Abstract
Objective
Immune-mediated inflammatory diseases (IMIDs) are a group of chronic conditions characterized by dysregulated immune responses and tissue inflammation, posing a significant challenge to global health. However, comprehensive epidemiological analysis of the burden of these diseases remains limited. This study aimed to assess the trends in disease burden of six major IMIDs from 1990 to 2021 using the Global Burden of Disease (GBD) 2021 data, providing evidence for targeted prevention and control strategies.
Methods
Utilizing GBD 2021 data, we analyzed the epidemiological trends in age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized death rate (ASDR), and disability-adjusted life years (DALYs) for six IMIDs across global, 21 regions, 5 Socio-demographic Index (SDI) quintiles, and 204 countries and territories. Joinpoint regression analysis was employed to evaluate temporal trends and calculated the average annual percentage change (AAPC) and its 95% confidence interval (CI).
Results
From 1990 to 2021, global ASIR, ASPR, ASDR, and DALYs for asthma, atopic dermatitis (AD), and multiple sclerosis (MS) exhibited declining trends. In contrast, ASIR, ASPR, and DALYs for psoriasis (PsO) showed a comprehensive increasing trend. For inflammatory bowel disease (IBD) and rheumatoid arthritis (RA), ASIR increased significantly, while ASDR and DALYs decreased. Furthermore, significant regional heterogeneity in disease burden was observed: high-SDI regions typically demonstrated higher ASIR and ASPR but lower ASDR; conversely, low-SDI regions exhibited lower ASIR and ASPR alongside higher ASDR.
Conclusion
Despite significant spatiotemporal heterogeneity in the burden of the six IMIDs at global and regional levels, they collectively impose a substantial health burden worldwide. Consequently, future efforts require region-specific, differentiated public health interventions to address the ongoing challenge posed by IMIDs to global health systems.
Keywords: Immune-mediated inflammatory diseases, Global burden of disease, Socio-demographic index, Epidemiology
Highlights
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The global burden of six IMIDs shows substantial heterogeneity across regions.
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High-SDI countries bear a disproportionately higher IMIDs burden.
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The rise in global IMIDs incidence is linked to improved healthcare access and diagnosis.
1. Introduction
Immune-mediated inflammatory diseases (IMIDs) represent a diverse group of multisystem disorders characterized by chronic inflammation leading to tissue damage. This category encompasses conditions such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), psoriasis (PsO), atopic dermatitis (AD), asthma, and multiple sclerosis (MS) [1].IMIDs frequently involve multiple organ systems. For instance, inflammatory bowel disease may present with extraintestinal manifestations such as arthritis and cutaneous lesions, while rheumatoid arthritis can affect extra-articular organs including the skin, eyes, lungs, cardiovascular system, hematopoietic system, and kidneys [2,3]. Despite significant therapeutic advancements, IMIDs currently remain incurable. These conditions typically follow chronic and disabling courses, substantially compromising patients' quality of life and imposing considerable direct and indirect healthcare costs [4].Consequently, comprehensively assessing the global burden of IMIDs and optimizing evidence-based prevention and management strategies are critical public health priorities. Leveraging the latest data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 [5],this study systematically analyzes the epidemiological profiles (including age and sex distributions) of six major IMIDs—rheumatoid arthritis, IBD, multiple sclerosis, psoriasis, asthma, and atopic dermatitis—in 2021. Furthermore, it evaluates temporal trends in the global, regional, and national burden of these six IMIDs from 1990 to 2021. Our findings aim to guide targeted screening and preventive interventions while providing an evidence base for clinical practice guidelines and health policy formulation.
2. Methods
2.1. Data sources and extraction
Leveraging the most recent available data and advanced statistical modeling, the 2021 Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) comprehensively assessed the health loss attributable to 371 diseases and injuries, as well as 88 risk factors, across 204 countries and territories [6]. This study collected data on the incidence, prevalence, deaths, and disability-adjusted life years (DALYs) for IMIDs—specifically, asthma, inflammatory bowel disease (IBD), multiple sclerosis (MS), rheumatoid arthritis (RA), psoriasis (PsO), and atopic dermatitis (AD)—from the Global Health Data Exchange (GHDx) for the period 1990 to 2021. The extracted data included case counts, age-standardized rates, and their corresponding 95% uncertainty intervals (UIs). Following data extraction, analyses were stratified globally, regionally, nationally, and by Socio-demographic Index (SDI). The age and sex distributions of these six IMIDs were also investigated.
2.2. SDI
The SDI quantifies the level of socio-demographic development of a country or territory based on income, education, and fertility rates. SDI values range from 0 to 1, with higher values indicating better socioeconomic development [7]. In this study, countries and territories were categorized into five SDI quintiles (High, High-middle, Middle, Low-middle, and Low) to examine the association between the burden of IMIDs and socioeconomic development.
2.3. Median age at onset
To directly evaluate the potential influence of evolving diagnostic criteria on long-term disease trends, we calculated the median age at onset for the six IMIDs from 1990 to 2021. Using the age-specific incidence data from GBD 2021, we first converted the age groups into their midpoint values. The median age at onset for each disease was then defined as the age at which the cumulative number of incident cases reached 50% of the total.
2.4. Healthcare access and quality (HAQ) index
The Healthcare Access and Quality (HAQ) Index data were obtained from the GBD study. The HAQ Index is a composite metric that reflects the overall quality of a country's health system, scored on a scale from 0 (worst) to 100 (best) [8]. In this study, the HAQ Index served as a proxy measure for a region's capacity to implement complex diagnostic criteria. It was used to assess how spatial variations in diagnostic capability might influence the reported incidence of IMIDs.
2.5. Statistical analysis
To further analyze the temporal trends (1990–2021) in the age-standardized incidence, prevalence, mortality, and DALYs for the six IMIDs at the global, continental, and national levels, this study employed Joinpoint Regression Program (version 5.2.0.0; National Cancer Institute, USA) to calculate the Average Annual Percent Change (AAPC) and its corresponding 95 % confidence interval (CI). An AAPC >0 indicates an increasing trend, an AAPC <0 indicates a decreasing trend, and an AAPC not statistically different from 0 suggests a stable trend over time. All statistical analyses and graphical visualizations were performed using R software (version 4.3.2).
3. Results
3.1. Global burden of disease and trends of six immune-mediated diseases
In 2021, the global age-standardized incidence and prevalence rates of asthma were 516.7 [425.36–646.13] and 3,340.12 [2,905.24–3,832.24] per 100,000 population, respectively. The corresponding AAPCs were −1.15% [−1.22–−1.07] and −1.62% [−1.72–−1.51], both demonstrating significant declining trends (Table 1; Appendix 1, Table 1). The ASIR and absolute case counts of PsO, RA, and IBD displayed concurrent increases from 1990 to 2021. For PsO,the global ASIR increased from 57.01 [55.27–58.76] to 62.00 [60.14–63.87] (AAPC = +0.27% [0.25–0.28]), while incident cases surged from 2,852,676 [2,764,294–2,943,367] to 5,099,418 [4,945,748–5,254,031]. For RA, the global ASIR rose from 10.42 [9.32–11.64] to 11.80 [10.64–13.12] (AAPC = +0.41% [0.39–0.42]), with incident cases doubling from 488,269 [435,015–545,895] to 1,000,319 [902,687–1,114,213]. For IBD,the ASIR increased from 4.22 [3.72–4.88] to 4.45 [3.87–5.19] (AAPC = +0.16% [0.07–0.24]), and incident cases rose from 199,236 [174,584–232,676] to 375,140 [327,686–436,925] (Appendix 1, Tables 2, 3, and 4). MS showed declining ASIR (AAPC = −0.11% [−0.14–−0.09]) and ASDR (AAPC = −0.44% [−0.64–−0.25]). Despite this, absolute counts increased substantially: incident cases rose from 41,970 [36,606–48,235] to 62,920 [56,015–70,635], and deaths increased from 9108 [8711–9469] to 16,302 [15,357–17,040] (Appendix 1, Table 5). Notably, while ASDR declined for asthma (AAPC = −1.93% [−2.20– −1.66]) and RA (AAPC = −0.95% [−1.08–−0.82]), absolute death counts generally increased. Asthma deaths rose from 374,377 [304,600–492,653] to 436,193 [357,795–555,604], and RA deaths increased from 21,671 [19,287–24,202] to 37,330 [31,060–43,136] (Appendix 1, Tables 1 and 4).
Table 1.
Age-standardized incidence rates of asthma globally and regionally in 1990 and 2021, with trends from 1990 to 2021.
| location | Number of cases (95 % UI), | Age-standardized rate per 100,000 (95 % UI), | AAPCs (95 % CI), 1990 to 2021 | P |
|---|---|---|---|---|
| Global | −1.15(-1.22–−1.07) | P = 0 | ||
| 1900 | 41555628 (34158823–51705168) | 736.99 (615.03–905.18) | ||
| 2000 | 35576566 (29919533–43639590) | 584.87 (491.76–716.05) | ||
| 2010 | 37676592 (31152698–46691169) | 564.54 (465.28–703.86) | ||
| 2021 | 37864175 (31381241–46919994) | 516.70 (425.36–646.13) | ||
| Andean Latin America | −1.47(-1.56–−1.39) | P = 0 | ||
| 1990 | 614416 (483057–803435) | 1217.95 (968.44–1582.19) | ||
| 2000 | 531011 (423200–661439) | 961.24 (772.71–1191.62) | ||
| 2010 | 477266 (362896–631895) | 844.94 (643.48–1123.38) | ||
| 2021 | 486857 (372636–634611) | 772.86 (588.02–1010.83) | ||
| Australasia | −0.85(-0.94–−0.75) | P = 0 | ||
| 1990 | 132981 (109860–160255) | 766.26 (624.21–932.92) | ||
| 2000 | 145459 (123631–168912) | 812.94 (683.39–944.85) | ||
| 2010 | 119377 (98255–146535) | 597.01 (479.41–747.70) | ||
| 2021 | 132474 (106373–169991) | 588.51 (457.79–769.61) | ||
| Caribbean | −0.28(-0.31–−0.26) | P = 0 | ||
| 1990 | 516825 (431970–631182) | 1301.63 (1087.87–1591.60) | ||
| 2000 | 512023 (431737–612596) | 1243.85 (1050.27–1489.63) | ||
| 2010 | 522241 (437614–638066) | 1270.91 (1059.40–1555.94) | ||
| 2021 | 496235 (420578–599807) | 1193.84 (1000.88–1445.97) | ||
| Central Asia | −0.51(-0.56–−0.45) | P = 0 | ||
| 1990 | 356054 (293207–444386) | 476.42 (402.96–584.00) | ||
| 2000 | 351225 (288880–434481) | 466.06 (390.42–567.09) | ||
| 2010 | 348704 (286527–433963) | 437.89 (361.92–549.67) | ||
| 2021 | 392378 (323272–488303) | 409.26 (338.42–509.61) | ||
| Central Europe | 0.03(-0.08 - 0.14) | P = 0.545121 | ||
| 1990 | 1075613 (929147–1261365) | 892.00 (758.55–1067.59) | ||
| 2000 | 853947 (724385–995971) | 789.92 (664.29–962.18) | ||
| 2010 | 732561 (626730–868998) | 773.93 (630.74–967.18) | ||
| 2021 | 748581 (633748–896970) | 898.73 (725.29–1136.93) | ||
| Central Latin America | −1.55 (−1.61–−1.49) | P = 0 | ||
| 1990 | 1882809 (1504618–2396153) | 917.76 (744.48–1146.77) | ||
| 2000 | 1535080 (1255372–1908789) | 678.86 (564.73–834.08) | ||
| 2010 | 1489407 (1175009–1912321) | 631.27 (499.99–813.44) | ||
| 2021 | 1286937 (1024476–1625749) | 567.65 (448.44–726.23) | ||
| Central Sub-Saharan Africa | −0.99 (−1.06–−0.92) | P = 0 | ||
| 1990 | 503350 (404337–628271) | 664.31 (553.64–806.58) | ||
| 2000 | 616982 (500831–768188) | 621.49 (521.91–751.89) | ||
| 2010 | 768368 (612694–971606) | 578.19 (479.95–704.66) | ||
| 2021 | 814564 (658089–1009318) | 487.01 (406.36–584.51) | ||
| East Asia | −1.20 (−1.31–−1.08) | P = 0 | ||
| 1990 | 6125666 (4888912–7867795) | 533.00 (428.75–681.52) | ||
| 2000 | 4478178 (3653862–5653138) | 416.48 (336.84–536.36) | ||
| 2010 | 3791574 (3130351–4748805) | 367.09 (292.45–482.89) | ||
| 2021 | 4186100 (3403788–5420025) | 373.08 (291.39–504.20) | ||
| Eastern Europe | −1.52 (−1.54–−1.49) | P = 0 | ||
| 1990 | 1570036 (1319844–1919184) | 736.30 (606.21–913.90) | ||
| 2000 | 1170659 (974509–1415043) | 640.73 (520.51–805.93) | ||
| 2010 | 844510 (698597–1031371) | 526.97 (421.58–672.44) | ||
| 2021 | 681661 (548353–856411) | 460.11 (360.84–601.68) | ||
| Eastern Sub-Saharan Africa | −0.94 (−1.00–−0.89) | P = 0 | ||
| 1990 | 2616304 (2124519–3267430) | 922.41 (767.71–1131.01) | ||
| 2000 | 3011813 (2415738–3790477) | 831.17 (687.95–1017.20) | ||
| 2010 | 3572675 (2836826–4554567) | 775.52 (635.50–952.89) | ||
| 2021 | 3763381 (3047080–4688013) | 687.17 (568.56–836.70) | ||
| High-income Asia Pacific | −1.86 (−1.94–−1.78) | P = 0 | ||
| 1990 | 1371345 (1180028–1611731) | 906.62 (756.27–1103.89) | ||
| 2000 | 995250 (855011–1181439) | 659.18 (538.23–814.98) | ||
| 2010 | 710117 (614349–847644) | 503.42 (407.03–638.45) | ||
| 2021 | 657816 (563321–798484) | 506.95 (397.10–661.02) | ||
| High-income North America | −0.02 (−0.22 - 0.19) | P = 0.868 | ||
| 1990 | 3480482 (2856942–4403168) | 1424.69 (1139.12–1859.50) | ||
| 2000 | 2842083 (2357243–3479082) | 1097.34 (892.11–1370.19) | ||
| 2010 | 3626707 (3071000–4310383) | 1314.44 (1088.97–1602.29) | ||
| 2021 | 3990234 (3367140–4833774) | 1403.64 (1137.64–1766.66) | ||
| North Africa and Middle East | −0.98 (−1.02–−0.95) | P = 0 | ||
| 1990 | 2921395 (2435583–3575059) | 736.88 (629.40–878.37) | ||
| 2000 | 2983662 (2504117–3579014) | 659.86 (562.63–784.28) | ||
| 2010 | 3209614 (2682337–3895717) | 602.98 (510.54–724.67) | ||
| 2021 | 3283869 (2741022–3999766) | 541.22 (457.04–654.65) | ||
| Oceania | −1.25 (−1.28–−1.22) | P = 0 | ||
| 1990 | 51139 (43018–61234) | 714.49 (620.39–836.84) | ||
| 2000 | 59631 (50442–71970) | 662.81 (573.72–772.14) | ||
| 2010 | 64950 (55308–76858) | 580.75 (505.51–671.07) | ||
| 2021 | 69997 (60007–81955) | 484.35 (423.68–549.28) | ||
| South Asia | −1.84 (−2.00–−1.67) | P = 0 | ||
| 1990 | 7772518 (5867356–10272824) | 631.30 (506.66–800.78) | ||
| 2000 | 5539945 (4476907–6974880) | 414.01 (349.99–503.91) | ||
| 2010 | 7005441 (5599312–9266777) | 447.70 (366.62–578.13) | ||
| 2021 | 6160852 (5068273–7690976) | 358.65 (297.33–445.06) | ||
| Southeast Asia | −1.18 (−1.21–−1.15) | P = 0 | ||
| 1990 | 3543347 (2939406–4351020) | 701.31 (598.05–840.33) | ||
| 2000 | 3264377 (2739675–3934767) | 599.15 (508.53–714.33) | ||
| 2010 | 3329940 (2795762–4047817) | 562.76 (473.96–682.75) | ||
| 2021 | 3080819 (2634893–3658408) | 484.15 (410.27–580.20) | ||
| Southern Latin America | −0.16 (−0.20–−0.12) | P = 0 | ||
| 1990 | 355011 (293955–438518) | 703.92 (584.39–868.59) | ||
| 2000 | 353135 (302378–409815) | 658.09 (563.51–766.82) | ||
| 2010 | 372305 (296363–465825) | 667.40 (520.78–857.93) | ||
| 2021 | 385124 (317654–479431) | 669.63 (534.12–860.67) | ||
| Southern Sub-Saharan Africa | −1.54 (−1.69–−1.38) | P = 0 | ||
| 1990 | 342976 (273818–435782) | 551.42 (452.90–682.77) | ||
| 2000 | 380248 (302344–483354) | 544.70 (444.97–675.94) | ||
| 2010 | 275564 (224454–346686) | 380.20 (315.44–472.29) | ||
| 2021 | 271828 (218536–341727) | 340.03 (278.42–423.88) | ||
| Tropical Latin America | −1.23 (−1.48–−0.97) | P = 0 | ||
| 1990 | 2277234 (1772458–2998080) | 1339.29 (1062.70–1729.61) | ||
| 2000 | 1997524 (1593250–2506507) | 1096.25 (875.40–1378.61) | ||
| 2010 | 1764722 (1408762–2275197) | 984.23 (775.21–1289.04) | ||
| 2021 | 1661116 (1289369–2173044) | 894.57 (682.86–1191.46) | ||
| Western Europe | −0.84 (−0.90–−0.78) | P = 0 | ||
| 1990 | 2180450 (1900791–2516513) | 650.20 (552.53–774.66) | ||
| 2000 | 1661205 (1437702–1934760) | 520.16 (433.18–624.49) | ||
| 2010 | 1630870 (1399211–1911414) | 517.20 (428.45–623.87) | ||
| 2021 | 1564541 (1322165–1922154) | 498.80 (404.70–632.59) | ||
| Western Sub-Saharan Africa | −0.58 (−0.65–−0.51) | P = 0 | ||
| 1990 | 1865678 (1488804–2376502) | 724.56 (603.21–888.20) | ||
| 2000 | 2293131 (1825575–2932352) | 669.53 (553.04–823.69) | ||
| 2010 | 3019680 (2371077–3935305) | 641.13 (526.05–797.37) | ||
| 2021 | 3748811 (2969919–4766915) | 606.89 (502.78–741.36) | ||
| High SDI | −0.38 (−0.48–−0.27) | P = 0 | ||
| 1990 | 7654186 (6508234–9154631) | 992.24 (821.62–1227.95) | ||
| 2000 | 6131332 (5220935–7292058) | 797.36 (660.38–973.91) | ||
| 2010 | 6542708 (5621980–7748564) | 843.95 (696.47–1021.28) | ||
| 2021 | 6963673 (5888495–8342530) | 879.28 (709.23–1111.46) | ||
| High-middle SDI | ||||
| 1990 | 6177920 (5167960–7554138) | 611.55 (509.42–760.11) | −1.09 (−1.14–−1.04) | P = 0 |
| 2000 | 4975901 (4168208–5998324) | 507.57 (419.17–626.01) | ||
| 2010 | 4345923 (3642793–5291491) | 452.85 (366.75–576.86) | ||
| 2021 | 4316153 (3587256–5383727) | 435.94 (346.91–564.87) | ||
| Middle SDI | −1.22 (−1.32–−1.12) | P = 0 | ||
| 1990 | 12732473 (10312502–16080076) | 694.11 (572.53–863.44) | ||
| 2000 | 10482486 (8750211–12992757) | 557.57 (466.63–686.24) | ||
| 2010 | 10423666 (8576262–13179561) | 529.11 (431.69–678.16) | ||
| 2021 | 10033996 (8268722–12627011) | 473.69 (386.26–601.82) | ||
| Low-middle SDI | −1.44 (−1.56–−1.33) | P = 0 | ||
| 1990 | 9500735 (7643328–12176616) | 692.04 (577.76–853.24) | ||
| 2000 | 7976427 (6589293–9877297) | 525.02 (444.62–634.14) | ||
| 2010 | 8864266 (7192398–11239285) | 514.15 (426.26–635.59) | ||
| 2021 | 8371739 (6888205–10393161) | 443.65 (369.68–545.03) | ||
| Low SDI | −0.92 (−0.96–−0.88) | P = 0 | ||
| 1990 | 5441806 (4422576–6812636) | 805.13 (680.09–976.24) | ||
| 2000 | 5965585 (4885717–7440647) | 695.56 (588.14–839.57) | ||
| 2010 | 7456007 (5994444–9490107) | 670.50 (557.30–820.36) | ||
| 2021 | 8135642 (6601575–10130508) | 603.18 (507.44–724.81) |
3.2. Regional burden and trends of six immune-mediated diseases
Significant disparities were observed in the regional distribution of the burden of the six immune-mediated diseases. High-income North America exhibited a prominent burden for asthma and MS, achieving the highest global ASIR (1403.64 [1137.64–1766.66]) and ASPR (9717.74 [8485.1–11226.93]) for asthma, while also recording the highest global ASIR (3.58 [3.33–3.86]), ASPR (103.61 [96.44–111.33]), ASDR (0.81 [0.76–0.86]), and age-standardized DALY rates (49.15 [41.84–56.53]) for MS, with all these metrics showing a sustained upward trend (Table 1; Appendix 1, Tables 1 and 5). East Asia had the highest global ASIR for IBD and also experienced a significant increase in ASIR (AAPC = 2.05 [1.49–2.61]) alongside a rapid decline in age-standardized DALY rates (AAPC = −2.84 [−3.04–−2.63]) (Appendix 1, Table 3). Oceania presented a distinct polarization in disease burden, having the highest global ASDR (33.98 [24.05–51.08]) and age-standardized DALY rates (847.59 [626.75–1212.54]) for asthma, yet the lowest global burden for MS (ASIR: 0.15 [0.12–0.19]; ASPR: 1.61 [1.21–2.09]; ASDR: 0 [0–0]; age-standardized DALY rates: 0.46 [0.3–0.66]) and RA (ASIR: 2.56 [2.2–2.97]; ASPR: 50.75 [42.63–60.28]; ASDR: 0 [0–0]; age-standardized DALY rates: 7.06 [4.6–10.45]) (Appendix 1, Tables 1, 4, and 5). Western Europe led globally across all metrics for PsO, with the highest ASIR (115.3 [111.85–118.92]), ASPR (1155.86 [1119.41–1194.46]), and age-standardized DALY rates (99.78 [72.23–133.88]) (Appendix 1, Table 2). Sub-Saharan Africa generally exhibited the lowest global burden for most diseases: Southern Sub-Saharan Africa had the lowest asthma ASIR (340.03 [278.42–423.88]) and ASPR (1875.86 [1645.57–2166.61]) (Table 1; Appendix 1, Table 1); Central Sub-Saharan Africa had the lowest AD ASIR (146.06 [135.69–157.03]) and ASPR (981.16 [919.73–1036.77]) (Appendix 1, Table 6); Eastern Sub-Saharan Africa had the lowest PsO ASIR (22.88 [22.13–23.61]) and ASPR (150.22 [145.45–155.11]) (Appendix 1, Table 2); and Southern Sub-Saharan Africa also showed declining trends for RA ASIR (AAPC = −0.29 [−0.31–−0.27]) and ASPR (AAPC = −0.32 [−0.33–−0.31]) (Appendix 1, Table 4). Central Latin America had the lowest global IBD ASIR (0.57 [0.48–0.69]) and ASPR (5.56 [4.62–6.66]), but experienced significant increases in MS ASIR (AAPC = 1.09 [1.07–1.12]), ASPR (AAPC = 1.47 [1.44–1.50]), and age-standardized DALY rates (AAPC = 2.08 [1.81–2.35]), while also having the highest global ASDR (0.97 [0.84–1.09]) and age-standardized DALY rates (68.34 [53.32–86.47]) for RA (Appendix 1, Tables 3, 4, and 5). Finally, High-income Asia Pacific had the highest global ASPR (4596.03 [4402.96–4811.08]) and age-standardized DALY rates (202.07 [103.47–337.3]) for AD (Appendix 1, Table 6).
3.3. National burden and trends of six immune-mediated diseases
Significant variations were observed in the national burden distribution of the six immune-mediated diseases. For asthma, Haiti exhibited the highest ASIR (1617.12 [1355.96–1937.19]) and ASPR (11503.65 [10476.15–12510.43]). The top three countries with the highest ASDR were Papua New Guinea (40.40 [26.17–66.56]), Fiji (40.08 [30.59–50.18]), and Kiribati (30.09 [19.43–54.03]), while the lowest ASDR values were recorded in Monaco (0.15 [0.12–0.20]), Ukraine (0.17 [0.13–0.22]), and Greece (0.19 [0.18–0.21]). The ASDR in Papua New Guinea was 270 times higher than that in Monaco (Appendix 2). For AD, Japan (494.75 [467.73–525.79]) and France (474.06 [436.90–515.16]) had the highest ASIR, whereas the lowest rates were observed in Latvia (104.03 [98.40–109.82]), Rwanda (110.60 [102.95–118.35]), and Congo (123.77 [113.57–133.86]). IBD burden was prominent in high-income countries, with Canada showing the highest ASIR (26.83 [23.30–30.76]). Mexico had the globally lowest ASIR (0.20 [0.17–0.25]), while the Philippines (0.53 [0.44–0.65]) and Cambodia (0.58 [0.50–0.71]) were also low-burden regions. The highest ASDR occurred in the Netherlands (2.21 [1.85–2.43]), Germany (1.92 [1.63–2.10]), and France (1.38 [1.17–1.54]), with Sri Lanka (0.03 [0.02–0.04]) demonstrating the lowest mortality. MS ASIR was highest in Sweden (5.58 [4.91–6.34]), Norway (4.87 [4.18–5.61]), and Canada (4.74 [4.64–4.86]). The United Kingdom had the highest ASDR (1.34 [1.27–1.40]), while Kiribati and 19 other countries/territories reported zero mortality (0 [0–0]). RA ASIR peaked in Ireland (35.08 [31.79–38.82]) and Finland (28.33 [25.67–31.39]), with the lowest rates in Papua New Guinea (2.39 [2.04–2.77]) and Kiribati (2.43 [2.08–2.85]); Honduras showed the highest ASDR (1.65 [1.10–2.33]). For PsO, Germany had the highest ASIR (143.65 [138.96–148.67]), whereas Somalia (18.57 [17.93–19.21]) and Rwanda (18.92 [18.11–19.74]) had the lightest burden. A substantial disparity was observed in age-standardized DALY rates between Germany (137.45 [99.46–185.61]) and Somalia (9.99 [7.07–13.50]) (Appendix 2).
3.4. Association between six immune-mediated diseases and SDI
The ASIR and ASPR of most diseases peaked in high-SDI regions. This included asthma (ASIR: 879.28 [709.23–1111.46]; ASPR: 6755.31 [5831.78–7825.15]), IBD (ASIR: 11.59 [10.14–13.38]; ASPR: 132.76 [115.02–154.34]), PsO (ASIR: 92.25 [89.59–94.95]; ASPR: 852.3 [830.06–875.33]), and RA (ASIR: 16.88 [15.44–18.47]; ASPR: 282.73 [256.44–313.88]) (Table 1; Appendix 1, Tables 1–4; Fig. 1; Appendix 3, Figs. 1–3). However, low-SDI regions exhibited the highest mortality and disability burden for asthma (ASDR: 16.5 [11.73–24.82]; Age-standardized DALY rates: 527.36 [403.91–716.06]), while demonstrating the lightest burden for MS (ASIR: 0.41 [0.34–0.48]; ASPR: 8.1 [6.68–9.66]) and AD (ASIR: 164.02 [155.25–173.16]; ASPR: 1171.1 [1119.89–1223.87]) (Appendix 1.Table 2, Appendix 1, Tables 1, 5, and 6; Fig. 1; Appendix 3, Figs. 1-3). From 1990 to 2021, asthma showed declining trends in ASIR, ASPR, ASDR and age-standardized DALY rates across all SDI regions. In contrast, PsO displayed increasing trends globally, with the most rapid acceleration in high-middle SDI regions (AAPC for ASIR = 0.54, ASPR = 0.63, age-standardized DALY rates = 0.64). RA exhibited rising ASIR and ASPR in all regions, particularly pronounced in low-middle SDI areas, while demonstrating significant declines in ASDR and age-standardized DALY rates within high-SDI regions. MS and IBD experienced the fastest growth in ASIR and ASPR in middle-SDI regions. Notably, IBD showed decreasing ASDR and age-standardized DALY rates in all regions except high-SDI, whereas MS exhibited upward mortality trends in non-high-middle-SDI regions, with the most rapid ASDR increase in low-SDI areas (AAPC = 2.03) (Table 1; Appendix 1, Tables 1-5; Fig. 1; Appendix 3, Figs. 1-3).
Fig. 1.
Trends in age-standardized incidence rates of asthma (A), atopic dermatitis (B), inflammatory bowel disease (C), multiple sclerosis (D), psoriasis (E), and rheumatoid arthritis (F) in the five SDI regions from 1990 to 2021.
3.5. Burden of six immune-mediated diseases by age and sex in 2021
The six IMIDs exhibited distinct epidemiological patterns characterized by significant age and sex disparities in 2021. The ASIR and number of incident cases of asthma and AD peaked in children under 5 years of age. However, the prevalence and age-standardized DALY rates for AD were highest in children aged 5–9 years. For IBD, the number of incident cases peaked at 40–44 years of age in both males and females. MS incidence peaked in adults aged 30–34 years. The number of incident cases of RA peaked in women aged 55–59 years, while the incidence peak for PsO occurred in men aged 55–59 years. Notably, the disease burden of RA and MS was significantly higher in females than in males. Furthermore, the prevalence, mortality, and DALY rates for asthma and IBD, alongside the mortality rate for RA, all reached their highest levels in the oldest age group (≥90 years) (Fig. 2; Appendix 3, Figs. 4-8).
Fig. 2.
Trends in global asthma incidence (A), prevalence (B), mortality (C), and DALY rate (D) by age and sex from 1990 to 2021.
3.6. Trends in the median age at onset (1990–2021)
To evaluate the potential impact of evolving classification criteria on disease trend estimates, we analyzed changes in the global median age at onset for the six IMIDs from 1990 to 2021. The results showed that the median age at onset for asthma (7.5 years) and MS (32.5 years) remained entirely stable over this period. In contrast, the median age at onset for AD, IBD, PsO, and RA each increased by 5 years—from 2.5 to 7.5 years, 42.5 to 47.5 years, 37.5 to 42.5 years, and 47.5 to 52.5 years, respectively—with no marked fluctuations observed (Appendix 1, Table 7).
3.7. Spatial association between HAQ and IMIDs burden
An analysis of the spatiotemporal evolution of the global HAQ Index revealed distinct patterns. In 1990, North America, Western Europe, and Oceania had already established high-quality healthcare systems, whereas sub-Saharan Africa and South Asia were predominantly at "Very Low" levels (Fig. 3A). By 2019, substantial improvements were observed across most of East Asia, Eastern Europe, and Latin America. Notably, China advanced from "Medium" to "High" level, and the Republic of Korea progressed from "High" to "Very High" level. In contrast, improvements in sub-Saharan Africa remained relatively limited (Fig. 3B). Dynamically, the most rapid gains in the HAQ Index between 1990 and 2019 were concentrated in East Asia, the Middle East, and parts of Eastern Europe (Fig. 3C). Conversely, regions such as Zimbabwe experienced minimal improvement. This uneven pattern of healthcare quality advancement aligns broadly with the spatial distribution of reported IMIDs incidence. Specifically, regions with the most rapid improvements in the HAQ Index often exhibited a significant rise in IMIDs incidence. This correlation suggests that the observed increase is likely attributable to enhanced case detection following the upgrade of diagnostic infrastructure, rather than being directly driven by changes in diagnostic criteria.
Fig. 3.
Global healthcare access and quality (HAQ) index: Distribution and temporal changes (1990–2019). (A) Global Distribution of HAQ Index in 1990 The map shows the baseline global healthcare quality in 1990, categorized into five levels: Very Low, Low, Medium, High, and Very High. (B) Global Distribution of HAQ Index in 2019 This panel illustrates the state of healthcare quality in 2019. Comparison with (A) reveals broad improvements across most regions over the 29-year period. (C) Global Changes in HAQ Index, 1990–2019 The map quantifies the change in HAQ Index over the study period. Red indicates stagnation or decline (ΔHAQ ≤0). Blue shades represent improvements, categorized as: (C1) Minor (0 < ΔHAQ ≤15), (C2) Moderate (15 < ΔHAQ ≤30), and (C3) Substantial (ΔHAQ >30).
4. Discussion
IMIDs have emerged as a significant global public health challenge. Utilizing data from GBD 2021, this study provides a comprehensive analysis of the disease burden of six IMIDs—RA, IBD, MS, AD, asthma, and PsO—from 1990 to 2021. The results indicate substantial variations in these trends across sex, geographical regions, and SDI levels.
Specifically, between 1990 and 2021, global age-standardized incidence, prevalence, mortality rates, and DALYs for asthma, AD, and MS exhibited declining trends. This suggests that current disease management strategies may be yielding initial success in controlling disease progression. Notably, however, the age-standardized incidence rates of IBD, PsO, and RA continued to rise. This increase is likely attributable to a combination of factors, including enhanced detection rates driven by advancements in diagnostic techniques, global population aging, and urbanization and industrialization [9,10]. Further analysis revealed a pronounced socioeconomic gradient in the geographic distribution of the IMIDs burden, consistent with prior research, indicating that countries with higher SDI levels generally experience a higher disease burden [11]. This phenomenon may be attributed to several key factors. Firstly, high-SDI regions commonly face challenges including rapid urbanization, adoption of Westernized diets (high in fat and low in fiber), and reduced microbial diversity [[12], [13], [14]], which collectively elevate disease risk in genetically susceptible populations. Secondly, advanced healthcare systems in high-SDI areas facilitate early diagnosis and comprehensive case reporting. Concurrently, the advent of novel biologic therapies and widespread implementation of patient management strategies have significantly reduced mortality rates [10].Conversely, low-SDI regions demonstrate distinct challenges: weak primary healthcare infrastructure, inadequate occupational exposure protections, and limited health literacy contribute to persistently high rates of underdiagnosis and misdiagnosis. This results in substantial underestimation of the true disease burden. Furthermore, medication shortages and limited treatment access frequently lead to uncontrolled disease progression, exacerbating the complexity of disease management [10,15,16].Notably, the relatively lower burden observed in allergic conditions such as asthma and atopic dermatitis may partially reflect dietary and environmental differences. Of particular significance is the rapid escalation in age-standardized incidence of IBD within middle-SDI regions. This trend likely stems from the economic transition characterizing these nations, where rapid development coincides with dietary Westernization and rising obesity rates – established drivers of IBD incidence [17]. Historically, the global burden of IBD has been categorized into four epidemiological stages, with Asia currently experiencing the accelerated incidence phase (Stage 2). As the disease evolves in these regions, future management strategies may benefit from adapting established Western approaches – modified to address local needs – while incorporating lessons learned over the past three decades [18].At the national level, diseases including psoriasis, multiple sclerosis, and rheumatoid arthritis predominantly affect high-income nations in Western Europe and North America. Conversely, most burden metrics reach their lowest global levels in low-income regions such as sub-Saharan Africa. These pronounced geographical disparities underscore the critical need for context-specific health policies tailored to unique national epidemiological profiles, ensuring responsive care for the diverse health needs of populations affected by immune-mediated inflammatory diseases.
Furthermore, our analysis revealed significant age- and sex-stratified patterns in the burden of IMIDs. Regarding age distribution, AD and asthma exhibit high incidence during childhood, with children under 5 years and those aged 5–9 years remaining the primary high-risk groups [19,20], necessitating targeted interventions to reduce incidence and prevalence in this population.The number of incident cases and the incidence rate of MS peaked synchronously in the 30–44 year age group, indicating that young to middle-aged adults constitute the most affected demographic. Conversely, while IBD had the highest number of incident cases in the 40–44 year group, its incidence rate peaked in the 60–64 year age group. However, diagnostic and therapeutic focus on older adult patients within this group remains notably inadequate compared to the overall patient population. For instance, a systematic review of randomized controlled trials for IBD therapeutics revealed that participants aged 65 years and older constituted less than 1% of the study cohorts, highlighting the need for optimized, age-specific clinical management strategies [21]. The burden of psoriasis and RA followed a rise-decline pattern with increasing age, concentrating predominantly in middle-aged and older adults. Sex disparity analysis indicated no significant differences in the distribution of asthma, IBD, PsO, or AD between sexes. In contrast, MS and RA exhibited pronounced sex biases, with females bearing a significantly higher disease burden than males. Previous research suggests potential mechanisms for this divergence, including sex hormone levels, sex chromosome complement; and sex-specific environmental factors, such as sexually dimorphic microbiota [22,23]. Notably, while females are generally considered more susceptible to immune-related disorders, affected male patients often present with more severe clinical manifestations and higher mortality rates [24].Additionally, mortality rates for MS, asthma, IBD, and RA all peaked in the very elderly population (≥90 years). This elevated risk is closely associated with immunosenescence, heightened susceptibility to infections, increased prevalence of comorbidities, and potentially lower health-seeking behaviors among older patients [[25], [26], [27], [28]]. As global aging intensifies, research aimed at improving the quality of life and survival outcomes for elderly patients is imperative. Collectively, these factors underscore the urgent need for targeted research and tailored strategies to effectively address and manage the evolving disease burden across all age groups.
Given that the evolution of diagnostic criteria may influence long-term disease burden trends of IMIDs, we introduced the stability of the median age at onset as a core internal reference and used the HAQ index as an indicator of the implementation capacity of diagnostic criteria for evaluation. The results showed that the median age at onset for most IMIDs remained stable or exhibited only minor fluctuations over the 32-year period, indicating that updates in diagnostic criteria did not fundamentally alter their age distribution at onset. Spatial analysis of the HAQ index further reinforced this conclusion: the impact of evolving diagnostic criteria is highly dependent on the implementation capacity of regional healthcare systems. Regions with high HAQ levels, supported by well-developed healthcare infrastructure, can rapidly adopt new diagnostic criteria, leading to higher reported incidence rates, which reflects their superior case identification and registration capabilities. Conversely, regions with low HAQ levels face significant delays in the application of updated diagnostic criteria due to limited diagnostic capacity, resulting in a large number of cases going unrecognized and masking the true disease burden. In regions with rapidly improving HAQ levels, such as East Asian countries, the observed increase in incidence rates is likely a consequence of enhanced diagnostic capacity following improvements in healthcare infrastructure, rather than a direct result of changes in the diagnostic criteria themselves.
IMIDs result from a complex interplay of genetic predisposition, immune dysregulation, environmental exposures, hormonal influences, and infections [29]. Modifying the environmental and behavioral factors within this interplay offers broad health benefits. Primary prevention efforts should focus on strengthening education for both healthcare professionals and the public regarding potential protective factors and disease triggers. This knowledge should be integrated into practical healthcare guidelines, advising individuals on strategies to reduce environmental toxin exposure and adopt healthier lifestyles. Key lifestyle modifications include maintaining a nutritious diet, engaging in regular physical activity, weight management, ensuring adequate sleep, and employing stress management and relaxation techniques [30]. At the global level, actively promoting environmental improvement strategies is crucial. Measures such as curbing fossil fuel use, reducing pollution emissions, and vigorously promoting sustainable energy sources are essential for lowering pervasive environmental exposure risks and enhancing population health resilience.Given the pronounced regional disparities in IMIDs burden, implementing stratified strategies is key to optimizing prevention and management. In high-SDI regions, early screening programs and precision management approaches can help alleviate disease burden. In contrast, low-SDI regions, particularly remote areas, often lack specific management protocols for IMIDs. Priority here should be given to improving basic health infrastructure, training specialized healthcare personnel, and ensuring reliable access to essential medications [31]. Furthermore, in high-latitude regions of North America and Western Europe, where insufficient sunlight exposure is prevalent, promoting vitamin D-fortified foods may contribute to reducing the burden of MS, IBD, and psoriasis [9,32].Concurrently, on a global scale, considering trends of population growth and accelerated aging, the burden of IMIDs is likely to increase further. Therefore, there is an urgent imperative to develop and implement robust, evidence-based public health intervention frameworks. Such frameworks must incorporate multi-level, differentiated strategies to effectively mitigate the physical, mental, and societal impacts of IMIDs.
5. Limitations
This study has several limitations. First, the lack of universal consensus for many IMIDs results in diagnoses primarily reliant on symptomatic presentations. Variations in descriptive terminology for IMIDs symptoms across countries contribute to inconsistencies in diagnosis and consequent estimates of incidence and prevalence. Second, the variable quality of raw data from different nations may introduce biases, potentially compromising the accuracy of true IMIDs burden estimates. Additionally, mortality data for psoriasis and atopic dermatitis were not included due to unavailability. Third, heterogeneity in data sources precluded the inclusion of racial factors in our analysis. Fourth, while IMIDs encompass multiple diseases, insufficient nationally representative data—particularly for rarer conditions or those lacking clearly defined diagnostic codes—limited the Global Burden of Disease (GBD) 2021 study's capacity to comprehensively model all relevant conditions. Future research should prioritize investigating the potential significant impacts of other immune-mediated diseases on global health through dedicated burden-of-disease studies. Fifth, the use of the median age of onset and the HAQ Index as proxies could not fully disentangle the effects of improved diagnostic capacity from true changes in disease incidence, and the reliability of GBD estimates remains constrained in regions with poor underlying data.
6. Conclusion
In summary, the disease burden of six major IMIDs exhibits significant heterogeneity across geographic regions and socioeconomic strata. Countries and regions with higher SDI disproportionately bear a greater share of this burden. Strengthening healthcare infrastructure, addressing modifiable risk factors, and investing in research and policy reforms are imperative to mitigate the global burden of IMIDs over the coming decades.
CRediT authorship contribution statement
Mengyu Huang: Writing – original draft, Data curation. Zhaoli Ma: Data curation. Xiu Luo: Investigation, Conceptualization. Qian Ren: Writing – review & editing, Supervision.
Funding
This work was supported by the Science and Technology Major Project of Gansu Province (grant number 24ZDNA003).
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Footnotes
Supplementary data to this article can be found online at https://doi.org/10.1016/j.jtauto.2025.100330.
Appendix A. Supplementary data
The following are the Supplementary data to this article.
Data availability
Data will be made available on request.
References
- 1.Dong Y., Chen X., Abdelnaby T., Guyonnet V., Cai X., Wang S. Regulatory potential of food-derived bioactive peptides on gut microbiota: a new perspective against immune-mediated inflammatory diseases. J. Agric. Food Chem. 2025;73:17403–17416. doi: 10.1021/acs.jafc.5c06148. [DOI] [PubMed] [Google Scholar]
- 2.Rogler G., Singh A., Kavanaugh A., Rubin D.T. Extraintestinal manifestations of inflammatory bowel disease: current concepts, treatment, and implications for disease management. Gastroenterology. 2021;161:1118–1132. doi: 10.1053/j.gastro.2021.07.042. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Misra D.P. Clinical manifestations of rheumatoid arthritis, including comorbidities, complications, and long-term follow-up. Best Pract. Res. Clin. Rheumatol. 2025;39 doi: 10.1016/j.berh.2024.102020. [DOI] [PubMed] [Google Scholar]
- 4.Monteleone G., Moscardelli A., Colella A., Marafini I., Salvatori S. Immune-mediated inflammatory diseases: common and different pathogenic and clinical features. Autoimmun. Rev. 2023;22 doi: 10.1016/j.autrev.2023.103410. [DOI] [PubMed] [Google Scholar]
- 5.Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the global burden of disease study 2021. Lancet. 2024;403:2133–2161. doi: 10.1016/S0140-6736(24)00757-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.The burden of diseases, injuries, and risk factors by state in the USA, 1990–2021: a systematic analysis for the global burden of disease study 2021. Lancet. 2024;404:2314–2340. doi: 10.1016/S0140-6736(24)01446-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Cheng Z., Lv J., Guo H., Liu X. Global, regional, and national burden of ischemic stroke, 1990–2021: an analysis of data from the global burden of disease study 2021. eClinicalMedicine. 2024;75 doi: 10.1016/j.eclinm.2024.102758. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Assessing performance of the healthcare access and quality index, overall and by select age groups, for 204 countries and territories, 1990–2019: a systematic analysis from the global burden of disease study 2019. Lancet Global Health. 2022;10:e1715–e1743. doi: 10.1016/S2214-109X(22)00429-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Piovani D., Danese S., Peyrin-Biroulet L., Bonovas S. Environmental, nutritional, and socioeconomic determinants of IBD incidence: a global ecological study. J. Crohns Colitis. 2020;14:323–331. doi: 10.1093/ecco-jcc/jjz150. [DOI] [PubMed] [Google Scholar]
- 10.Tang K., Zhu L., Shan S., Luo Z., Zhou J., Ying J., Wu J., Shen G., Song P. Global, regional and national trends in the epidemiology of rheumatoid arthritis from 1990 to 2021: an age-period-cohort effect analysis of the global burden of disease study 2021. RMD Open. 2025;11 doi: 10.1136/rmdopen-2024-005383. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Cao F., He Y.-S., Wang Y., Zha C.-K., Lu J.-M., Tao L.-M., Jiang Z.-X., Pan H.-F. Global burden and cross-country inequalities in autoimmune diseases from 1990 to 2019. Autoimmun. Rev. 2023;22 doi: 10.1016/j.autrev.2023.103326. [DOI] [PubMed] [Google Scholar]
- 12.Christ A., Lauterbach M., Latz E. Western diet and the immune system: an inflammatory connection. Immunity. 2019;51:794–811. doi: 10.1016/j.immuni.2019.09.020. [DOI] [PubMed] [Google Scholar]
- 13.Christovich A., Luo X.M., Microbiota Gut, Gut Leaky. And autoimmune diseases. Front. Immunol. 2022;13 doi: 10.3389/fimmu.2022.946248. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Akdis C.A. Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity and other chronic conditions? Nat. Rev. Immunol. 2021;21:739–751. doi: 10.1038/s41577-021-00538-7. [DOI] [PubMed] [Google Scholar]
- 15.Zhang S., Gao Z., Wu L., Zhong Y., Gao H., Tao F., Wu X. Global patterns of asthma burden related to environmental risk factors during 1990–2019: an age-period-cohort analysis for global burden of disease study 2019. Environ. Health. 2024;23:20. doi: 10.1186/s12940-024-01060-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Hernández-Negrín H., Roque-Dapresa Y., Martínez-Morales O., Mederos-Portal A. Using multiple cause-of-death analysis to estimate systemic autoimmune disease mortality burden in Low- and middle-income countries. MEDICC Rev. 2021;23:69. doi: 10.37757/MR2021.V23.N2.12. [DOI] [PubMed] [Google Scholar]
- 17.Chen L., Cheng S., Zhang B., Zhong C. Burden of inflammatory bowel disease among elderly, 1990–2019: a systematic analysis based on the global burden of disease study 2019. Autoimmun. Rev. 2025;24 doi: 10.1016/j.autrev.2024.103708. [DOI] [PubMed] [Google Scholar]
- 18.Kaplan G.G., Windsor J.W. The four epidemiological stages in the global evolution of inflammatory bowel disease. Nat. Rev. Gastroenterol. Hepatol. 2021;18:56–66. doi: 10.1038/s41575-020-00360-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Kaviany P., Shah A. Current practices in pediatric asthma care. Clin. Chest Med. 2024;45:611–623. doi: 10.1016/j.ccm.2024.02.028. [DOI] [PubMed] [Google Scholar]
- 20.Pareek A., Kumari L., Pareek A., Chaudhary S., Ratan Y., Janmeda P., Chuturgoon S., Chuturgoon A. Unraveling atopic dermatitis: insights into pathophysiology, therapeutic advances, and future perspectives. Cells. 2024;13:425. doi: 10.3390/cells13050425. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Kochar B., Kalasapudi L., Ufere N.N., Nipp R.D., Ananthakrishnan A.N., Ritchie C.S. Systematic review of inclusion and analysis of older adults in randomized controlled trials of medications used to treat inflammatory bowel diseases. Inflamm. Bowel Dis. 2021;27:1541–1543. doi: 10.1093/ibd/izab052. [DOI] [PubMed] [Google Scholar]
- 22.Billi A., Kahlenberg J.M., Gudjonsson J.E. Sex bias in autoimmunity. Curr. Opin. Rheumatol. 2019;31:53–61. doi: 10.1097/BOR.0000000000000564. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Alpízar-Rodríguez D., Pluchino N., Canny G., Gabay C., Finckh A. The role of female hormonal factors in the development of rheumatoid arthritis. Rheumatology. 2017;56:1254–1263. doi: 10.1093/rheumatology/kew318. [DOI] [PubMed] [Google Scholar]
- 24.Xing E., Billi A.C., Gudjonsson J.E. Sex bias and autoimmune diseases. J. Invest. Dermatol. 2022;142:857–866. doi: 10.1016/j.jid.2021.06.008. [DOI] [PubMed] [Google Scholar]
- 25.Nawrot J., Boonen A., Peeters R., Starmans M., van Onna M. Rheumatologists' views and experiences in managing rheumatoid arthritis in elderly patients: a qualitative study. J. Rheumatol. 2018;45:590–594. doi: 10.3899/jrheum.170773. [DOI] [PubMed] [Google Scholar]
- 26.Wang K., Zhao Y., Cao X. Global burden and future trends in psoriasis epidemiology: insights from the global burden of disease study 2019 and predictions to 2030. Arch. Dermatol. Res. 2024;316:114. doi: 10.1007/s00403-024-02846-z. [DOI] [PubMed] [Google Scholar]
- 27.Cao Y., Chen S., Chen X., Zou W., Liu Z., Wu Y., Hu S. Global trends in the incidence and mortality of asthma from 1990 to 2019: an age-period-cohort analysis using the global burden of disease study 2019. Front. Public Health. 2022;10 doi: 10.3389/fpubh.2022.1036674. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Adamczyk-Sowa M., Nowak-Kiczmer M., Jaroszewicz J., Berger T. Immunosenescence and multiple sclerosis. Neurol. Neurochir. Pol. 2022;56:220–227. doi: 10.5603/PJNNS.a2022.0045. [DOI] [PubMed] [Google Scholar]
- 29.Fugger L., Jensen L.T., Rossjohn J. Challenges, progress, and prospects of developing therapies to treat autoimmune diseases. Cell. 2020;181:63–80. doi: 10.1016/j.cell.2020.03.007. [DOI] [PubMed] [Google Scholar]
- 30.Miller F.W. Environment, lifestyles, and climate change: the many nongenetic contributors to the long and winding road to autoimmune diseases. Arthritis Care Res. 2025;77:3–11. doi: 10.1002/acr.25423. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Boutros P., Kassem N., Boudo V., Sié A., Munga S., Maggioni M.A., Golec M., Simion R., Bärnighausen T., Winkler V., Barteit S. Understanding the risk factors, burden, and interventions for chronic respiratory diseases in Low- and middle-income countries: a scoping review. Public Health Rev. 2024;45 doi: 10.3389/phrs.2024.1607339. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Springate D.A., Parisi R., Kontopantelis E., Reeves D., Griffiths C.E.M., Ashcroft D.M. Incidence, prevalence and mortality of patients with psoriasis: a U.K. population‐based cohort study. Br. J. Dermatol. 2017;176:650–658. doi: 10.1111/bjd.15021. [DOI] [PMC free article] [PubMed] [Google Scholar]
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Supplementary Materials
Data Availability Statement
Data will be made available on request.