Epidemiology of giant cell arteritis: a critical review

GCA is a large vessel vasculitis of unknown aetiology characterized by the presence of giant cells in biopsy specimens from large arteries. GCA shows a striking age tropism with a marked increase in incidence with age over 50 years. GCA is classified using the ACR criteria, developed in 1990 [1]. Prospective studies from Scandinavia report annual incidence figures for biopsy-proven GCA of 15–35 per 100 000 individuals aged over 50 years, similar rates have been reported from Olmsted County (Minnesota, USA) and in a UK community based study (reviewed in [2]). The incidence increases with age, peaking aged 80 years or older; very few cases occur aged less than 50 years. Most series from Northern Europe report a greater incidence in women, with a female to male ratio of around 2.5:1; the female excess is lower in southern European countries and Israel whilst in Northwest Spain, India and Turkey the ratio is equal. In Olmsted County between 1950–54 and 1980–84 there was an increase from 6.7/100 000 to 28.5/100 000 in persons aged >50 years. The rate then stabilized and has not risen further. A similar increase in incidence has been documented in Göteborg, Sweden between 1976 and 1995 from 16.8/100 000 to 30.1/100 000 persons aged >50 years. GCA appears to be more common in Caucasian populations compared with non-Caucasians, however, there are few studies directly comparing different populations [2]. The incidence is highest in Scandinavians and in populations descended from them. The Viking heritage of the UK might be responsible for the relatively high frequency of GCA seen in the UKGPRD study; the incidence is highest in East Anglia, an area with marked Viking ancestry [3]. GCA is much less common in southern European populations, which have a different genetic background [4]. The Olmsted county population is descended from Scandinavian migrants to the USA. Studies from Tennesse and Texas have reported a much lower incidence in African-Americans and Hispanics. There is a low prevalence in Japan compared with Europe [5]. The epidemiology of a rare disease such as GCA poses challenges to epidemiologists. One difficulty is case definition. The ACR (1990) criteria for GCA are sensitive and specific and have been used in most recent studies. The age criterion (age >50 years) means that patients presenting with a large vessel vasculitis below 50 years of age are often considered not to have GCA. The ACR did not mandate a biopsy. Many studies have been hospital based and only include biopsy proven cases. Many cases are managed solely in the community without a biopsy leading to uncertainty as to the veracity of the diagnosis. The UKGPRD study only validated a small sample (50) of cases of which only five had a biopsy and two were positive [3]. Novel techniques for diagnosis such as temporal artery ultrasound, large vessel angiography of FDG-PET imaging are not considered in the current classification schemes. A further difficulty is case capture. GCA is rare, occurs in the elderly and therefore a large elderly population is required to determine the incidence and prevalence, and this poses questions of feasibility. A large population increases the risk of incomplete case detection but permits a reasonable number of cases to be collected in a practicable time frame; whereas a smaller population requires a much longer time frame to collect the necessary cases, which also may not be feasible. Statistical methods of capture–recapture analysis enable estimates to be made of the number of missing cases. The existing literature on the epidemiology of GCA contains a number of deficiencies. Many of the existing studies only report biopsy positive cases and this leads to an underestimate of the number of cases. The biopsy rate varies between centres. The histological detection of vasculitis is dependent on an adequate length specimen and examination of several sections. Furthermore skip lesions occur so that even if the above conditions are met, evidence of vasculitis may not be seen. A number of the earlier studies were hospital based and GCA is often managed in the community. A number were conducted retrospectively again leading to potential bias. There have been several community based studies (e.g. UKGPRD and Thin databases), however, it is unclear how robust was the case definition. There have been very few studies conducted since 2000. There is therefore an urgent need for a large-scale prospective community based study with robust methods of diagnosis and classification, and appropriate statistical power.