Key Points
Question
What are the risks of developing new-onset psychiatric or autoimmune diseases after diagnosis of alopecia areata?
Findings
This cohort study of 3 372 491 patients found that those newly diagnosed with alopecia areata had a higher prevalence and incidence of psychiatric and autoimmune comorbidities. Patients with alopecia areata had a significantly higher risk of developing a new-onset psychiatric or other autoimmune disease than patients without alopecia areata.
Meaning
These findings suggest that individuals with vs without alopecia areata have higher risks of developing psychiatric and/or autoimmune comorbidities after diagnosis; early treatment with effective therapies may reduce these risks and thereby reduce the burden of disease for patients.
This cohort study evaluates the prevalence, incidence, and risk of new-onset autoimmune and psychiatric comorbidities after alopecia areata diagnosis in adolescent and adult patients.
Abstract
Importance
Alopecia areata (AA) has been associated with multiple comorbidities, yet information regarding the timing of comorbidity development after AA diagnosis is limited.
Objective
To evaluate the prevalence and new-onset incidence of psychiatric and autoimmune comorbidities in patients with AA in the US.
Design, Setting, and Participants
This retrospective cohort analysis used data collected from January 1, 2007, to April 30, 2023, from the Merative MarketScan Research Databases, which contains medical and drug claims data from more than 46 million patients in the US. Data from adolescent and adult patients (aged 12-64 years) diagnosed with AA and patients without AA (ie, controls) were evaluated. For some analyses, patients with AA were matched (1:4) to controls based on sex, age, and geographic region.
Main Outcomes and Measures
Prevalence (at the time of AA diagnosis) and incidence (new onset after AA diagnosis) of psychiatric and autoimmune diseases were reported as percentage of patients. Risk of developing a new-onset psychiatric or autoimmune disease after AA diagnosis was calculated as adjusted hazard ratios (AHRs) with 95% CIs.
Results
At baseline, 63 384 patients with AA and 3 309 107 without AA were identified. After matching, there were 16 512 and 66 048 patients in the AA and control groups, respectively, with a mean (SD) age of 36.9 (13.4) years and 50.6% of whom were female. Compared with the unmatched controls, patients with AA had higher prevalence of psychiatric (30.9% vs 26.8%; P < .001) and autoimmune (16.1% vs 8.9%; P < .0001) comorbidities at AA diagnosis; incidence was also higher in patients with AA (without history of these comorbidities) vs the matched control group. Patients with AA vs controls had a significantly higher risk of developing a psychiatric (AHR, 1.3; 95% CI, 1.3-1.4) or autoimmune (AHR, 2.7; 95% CI, 2.5-2.8) comorbidity.
Conclusions and Relevance
In this cohort study, patients with AA had a higher prevalence of autoimmune and psychiatric comorbidities at AA diagnosis and demonstrated an elevated risk of new-onset autoimmune and psychiatric comorbidities after their diagnosis. These data highlight the most common comorbidities among patients with AA and may help physicians counsel and monitor patients newly diagnosed with AA.
Introduction
Alopecia areata (AA) is a chronic, immune-mediated disorder characterized by sudden, inflammatory, nonscarring hair loss that can be limited or extensive, involving the entire scalp and body hair.1,2,3 Both genetic4 and environmental factors5 play a role in AA, with reports suggesting that an upregulation of inflammatory cytokines (eg, interferon-γ and interleukin 15) that signal through Janus kinases and other pathways may be involved.6 These inflammatory pathways, however, are not unique to AA but are known to play roles in several autoimmune diseases, such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis.7,8 Alopecia areata itself has been associated with many other systemic disorders, including atopic dermatitis, inflammatory bowel disease, and rheumatoid arthritis.9 Studies have shown that patients with AA have increased rates of psychiatric conditions,10 including depression and posttraumatic stress disorder.11,12 A meta-analysis conducted by Toussi et al13 found higher incidences of mental health disorders, including anxiety, attention-deficit/hyperactivity disorder, and depression, in patients with AA.
Altogether, the potential comorbidity burden of patients with AA may contribute to a reduced health-related quality of life,14,15,16,17,18 yet most studies that have assessed comorbidities associated with AA are limited.19 Although some studies examine a correlation between AA and psychiatric or autoimmune disorders, none have assessed the risks of developing psychiatric and autoimmune comorbidities in patients with newly diagnosed AA. Thus, there remains a lack of evidence of the comorbidity burden among those with AA in the US, particularly that of new-onset comorbidities after AA diagnosis. Therefore, the objective of this study was to evaluate the prevalence of autoimmune and psychiatric comorbidities at the time of AA diagnosis, as well as the incidence and risk of developing new-onset autoimmune and psychiatric comorbidities after AA diagnosis in patients in the US.
Methods
Study Design and Patient Selection
This cohort study used data from the Merative MarketScan Research Databases collected between January 1, 2007, and April 30, 2023. As a retrospective study that used anonymized data, this work is classified as non–human participant research as defined by 45 CFR 46.104(d) and therefore exempt from institutional review board approval and informed consent. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
For this study, the index date was defined as the earliest date of confirmed diagnosis of AA, determined by inpatient and outpatient claims. For controls, the index date was randomly assigned based on the index distribution among patients with AA. The study baseline period was defined as 12 months or more before the index date, and the study follow-up period was defined as 12 months or more after the index date (eFigure 1 in Supplement 1).
For the control group, patients included in the analysis met the following criteria: aged 12 to 64 years, maintained continuous enrollment (medical) for 12 months or more before and after the index date (ie, baseline and follow-up periods), and not diagnosed with AA during the study period. Likewise, patients in the AA group were aged 12 to 64 years, maintained continuous enrollment for 12 months or more before and after the index date, and had either 1 or more qualifying AA inpatient encounters or 2 or more outpatient claims with a diagnosis code for AA (International Statistical Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] code L63.x or International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 704.01) during index identification period, and without any AA diagnosis during the baseline period using previously validated methods.20
To limit our analysis to new-onset comorbidities, for the analyses on incidence and risk of autoimmune and psychiatric comorbidities, we excluded patients if they had recorded diagnoses of other immune-mediated inflammatory skin disorders (eg, atopic dermatitis, eczema, or other pigmentation disorders), autoimmune diseases (eg, type 1 diabetes, celiac disease, or systemic lupus erythematosus), or psychiatric diseases (eg, depression or anxiety) (eTable 1 in Supplement 1) during the baseline period (ie, ≥12 months to the start of baseline continuous enrollment). Individuals’ race and ethnicity could not be reported because that information is not captured in the Merative MarketScan database.
Outcomes
Prevalence of psychiatric or autoimmune comorbidities, reported as percentage of patients, was assessed among those diagnosed with AA and the control group at baseline. The incidence of new-onset psychiatric and autoimmune diseases during the first 12-month follow-up was analyzed among patients who did not have any comorbidities of interest at baseline and was reported as a percentage of patients. The risk of developing a psychiatric or autoimmune disease during the total available follow-up period, reported as adjusted hazard ratios (AHRs) and 95% CIs, was also determined.
Statistical Analysis
Patients diagnosed with AA were matched with the control group 1:4 based on sex, age, and geographic region. Prevalence in the prematched populations was calculated by dividing the total number of patients who had a confirmed diagnosis of a psychiatric or autoimmune disease by the total number of patients included in the study for each group. Incidence of these comorbidities in the matched populations was calculated by dividing the number of new diagnoses of conditions by the total number of eligible cohort patients. Fisher exact tests or χ2 tests were used to assess statistical significance of prevalence and incidence of psychiatric and autoimmune comorbidities. The risks of developing psychiatric and autoimmune comorbidities, reported as AHRs and 95% CIs, were estimated by Cox proportional hazards regressions, controlling for age, sex, geographic region, obesity, and Charlson Comorbidity Index. A 2-sided P < .05 was considered statistically significant.
Results
Prevalence
At baseline, 63 384 patients with AA (62.4% female and 37.6% male), and 3 309 107 non-AA control patients (52.1% female and 47.9% male) were identified (eTable 2 in Supplement 1). The mean (SD) age at index in the AA and control groups was 39.3 (14.0) years and 39.8 (15.3) years, respectively. For any psychiatric disease, the overall prevalence was 30.9% in patients with AA compared with 26.8% in the control group (P < .001) (Table 1). Patients with AA vs the control group had significantly higher rates of anxiety (15.5% vs 12.3%), sleep disturbance (10.4% vs 8.9%), and depression (9.3% vs 7.6%) (P < .001). For any autoimmune or immune-mediated disease, the overall prevalence was 16.1% in patients with AA compared with 8.9% in the control group (P < .001). Patients with AA vs the control group had significantly higher rates of atopic dermatitis (5.1% vs 2.0%), psoriasis (2.4% vs 1.2%), and rheumatoid arthritis (2.3% vs 1.3%) (P < .001).
Table 1. Prevalence of Comorbidities Associated With Alopecia Areata (Before Matching).
| Comorbidity | Patients with alopecia areata, No. (%) (n = 63 384) | Controls, No. (%) (n = 3 309 107) | P valuea |
|---|---|---|---|
| Any psychiatric disease | 19 596 (30.9) | 885 835 (26.8) | <.001 |
| Anxiety | 9816 (15.5) | 406 384 (12.3) | <.001 |
| Sleep disturbance | 6619 (10.4) | 293 232 (8.9) | <.001 |
| Depression | 5896 (9.3) | 251 824 (7.6) | <.001 |
| Substance misuse or dependence | 3648 (5.8) | 19 6751 (5.9) | .046 |
| Adjustment disorder | 2838 (4.5) | 113 199 (3.4) | <.001 |
| Dysthymic disorder | 1852 (2.9) | 78 170 (2.4) | <.001 |
| Panic disorder | 979 (1.5) | 39 781 (1.2) | <.001 |
| Bipolar disorder | 942 (1.5) | 43 923 (1.3) | <.001 |
| Alcohol misuse or dependence | 861 (1.4) | 43 393 (1.3) | .31 |
| Suicidal ideation and attempts | 449 (0.7) | 23 894 (0.7) | .70 |
| Sexual dysfunction | 390 (0.6) | 21 165 (0.6) | .46 |
| Eating disorder | 253 (0.4) | 10 241 (0.3) | <.001 |
| Personality disorder | 169 (0.3) | 6916 (0.2) | .002 |
| Social phobia | 143 (0.2) | 7253 (0.2) | .76 |
| Schizophrenia | 136 (0.2) | 5464 (0.2) | .003 |
| Agoraphobia | 117 (0.2) | 5183 (0.2) | .09 |
| Any autoimmune or immune-mediated disease | 10 172 (16.0) | 292 995 (8.9) | <.001 |
| Atopic dermatitis | 3224 (5.1) | 65 451 (2.0) | <.001 |
| Psoriasis | 1550 (2.4) | 40 379 (1.2) | <.001 |
| Rheumatoid arthritis | 1434 (2.3) | 43 190 (1.3) | <.001 |
| Vitiligo | 908 (1.4) | 16 770 (0.5) | <.001 |
| Systemic lupus erythematosus | 858 (1.4) | 14 757 (0.4) | <.001 |
| Inflammatory bowel disease | 795 (1.3) | 29 443 (0.9) | <.001 |
| Type 1 diabetes | 774 (1.2) | 42 858 (1.3) | .11 |
| Ulcerative colitis | 497 (0.8) | 18 450 (0.6) | <.001 |
| Uveitis | 470 (0.7) | 15 943 (0.5) | <.001 |
| Crohn disease | 433 (0.7) | 15 052 (0.5) | <.001 |
| Graves disease | 394 (0.6) | 12 710 (0.4) | <.001 |
| Pernicious anemia | 350 (0.6) | 11 841 (0.4) | <.001 |
| Sjogren disease | 339 (0.5) | 7028 (0.2) | <.001 |
| Multiple sclerosis | 307 (0.5) | 10 977 (0.3) | <.001 |
| Celiac disease | 288 (0.5) | 8868 (0.3) | <.001 |
| Linear morphea | 243 (0.4) | 4497 (0.1) | <.001 |
| Scleroderma | 144 (0.2) | 3907 (0.1) | <.001 |
| Addison disease | 107 (0.2) | 3800 (0.1) | <.001 |
| Dermatomyositis | 80 (0.1) | 2884 (0.1) | .001 |
| Idiopathic thrombocytopenic purpura | 71 (0.1) | 2654 (0.1) | .007 |
| Myasthenia gravis | 62 (0.1) | 1936 (0.1) | <.001 |
| Rheumatic fever | 35 (0.1) | 970 (0.03) | <.001 |
| Guillain-Barré syndrome | 24 (0.04) | 804 (0.02) | .04 |
| Pemphigus vulgaris | 13 (0.02) | 299 (<0.01) | .006 |
χ2 Tests were used to obtain P values.
Incidence
After matching, there were 16 512 and 66 048 patients in the AA and control groups, respectively (Table 2). The overall mean (SD) age was 36.9 (13.4) years, 50.6% were female, and 49.4% were male. The mean (SD) Charlson Comorbidity Index score was 0.1 (0.5) for patients with AA and 0.1 (0.4) for the control group. Within the first 12 months after AA diagnosis, the overall incidence for any psychiatric disease was 10.2% for patients with AA and 6.8% for the control group (P < .001). Psychiatric diseases with the highest incidence for patients with AA compared with the control group were anxiety (4.0% vs 2.6%), sleep disturbance (2.6% vs 1.7%), and depression (1.9% vs 1.2%) (P < .001) (Table 3). Likewise, overall incidence for any autoimmune or immune-mediated disease within the first 12 months after AA diagnosis was 6.2% for patients with AA and 1.5% for the control group (P < .001). Autoimmune and immune-mediated disorders with the highest incidence for patients with AA vs the control group were atopic dermatitis (2.2% vs 0.3%), vitiligo (1.0% vs 0.1%), and psoriasis (0.9% vs 0.2%) (P < .001).
Table 2. Demographics of Incidence Analysis Cohort (After Matching)a.
| Characteristic | Patients with alopecia areata (n = 16 512) | Controls (n = 66 048) |
|---|---|---|
| Age at index date, y | ||
| Mean (SD) | 36.9 (13.4) | 36.9 (13.4) |
| Median (range) | 37 (12-64) | 37 (12-64) |
| Age group, y | ||
| 12-17 | 1514 (9.2) | 6056 (9.2) |
| 18-29 | 3635 (22.0) | 14 540 (22.0) |
| 30-39 | 4300 (26.0) | 17 200 (26.0) |
| 40-49 | 3638 (22.0) | 14 552 (22.0) |
| 50-64 | 3425 (20.7) | 13 700 (20.7) |
| Sex | ||
| Female | 8350 (50.6) | 33 400 (50.6) |
| Male | 8162 (49.4) | 32 648 (49.4) |
| Health care plan | ||
| Encounter | 2601 (15.8) | 9637 (14.6) |
| Fee for service | 13 911 (84.3) | 56 411 (85.4) |
| Charlson Comorbidity Index score | ||
| Mean (SD) | 0.1 (0.5) | 0.07 (0.4) |
| Median (range) | 0 (0-10) | 0 (0-10) |
| Region | ||
| Midwest | 3048 (18.5) | 12 192 (18.5) |
| Northeast | 3987 (24.1) | 15 948 (24.2) |
| South | 6204 (37.6) | 24 816 (37.6) |
| West | 3273 (19.8) | 13 092 (19.8) |
| Health care plan | ||
| CDHP | 1182 (7.4) | 4551 (7.2) |
| Comprehensive | 314 (2.0) | 1194 (1.9) |
| EPO | 292 (1.8) | 957 (1.5) |
| HDHP | 914 (5.7) | 3604 (5.7) |
| HMO | 2481 (15.4) | 9295 (14.6) |
| POS | 1546 (9.6) | 5596 (8.8) |
| POS with capitation | 128 (0.8) | 376 (0.6) |
| PPO | 9213 (57.3) | 38 085 (59.8) |
| Obesityb | 395 (2.4) | 1244 (1.9) |
Abbreviations: CDHP, consumer-directed health plan; EPO, exclusive provider organization; HDHP, high-deductible health plan; HMO, health maintenance organization; POS, point of service; PPO, preferred provider organization.
Data are presented as number (percentage) of participants unless otherwise indicated.
Including International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes E66.0x, E66.1, E66.2, E66.8, E66.9, Z68.3x, and Z68.4x.
Table 3. Incidence of Comorbidities Associated With Alopecia Areata for the 1-Year Follow-Up (After Matching).
| Comorbidity | Patients with alopecia areata, No. (%) (n = 16 512) | Controls, No. (%) (n = 66 048) | P valuea |
|---|---|---|---|
| Any psychiatric disease | 1679 (10.2) | 4503 (6.8) | <.001 |
| Anxiety | 668 (4.0) | 1749 (2.6) | <.001 |
| Sleep disturbance | 432 (2.6) | 1123 (1.7) | <.001 |
| Depression | 318 (1.9) | 816 (1.2) | <.001 |
| Substance misuse or dependence | 292 (1.8) | 940 (1.4) | .03 |
| Adjustment disorder | 157 (1.0) | 419 (0.6) | <.001 |
| Dysthymic disorder | 74 (0.5) | 212 (0.3) | .006 |
| Panic disorder | 50 (0.3) | 128 (0.2) | .04 |
| Bipolar | 29 (0.2) | 77 (0.1) | <.001 |
| Alcohol misuse or dependence | 60 (0.4) | 201 (0.3) | .06 |
| Suicidal ideation and attempts | 38 (0.2) | 92 (0.1) | .27 |
| Sexual dysfunction | 44 (0.3) | 53 (0.1) | .003 |
| Eating disorder | 40 (0.2) | 138 (0.2) | .46 |
| Personality disorder | 4 (0.02) | 10 (0.02) | .50b |
| Social phobia | 5 (0.03) | 12 (0.02) | .36b |
| Schizophrenia | 3 (0.02) | 16 (0.02) | .78b |
| Agoraphobia | 2 (0.02) | 14 (0.02) | .75b |
| Any autoimmune or immune-mediated disease | 1025 (6.2) | 962 (1.5) | <.001 |
| Atopic dermatitis | 358 (2.2) | 184 (0.3) | <.001 |
| Vitiligo | 159 (1.0) | 70 (0.1) | <.001 |
| Psoriasis | 155 (0.9) | 109 (0.2) | <.001 |
| Systemic lupus erythematosus | 97 (0.6) | 39 (0.1) | <.001 |
| Rheumatoid arthritis | 32 (0.2) | 63 (0.1) | .001 |
| Inflammatory bowel disease | 31 (0.2) | 73 (0.1) | .02 |
| Type 1 diabetes | 31 (0.2) | 119 (0.2) | .92 |
| Sjogren disease | 30 (0.2) | 6 (0.01) | <.001 |
| Celiac disease | 28 (0.2) | 42 (0.1) | <.001 |
| Graves disease | 26 (0.2) | 39 (0.1) | <.001 |
| Ulcerative colitis | 23 (0.1) | 49 (0.07) | .02 |
| Uveitis | 21 (0.1) | 70 (0.1) | .55 |
| Pernicious anemia | 18 (0.1) | 49 (0.1) | .21 |
| Linear morphea | 16 (0.1) | 19 (0.03) | <.001 |
| Addison disease | 11 (0.1) | 7 (0.01) | <.001 |
| Crohn disease | 10 (0.06) | 28 (0.04) | .44 |
| Multiple sclerosis | 7 (0.04) | 27 (0.04) | >.99 |
| Idiopathic thrombocytopenic purpura | 7 (0.04) | 13 (0.02) | .10 |
| Scleroderma | 6 (0.04) | 12 (0.02) | .23b |
| Myasthenia gravis | 5 (0.03) | 2 (<0.01) | .005b |
| Dermatomyositis | 1 (0.01) | 7 (0.01) | >.99b |
| Pemphigus vulgaris | 1 (0.01) | 1 (<0.01) | .36b |
| Guillain-Barré syndrome | 0 | 0 | NA |
| Rheumatic fever | 0 | 1 (<0.01) | NA |
Abbreviation: NA, not applicable.
χ2 Tests were used to obtain P values unless otherwise noted.
Fisher exact tests were used to obtain P values.
Patients with AA vs controls had a significantly higher risk of developing a psychiatric (AHR, 1.3; 95% CI, 1.3-1.4) or autoimmune comorbidity (AHR, 2.7; 95% CI, 2.5-2.8). Psychiatric disorders with the highest risk included adjustment disorder (AHR, 1.5; 95% CI, 1.3-1.6; P < .001), panic disorder (AHR, 1.4; 95% CI, 1.2-1.7; P < .001), and sexual dysfunction (95% CI, 1.4; 95% CI, 1.1-1.8; P = .003) (Figure, A). Autoimmune and immune-mediated disorders with the highest risk included systemic lupus erythematosus (AHR, 5.7; 95% CI, 4.6-7.2; P < .001), atopic dermatitis (AHR, 4.3; 95% CI, 3.9-4.8; P < .001), and vitiligo (AHR, 3.8; 95% CI, 3.2-4.4; P < .001) (Figure, B).
Figure. Adjusted Hazard Ratios (AHRs) for Development of Psychiatric or Autoimmune and Immune-Mediated Comorbidities in Patients With Alopecia Areata (AA) vs Controls.
Patients with AA had a significantly higher risk of developing psychiatric and autoimmune comorbidities compared with the control population.
aUnivariate analysis.
Discussion
This study found that patients who were diagnosed with AA were more likely to be diagnosed with a new-onset psychiatric or autoimmune disorder within the first year after AA diagnosis. This study builds on prior evaluations that demonstrated that patients with AA often have comorbid autoimmune, immune-mediated, and psychiatric disorders.9,18 Prior research has shown that compared with healthy controls, patients with AA had a significantly higher likelihood of having several comorbidities, including systemic lupus erythematosus, metabolic syndrome, and Hashimoto thyroiditis,8 as well as an increased likelihood of comorbid anxiety and depression.21 A systematic literature review12 of 37 studies examining patient perspectives reported consistently negative mental health outcomes in those with AA, including emotional distress, reduced social functioning, and increased stress. However, unlike those studies, which have demonstrated an association between AA and existing comorbidities, our analysis is one of the first studies, to our knowledge, to examine the risk of developing these comorbidities after AA diagnosis.
Despite the well-known associations with autoimmune and psychiatric disorders, the causes of these comorbidities in AA remain unknown.22 Stress, in addition to genetics and the microbiome, has been identified as a factor that exacerbates certain diseases by upregulating and activating inflammatory signaling cascades.23 A recent systematic review found that patients often reported stressful life events, such as emotional stress and neglect, occurring before their AA diagnosis.13 Furthermore, a previous study found that in patients with AA, there is a marked increase in proinflammatory signaling molecules, including interferon-γ, tumor necrosis factor α, and various interleukins, which were all elevated in the sera of patients with AA.24 Additionally, studies24,25,26 have shown that proinflammatory factors, such as apoptotic neuropeptide substance P, and inflammatory cortisol-releasing hormone receptors are increased locally in the affected areas in patients with AA. In line with these findings, a year-long observational study among patients with AA showed high rates of depression and anxiety among patients with AA.15 Although the association between the severity of AA and the severity of depression and anxiety did not reach statistical significance (likely due to small sample size), the findings highlight the potential synergistic nature of AA and depression.15
Therefore, it is perhaps unsurprising that AA has been consistently linked to high prevalences of psychiatric and autoimmune disorders and worse scores in health-related quality-of-life measures.8,12,13,15,21,27,28 Moreover, the high prevalence of comorbidities is also associated with a high economic burden. A previous study published in 2022 assessing patients in the US showed that those with vs without AA have nearly $2000 more in all-cause medical costs annually.29 The elevated cost is thought to be at least partially due to comorbidities associated with AA, including hyperlipidemia, hypertension, thyroid disorders, depression, and anxiety.30 Another study, published in 2023, reported that patients with AA who had at least 1 Charlson Comorbidity Index comorbidity, vs those who did not, had 104.4% higher medical costs.31
Overall, our study emphasizes the persistent unmet needs of patients with AA and the importance of studying the collective burden of AA and its comorbidities because their combination may have a worse impact than any one disease alone. Because AA and many of these comorbidities share underlying signaling pathways,18 it is not unreasonable to think effective and tolerable treatment could address multiple disorders—that is, AA and various comorbidities—simultaneously. Indeed, the Janus kinase inhibitor baricitinib is approved by the US Food and Drug Administration for treatment of AA and rheumatoid arthritis32 and by the European Medicines Agency for the treatment of atopic dermatitis and juvenile idiopathic arthritis. Additionally, there is some evidence of interplay between depressive and dermatologic disorders and that treating the latter with advanced therapies can likewise reduce the impact of the former.33
Longer-term studies are needed to determine the most effective treatment that can maximize patient health and minimize patient cost. Future studies should assess whether, for patients with AA who have psychological or autoimmune comorbidities, the use of a single therapy can treat both indications more cost-effectively than multiple therapies. Likewise, further research is needed to understand whether earlier and/or more aggressive treatment of AA may limit the development of comorbidities.
Strengths and Limitations
The strengths of this study include that it is, to our knowledge, the first study to determine new-onset psychiatric and autoimmune comorbidity incidence in patients with AA compared with a non-AA population. Likewise, this study analyzed data from a large, diverse population of patients with AA. The limitations of this study include that, as with all retrospective studies, causality cannot be inferred. Moreover, diagnosis of comorbidity states was based on diagnostic codes, and we did not have access to characteristics, such as laboratory values (eg, antibodies), that may have indicated underlying comorbidity before AA diagnosis but that did not result in official diagnosis of a comorbidity. Likewise, it is possible that, after an AA diagnosis, patients may be more closely monitored compared with controls, which may also contribute to overestimated rates of new-onset comorbidity. Results may not be generalizable to those outside commercial health coverage. Lastly, because this study did not account for varying levels of disease severity, disease burden and risk of comorbidities associated with the disease may be underestimated.
Conclusions
This cohort study found that patients with AA have a higher incidence of several new-onset psychiatric and autoimmune comorbidities within the first year of diagnosis, which could further exacerbate the disease burden and reduce quality of life of those affected. Routine monitoring of patients with AA, especially those at risk of developing comorbidities, may permit earlier and more effective intervention.
eFigure. Study Design
eTable 1. Diagnostic Codes for Exclusion (Incidence Analysis Only)
eTable 2. Demographics of Prevalence Analysis Cohort (Unmatched)
Data Sharing Statement
References
- 1.Darwin E, Hirt PA, Fertig R, Doliner B, Delcanto G, Jimenez JJ. Alopecia areata: review of epidemiology, clinical features, pathogenesis, and new treatment options. Int J Trichology. 2018;10(2):51-60. doi: 10.4103/ijt.ijt_99_17 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Sibbald C. Alopecia areata: an updated review for 2023. J Cutan Med Surg. 2023;27(3):241-259. doi: 10.1177/12034754231168839 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Benigno M, Anastassopoulos KP, Mostaghimi A, et al. A large cross-sectional survey study of the prevalence of alopecia areata in the United States. Clin Cosmet Investig Dermatol. 2020;13:259-266. doi: 10.2147/CCID.S245649 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Pratt CH, King LE Jr, Messenger AG, Christiano AM, Sundberg JP. Alopecia areata. Nat Rev Dis Primers. 2017;3:17011. doi: 10.1038/nrdp.2017.11 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Ito T, Tokura Y. The role of cytokines and chemokines in the T-cell-mediated autoimmune process in alopecia areata. Exp Dermatol. 2014;23(11):787-791. doi: 10.1111/exd.12489 [DOI] [PubMed] [Google Scholar]
- 6.King B, Ohyama M, Kwon O, et al. ; BRAVE-AA Investigators . Two phase 3 trials of baricitinib for alopecia areata. N Engl J Med. 2022;386(18):1687-1699. doi: 10.1056/NEJMoa2110343 [DOI] [PubMed] [Google Scholar]
- 7.Banerjee S, Biehl A, Gadina M, Hasni S, Schwartz DM. JAK-STAT signaling as a target for inflammatory and autoimmune diseases: current and future prospects. Drugs. 2017;77(5):521-546. doi: 10.1007/s40265-017-0701-9 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Ly S, Manjaly P, Kamal K, et al. Comorbid conditions associated with alopecia areata: a systematic review and meta-analysis. Am J Clin Dermatol. 2023;24(6):875-893. doi: 10.1007/s40257-023-00805-4 [DOI] [PubMed] [Google Scholar]
- 9.Huang KP, Mullangi S, Guo Y, Qureshi AA. Autoimmune, atopic, and mental health comorbid conditions associated with alopecia areata in the United States. JAMA Dermatol. 2013;149(7):789-794. doi: 10.1001/jamadermatol.2013.3049 [DOI] [PubMed] [Google Scholar]
- 10.Hunt N, McHale S. The psychological impact of alopecia. BMJ. 2005;331(7522):951-953. doi: 10.1136/bmj.331.7522.951 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Drake L, Li SJ, Reyes-Hadsall S, Lee K, Huang K, Mostaghimi A. Post-traumatic stress disorder in patients with alopecia areata: a survey study in the USA. Skin Appendage Disord. 2023;9(5):342-345. doi: 10.1159/000530356 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Mostaghimi A, Napatalung L, Sikirica V, et al. Patient perspectives of the social, emotional and functional impact of alopecia areata: a systematic literature review. Dermatol Ther (Heidelb). 2021;11(3):867-883. doi: 10.1007/s13555-021-00512-0 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Toussi A, Barton VR, Le ST, Agbai ON, Kiuru M. Psychosocial and psychiatric comorbidities and health-related quality of life in alopecia areata: a systematic review. J Am Acad Dermatol. 2021;85(1):162-175. doi: 10.1016/j.jaad.2020.06.047 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Villasante Fricke AC, Miteva M. Epidemiology and burden of alopecia areata: a systematic review. Clin Cosmet Investig Dermatol. 2015;8:397-403. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Marahatta S, Agrawal S, Adhikari BR. Psychological impact of alopecia areata. Dermatol Res Pract. 2020;2020:8879343. doi: 10.1155/2020/8879343 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Sellami R, Masmoudi J, Ouali U, et al. The relationship between alopecia areata and alexithymia, anxiety and depression: a case-control study. Indian J Dermatol. 2014;59(4):421. doi: 10.4103/0019-5154.135525 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Shi Q, Duvic M, Osei JS, et al. Health-related quality of life (HRQoL) in alopecia areata patients—a secondary analysis of the National Alopecia Areata Registry Data. J Investig Dermatol Symp Proc. 2013;16(1):S49-S50. doi: 10.1038/jidsymp.2013.18 [DOI] [PubMed] [Google Scholar]
- 18.Islam N, Leung PS, Huntley AC, Gershwin ME. The autoimmune basis of alopecia areata: a comprehensive review. Autoimmun Rev. 2015;14(2):81-89. doi: 10.1016/j.autrev.2014.10.014 [DOI] [PubMed] [Google Scholar]
- 19.Lee S, Lee H, Lee CH, Lee WS. Comorbidities in alopecia areata: a systematic review and meta-analysis. J Am Acad Dermatol. 2019;80(2):466-477.e16. doi: 10.1016/j.jaad.2018.07.013 [DOI] [PubMed] [Google Scholar]
- 20.Lavian J, Li SJ, Lee EY, et al. Validation of case identification for alopecia areata using International Classification of Diseases coding. Int J Trichology. 2020;12(5):234-237. doi: 10.4103/ijt.ijt_67_20 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Okhovat JP, Marks DH, Manatis-Lornell A, Hagigeorges D, Locascio JJ, Senna MM. Association between alopecia areata, anxiety, and depression: a systematic review and meta-analysis. J Am Acad Dermatol. 2023;88(5):1040-1050. doi: 10.1016/j.jaad.2019.05.086 [DOI] [PubMed] [Google Scholar]
- 22.Euesden J, Danese A, Lewis CM, Maughan B. A bidirectional relationship between depression and the autoimmune disorders: new perspectives from the National Child Development Study. PLoS One. 2017;12(3):e0173015. doi: 10.1371/journal.pone.0173015 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Jeppesen R, Benros ME. Autoimmune diseases and psychotic disorders. Front Psychiatry. 2019;10:131. doi: 10.3389/fpsyt.2019.00131 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Teraki Y, Imanishi K, Shiohara T. Cytokines in alopecia areata: contrasting cytokine profiles in localized form and extensive form (alopecia universalis). Acta Derm Venereol. 1996;76(6):421-423. doi: 10.2340/0001555576421423 [DOI] [PubMed] [Google Scholar]
- 25.Ahn D, Kim H, Lee B, Hahm DH. Psychological stress-induced pathogenesis of alopecia areata: autoimmune and apoptotic pathways. Int J Mol Sci. 2023;24(14):11711. doi: 10.3390/ijms241411711 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Simakou T, Butcher JP, Reid S, Henriquez FL. Alopecia areata: a multifactorial autoimmune condition. J Autoimmun. 2019;98:74-85. doi: 10.1016/j.jaut.2018.12.001 [DOI] [PubMed] [Google Scholar]
- 27.Hirani R, Grunfeld M, Khan U, Marmon S. Addressing the psychosocial burden of alopecia areata in clinical practice. JAAD Int. 2022;10:84-85. doi: 10.1016/j.jdin.2022.12.003 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Chu SY, Chen YJ, Tseng WC, et al. Psychiatric comorbidities in patients with alopecia areata in Taiwan: a case-control study. Br J Dermatol. 2012;166(3):525-531. doi: 10.1111/j.1365-2133.2011.10714.x [DOI] [PubMed] [Google Scholar]
- 29.Mostaghimi A, Xenakis J, Meche A, Smith TW, Gruben D, Sikirica V. Economic burden and healthcare resource use of alopecia areata in an insured population in the USA. Dermatol Ther (Heidelb). 2022;12(4):1027-1040. doi: 10.1007/s13555-022-00710-4 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Senna M, Ko J, Tosti A, et al. Alopecia areata treatment patterns, healthcare resource utilization, and comorbidities in the US population using insurance claims. Adv Ther. 2021;38(9):4646-4658. doi: 10.1007/s12325-021-01845-0 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Gao W, Mostaghimi A, Gandhi K, et al. Patient characteristics associated with all-cause healthcare costs of alopecia areata in the United States. J Med Econ. 2023;26(1):441-444. doi: 10.1080/13696998.2023.2188843 [DOI] [PubMed] [Google Scholar]
- 32.Eli Lily and Company. OLUMIANT Prescribing Information. Updated June 2022. Accessed June 12, 2024. https://uspl.lilly.com/olumiant/olumiant.html#pi
- 33.Mar K, Rivers JK. The mind body connection in dermatologic conditions: a literature review. J Cutan Med Surg. 2023;27(6):628-640. doi: 10.1177/12034754231204295 [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
eFigure. Study Design
eTable 1. Diagnostic Codes for Exclusion (Incidence Analysis Only)
eTable 2. Demographics of Prevalence Analysis Cohort (Unmatched)
Data Sharing Statement