Geospatial clustering of childhood IgA vasculitis and IgA vasculitis-associated nephritis

Abstract

ObjectivesResearch on spatial variability of the incidence of IgA vasculitis (IgAV) in children and its potential implications for elucidation of the multifactorial aetiology and pathogenesis is limited. We intended to observe spatial variability of the incidence of IgAV and IgA vasculitis-associated nephritis (IgAVN) using modern geostatistical methods, and hypothesised that their spatial distribution may be spatially clustered.MethodsPatients' data were retrospectively collected from 2009 to 2019 in five Croatian University Hospital Centres for paediatric rheumatology, and census data were used to calculate the incidence of IgAV. Using spatial empirical Bayesian smoothing, local Morans’ I and local indicator of spatial autocorrelation (LISA), we performed spatial statistical analysis.Results596 children diagnosed with IgAV were included in this study, of which 313 (52.52%) were male. The average annual incidence proportion was estimated to be 6.79 per 100 000 children, and the prevalence of IgAVN was 19.6%. Existence of spatial autocorrelation was observed in both IgAV and IgAVN; however, clustering distribution differed. While IgAV showed clustering in Mediterranean and west continental part around cities, IgAVN was clustered in the northern Mediterranean and eastern continental part, where a linear cluster following the Drava and Danube river was observed.ConclusionIgAV incidence in Croatia is similar to other European countries. Spatial statistical analysis showed a non-random distribution of IgAV and IgAVN. Although aetiological associations cannot be inferred, spatial analytical techniques may help in investigating and generating new hypotheses in non-communicable diseases considering possible environmental risk factors and identification of potential genetic or epigenetic diversity.

Pathogenesis of IgA Vasculitis: An Up-To-Date Review

“…The onset is more frequent during September to April and less common during summer. Recently, according to a Croatian study, geospatial clustering of IgAV along the course of Drava and Danube rivers, similar to the spatial distribution of Balkan endemic nephropathy triggered by daily exposure to environmental factors was observed (aristolochic acid) ( 20 , 21 ). The temporal and geospatial associations imply that environmental factors are involved in the pathogenesis of IgAV.…”

New Insights and Challenges Associated With IgA Vasculitis and IgA Vasculitis With Nephritis—Is It Time to Change the Paradigm of the Most Common Systemic Vasculitis in Childhood?

“…The fact that IgAV is not equally present in different parts of the world is also well-known, since it has the highest occurrence in East Asians, intermediate in Europeans, and the lowest in individuals of African ancestry ( 2 , 15 ). Nevertheless, only recently a study on spatial variability of the incidence of IgAV and IgAVN using modern geostatistical methods has been performed ( 18 ). This research is important for several reasons.…”

IgA vasculitis or Henoch-Schönlein purpura: genetics and beyond

“…Considering that it is known that in IgAV various infections are often triggers for the development of the disease, it would be interesting to investigate whether similar observations apply in IgAV. This question can be viewed in the context of the latest research investigating the spatial distribution of IgAV applying modern geostatistical methods, according to which the linear clustering of IgAVN in the eastern part of Croatia follows the course of the Drava and, partially Danube, rivers [2]. From the nephrological aspect, intriguing is the fact that in the vicinity of these locations are areas of Balkan endemic nephropathy.…”

“…Notwithstanding that hotspot clusters of disease occur in areas where there is substantial overlap of genetic and environmental influences, in different proportions, it would be interesting to investigate whether there are potential susceptibility loci in this group of patients. Such hotspots appear to be present in other parts of the world as the incidence of IgAV varies depending on geographical area, and from the research, it is also evident that the prevalence of nephritis in patients with IgAV is quite wide, depending on individual studies and countries where they have been implemented [1,2]. The geospatial distribution of gene risk has been demonstrated in IgAN, in such a way that the risk of developing the disease increases with Eastward and Northward distance from Africa [22].…”

“…Considering the fact that the IgA vasculitis (IgAV), formerly known as Henoch-Schönlein purpura, is the most common systemic vasculitis in childhood, with an incidence fluctuating from 3 to 27 cases per 100 000 children [1,2], it would be expected that there are uniform guidelines for diagnosis and treatment of this clinical entity and that we know a lot about the etiopathogenesis of the disease. However, everyday clinical practice confronts us with many unanswered questions and dilemmas concerning IgAV disease severity, duration of the autoimmune process, optimal treatment choices, and prognosis, and all of them arise from insufficient knowledge of the mechanisms of disease development.…”