Sex Differences in Epidemiology, Mechanisms, and Management of Atopic Dermatitis

Sex differences in disease are of increasing importance. They depend primarily on the hormonal status, which can influence immune responses and metabolic pathways, as well as response to treatments. Sex differences have been described for both innate and adaptive immune cells, and sex hormones are important regulators of Th2 immunity. Atopic dermatitis (AD) is a common inflammatory skin disorder with a chronic and relapsing course. AD prevalence rates have increased over recent decades, especially in urbanized and industrialized regions. Approximately 5%–20% of children and 5%–8% of adults suffer from AD. AD is more prevalent in adolescent females and females of child-bearing age, who also suffer from more severe and persistent AD symptoms compared to males. Menstrual periods and pregnancy frequently lead to a worsening of AD symptoms. Indeed, estrogens potentiate, while androgens reduce Th2 immune response and increase T regulatory cell activity. Sex hormones also affect the skin barrier function. Monoclonal antibodies against Th2 cytokines are more effective in females. Major concerns about treatment arise in pregnant females and those planning a pregnancy. Only cyclosporine and azathioprine (off-label) are suggested in pregnancy when the benefits exceed the potential side effects, but they are both contraindicated during breastfeeding. Methotrexate and systemic corticosteroids are contraindicated during pregnancy and lactation. Some reports have described safe and effective use of dupilumab during pregnancy, but evidence remains limited; therefore, it is not recommended during pregnancy because of the scarce data on safety. There is no data about tralokinumab and lebrikizumab use during pregnancy, so their use is preventively avoided. Abrocitinib, baricitinib, and upadacitinib are contraindicated during pregnancy and breastfeeding, and some teratogenic effects have been described in animal models.