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Atopic dermatitis: researchers quantify risk of heavy traffic, question drug safety restrictions, and more

Novel Insights into Atopic Dermatitis

Symposium presented Sunday, February 26, 2023

Moderators

Peck Y. Ong, MD
Associate Professor, Clinical Pediatrics, USC Keck School of Medicine/Children's Hospital of Los Angeles

Katherine L. Tuttle, MD
Assistant Professor of Pediatrics and Medicine, University of Rochester

Presenters

Michael Z. Nevid, MD
Fellow, Pediatric Allergy and Immunology, National Jewish Health, Denver
Association of Atopic Dermatitis with Proximity to Major Roads

Alexandro Chu, BHSc
Medical Student, McMaster University
Cancer Risk With Topical Pimecrolimus and Tacrolimus For Atopic Dermatitis: Systematic Review and Bayesian Meta-Analysis

Summary:
The contribution of high-traffic roads to atopic dermatitis and the association of cancer with pimecrolimus and tacrolimus are featured among the studies presented in this session.


Are children who live close to a heavily traveled road more likely to develop atopic dermatitis (AD)? Does treatment of AD with topical calcineurin inhibitors (TCIs) carry a risk of cancer, as stated in product inserts? Speakers address these and other questions in this presentation of recent studies.

Inverse relationship between AD and distance from heavy traffic

“Children who live at least 1 km from a heavily traveled road or highway are 26.1% less likely to develop AD than those who live within 500 m,” reported Michael Z. Nevid, MD, who researched the question with colleagues at National Jewish Hospital in Denver. Dr. Nevid is a fellow in pediatric allergy and immunology there.

Working with a large pediatric practice, the researchers’ 13-year retrospective chart review identified patients with AD using a search of diagnostic codes and compared them to an age- and sex-matched control group of children without AD; each group had more than 7,000 subjects. Patient residential addresses were geocoded to coordinates and distance from a major road with an average annual daily traffic of more than 10,000 vehicles based on traffic data were obtained from the Colorado Department of Transportation.

“We found an 18.8% decrease in odds of AD for each factor 10 increase in distance from a road,” said Dr. Nevid. “There is an inverse relationship between distance from a heavy-travel road and risk of AD.”

Dr. Nevid suggested that future research assess the biologic mechanisms underpinning the inverse association between distance from major roads and AD risk. This could be done with skin tape samples or in vitro studies. He said that therapeutic options being considered include tapinarof, a cream that is approved for treatment of psoriasis.

Pimecrolimus and tacrolimus found to be safe for treatment of atopic dermatitis

AD affects millions of people worldwide and is managed effectively by topical treatments, including the TCIs pimecrolimus and tacrolimus. In 2005 and 2011, the US Food and Drug Administration released reports associating TCIs with theoretical cancer risk, resulting in Black Box warnings.

Alexandro Chu, BHSc, and his colleagues recently published a systematic review and meta-analysis designed to assess the credibility of the warnings associated with TCIs. Mr. Chu is a first-year medical student at McMaster University.

The researchers identified randomized controlled trials, including comparative and noncomparative nonrandomized studies, for a total of 121 studies that included 3.4 million patients who were followed for a mean of 11 months.

Results showed that the absolute risk of any cancer with TCI exposure did not differ from that of controls (absolute risk: 4.70 per 1,000 with TCI versus 4.56 per 1,000, which reflects moderate-certainty evidence); nor did it differ from the general US population (4.60 per 1,000). Findings were similar in infants, children, and adults.

Mr. Chu said that the findings support the safe use of TCIs in the management of patients with AD and further suggested that guidelines, product inserts and packaging, and continuing education programs for care providers be updated to reflect the higher certainty evidence. He noted that updated atopic dermatitis practice guidelines will be released soon by the American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma & Immunology Joint Task Force on Practice Parameters.

Additional studies presented in this session

  • Low non-lesional filaggrin mediates longitudinal Staphylococcus aureus skin colonization, leading to worse atopic dermatitis clinical outcomes in the MPAACH cohort, presented by Arya Dahal, MD/PhD candidate at the University of Cincinnati College of Medicine
  • Stratum corneum lipid biomarkers at two months of age predict future onset of atopic dermatitis, presented by Evgeny Berdyshev, PhD, professor at National Jewish Health, Denver
  • Crosstalk between aryl hydrocarbon receptor (AHR) pathway and IL-13 signaling in human keratinocytes and implications for atopic dermatitis, presented by Steven P. Proper, PhD, DO, assistant professor at Western Michigan University Homer Stryker School of Medicine

Selected references

Berdyshev E, Kim J, Kim BE, et al. Stratum corneum lipid and cytokine biomarkers at two months of age predict the future onset of atopic dermatitis. J Allergy Clin Immunol 2023; Feb 22:S0091-6749(23)00227-0. doi: 10.1016/j.jaci.2023.02.013

Dahal A, Chan W-C, Almasri, C, et al. Low non-lesional filaggrin mediates longitudinal Staphylococcus aureus skin colonization, leading to worse atopic dermatitis clinical outcomes in the MPAACH cohort. J Allergy Clin Immunol 2023 (February);151(2, supplement):AB192. Abstract. doi: 10.1016/j.jaci.2022.12.601

Devasenapathy N, Chu A, Wong M, et al. Cancer risk with topical calcineurin inhibitors, pimecrolimus and tacrolimus, for atopic dermatitis: a systematic review and meta-analysis. Lancet Child Adolesc Health 2023;7(1):13-25. doi: 10.1016/S2352-4642(22)00283-8

Nevid M, Hui J, Crooks J, et al. Association of atopic dermatitis with proximity to major roads. J Allergy Clin Immunol 2023 (February);151(2, supplement):AB193. Abstract. doi: 10.1016/j.jaci.2022.12.604

Proper S, Appiagyei A, Dwyer A, et al. Crosstalk between aryl hydrocarbon receptor (AHR) pathway and IL-13 signaling in human keratinocytes and implications for atopic dermatitis. J Allergy Clin Immunol 2023 (February):151(2, supplement):AB 192. Abstract. doi: 10.1016/j.jaci.2022.12.600

Disclosures

None of the faculty have relevant disclosures.

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