Age of onset defines two distinct profiles of atopic dermatitis in adults

Abstract

Background The incidence of adult‐onset atopic dermatitis (AOAD) is increasing. However, the unique characteristics of AOAD compared to pediatric‐onset AD persisting into adulthood (POAD) are underexplored, hampering the development of targeted‐therapeutics for this growing population. We thus assessed the profile of AOAD in skin and blood compared to that of POAD. Methods We collected skin biopsies and blood from adults with AOAD, POAD, and healthy controls (n = 15 in each group). Skin samples were analyzed by RNA sequencing, qRT‐PCR, and immunohistochemistry, and Olink Proseek multiplex assay was used to identify the serum proteomic profile. Results Compared to healthy controls, both AOAD and POAD showed cutaneous immune and barrier dysregulations with a shared Th2/Th22 hyperactivation. Overall, POAD showed greater inflammation in lesional skin, with more prominent expression of Th2/Th17/Th22 markers (CCL17/22, S100A8/9, IL‐36A, PI3/Elafin, DEFB4) in POAD compared to AOAD (p‐value < .05). In contrast, higher Th1‐(IFN‐γ, IL‐2, IL‐15, CCL5) upregulation and Th1‐skewing were seen in AOAD. The epidermal barrier was also more compromised in POAD, with greater epidermal hyperplasia and lower expression of markers related to terminal differentiation, lipids, and cell adhesion. In parallel with increased rates of cardiovascular comorbidities, AOAD demonstrated many more significantly dysregulated proteins in serum (n = 148) compared to POAD (n = 86), including pro‐inflammatory and cardiovascular‐risk markers. Th1‐related products showed significant correlations between their skin and blood expressions only in AOAD subjects. Conclusion Age‐of‐onset delineates two distinct endophenotypes in adult AD potentially suggesting the need for broader (beyond Th2) therapeutic targeting in AOAD.

OX40 in the Pathogenesis of Atopic Dermatitis—A New Therapeutic Target

“…Effector T cells also survive as memory T cells, which enable rapid recall effector responses when antigen is re-encountered and lead to the self-renewal of the long-lived memory T cell populations thought to be responsible for disease recurrence [ 40 , 42 ]. Compared with adult AD, pediatric AD is associated with reduced levels of Th1-driven inflammation [ 43 ] and increased levels of Th17- and Th22-driven inflammation [ 14 , 32 ], reflecting the higher incidence of impetiginized, weeping lesions [ 2 ].…”

The pathogenetic role of Th17 immune response in atopic dermatitis

“…Increased Th17 in infancy has also been demonstrated in proteomic blood analysis [23 ▪▪ ]. Facheris et al [24 ▪▪ ] build on these results, showing that pediatric-onset AD that persists into adulthood has significantly higher Th17-related upregulation compared with adult onset AD.…”

Adipokines in atopic dermatitis: the link between obesity and atopic dermatitis

“…According to the findings, there is a more consistent association between AD and obesity in younger children [ 12 ]. Meanwhile, early onset of AD and children with AD are correspondingly associated with stronger Th17-skewing [ 39 , 43 ]. It may be necessary to pay more attention to weight management to prevent AD in younger children.…”

“…Onset age may also influence T-cell differentiation. Adult-onset AD exhibits a more pronounced Th1-skewing, compared with the notable upregulation of Th17 response in pediatric-onset AD [ 39 – 42 ]. Children with AD exhibit similar or heightened levels of Th2 cytokines and overexpression of Th17-related markers, akin to adult patients with psoriasis [ 43 ].…”