Abstract
Our study investigated the association between atopic dermatitis (AD) and inflammatory bowel disease using the All of Us Research Program, a US National Institutes of Health database providing health information on over 300 000 Americans. This cross-sectional study demonstrated that individuals with AD have an approximately twofold increase in odds of having inflammatory bowel disease, Crohn disease and ulcerative colitis, compared with individuals without AD.
Dear Editor, Atopic dermatitis (AD) is a chronic inflammatory skin disease classically associated with asthma and allergies, but association with other immune-mediated diseases, including rheumatoid arthritis and vitiligo, has also been documented.1 While multiple studies have suggested an association between AD and inflammatory bowel disease (IBD), the relationship between AD and IBD is not well characterized.2 Our study investigated the association between AD and IBD using the All of Us Research Program (AoURP), a US National Institutes of Health (NIH) database providing health information on over 300 000 Americans.
We conducted a cross-sectional analysis of the AoURP, including US adults aged 18 years and older, from 2018 to the present. The AoURP aims to recruit a diverse cohort of over 1 million individuals from over 340 sites across the USA, with an emphasis on demographic populations historically underrepresented in biomedical research.3 The database contains information from electronic health records (EHR), health questionnaires, digital health technology and biospecimens. The study was approved by the NIH All of Us institutional review board, and all participants provided written informed consent during study enrolment. All of Us data and biospecimens are deidentified prior to being shared with researchers. This study was deemed not to be human participant research by the Yale University Institutional Review Board.
To identify participants with AD, we utilized the Systematized Nomenclature of Medicine (SNOMED) diagnostic code 43116000 and/or International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) code L20. Crohn disease (CD) and ulcerative colitis (UC) were identified using the following SNOMED and/or ICD-10-CM codes, respectively: 34000006/K50 and 64766004/K51. To compare participants with AD against those without AD, we used χ2-tests for categorical variables and unpaired t-tests for continuous variables. We used multivariable logistic regression to calculate adjusted odds ratios (aORs) and establish whether AD is associated with IBD, CD and UC, adjusting for age, sex, race/ethnicity, smoking status, immune-mediated diseases (rheumatoid arthritis, type 1 diabetes mellitus, coeliac disease, primary sclerosing cholangitis, sarcoidosis, asthma and ankylosing spondylitis) independently associated with IBD,4 and body mass index (BMI).5
Our analysis included a total of 296 440 participants, including 9471 with AD and 286 969 without AD (Table 1). Mean (SD) age was 55.5 (17.0) years, and 58.4% were women. Participants with AD vs. those without AD were significantly different in age (mean 59.5 years vs. 55.4 years), sex (65.2% vs. 58.2% female), race (55.7% vs. 49.0% White), BMI (mean 30.6 kg m–2 vs. 29.8 kg m–2) and immune-mediated diseases associated with IBD (40.5% vs. 15.6%) (all P < 0.001). Participants with AD vs. those without AD were more likely to have IBD overall (3.5% vs. 1.3%), CD (2.0% vs. 0.8%) and UC (2.1% vs. 0.7%) (all P < 0.001). Multivariable analysis showed that AD was significantly associated with IBD [aOR 1.97, 95% confidence interval (CI) 1.75–2.21; P < 0.001]. Additionally, AD was significantly associated with CD (aOR 1.91, 95% CI 1.64–2.22) and UC (aOR 2.02, 95% CI 1.74–2.35) individually (both P < 0.001) (Table 2).
Table 1.
Demographic and clinical characteristics of participants with atopic dermatitis (AD) vs. participants without AD
| Characteristic | Participants with AD (n = 9471) | Participants without AD (n = 286 969) | P-value |
|---|---|---|---|
| Age, years; mean (SD) | 59.5 (17.0) | 55.4 (17.0) | < 0.001 |
| Sex | < 0.001 | ||
| Female | 6178 (65.2) | 167 032 (58.2) | |
| Male | 3006 (31.7) | 109 826 (38.3) | |
| Other | 287 (3.0) | 10 111 (3.5) | |
| Race and ethnicity | < 0.001 | ||
| Asian | 337 (3.6) | 9008 (3.1) | |
| Black | 1768 (18.7) | 63 979 (22.3) | |
| Hispanic | 1468 (15.5) | 53 779 (18.7) | |
| White | 5275 (55.7) | 140 698 (49.0) | |
| Other race | 623 (6.6) | 19 505 (6.8) | |
| Ever smoker | 0.18 | ||
| No | 5773 (61.0) | 172 927 (60.3) | |
| Yes | 3698 (39.0) | 114 042 (39.7) | |
| BMI, kg m–2; mean (SD) | 30.6 (7.8) | 29.8 (7.6) | < 0.001 |
| IBD | 335 (3.5) | 3781 (1.3) | < 0.001 |
| Crohn disease | 194 (2.0) | 2267 (0.8) | < 0.001 |
| Ulcerative colitis | 202 (2.1) | 2131 (0.7) | < 0.001 |
| Immune-mediated diseasesa | 3837 (40.5) | 44 656 (15.6) | < 0.001 |
All values are presented as n (%) unless otherwise indicated. BMI, body mass index; IBD, inflammatory bowel disease. aImmune-mediated diseases include rheumatoid arthritis, type 1 diabetes mellitus, coeliac disease, primary sclerosing cholangitis, sarcoidosis, asthma and ankylosing spondylitis. P-values in bold are statistically significant at P < 0.05.
Table 2.
Association of atopic dermatitis with inflammatory bowel disease (IBD), Crohn disease and ulcerative colitis
| Univariable analysis, odds ratio (95% CI) |
P-value | Multivariable analysisa,odds ratio (95% CI) | P-value | |
|---|---|---|---|---|
| IBD | 2.75 (2.45–3.08) | < 0.001 | 1.97 (1.75–2.21) | < 0.001 |
| Crohn disease | 2.91 (2.52–3.37) | < 0.001 | 1.91 (1.64–2.22) | < 0.001 |
| Ulcerative colitis | 2.63 (2.26–3.05) | < 0.001 | 2.02 (1.74–2.35) | < 0.001 |
CI, confidence interval. aMultivariable model adjusted for age, sex, race/ethnicity, smoking status, immune-mediated diseases (rheumatoid arthritis, type 1 diabetes mellitus, coeliac disease, primary sclerosing cholangitis, sarcoidosis, asthma and ankylosing spondylitis) and body mass index. P-values in bold are statistically significant at P < 0.05.
This cross-sectional study demonstrated that individuals with AD, compared with individuals without AD, have an approximately twofold increase in odds of having IBD, CD and UC. Our results corroborate previous literature suggesting an association between AD and IBD, including a two-sample bidirectional Mendelian randomization study that demonstrated a causal effect between AD and IBD.2,6
Our study provides further evidence of the association between AD and IBD, and our results suggest that screening for IBD in patients with AD who develop gastrointestinal symptoms may improve clinical outcomes by facilitating early diagnosis and appropriate management. Limitations include use of EHR codes to select diagnoses, lack of data on severity of disease and the cross-sectional nature of the study, which limits ability to examine the temporal relationship between diagnoses. Furthermore, data from the All of Us cohort may not be representative of the US population. Strengths of our study include the large, diverse cohort including participants historically underrepresented in research and the adjustment for immune-mediated comorbidities, which could otherwise confound the association between AD and IBD.
The association between AD and IBD may be attributed to potential shared pathogenesis pathways. Both diseases involve barrier dysfunction, which may facilitate passage of pathogens with consequent inflammation, as well as failure to maintain homeostasis with microbiota.2 Additionally, many genes (IL1RL1, IL18R1, IL18RAP, ADAD1, BLTP1, LRRC32, STAT3, RTEL1, ZGPAT, SLC9A4, IL13, EMSY, TNFRSF6B and IL2/IL21) have been implicated in both AD and IBD, and certain environmental factors, such as stress and urban living, may confer risk of both diseases.2 Additional research is needed to further elucidate overlapping pathophysiological mechanisms between AD and IBD, and knowledge of this relationship may help optimize care of patients with AD.
Acknowledgements
The All of Us Research Program is supported by the National Institutes of Health, Office of the Director: Regional Medical Centers: 1 OT2 OD026549; 1 OT2 OD026554; 1 OT2 OD026557; 1 OT2 OD026556; 1 OT2 OD026550; 1 OT2 OD 026552; 1 OT2 OD026553; 1 OT2 OD026548; 1 OT2 OD026551; 1 OT2 OD026555; IAA #: AOD 16037; Federally Qualified Health Centers: HHSN 263201600085U; Data and Research Center: 5 U2C OD023196; Biobank: 1 U24 OD023121; The Participant Center: U24 OD023176; Participant Technology Systems Center: 1 U24 OD023163; Communications and Engagement: 3 OT2 OD023205; 3 OT2 OD023206; and Community Partners: 1 OT2 OD025277; 3 OT2 OD025315; 1 OT2 OD025337; 1 OT2 OD025276. In addition, the All of Us Research Program would not be possible without the partnership of its participants.
Contributor Information
Marina Z Joel, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
William Damsky, Departments of Dermatology; Pathology.
Jeffrey M Cohen, Departments of Dermatology; Biomedical Informatics & Data Science, Yale School of Medicine, New Haven, CT, USA.
Mitchel Wride, Yale School of Medicine, New Haven, CT, USA.
Funding sources
M.Z.J. is funded by the Kelly Gene Cook Sr. Charitable Foundation. W.D. has been provided research support from AbbVie, Advanced Cell Diagnostics/Bio-Techne Bristol Myers Squibb, Incyte and Pfizer.
Data availability
The data underlying this article will be shared on reasonable request to the corresponding author.
Ethics statement
This study has been deemed by the Yale University Institutional Review Board not to be human participants research.
References
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Associated Data
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Data Availability Statement
The data underlying this article will be shared on reasonable request to the corresponding author.