further investigation. Mononuclear and giant cells in GCA display the cytoplasmic accumulation of estrogen receptor (ER) alpha. Cytoplasmic ER-alpha is also seen in media smooth-muscle cells in GCA and in non-GCA controls, but nucleotide sequence analysis of the ER-alpha gene revealed no differences between GCA patients and controls. In the future, comprehensive morphological, cell biological and immunological research will be required for a better understanding of the complex etiology and pathogenesis of GCA.
Aging↗
The epidemiology of biopsy-positive giant cell arteritis: special reference to cyclic fluctuations.
OBJECTIVE: The aim of this work was to study changes in the incidence of biopsy-proven giant cell arteritis (GCA) over a period of 20 yr in Göteborg, Sweden. METHODS: All cases of biopsy-verified GCA between 1976 and 1995 were included in the study. The annual incidence was calculated for the whole material, for women and men separately, and its fluctuations were tested statistically. In addition, the monthly variation during the last 9 yr could be statistically analysed for the whole material. RESULTS: In total, 665 patients were diagnosed with biopsy-verified GCA during the 20 yr period. The average annual incidence was 22.2/100000 inhabitants over 50 yr of age (women 29.8, men 12.5). The annual incidence increased significantly with time (P<0.001) for both men and women. Statistical analysis did not reveal any cyclic fluctuation in the annual incidence (P=0.26), while the monthly number of positive biopsies showed significant fluctuation with peaks in late winter and autumn (P=0.041). CONCLUSIONS: The annual incidence of biopsy-positive GCA increased during the years 1976 through 1995. The significant seasonal variation, as well as considerable variation in annual incidence, might be due to the influence of exogenous triggering factors, such as infections. Further support for an exogenous aetiology, in terms of a statistically significant cyclic fluctuation of the annual incidence, was not found, however.
Biopsy↗
Search for varicella zoster virus in giant cell arteritis.
Polymerase chain reaction and immunohistochemical analyses of formalin-fixed temporal arteries from 10 pathologically verified cases of giant cell arteritis did not reveal varicella zoster virus antigen or DNA.
Aged↗
The role of CT in the diagnosis of sacro-iliitis.
OBJECTIVE: Ankylosing spondylitis is a progressive, debilitating disease in which early diagnosis and early treatment can improve the prognosis. Radiographic confirmation is essential for diagnosis but conventional radiography has not proved useful, particularly in the early course of the disease. The aims of this study were to correlate the findings at conventional radiography with those at CT, and to correlate the duration of clinical symptoms with the radiological findings. MATERIAL AND METHODS: Forty patients with clinical sacro-iliitis and 13 controls were evaluated by means of conventional radiography and CT. RESULTS: Conventional radiography was positive in 10/40 patients and CT in 30/40 patients. Conventional radiography was positive in only 2/14 patients with a symptom duration of less than 2 years while CT was positive in 10/14 such patients. CONCLUSION: The study demonstrated a considerably higher sensitivity in CT than in conventional radiography in detecting the subtle changes necessary for the radiological diagnosis of sacro-iliitis, particularly in cases of short duration. CT allows an early start to be made in treatment with a consequently improved prognosis. The use of conventional radiography cannot be recommended because its low sensitivity delays diagnosis in many instances.
Adolescent↗
The effect of glucocorticoids on fat and lean tissue masses in giant cell arteritis.
The aim of the present prospective study over a follow-up period of two years was to assess the influence of various doses of glucocorticosteroids on the total body fat and lean tissue masses and their regional distribution, using DXA technique, in twenty-four patients with giant cell arteritis (GCA). Treatment with glucocorticoids for two years, using high doses of prednisolone the first six months and lower doses thereafter, resulted in a significant increase in total body fat as well as in trunk fat expressed either as absolute values or as a proportion of body weight. The abnormal accumulation of fat mass remained also after switching to a low dose glucocorticoid schedule. There was no redistribution of fat from peripheral areas to central parts of the body and there was no depletion of lean tissue at peripheral sites.
Absorptiometry, Photon↗
No additive effect of cyclosporin A compared with glucocorticoid treatment alone in giant cell arteritis: results of an open, controlled, randomized study.
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Aged↗
The ineffectiveness of cyclical oral clodronate on bone mineral density in glucocorticoid-treated patients with giant-cell arteritis.
OBJECTIVES AND DESIGN: The aim of the present study was to determine whether cyclic oral administration of clodronate, a bisphosphonate, every second month prevents rapid bone loss during the first year of glucocorticoid treatment in patients with giant-cell arteritis (GCA). The trial was designed as a prospective double blind study, assessing total body mineral content (BMC) and bone mineral density (BMD) using DXA technique. Supplementation of calcium was given to both groups of patients. SETTING: The outpatient clinics of the rheumatic and infectious diseases of Sahlgren University Hospital of the city of Göteborg on the west coast of Sweden. SUBJECTS: Twenty-seven patients with confirmed GCA were consecutively included during a 15-month period. RESULTS: An early influence on bone turnover was found with a temporary decrease in BMC after six months of glucocorticoid treatment, which was normalized after 12 months in both study groups. No significant differences between the patients given clodronate and calcium and the controls, who got supplementation with calcium alone, was observed at any assessment point. However, there was a significant and prolonged depression of the osteocalcin levels in the clodronate-treated patients. CONCLUSIONS: Oral administration of clodronate in a moderately high dose given cyclically every other month had no additive effect on BMD compared with calcium supplementation alone during the first year of glucocorticoid treatment. A larger material might have revealed some differences between the categories. In most patients with GCA, however, the BMD seems to recover after one year of glucocorticoid treatment, provided there is good control of the inflammation and patients are kept physically active. It needs to be elucidated whether there are subsets of patients who might benefit from bone sparing agents: women near menopause with a high turnover rate of bone, individuals who have low BMD from the start of glucocorticoid treatment or patients requiring high doses of glucocorticoids during a long period of time.
Administration, Oral↗
Atrophy of the aortic media in giant cell arteritis.
Aortic tissue from seven patients with giant cell arteritis (GCA) was investigated using light microscopy and immunocytochemistry. Four surgical cases and three autopsy cases were included. All the specimens displayed a severe reduction in the size and number of media smooth muscle cells immunopositive for alpha-smooth muscle actin (alpha-SMA). A subtotal loss of alpha-SMA-positive cells was seen in non-inflamed media tissue, continuing gradually towards multiple calcified acellular lesions totally devoid of alpha-SMA immunoreactivity. There was a slight to moderate granulomatous inflammatory reaction in the tissue surrounding part of the acellular lesions. Foreign body giant cell reaction and elastin degradation were found at the ends of the acellular calcified areas. The present findings indicate that the atrophy and the loss of alpha-SMA-positive cells in the aortic media in GCA is primary, and that the granulomatous reaction is secondary and directed against atrophic calcified media tissue.
Actins↗
The influence of sectional interval on the reliability of temporal arterial biopsies in polymyalgia rheumatica.
Temporal arterial biopsies from 27 patients with a clinical diagnosis of pure polymyalgia rheumatica (PMR) were examined using light microscopy on paraffin and plastic sections. The primary routine examination of the paraffin-embedded parts of the biopsies (biopsy length: 12.7 +/- 4.5 mm, sub-segments: 4.9 +/- 1.2 mm) revealed 4 positive cases, whereas the primary examination of the smaller plastic-embedded parts showed inflammation in 6 cases (biopsy length: 2.7 +/- 1.2 mm, sub-segments: 0.7 +/- 0.3 mm). Serial sectioning with a 50 microns interval of arteries which were negative primarily revealed three new positive cases in the paraffin-embedded material (total length: 174.0 mm), whereas sectioning the plastic-embedded material (total length: 52.8 mm) produced one more positive artery. All the new cases displayed a focal inflammatory process in atrophic, calcified arterial segments. The high yield of positive biopsies in the present material (11 of 27; 40.7%) demonstrates the diagnostic value of temporal arterial biopsy in PMR and the importance of a careful histologic examination. The results also indicate the influence of biopsy length on the yield of positive biopsies. The division of fixed temporal arterial biopsies into approximately 1-mm-long sub-segments before the embedding and the further serial sectioning of those negative biopsies which are atrophic and/or calcified is recommended in cases of pure PMR.
Aged↗
Giant cell arteritis.
Whereas giant cell arteritis (GCA) was considered a rare disease 50 years ago, the generalized arteritis is now recognized as an important and significant cause of morbidity in elderly people; its cause and pathogenesis is poorly understood. Glucocorticosteroids are the drug of choice in all clinical types of GCA. In contrast to corticosteroids, nonsteroidal anti-inflammatory drugs have no proven effect on vascular complications to GCA, and cannot be recommended.
Adrenal Cortex Hormones↗
Giant cell arteritis. Epidemiology and treatment.
Giant cell arteritis (GCA) was considered a rare disease 50 years ago; however, it is now known to be an important and significant cause of morbidity and mortality in elderly people. GCA is a generalised arteritis, although the aetiology and pathogenesis of this disorder are poorly understood. It is likely that there are environmental or genetic factors that significantly influence the risk for the disease in different populations. Epidemiological studies have shown the highest incidence in Northern Europe and in Minnesota, US; which are populations of the same descent. Much lower incidence figures have been reported from more Southern regions of Europe and elsewhere. Possibly, the incidence of the disease is increasing as suggested by recent surveys. Glucocorticosteroids are the drugs of choice in all clinical types of GCA. Most studies have been performed with prednisolone. There is no general agreement concerning the initial dosage, but 10 to 40 mg/day is 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. Because of the low dosage required, the frequency of corticosteroid-related adverse effects is relatively low. The median duration of treatment is about 5 years. Nonsteroidal anti-inflammatory drugs, in contrast to corticosteroids, have no proven preventive effect on vascular complications of GCA, and cannot be recommended.
Adrenal Cortex Hormones↗