Association of atopic dermatitis with Graves’ disease and Hashimoto’s thyroiditis: A case-control study in the All of Us research program

To the Editor: Smith et al1Smith B. Collier M.R. Devjani S. Han G. Wu J.J. Association between atopic dermatitis and thyroid disease among U.S. adults in the 2001-2006 National Health and Nutrition Examination Survey.J Am Acad Dermatol. 2023; 88: 889-891https://doi.org/10.1016/j.jaad.2022.10.017Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar show atopic dermatitis (AD) to be significantly associated with thyroid dysfunction and suggest that this association may be due to shared autoimmune processes/cytokine dysregulation. However, their study is limited by the lack of specificity in the survey question used to interrogate thyroid disease. Indeed, "thyroid problem" may refer to a host of conditions precipitating both hypothyroid and hyperthyroid states. In order to suggest underlying immune dysregulation as a potential overlap between thyroid disease and AD, it is important to specifically analyze the prevalence of Graves' disease (GD) and Hashimoto's thyroiditis (HT) in AD patients. Here, we extend the work by Smith et al1Smith B. Collier M.R. Devjani S. Han G. Wu J.J. Association between atopic dermatitis and thyroid disease among U.S. adults in the 2001-2006 National Health and Nutrition Examination Survey.J Am Acad Dermatol. 2023; 88: 889-891https://doi.org/10.1016/j.jaad.2022.10.017Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar by performing such an analysis. We conducted a nested case-control study in the All of Us Research Program, a National Institutes of Health initiative to collect health data on a sample of over 1 million Americans that reflects the geographic, racial/ethnic, and socioeconomic diversity within the United States.2All of Us Research Program Investigators Denny J.C. Rutter J.L. et al.The "All of Us" Research Program.N Engl J Med. 2019; 381: 668-676https://doi.org/10.1056/NEJMsr1809937Crossref PubMed Scopus (646) Google Scholar We identified 13,756 patients with AD using International Classification of Diseases, 10th Revision Clinical Modification code L20 and the Systematized Nomenclature of Medicine code 43116000. Each case was matched to 4 age-, race/ethnicity-, and sex-matched controls. International Classification of Diseases, 10th Revision/Systematized Nomenclature of Medicine codes were used to query the presence of GD (E05/353295004) and HT (E06.3/21983002). Odds ratios were calculated at 95% CI using the chi square test or Fisher's exact test for categorical variables and the unpaired Student t test for continuous variables. Patients with AD, compared to controls, were more likely to have GD (0.2% vs 0.04%, P < .001) and HT (2% vs 0.5%, P < .001) (Table I). 48.9% of patients with HT received that diagnosis before the diagnosis of AD, 43% received the diagnosis after, and 8.1% received a diagnosis of HT at the same time as the AD diagnosis. 30% of patients with GD received that diagnosis before the diagnosis of AD, 63.3% received the diagnosis after, and 6.7% received a diagnosis of GD at the same time as the AD diagnosis. In multivariable logistic regression analysis adjusted for age, educational attainment, income, insurance type, number of primary care physician visits within the past 12 months (proxy for interaction with health care system), race, sex, and smoking, these associations persisted: GD (Odds ratio 4.55, 95% CI 2.28-9.10) and HT (Odds ratio 3.04, 95% CI 2.17-4.25) (Table II).Table IDemographic characteristics and thyroid disease in patients with atopic dermatitis versus controlsCharacteristicCases (N = 13,756)Controls (N = 55,024)P valueAge, mean (SD)47.2 (18.2)47.2 (18.2)1.00Female9229 (67.6)37,196 (67.6)1.00Race/Ethnicity1.00 Asian450 (3.3)450 (3.3) Black2325 (16.9)2325 (16.9) Hispanic1963 (14.3)1963 (14.3) White8311 (60.4)8311 (60.4) Other707 (5.1)707 (5.1)Graves' disease30 (0.2)21 (0.04)<.001Hashimoto's thyroiditis270 (2.0)264 (0.5)<.001Inflammatory bowel disease248 (1.8)880 (1.6).09Rheumatoid arthritis765 (5.6)957 (1.7)<.001SLE385 (2.8)1102 (2.0)<.001Type 1 diabetes711 (5.2)620 (1.1)<.001Vitiligo157 (1.1)88 (0.16)<.001SD, Standard deviation; SLE, systemic lupus erythematosus. Open table in a new tab Table IIAssociation of atopic dermatitis with thyroid disease in univariate and multivariate analysisDiseaseUnivariable OR (95% CI)P valueMultivariable OR (95% CI)∗OR adjusted for age, educational attainment, income, insurance type, number of primary care physician visits within the past 12 months, race, sex, and smoking.P valueGraves' disease5.72 (3.28-10.00)<.0014.55 (2.28-9.10)<.001Hashimoto's thyroiditis4.15 (3.50-4.93)<.0013.04 (2.17-4.25)<.001OR, Odds ratio.∗ OR adjusted for age, educational attainment, income, insurance type, number of primary care physician visits within the past 12 months, race, sex, and smoking. Open table in a new tab SD, Standard deviation; SLE, systemic lupus erythematosus. OR, Odds ratio. Our analysis clarifies the link between thyroid dysfunction and AD, showing specifically that GD and HT are associated with AD. This supports the hypothesis by Smith et al1Smith B. Collier M.R. Devjani S. Han G. Wu J.J. Association between atopic dermatitis and thyroid disease among U.S. adults in the 2001-2006 National Health and Nutrition Examination Survey.J Am Acad Dermatol. 2023; 88: 889-891https://doi.org/10.1016/j.jaad.2022.10.017Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar that immune dysregulation may explain the association between AD and thyroid disease. However, the precise nature of this shared immune dysregulation remains to be understood. Our study is limited by its retrospective nature and inability to stratify patients by AD severity. Nonetheless, it shows GD and HT to be important comorbidities in patients with AD. Future genome-wide association studies to identify potentially shared HLA loci, may further elucidate the link between AD and GD and HT. Additional studies to explore a possible link between AD treatment and GD/HT development, or vice versa, may also be valuable. None disclosed. Reply to "Association of atopic dermatitis with Graves' disease and Hashimoto's thyroiditis: A case-control study in the All of Us research program"Journal of the American Academy of DermatologyVol. 89Issue 4PreviewTo the Editor: We appreciate the interest and follow up to our article, "Association between atopic dermatitis and thyroid disease among U.S. adults in the 2001-2006 National Health and Nutrition Examination Survey,"1 by Joshi et al.2 Joshi et al2 discuss that our study1 is limited by the utilization of the National Health and Nutrition Examination Survey (NHANES) database. NHANES is a self-reported survey, which may limit the specificity and reliability of some diagnoses. To assess thyroid disease, participants in these NHANES survey years were asked "Has a doctor or other health professional ever told you that you had a thyroid problem?" As Joshi et al2 noted, this question does not specify the etiology of individuals' thyroid dysfunction. Full-Text PDF