Atopic dermatitis (AD) is an inflammatory dermatosis with a pathogenesis believed to be due to a combination of genetic, immunologic and environmental factors that affects up to 5% of adults and 20% of children worldwide. 1,2 Common genetic factors include polymorphisms in the filaggrin structural protein, interleukin (IL)-4 receptor and vitamin D receptor. [3][4][5] AD is driven by multiple immune pathways, most commonly with activation of Th2 and Th22 T-cell subsets. 6 Crosstalk between commensals and the host immune system modulates adaptive and innate immune responses in AD. 7 Staphylococcus aureus (SA) in AD lesions and surrounding normal skin was first noted by Leyden et al. in the 1970s; since then, the understanding of its role in AD has drastically evolved. 8,9 SA is a well-established exacerbator of AD; it is frequently isolated from the skin of AD patients and increased SA density is found during flares. 10 A meta-analysis in 2016 reported a pooled prevalence of SA colonization among AD patients of 70% in lesional skin, 39% in non-lesional skin and 62% in the nose. 11 More recently, Kong et al 12 found that AD treatments and flares were closely associated with shifts in the cutaneous microbial diversity. While current evidence has established that SA proliferates during flares and plays a role in the cycle of epidermal breakdown and inflammation, a true causal relationship has not been established. Herein, we will summarize the
Acute stress is a physiological response of an organism to adverse conditions, contributing to survival; however, persistence through time may lead to disease. Indeed, exacerbation of inflammatory conditions such as psoriasis has been reported to follow stressors in susceptible patients. Because chronic stress cannot ethically be elicited in patients under controlled laboratory conditions, we studied genetically modified mice that naturally develop psoriasiform dermatitis, and subjected them to an ethological chronic social contact stress paradigm. Although we found elevated pro-inflammatory neuropeptide production of substance P (SP), calcitonin-gene-related peptide (CGRP) and nerve-growth factor (NGF) mRNA in the dorsal root ganglia (DRG) as well as pro-inflammatory cytokines in response to the social stressor, stress paradoxically prevented the development of the skin lesions. This effect of stress could be reversed by the treatment with glucocorticoid (GC) receptor blockers, suggesting that it was mediated through the upregulation of corticosterone secretion. Extrapolating to humans, the worsening of disease in susceptible patients with psoriasis could be attributed to a defect in the Hypothalamic-Pituitary-Adrenal (HPA) axis with an impaired production of GC during situations of adversity, thus rendering them unable to counteract the pro-inflammatory effects of chronic stressors.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.