The epidemiology of biopsy-positive giant cell arteritis: special reference to changes in the age of the population

C. Nordborg, H. Johansson, V. Petursdottir1 and E. Nordborg2

Departments of Clinical Pathology and
2 Rheumatology, Sahlgrenska University Hospital, Göteborg, Sweden and
1 Department of Pathology, University of Iceland, Reykjavik, Iceland


    Abstract
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
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.

KEY WORDS: Giant cell arteritis, Epidemiology, Incidence, Age.


    Introduction
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Giant cell arteritis (GCA) is an inflammatory disorder mainly involving the large and medium-sized arteries that affects people aged 50 yr and older, with a clear female predominance. Its incidence is highest in Scandinavia and in populations with a strong Scandinavian ethnic background [1–6; for references see [7]). Previous studies of populations in Scandinavia, Olmsted County, Minnesota, and north-western Spain report an increase in GCA incidence with time [811]. As GCA is a disorder of older people, one might ask whether this increase could be related to an increasing number of elderly people in the population. The purpose of the present investigation was to elucidate statistically whether the observed increase in GCA incidence in Göteborg could be explained in terms of a general change in age composition. The present study is an extension of a previous epidemiological study of the same population [10].


    Patients and methods
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
The sources of information about the temporal artery biopsies were the files at the Department of Pathology, Sahlgrenska University Hospital, which is the referral centre for clinical histopathology in Göteborg. The biopsies were taken at four referring clinics in Göteborg; referring clinics outside Göteborg were not included. In 1993–1995, a minority of the biopsies (165 of 872) were referred to a private laboratory outside Göteborg (Medilab, Malmö). These biopsies were also included in the study. The investigation therefore comprised all the positive and negative temporal artery biopsies in Göteborg between 1 January 1976 and 31 December 1995.

Owing to the retrospective, morphology-based nature of this study, patients with only a clinical diagnosis of GCA, in whom a temporal artery biopsy was not performed, were not included. Our data of incidence should thus be regarded as minimum values. The recommended criteria for temporal artery biopsy in Göteborg throughout the investigated period were polymyalgic symptoms and/or temporal cranial symptoms+an increased erythrocyte sedimentation rate+age above 50 yr and no signs of rheumatic disease other than GCA. Alternative criteria were general symptoms of disease+increased erythrocyte sedimentation rate where no other cause was found. The general policy in Göteborg is to perform a biopsy before steroid therapy. If this is not possible, the biopsy is generally taken shortly thereafter. There is ample evidence in the literature that the inflammatory reaction remains for a long time after the initiation of high-dose steroid therapy [1214].

With very few exceptions, the biopsies taken in Göteborg are unilateral. Serial biopsies are not and have not been performed in Göteborg and a second biopsy is uncommon. The indication for a second biopsy is generally a negative first biopsy. The results have therefore not been influenced by double or multiple positive biopsies. We do not have complete information as to the length of the 4971 biopsies included in this retrospective study. According to scattered samples, there has been no significant change in length over the years [10].

Every biopsy report was checked; the slides were re-examined in the case of an inconclusive statement. To receive a diagnosis of GCA, the biopsy had to show signs of arteritis with a mononuclear cell infiltrate in the arterial wall with or without the admixture of giant cells.

The yearly incidence of biopsy-positive GCA was assessed separately for women and men.

Statistical methods
A Poisson model (Breslow) was used to study the relationship between calendar year, age and the risk of GCA. The hazard function of individuals older than 50 yr was assumed to be: exp[ß01·(calendar year-1975)+ß2·age+ß3·age·(calendar year-1975)]. The coefficients ß1, ß2 and ß3 reflected trends in the risk. ß123=0 corresponded to no change in risk.

A logistic model was used to test if there was a change in the proportion of positive temporal artery biopsies with time.


    Results
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Göteborg is the second largest city in Sweden. Its population is predominantly Caucasian with an average of 433 337 inhabitants (range 424 085 to 449 189) during the studied 20-yr period. The number of both women and men aged 50 yr and older decreased slightly during the period (women: 86 048 to 81 403; men: 69 954 to 64 749), while the number of immigrants aged 45 and over increased (4900 to 11 547) [15].

The number of temporal artery biopsies examined during the period was 4971. A total of 13.4% (n=665) were positive for GCA. Of these, 664 patients were aged 50 and over. Only one male patient was 49 yr of age. The average annual incidence for the population over 50 yr of age was 22.2/100 000 (women 29.8, men 12.5) [10].

The annual incidence of biopsy-positive GCA in the population aged 50 yr and over increased significantly for both men and women between 1976 and 1995 (P < 0.001 for both). The estimated yearly increase in incidence was 5.2% for men and 13.9% for women. Like the positive biopsy incidence, the total biopsy rate increased during the period. However, according to a logistic test there was no significant time trend with regard to the proportion of inflamed arteries among the biopsies (P=0.14).

In the investigated population, there was a significant positive correlation between the incidence of biopsy-positive GCA and age for women as well as for men (P < 0.001 for both).

From 1976 to 1995, there was a shift toward higher age in the general population; in 1976, the mean age of people aged 50 yr and older was 63.2 (men) and 65.0 (women), whereas in 1995 it was 65.0 (men) and 68.1 (women) (Fig. 1Go). After compensating for changes in the age composition of the general population, the incidence of biopsy-proven GCA still increased significantly during the period (women P < 0.001, men P=0.0072) (Fig. 2Go).



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FIG. 1. The age of males and females, aged 50 and older, in Göteborg in 1976 to 1995.

 


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FIG. 2. The incidence (per 1000 and year) of biopsy-positive giant cell arteritis in Göteborg in 1976 to 1995. The figures were adjusted with regard to the changing age of the general population in Göteborg. The value for every year corresponds to an age of 65 yr.

 
For women aged 50 yr or older, the risk of developing GCA increased more among younger subjects than older ones during the investigated period (P=0.030). Although not statistically significant, there was a similar trend among the men (P > 0.30).


    Discussion
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Several studies from Göteborg and other centres report an increase in GCA incidence, but hitherto its relationship to demographic changes has not been analysed (for references, see [7]). The age of the population of Göteborg increased substantially during the investigated period. As the risk of developing GCA increases significantly with age, the changes in age composition should have had some impact on the incidence figures. However, when corrected for this demographic change, there was still a highly significant increase in GCA incidence, which indicates that the increase in age is of minor importance and that one or several other influential factors should be sought.

The immigration to the Göteborg region increased during the investigated period. However, the immigrants come mainly from Southern Europe or northern Africa, i.e. from populations with a considerably lower GCA incidence than in Scandinavia. Therefore, the noticed increase in GCA incidence could not be explained in terms of immigration. Instead, this might, to a minor extent, have reduced the positive trend.

The positive and negative biopsies increased proportionally. There was no significant trend towards higher or lower percentage of positive biopsies during the period, which indicates that the increase in the number of positive cases could not be explained in terms of an increased propensity for temporal artery biopsy. During the investigated period, the recommended criteria for temporal artery biopsy were kept constant among clinicians in the fields of rheumatology, infectious diseases and internal medicine. Furthermore, in Göteborg there is continuous education of general practitioners regarding GCA. Nevertheless, a retrospective study will always give minimum figures, and the possibility could not be excluded that an increased awareness of the disorder among clinicians and patients might have influenced the results by increasing the number of detected new cases and hence the biopsy frequency. However, the risk of developing GCA increased more in the younger than the older part of the female population, which could probably not be explained in terms of increased awareness, but instead indicates the influence of some other factor(s). Changes related to the metabolism of female sex hormones might be of special interest in this context.

Why is GCA more common in women and why does it increase with age? In the general population, small, focal calcifications are found in the arterial internal elastic membrane (IEM). Interestingly, their age and sex distribution is similar to that of GCA, i.e. they are more common in women and they increase with age [16, 17]. Visualized by light and electron microscopy, the inflammatory process of GCA starts with the formation of foreign-body giant cells, which attack these IEM calcifications. The occurrence of this degenerative lesion in the general population might thus explain the age and sex distribution of the disorder [17]. However, it remains to be elucidated why only a minority of the population react to their IEM calcifications. It may be speculated that infections might play a role by activating the immune system or, more directly, by inducing the formation of foreign-body giant cells (for references see [7]).


    Acknowledgments
 
The skilled technical assistance of M. Persson is gratefully acknowledged. This study was supported by grants from the Göteborg Medical Society, the Swedish Heart–Lung Foundation, the Swedish Rheumatism Association, Rune och Ulla Amlöfs Stiftelse and Syskonen Holmströms Donationsfond.


    Notes
 
Correspondence to: Claes Nordborg, Department of Pathology, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden. E-mail: claes.nordborg{at}path.gu.se Back


    References
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 

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Submitted 22 November 2001; Accepted 18 October 2002





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