What are the factors contributing to the increasing incidence of autoimmune diseases in the US population, particularly among women and individuals from diverse ethnic backgrounds?

Why Autoimmune Diseases Are Rising in the US

The increasing incidence of autoimmune diseases in the US over the past three decades reflects a complex interplay of environmental exposures, climate change impacts, lifestyle modifications, and persistent sociodemographic disparities, with nearly 50% increases documented in multiple conditions since 2000. 1, 2

Documented Temporal Trends

The evidence demonstrates clear upward trajectories across multiple autoimmune conditions:

• Autoimmune hepatitis incidence has increased nearly 50% in Spain, Denmark, Sweden, and the Netherlands since 2000, with Denmark showing a doubling of incidence from 1994 to 2012, reaching a point prevalence of 24 per 100,000 by 2012. 1, 2

• Type 1 diabetes mellitus attributed to high temperature exposure shows a global increase in age-standardized disability-adjusted life-year rates (estimated annual percentage change = 0.88), with high-income countries experiencing the steepest rise (estimated annual percentage change = 1.36). 3

• The rapidity of these changes—occurring over decades rather than centuries—indicates environmental rather than genetic drivers, as genetic shifts in populations require far longer timeframes to manifest. 4

Primary Environmental and Lifestyle Contributors

The evidence points to multiple modifiable risk factors driving this epidemic:

Climate Change and Temperature Effects

• Rising global temperatures directly contribute to increased type 1 diabetes burden, with high-income countries showing the strongest association between temperature exposure and disease rates. 3
• Climate change impacts include increased heat, storms, floods, wildfires, droughts, UV radiation exposure, malnutrition, and changing infection patterns, all of which may trigger or perpetuate autoimmune responses. 4

Pollutants and Xenobiotics

• Environmental pollutants, occupational exposures, and xenobiotic chemicals create chronic low-level inflammation that may eventually cross thresholds leading to immune system activation and clinical autoimmunity. 4
• Crystalline silica exposure and cigarette smoke represent specifically identified environmental triggers with proven associations to autoimmune disease development. 5

Lifestyle Modifications

• Changes in diet, obesity (particularly high body-mass index), exercise patterns, and sleep disruption contribute to autoimmune disease burden, with asthma due to high body-mass index showing increasing trends in low-middle income countries. 4, 3
• Smoking remains a significant modifiable risk factor, with multiple sclerosis due to smoking showing increasing trends in low and low-middle income countries. 3

Infectious Triggers

• Chronic infections, particularly Epstein-Barr virus, show very strong associations with autoimmune disease development, especially multiple sclerosis following late infection or infectious mononucleosis. 6
• Gut microbiota alterations and their interactions with pharmaceutical agents may lead to organ-specific autoimmunity through mechanisms including molecular mimicry, epitope spreading, and bystander activation. 7

Disproportionate Impact on Women and Ethnic Minorities

The rising incidence shows marked disparities across demographic groups:

Female Predominance

• Women comprise 71-95% of adult autoimmune hepatitis cases and 60-76% of pediatric cases, with a female-to-male ratio of approximately 6:1 in most populations. 1, 2
• Women display higher global age-standardized disability-adjusted life-year rates for asthma due to high body-mass index (44.1 per 100,000 population), while men show higher rates for other autoimmune conditions due to specific risk factors. 3
• Autoimmune diseases are on average more frequent in women, with conditions characterized by cardiovascular inflammation promoting hypertension, left ventricular hypertrophy, and atherosclerosis. 1

Ethnic and Geographic Disparities

• Alaskan Natives demonstrate the highest documented autoimmune hepatitis prevalence at 42.9 per 100,000 persons, presenting characteristically with acute icteric disease. 8, 2
• Hispanic patients, particularly Mexican Americans, commonly present with established cirrhosis at initial autoimmune hepatitis evaluation, with aggressive biochemical and histological features. 8
• African American patients demonstrate accelerated autoimmune hepatitis progression, higher cirrhosis rates at presentation, increased treatment failure frequency, and elevated mortality compared to White Americans. 8
• Indigenous North American populations face disproportionately severe rheumatoid arthritis risk, with prevalence rates substantially higher than non-Indigenous populations, driven by the HLA-DRB1*1402 allele creating predominantly seropositive, severe disease. 8
• Black and Asian children show higher prevalence and severity of atopic dermatitis, with black adults and children experiencing more impaired quality of life. 1

Mechanistic Pathways

The evidence supports a multi-hit model of autoimmune disease development:

• Exposures during sensitive developmental or hormonal periods set the stage for effects of later exposures, with synergistic and additive impacts of exposure mixtures resulting in chronic low-level inflammation. 4
• This inflammation eventually passes thresholds leading to immune system activation and autoimmunity, with further molecular and pathologic changes culminating in complete clinical syndromes. 4
• Epigenetic modifications—including DNA methylation and histone modification—mediate environmental effects on immune responses without involving DNA sequence changes, providing a mechanism linking environmental exposures to disease expression. 5
• Autoimmune diseases may appropriately be described as auto-immuno-deficiency syndromes, emphasizing the role of immuno-deficiencies and chronic infections in development of overlapping disease syndromes. 6

Persistent Sociodemographic Inequalities

Despite overall progress in reducing some disease burdens:

• Sociodemographic Index-related inequalities have remained stable for most autoimmune diseases attributed to modifiable risk factors over the past three decades, indicating that advances have not equitably benefited all populations. 3
• Significant positive associations exist between Sociodemographic Index and age-standardized disability-adjusted life-year rates for rheumatoid arthritis and multiple sclerosis due to smoking, as well as type 1 diabetes due to low temperatures, while other autoimmune diseases show negative associations. 3
• The estimated prevalence of atrophic gastritis reaches up to 15% in US populations and may be greater in non-White racial/ethnic minority groups and early-generation immigrants from high-risk countries, reflecting both genetic susceptibility and environmental exposure patterns. 1

Critical Gaps and Underdiagnosis

The true burden likely exceeds documented rates:

• 25-37% of autoimmune hepatitis patients are asymptomatic at diagnosis and may remain undetected, while 13-32% already have cirrhosis at diagnosis, suggesting substantial delayed recognition. 2
• Atrophic gastritis is typically asymptomatic and may go undiagnosed, with inconsistent histopathology reporting contributing to underdiagnosis of this precancerous condition. 1