The environment, geo-epidemiology, and autoimmune disease: Rheumatoid arthritis

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Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease characterized by a distinctive pattern of bone and joint destruction. RA patients have an increased risk of death. The incidence and prevalence of RA vary across populations, statistical methods, and disease definitions. In North America and Northern Europe, the incidence of RA is estimated at 20–50 cases per 100,000 population and the prevalence at 0.5–1.1%. Lower incidences and prevalences have been reported in Southern Europe, and few data are available for developing countries. Some studies showed declining incidences and prevalences after the 1960s. RA is a multifactorial disease that results from interactions between genetic and environmental factors. The main genetic factors are HLA-DRB1 and the tyrosine-phosphatase gene PTPN22. Among environmental factors implicated in the development of RA, smoking shows the strongest association with RA susceptibility and is also linked to worse outcomes. The aim of this review is to discuss the available data on the incidence and prevalence of RA, as well as the genetic and environmental risk factors associated with RA.

Introduction

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease characterized by a distinctive pattern of bone and joint destruction. RA is also a systemic disease, and several patient subsets can be distinguished based on the presence of extra-articular manifestations. For example, the concomitant presence or absence of anti-cyclic citrullinated peptide antibody (ACPA) and rheumatoid factor (RF) defines two important patient subsets [1].

Several epidemiological studies of RA have been published. They show variations in the incidence and prevalence of RA across populations. Further variation include occurs as a result of differences in statistical methods and case-ascertainment criteria. Several large prospective studies have improved our knowledge of the risk factors for RA. Unfortunately, the available epidemiological data often come from retrospective studies and underpowered case-control studies. Here, we review the main data on the epidemiology of RA and on the environmental factors involved in the disease.

Section snippets

Incidence

The incidence of RA varies across populations. Estimates from North America and Northern Europe range from 20–50 cases per 100,000 population. In Southern Europe, lower incidences of 9–24 cases per 100,000 population have been reported. The incidence of RA in developing countries is unknown [2], [3], [4], [5].

Prevalence and geographic variation

Studies done in North America and Northern Europe have shown prevalences of 0.5–1.1%. In Southern Europe, lower prevalences of 0.3–0.7% have been found [6], [7], [8], [9]. Table 1 reports

Risk factors for rheumatoid arthritis

RA is a multifactorial disease that results from interactions between genetic and environmental factors. Personal and lifestyle factors influence the course of the disease. A comparison of smoking history between twins with RA and their unaffected co-twins established that smoking was closely associated with RA [23]. In this study, of the 13 pairs of monozygotic twins discordant for RA and smoking history, the twin who had RA was also the twin with a history of smoking in 12 of the pairs. Below

Conclusions

Epidemiological studies have found substantial variations in the incidence and prevalence of RA across time periods and geographic regions. A substantial decline in RA incidence over time, with a shift toward an older age at onset, was found in several studies. There are virtually no epidemiologic data from developing countries. ACPA-positive patients with RA differ from ACPA-negative patients regarding genetic (HLA-DRB1 and PTPN22) and environmental (smoking) risk factors for RA.

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