11Epidemiology of systemic sclerosis
Section snippets
Case definition and classification of SSc
The two main subtypes of SSc are defined by the extent of skin involvement: limited cutaneous systemic sclerosis (lcSSc) and diffuse cutaneous systemic sclerosis (dcSSc). In lcSSc, skin involvement is confined to the face, neck and the area distal to elbows and knees. In dcSSc, skin involvement extends proximally to involve upper arms, thighs and/or trunk [1]. The American College of Rheumatology (ACR) classification criteria for SSc [2], listed in Table 1, are insensitive for lcSSc [3].
Incidence of SSc
Varying prevalence and incidence rates of SSc have been reported due to the differences in the geographic area surveyed, the definition of disease and the method of case ascertainment [7]. In Table 2, we have summarised prevalence and incidence rate data from more recent epidemiological studies of SSc. In three studies in which ‘incidence’ was measured, the rates were very similar (22.8, 19.3 and 23 new cases/million/year in South Australia, Detroit and Northwestern Spain, respectively) [8], [9]
Prevalence of SSc
Improved survival has contributed to the higher prevalence of SSc reported in recent studies. The prevalence of SSc in the South Australian, Detroit and Spanish studies was broadly similar (233, 242 and 277 cases/million, respectively) (Table 2). Possible reasons for the higher prevalence of 443 cases/million reported in Quebec include case ascertainment methods (which included physician billing) and the long ascertainment period (10 years) [12].
Geographic variation in SSc disease frequency
Allowing for variation in case definition, the reported prevalence of SSc is consistently higher in USA and Australia than in Japan and Europe. In Europe, a north–south gradient has been observed with lower rates reported in northern European countries (Table 2) [3].
A number of geographical clusters of SSc have been reported in several countries. Silman [13] reported a high prevalence (150 cases/million) in three areas close to two major airports in the UK [14]. A cluster of SSc and
Time trends in incidence of SSc
Studies from the USA suggest that the incidence of SSc has increased over the last 60 years. The incidence in Tennessee in 1947 was estimated to be 0.6 new cases/million/year [18] whilst in Detroit in 1991, the incidence was 19 cases/million/year [9]. Variations in study methodology, increased disease awareness and improvement in diagnosis may explain this apparent change. Using the same methods in the same region of Pennsylvania, Steen et al. demonstrated an increase in the mean incidence of
Racial variation in SSc disease frequency
Several studies have reported a higher incidence of SSc in black populations and that these patients are more likely to have severe disease than white patients. In Michigan, the incidence of SSc in black women was 22.5 cases/million/year whilst in white women it was 12.8 cases/million/year [23]. Fifty percent of black women with SSc had dcSSc compared with only 25% of white women with SSc [23]. In a French multiethnic study, there was a trend towards a higher prevalence of SSc among
Risk factors for the occurrence of systemic sclerosis
The complexity of SSc pathogenesis along with its heterogeneous clinical manifestations suggests that no single genetic or environmental trigger is likely to be responsible.
Skin involvement
A link between dcSSc and major internal organ complications was first described in the 1960s and has been confirmed in recent studies [55]. The severity of skin sclerosis can be quantified using the modified Rodnan skin score (mRss) [56]. This is a surrogate measure of overall disease severity and has prognostic significance, especially in dcSSc [57]. Among patients with less than 3 years of disease, survival rates at 10 years were 80% for those whose skin thickening improved and 60% for those
Malignancy in SSc
There appears to be an association between SSc and malignancy. In a Swedish population-based cohort study of over 1000 patients, performed between 1965 and 1983, the standardised incidence ratio (SIR) of cancer in SSc patients compared with a cohort from the Swedish National Cancer Registry was 1.5 [85]. High SIR were noted for lung cancer (SIR 4.9), skin cancer (SIR 4.2), hepatocellular carcinoma (SIR 3.3) and haemopoietic malignancies (SIR 2.3). In another cohort [86], a similar increase
Morbidity in SSc
Joint contractures, combined with muscle inflammation or atrophy, arthralgias or arthritis, collectively impair mobility [87]. Fatigue and pain impact on physical functioning and quality of life [88]. In a systematic review of 1127 patients with SSc, impaired physical and mental health-related quality of life (HRQoL) was common [87]. In another systematic review, depression was more prevalent in patients with SSc than in other patient groups, affecting 36–65% of patients with SSc, depending on
Mortality in SSc
Despite advances in early recognition of disease and effective treatment for some of its complications, most notably SRC, the mortality of SSc continues to be high. Five-year survival rates in the Detroit [9] and Spanish studies [10] were 78% and 84%, respectively, while the 10-year survival rates were 55% and 65%, respectively. Survival has improved over the past three decades [93]. In the Pittsburgh cohort, 10-year survival rates improved from 54% to 66% between 1972 and 1996 [93].
Most of the
Limitations and methodological considerations in quantifying burden of disease in SSc
Accurate quantitation of the incidence and prevalence of SSc is limited by the relative infrequency of the disease and its heterogeneous manifestations. Furthermore, many milder cases of lcSSc may not come to medical attention. Thus, estimation of disease frequency is affected by selection and misclassification bias. Studies of occupational and environmental risk factors for the occurrence of SSc are likewise limited by disease infrequency and recall bias due to differential reporting of
Summary
In SSc, digital ulceration, amputation and joint contractures cause significant morbidity, while cardiac, pulmonary, gastrointestinal, muscle and renal manifestations can have even more devastating effects on HRQoL and life expectancy. This is despite advances in early detection and in therapies for some of the disease complications. Recognition that the two clinical subtypes, dcSSc and lcSSc, have differing courses has been a major advance, but as there is considerable overlap, all patients
Acknowledgements
We thank Dr Jill Byron for her assistance with preparation of the article.
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