Data was sourced from the GBD 2021 database, which comprehensively collects data on 371 diseases from 204 countries and territories (1). All data are freely available through the Global Health Data Exchange platform.¹ The original data sources and fitting methods for the GBD Study 2021 have been thoroughly detailed in a previous study (6). The GBD 2021 categorizes causes into four levels, ranging from level 1 infectious, maternal, neonatal, and nutritional diseases to level 4 latent tuberculosis infection. AA is listed as a Level 3 cause of the GBD 2021. In GBD 2021, AA is identified using International Classification of Diseases (ICD)-10 codes L63–L63.9 and ICD-9 codes 704.0–704.9 (6).

The United Nations has come to formally define adolescence as the period between 10 and 19 years of age (7). In order to investigate in more detail, we divided adolescents into younger adolescents (aged 10–14 years) and older adolescents (aged 15–19 years), in addition to young adults aged 20–24 years (8). We collected data for AA from both sexes across three age groups: 10–14, 15–19, and 20–24 years old. The numbers of prevalent cases, incident cases, and prevalence and incidence rates, in addition to the numbers and rates for DALYs, were directly extracted from the GBD 2021. DALYs were obtained by calculating the sum of the years of life lost and years lived with disability (6). The Socio-demographic Index (SDI) is a composite indicator of background social and economic conditions that influence health outcomes in each location. It is the geometric mean of 0 to 1 indices of total fertility rate for those younger than 25 years old, mean education for those 15 years old and above, and lag-distributed income per capita. The GBD 2021 categorizes countries and territories into five SDI quintiles ranging from low to high development levels (6).

To estimate the age-standardized prevalence rate (ASPR), incidence rate (ASIR), and DALY rate (ASDR) of AA among adolescents and young adults, age standardization was performed using the direct method, which assumes the rates distribution is a weighted sum of independent Poisson random variables (9). By using these standardized metrics to quantify the differences in the burden of AA across various time periods, sex, and locations, the impact of variations in population age structures can be controlled. All rates were reported per 100,000 population. The 95% uncertainty intervals (UIs) were defined by the 25th and 75th values of the ordered 1,000 estimates based on the GBD algorithm.

The age-standardized rate calculation formula is as follows: Age − standardized rate = ∑ i = 1 A a i w i ∑ i = 1 A w i

Where, a i is the age-specific rate for the ith age group, and w i is the weight in the corresponding age subgroup of the chosen reference standard population (where i denotes the ith age class), and A represents the total number of age groups.

The Joinpoint regression analysis is an effective method for analyzing trends over time to identify the time points at which the trend significantly changes. This model adeptly identifies and quantitatively characterizes significant change points within the time-series data concerning age-standardized rates of AA across global, regional, and national levels. The model facilitated the computation of the annual percent change (APC) and its accompanying 95% confidence interval (CI) to delineate age-standardized rates trends across delineated time frames (10). Moreover, for a holistic appraisal of the observed trends, the average annual percent change (AAPC) was also calculated, encapsulating aggregated trend data spanning the study period of 1990–2021. The AAPC calculation formula is as follows: AAPC = { exp ( ∑ i = 1 B w i b i ∑ i = 1 B w i ) − 1 } × 100

Where, b i is the slope coefficient for the i th segment, with i indexing the segments within the desired range of years, and w i represents the length of each segment within that range, and B demotes the total number of segments.

From a statistical standpoint, an APC or AAPC estimate, alongside its 95% CI lower bound exceeding zero, denotes an upward trajectory in the specified interval. In contrast, an APC or AAPC estimate coupled with a 95% CI upper bound falling below zero signals a downward trend. When the 95% CI for the APC or AAPC encompasses zero, it implies that the trend has remained stable. All statistical analyses were conducted using the Joinpoint Regression Program (version 5.0.2) and R (version 4.3.2). Two-tailed p < 0.05 was considered statistically significant.

The global number of prevalence cases of AA among adolescents and young adults worldwide had increased by 16.46% compared to 1990, from 2712439.2 (95% UI: 2512374.3 to 2924044.1) in 1990 to 3,158,846 (95% UI: 2926498.6 to 3395234.3) in 2021 (Table 1). In addition, from 1990 to 2021, the ASPR of AA decreased from 173.8 (95% UI: 156.4 to 192.1) per 100,000 people to 166.5 (95% UI: 149.9 to 183.7) per 100,000 people, with an AAPC of −0.1374 (95% CI: −0.1396 to −0.1354) (Table 1; Supplementary Figure S1). At the same time, the global number of incidence cases of AA in 2021 reached 5881661.5 (95% UI: 5453313.4 to 6356782.1), higher than the 5055219.9 (95% CI: 4681475.9 to 5465260.6) in 1990 (Supplementary Table S1). The ASIR showed a downward trend, with an AAPC of −0.1404 (95% CI: −0.1425 to −0.1387), decreasing from 323.9 (95% UI: 288.8 to 360) per 100,000 people in 1990 to 310 (95% UI: 276.8 to 344.5) per 100,000 people in 2021 (Supplementary Table S1; Supplementary Figure S2). The DALYs caused by AA increased from 90,353 (95% UI: 57820.5 to 129223.3) in 1990 to 105334.5 (95% UI: 67557.2 to 150574.7) in 2021, with an increase of 16.58% (Supplementary Table S2). ASDR followed a declining trend, decreasing from 5.8 (95% UI: 3.7 to 8.4) per 100,000 people in 1990 to 5.6 (95% UI: 3.6 to 8.1) per 100,000 people in 2021, with an AAPC of −0.1351 (95% CI: −0.1382 to −0.1317) (Supplementary Table S2; Supplementary Figure S3).

The burden of AA among young males and females worldwide had decreased from 1990 to 2021 (Figure 1A). In 2021, the ASPR of young females was about 72.8% higher than that of young males (212.2 per 100,000 vs. 122.8 per 100,000) (Table 1). In the past 30 years, the gender gap in ASPR had slightly increased, with a more pronounced decline in male patients (AAPC: -0.1615, 95% CI: −0.1641 to −0.1588) compared to females (AAPC: -0.1108, 95% CI: −0.1126 to −0.1089) (Table 1). Similarly, the ASIR of young females (AAPC: -0.1125, 95% CI: −0.1143 to −0.1105) and young males (AAPC: -0.1673, 95% CI: −0.1700 to −0.1643) showed a decreasing trend (Supplementary Table S1). The ASDR of male and female patients also showed a decreasing trend, with AAPC of −0.1085 (95% CI: −0.1122 to −0.1046) for young females and −0.1568 (95% CI: −0.1644 to −0.1494) for young males (Supplementary Table S2).

The age specific prevalence rate, incidence rate and DALYs rate of AA in 2021 were mainly concentrated in young adults aged 20–24 (Figure 1C). The decline in age specific prevalence rate among the global 20–24 age group was most significant from 1990 to 2021 (AAPC: -0.1628, 95% CI: −0.1660 to −0.1597). The prevalence rates of individuals aged 10–14 and 15–19 also decreased during this period, with AAPCs of −0.1384 (95% CI: −0.1403 to −0.1364) and −0.0764 (95% CI: −0.0778 to −0.0748), respectively (Supplementary Table S3). In addition, from 1990 to 2021, the age specific incidence rate of the 20–24 age group declined the most, with the AAPC of −0.1691 (95% CI: −0.1714 to −0.1667). The age specific DALYs rate of AA among the 10–24 age group also declined (Supplementary Table S3).

From 1990 to 2021, except for low SDI regions, the burden of AA in other regions had shown a decreasing trend over time (Figure 1B). From 1990 to 2021, the low SDI regions gradually increased and surpassed the low-middle SDI regions over time, while the high SDI regions had the highest ASPR, ASIR, and ASDR for AA (Figure 1B). Although regions with high SDI had the highest burden of AA, during this period, the ASPR, ASIR, and ASDR in these regions decreased the most compared to other SDI regions, with AAPCs of −0.1051 (95% CI: −0.1158 to −0.0938), −0.1180 (95% CI: −0.1292 to −0.1059), and −0.1144 (95% CI: −0.1268 to −0.1017), respectively (Table 1; Supplementary Tables S1, S2). In addition, from 1990 to 2021, ASPR, ASIR, and ASDR in high-middle SDI regions ranked second, while ASPR, ASIR, and ASDR in middle SDI regions showed the second largest decline. Only ASPR, ASIR, and ASDR in low SDI regions showed an upward trend, with AAPCs of 0.0050 (95% CI: 0.0047 to 0.0053), 0.0049 (95% CI: 0.0047 to 0.0052), and 0.0266 (95% CI: 0.0224 to 0.0307), respectively (Table 1; Supplementary Tables S1, S2).

Based on the 21 regions partitioned by the GBD 2021 database, we analyzed the differential characteristics of ASPR, ASIR, and ASDR in adolescents and young adults AA in each region (Figure 2; Supplementary Figures S4, S5). South Asia reported very high numbers in 2021, with 1,438,950 prevalence cases, 773981.7 incidence cases, and 25782.5 DALYs. Although South Asia had the highest prevalence cases and incidence cases, in terms of standardized rates, high-income North America had the highest ASPR (233.3 per 100,000 people), ASIR (435.2 per 100,000 people), and ASDR (7.7 per 100,000 people) in 2021. The ASPR (144.9 per 100,000 people), ASIR (269.4 per 100,000 people), and ASDR (4.8 per 100,000 people) in South Asia were the lowest. From 1990 to 2021, except for South Asia, Western Europe, North Africa, and the Middle East, ASPR and ASIR in other GBD regions showed a downward trend (AAPCs<0). The ASDR in South Asia, Western Europe, sub Saharan Africa, sub Saharan Africa, North Africa, and the Middle East showed an upward trend (AAPCs>0), while in other regions it showed a downward trend (AAPCs<0) (Table 1; Supplementary Tables S1, S2).

The top five countries in terms of ASPR (per 100,000 people) for AA in 2021 were the United States (233.90), Greenland (228.46), Canada (227.49), New Zealand (205.75), and Argentina (204.85) (Figure 3A; Supplementary Table S4). From 1990 to 2021, the United States had the largest decline in ASPR (AAPC: −0.3747), while the United Arab Emirates had the largest increase (AAPC: 0.1141) (Figure 3B). The top five countries in terms of ASIR (per 100,000 people) for AA were the United States (436.08), Greenland (427.80), Canada (426.13), New Zealand (384.40), and Argentina (383.48). The country with the lowest ASIR was Qatar (254.43) (Supplementary Figure S6; Supplementary Table S4). From 1990 to 2021, the United Arab Emirates had the largest increase in ASIR (AAPC: 0.1138), while the United States had the largest decrease (AAPC: −0.4081) (Supplementary Figure S6). The ASDR for AA in 2021 was the highest in the United States (7.75 per 100,000), and Qatar had the lowest (4.55 per 100,000) (Supplementary Figure S7; Supplementary Table S4). From 1990 to 2021, the United Arab Emirates had the largest increase in ASDR (AAPC: 0.1024), while the United States had the largest decrease (AAPC: −0.3930) (Supplementary Figure S7).

On a global scale, AA was significantly positively correlated with various diseases, such as anxiety disorders, atopic dermatitis, depressive disorders, dietary iron deficiency, rheumatoid arthritis, and urticaria, etc. Among the three age groups of 10–24 years, AA showed a stronger correlation with anxiety disorders, followed by depressive disorders, rheumatoid arthritis, and urticaria. From the perspective of gender, both men and women with AA had a stronger correlation with psoriasis, followed by anxiety disorders. In regions with a higher SDI, both anxiety disorders and depressive disorders showed a stronger correlation with AA, while in regions with a lower SDI, the correlation between psoriasis and AA was more obvious (Figure 4).