Patients who have severe manifestations of systemic sclerosis are seen more often in Eastern Europe than in other parts of Europe, according to a recent large database study.
However, referral bias precluded the identification of genetic or environmental factors contributing to the disease, wrote the authors.
Baseline data from the European League Against Rheumatism Scleroderma Trials and Research database were used to identify 3,661 systemic sclerosis (SSc) patients from a total of 61 European cities.
Of these, a total of 1,390 (38%) had diffuse systemic sclerosis and 2,263 (62%) had limited systemic sclerosis. The specific type of systemic sclerosis was unknown for just eight patients.
The mean age of all the patients was 55 years, and 87% were female, according to Dr. Ulrich A. Walker, of the department of rheumatology at the University of Basel (Switzerland), and his coauthors on the study.
In an attempt to identify genetic or environmental factors underlying the disease, the researchers analyzed data from 2004–2007 to discover whether there were any specific geographic differences in systemic sclerosis organ involvement as reflected by the presence of anticentromere autoantibodies and antitopoisomerase I (Scl-70).
The authors also looked for the existence of any geographic clusters of diffuse versus limited type of systemic sclerosis (Ann. Rheum. Dis. 2008 July 22 [doi:10.1136/ard.2008.091348]).
On bivariate analysis, no association was found between clinical subtype or autoantibodies and geographic location. However, one interesting finding was that there were more female patients with systemic sclerosis found in Western regions.
Additionally, Scl-70 was found more frequently in patients in Eastern Europe, the researchers said.
For partial correlations, data were adjusted for variables previously shown to determine particular organ manifestations, including autoantibody status, clinical subtype (either diffuse or limited), and the age at onset of Raynaud's phenomenon.
The association between female patients and Western European centers remained significant after adjustment for autoantibody status.
However, the link did not remain significant after subsequent adjustment for clinical subset.
“The highest correlation coefficient between disease presentations and geographical position was observed between diastolic dysfunction and longitude,” Dr. Walker and his colleagues wrote.
However, because the centers that were near each other geographically did not have similar frequencies of diastolic dysfunction, the study authors hypothesized that “such differences may be attributed to observer-dependent differences in unstandardised echocardiographic assessment.”
Cluster analysis was performed to determine if any features of systemic sclerosis were distributed in “pockets” rather than according to geographic longitude/latitude.
Within the six cities that had at least two centers with more than 15 SSc patients each (including Berlin, Madrid, Milan, Paris, Prague, and Lublin, in Poland), five of the locations showed significant within-city differences in clinical subsets and two places showed significant within-city differences in prevalence of autoantibodies. This particular finding reflected significant variation in systemic sclerosis presentation that was not explained by geographic factors.
Although geographic variations in systemic sclerosis prevalence and incidence have previously been described, variation in individual disease presentation had not been well studied, they said.
A previous study that was conducted in London found a higher prevalence of systemic sclerosis near airports.
There was also an Australian study that linked the disease with occupational exposure to silica dust.
However, the current cross-sectional study did not find a link between environment and systemic sclerosis.
The investigators also assessed referral bias by analyzing systemic sclerosis presentation and autoantibody status among centers located in the same cities or nearby.
The authors concluded that although “significant differences exist with regard to some disease presentations,” there was “no clear geographical trend with regard to key factors.”
The differences that were found to exist within cities and between those cities in close proximity are most likely explained by recruitment bias, the researchers continued.
Although the study “suggests that eastern European centres care for SSc patients with more severe manifestations than seen in other centres,” the authors added that the evident “large local variability of SSc manifestations within adjacent centres suggests a substantial referral bias and precludes the identification of genetic or environmental factors.”
The authors made no disclosures regarding any conflicts of interest.