To the Editor:
The small-vessel vasculitides associated with antineutrophil cytoplasmic antibodies (AASV) are a group of rare conditions characterized by inflammation and necrosis of blood vessel walls. The etiology of these conditions is largely unknown, but genetic and environmental factors have been related with the pathogenesis of AASV. Clues to the role of the environmental factors have been obtained by comparison of the incidence of the various entities of the AASV in different regions of the world1,2. Although evidence suggests that the overall incidence of AASV is similar throughout Europe3,4, reports support the idea of a north-south gradient of the granulomatosis with polyangiitis (Wegener’s) (GPA)/microscopic polyangiitis (MPA) ratio. GPA would be more common in the northern regions of the continent1,2,4,5, and MPA more common in the southern regions1,2,6. This latitudinal gradient is also documented in the Southern Hemisphere7.
These differences of topographic incidence might indicate a difference in pathogenesis between GPA and MPA due to the role of little-known environmental factors1,8. Gatenby and colleagues9 published a review of epidemiologic studies that describes the association between ambient ultraviolet (UV) radiation levels and the incidence of AASV. UV radiation has been suggested as a protective immunomodulatory factor on the onset of GPA that could explain the increase of the crude incidence rate with latitude observed for GPA. That study9 did not show an association of incidence of MPA with latitude.
To analyze the world distribution of the GPA/MPA ratio and the presence of a possible latitudinal gradient we obtained data of a systematic review of current evidence10 that include series with all the GPA and MPA patients attended in a referral center. Studies were identified by searching the Medline database via PubMed (1966 to 2009) and the Embase database via Ovid (1980 to 2009). The full electronic search strategies are described in the systematic review10. Using all the data, we created a world map showing percentage of GPA and MPA in each geographic area (Figure 1). We also added separately the percentage corresponding to patients with renal-limited vasculitis when they were included in the study sample. The identity of the geographic location is shown in a black box when all the patients had renal involvement. References for articles cited are given in Table 1.
Map shows the ratio of granulomatosis with polyangiitis (GPA)/microscopic polyangiitis (MPA)/renal-limited vasculitis (RLV). The geographic location is shown in a black box when all the patients had renal involvement.
References for cited articles.
Figure 1 shows the relationship between MPA and GPA in different locations. In Europe, there is a greater proportion of MPA in the south, in the Greek, Slovenian, and Spanish series, while GPA is more frequent in the north in the Czech, Danish, Dutch, French, German, Norwegian, and Swiss series. However, in the south an Italian series showed a greater proportion of GPA, and in the north, the Irish series showed an equal distribution of both entities. The 4 English series and the 2 Swedish series have a heterogeneous distribution. In these 2 countries, differences could be influenced by the design of the studies, with MPA predominance in the renal series and GPA predominance in the nonrenal series. Data for GPA/MPA ratios from the rest of the world are sparse.
These data emphasize a latitudinal gradient for the GPA/MPA ratio, as a major proportion of MPA in the majority of the south Europe series and a major proportion of GPA in the central Europe series are shown. However, the heterogeneous result of the English series and the results of the Swedish, Irish, and Italian series make it difficult to draw conclusions. Moreover, the majority of the reports illustrated in Figure 1 were not designed to obtain epidemiological variables (incidence and prevalence), the data are not adjusted by variables related with incidence of AASV such as sex, age or ethnicity, and many of them do not have complete case ascertainment. Population-based studies would be needed to test this association between latitude and disease.
In Europe, the GPA/MPA ratio shows a latitudinal gradient in the majority of published reports, although the exceptions make it difficult to confirm this north-south association. Examination of this ratio would yield interesting clues to the pathogenesis of AASV and would permit analysis of the interplay between genes and environment for both diseases.
