Antibiotic exposures could lead to overestimation of incident outcomes—a commentary on “Prevalence of type 2 inflammatory diseases in pediatric patients with atopic dermatitis: real-world evidence”
Authors: Shuo-Yan Gau
Journal: Journal of the American Academy of Dermatology (2021)

To the Editor: In the present retrospective cohort study, Paller et al1Paller A.S. Mina-Osorio P. Vekeman F. et al.Prevalence of type 2 inflammatory diseases in pediatric patients with atopic dermatitis: real-world evidence.J Am Acad Dermatol. 2021; https://doi.org/10.1016/j.jaad.2021.10.038Google Scholar reported a higher prevalence and increased future risk of patients with atopic dermatitis developing diseases involving type 2 inflammation, including asthma and rhinitis. Utilizing a robust claim database from the United States, the current study added real-world evidence regarding the association. In observational studies, the misinterpretation of results can occur due to confounders. Even though the authors had adjusted for many variables in this study, some residual confounders could have led to the overestimation or underestimation of results—for instance, the status of antibiotic exposure. Both prenatal and postnatal antibiotic exposure were considered to be critical risk factors for allergic disease in children.2Souza da Cunha S. Santorelli G. Pearce N. et al.Evidence for causal associations between prenatal and postnatal antibiotic exposure and asthma in children, England.Clin Exp Allergy. 2021; 51: 1438-1448https://doi.org/10.1111/cea.13999Google Scholar Exposure to antibiotics could affect the status of children's gut microbiomes, which could also lead to the destruction of the intestinal epithelial barrier. It was assumed that an imbalance of the gut microbiome and a damaged intestinal epithelium could pose a higher risk of the exacerbation of “allergic march,” leading to elevated immunoglobulin E-related allergic reactions and aeroallergen sensitization.3Maciag M.C. Phipatanakul W. Preventing the development of asthma: stopping the allergic march.Curr Opin Allergy Clin Immunol. 2019; 19: 161-168https://doi.org/10.1097/ACI.0000000000000501Google Scholar,4Chen I.L. Tsai M.K. Chung H.W. et al.The effects of antibiotic exposure on asthma in children with atopic dermatitis.Sci Rep. 2021; 11: 8526https://doi.org/10.1038/s41598-021-87981-7Google Scholar Moreover, according to several real-world evidences, antibiotic exposure was reported to have association with increasing risk of future allergic diseases, including asthma and allergic rhinitis.2Souza da Cunha S. Santorelli G. Pearce N. et al.Evidence for causal associations between prenatal and postnatal antibiotic exposure and asthma in children, England.Clin Exp Allergy. 2021; 51: 1438-1448https://doi.org/10.1111/cea.13999Google Scholar,4Chen I.L. Tsai M.K. Chung H.W. et al.The effects of antibiotic exposure on asthma in children with atopic dermatitis.Sci Rep. 2021; 11: 8526https://doi.org/10.1038/s41598-021-87981-7Google Scholar,5Yamamoto-Hanada K. Yang L. Narita M. Saito H. Ohya Y. Influence of antibiotic use in early childhood on asthma and allergic diseases at age 5.Ann Allergy Asthma Immunol. 2017; 119: 54-58https://doi.org/10.1016/j.anai.2017.05.013Google Scholar Given the potential use of antibiotics for infections in children, the issue could be a critical confounder influencing the result. However, since comedication records and maternal information in the baseline were not available in the current study, readers should be careful while interpreting the reported results. Issues regarding medical surveillance could also have influenced the results. People with atopic dermatitis could have a higher tendency to utilize medical resources. In this case, surveillance bias could have posed a threat for risk overestimation, as these patients would have had a higher tendency to be examined for related inflammatory diseases. I would like to recommend the authors include the record of medical utilization as an additional variable to manage the potential biases. Moreover, using a negative control outcome could also be a potential way to address the issue. None disclosed.