Rheumatoid arthritis (RA) is a chronic, autoimmune, inflammatory disease that primarily affects the joints, leading to pain, swelling, and stiffness, particularly after rest. It is a systemic condition, meaning it can also affect other parts of the body, including the skin, eyes, lungs, heart, nerves, and blood. RA affects millions globally, and understanding its prevalence helps grasp its public health impact.
Global and Regional Occurrence
In 2020, an estimated 17.6 million people globally had rheumatoid arthritis, with an age-standardized prevalence rate of 208.8 cases per 100,000 population. This represents a 14.1% increase in prevalence since 1990. Projections suggest that this number could rise significantly, with forecasts indicating 31.7 million individuals living with RA worldwide by 2050.
The occurrence of RA varies considerably across different geographical regions. For example, in 2017, high-income North America showed the highest age-standardized prevalence, at 377.6 cases per 100,000 population, followed by Western Europe (346.8 per 100,000) and the Caribbean (338.9 per 100,000). In contrast, regions such as Southeast Asia (100.9 per 100,000), Oceania (135.3 per 100,000), and Western Sub-Saharan Africa (135.7 per 100,000) reported lower age-standardized rates.
Data collection methods and definitions of the disease can influence reported prevalence figures. Studies on RA prevalence often use periodic prevalence methods, considering the disease’s fluctuating nature. Some studies rely on population-based data, while others use medical claims data or disease registries, which can affect the comparability of results across different regions and time periods. The prevalence of RA is generally higher in industrialized countries, which might be partly explained by factors like a higher average age in these populations, increased exposure to environmental toxins, and potentially under-diagnosis in low- and middle-income countries.
Demographic Patterns
Women are significantly more affected than men, with a female-to-male ratio typically around 2:1 to 3:1 globally. This disparity is particularly noticeable among menstruating women, and while RA can occur at any age in both sexes, the majority of patients are middle-aged women, often comprising over 70% of RA cohorts.
The overall likelihood of developing RA tends to increase with age. The typical onset of RA often occurs in middle age, with symptoms commonly starting between ages 30 and 50, although it can affect individuals at any point in their lives, from childhood to older adulthood. For women, disease occurrence often increases from the age of menarche and peaks around menopause.
Variations in prevalence are also observed among different ethnic and racial groups. In the United States, about 1% of the population has RA, and while white Americans are generally thought to have a higher prevalence, there are exceptions. For instance, certain American Indian populations, such as the Pima and Pagago Indians, exhibit a much higher prevalence rate of 5.3%. Conversely, Asian and Hispanic populations generally appear to have lower rates of RA compared to Caucasians, though more comprehensive data are needed for definitive conclusions.
Factors Influencing Occurrence
The development of rheumatoid arthritis is influenced by a complex interplay of genetic and environmental factors. Genetic predisposition plays a substantial role, with the heritability of RA estimated to be around 60%. The human leukocyte antigen (HLA) locus is considered the most significant genetic risk factor. Specifically, HLA-DRB1 alleles that encode a five-amino acid sequence motif, often referred to as the ‘shared epitope’ (SE), are strongly associated with an increased risk and severity of RA. Other non-HLA genes, such as PTPN22, IL23R, TRAF1, CTLA4, IRF5, STAT4, CCR6, and PADI4, have also been linked to RA susceptibility.
Environmental factors are also recognized as triggers or risk enhancers for RA. Smoking is widely considered the most robust environmental risk factor for RA. It is particularly associated with anti-citrullinated protein antibody (ACPA) positive RA, especially in individuals with the shared epitope (SE) genetic background. Exposure to silica, often in occupational settings, is another documented environmental factor that can increase RA risk, particularly for men, and has also been primarily linked to seropositive RA. Other environmental exposures, such as certain infections, pollutants, and toxic chemicals, are also thought to contribute by promoting inflammation, increasing oxidative stress, and modulating immune responses.
The interaction between these genetic and environmental factors significantly influences an individual’s likelihood of developing RA. For example, the risk of developing ACPA-positive RA is considerably higher in silica-exposed current smokers, highlighting a synergistic effect between these exposures. This complex interplay, often described as a “Bermuda triangle” of genetics, environment, and autoimmunity, ultimately shapes the overall prevalence of RA within populations.