JAK inhibitors increase sebum production in human sebocytes and facial skin of patients with atopic dermatitis: Implications for JAK inhibitor-induced acne
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Presented at: Society for Investigative Dermatology 2025
Date: 2025-05-07 00:00:00
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Summary: Abstract Body: Janus kinase inhibitor-associated acne (JAKne) is a treatment-emergent adverse event of JAK inhibitors (JAKi), typically mild to moderate and manageable with topical therapies, though its mechanism remains unclear. Dyslipidemia associated with both non-selective and JAK1-selective inhibitors suggests a potential link to lipid metabolism. This study investigated the effects of the JAK1-selective inhibitor upadacitinib on sebum production in atopic dermatitis (AD) patients and sebocytes to elucidate its role in JAKne. Among 26 AD patients treated with upadacitinib, 8 (30.8%) developed acne. The JAKne group showed significantly higher baseline sebum levels and a greater percent increase in sebum levels compared to the No JAKne group. In vitro, upadacitinib (1μM) significantly increased neutral lipid accumulation in SZ95 sebocytes, reversing IL-4/IL-13-induced lipogenesis suppression. Transcriptomic analysis showed upregulation of fatty acid metabolism-related genes (e.g., PPARγ coactivator-1, phospholipase A2) and downregulation of adipogenesis inhibitors (e.g., TGM2). Upadacitinib also counteracted IL-4/IL-13-induced pro-inflammatory gene expressions (e.g., IL-7 and CCL26) and lipogenesis-inhibiting gene expressions (e.g., ERK3/MAPK6, and CCAAT/enhancer-binding protein zeta). In conclusion, upadacitinib increases sebum production in AD patients, particularly those with high baseline sebum levels, implicating lipogenesis as a potential mechanism for JAKne development. These findings provide insight into JAKne pathogenesis and the role of lipid metabolism in JAKi-associated adverse events. Song-Ee Kim<sup>1, 2</sup>, Yumi Jang<sup>1, 2</sup>, Sang Eun Lee<sup>1, 2</sup> 1. Dermatology, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of). 2. Gangnam Severance Hospital, Seoul, Seoul, Korea (the Republic of). Epidermal Structure and Barrier Function