Rosacea is a common chronic inflammation of sebaceous gland-rich facial skin characterized by severe skin dryness, elevated pH, transepidermal water loss, and decreased hydration levels. Until now, there has been no thorough molecular analysis of permeability barrier alterations in the skin of patients with rosacea. Thus, we aimed to investigate the barrier alterations in papulopustular rosacea samples compared with healthy sebaceous gland-rich skin, using RNA sequencing analysis (n = 8). Pathway analyses by Cytoscape ClueGO revealed 15 significantly enriched pathways related to skin barrier formation. RT-PCR and immunohistochemistry were used to validate the pathway analyses. The results showed significant alterations in barrier components in papulopustular rosacea samples compared with sebaceous gland-rich skin, including the cornified envelope and intercellular lipid lamellae formation, desmosome and tight junction organizations, barrier alarmins, and antimicrobial peptides. Moreover, the barrier damage in papulopustular rosacea was unexpectedly similar to atopic dermatitis; this similarity was confirmed by immunofluorescent staining. In summary, besides the well-known dysregulation of immunological, vascular, and neurological functions, we demonstrated prominent permeability barrier alterations in papulopustular rosacea at the molecular level, which highlight the importance of barrier repair therapies for rosacea.

The immunological barrier of the healthy skin is considered to be unified on the whole body surface—however, recent indirect findings have challenged this dogma since microbial and chemical milieu (e.g., sebum, sweat, and pH) exhibit remarkable differences on topographically distinct skin areas. Therefore, in the present study, we performed whole transcriptomic and subsequent pathway analyses to assess differences between sebaceous gland rich (SGR) and sebaceous gland poor (SGP) regions. Here, we provide the first evidence that different skin regions exhibit a characteristic innate and adaptive immune and barrier milieu as we could detect significantly increased chemokine (CCL2, 3, 19, 20, 23, 24) and antimicrobial peptide (S100A7, A8, A9, lipocalin, β-defensin-2) expression, altered barrier (keratin 17, 79) functions, and a non-inflammatory Th17/IL-17 dominance in SGR skin compared to SGP. Regarding pro-inflammatory molecules (IL-1α, IL-6, IL-8, IL-33, TNF-α), similarly low levels were detected in both regions. Our data may explain the characteristic topographical localization of some immune-mediated and autoimmune skin disorders and we also propose that the term “healthy skin control sample,” widely used in experimental Dermatology, should only be accepted if researchers carefully specify the exact region of the healthy skin (along with the site of the diseased sample).

Background: Numerous generic, skin‐ and disease‐specific health‐related quality of life (HRQoL) measures are available for patients with hidradenitis suppurativa (HS). Yet, robust psychometric evidence is lacking in many aspects of these outcome measures.Objectives: We sought to determine convergent and known‐groups validity of multiple generic and skin‐specific HRQoL measures and to identify predictors of impaired HRQoL in patients with HS.Methods: Between 2017 and 2019, a multicentre cross‐sectional study was carried out involving 200 consecutive HS patients. HRQoL outcomes included the EQ‐5D‐5L, EQ visual analogue scale (EQ VAS), Skindex‐16, Dermatology Life Quality Index (DLQI) and DLQI‐Relevant (DLQI‐R). Disease severity was graded by HS‐Physician’s Global Assessment (HS‐PGA) scale and the Modified Sartorius scale (MSS).Results: Overall, 77%, 56%, 51%, 46% and 28% reported problems in the pain/discomfort, usual activities, anxiety/depression, mobility and self‐care dimensions of EQ‐5D‐5L. Mean ± SD EQ VAS, DLQI and DLQI‐R scores were 64.29 ± 22.68, 11.75 ± 8.11 and 12.19 ± 8.33, respectively. Skindex‐16 responses indicated that the emotional burden of HS (64.55 ± 29.28) far exceeded those of functioning (49.40 ± 34.70) and physical symptoms (46.74 ± 29.36). EQ‐5D‐5L, EQ VAS, DLQI, DLQI‐R and Skindex‐16 total scores had moderate or strong correlations with each other (range: |0.487| to |0.993|), weak or moderate correlations with HS‐PGA (|0.350| to |0.433|) and weak correlations with MSS (|0.324| to |0.389|). DLQI‐R slightly outperformed DLQI both in terms of convergent and known‐groups validity. Being female, lower education level, more severe disease and genital involvement were associated with worse HRQoL (P < 0.05).Conclusion: This study provides high‐quality evidence that among skin‐specific outcomes, the DLQI, DLQI‐R and Skindex‐16, and among generic instruments, the EQ‐5D‐5L are suitable to be used in HS patients. In future research, we recommend the use of existing well‐validated HRQoL tools instead of developing new measures for each study. The development of composite measures that combine physician‐ and patient‐reported outcomes is not supported by evidence in HS.[Correction added on 25 July 2020, after first online publication: in the Abstract section, the ± signs were missing and have been added to this version.]

Background: Hidradenitis suppurativa (HS) is a chronic, inflammatory disease of the apocrine gland‐rich (AGR) skin region. The initial steps of disease development are not fully understood, despite intense investigations into immune alterations in lesional HS skin.Objectives: We aimed to systematically investigate the inflammatory molecules involved in three stages of HS pathogenesis, including healthy AGR, non‐lesional HS and lesional HS skin, with the parallel application of multiple mRNA and protein‐based methods.Methods: Immune cell counts (T cells, dendritic cells, macrophages), Th1/Th17‐related molecules (IL‐12B, TBX21, IFNG, TNFA, IL‐17, IL10, IL‐23A, TGFB1, RORC, CCL20), keratinocyte‐related sensors (TLR2,4), mediators (S100A7, S100A8, S100A9, DEFB4B, LCN2, CAMP, CCL2) and pro‐inflammatory molecules (IL1B, IL6, TNFA, IL‐23A) were investigated in the three groups by RNASeq, RT‐qPCR, immunohistochemistry and immunofluorescence.Results: Epidermal changes were already detectable in non‐lesional HS skin; the epidermal occurrence of antimicrobial peptides (AMPs), IL‐1β, TNF‐α and IL‐23 was highly upregulated compared with healthy AGR skin. In lesional HS epidermis, TNF‐α and IL‐1β expression remained at high levels while AMPs and IL‐23 increased even more compared with non‐lesional skin. In the dermis of non‐lesional HS skin, signs of inflammation were barely detectable (vs. AGR), while in the lesional dermis, the number of inflammatory cells and Th1/Th17‐related mediators were significantly elevated.Conclusions: Our findings that non‐lesional HS epidermal keratinocytes produce not only AMPs and IL‐1β but also high levels of TNF‐α and IL‐23 confirm the driver role of keratinocytes in HS pathogenesis and highlight the possible role of keratinocytes in the transformation of non‐inflammatory Th17 cells (of healthy AGR skin) into inflammatory cells (of HS) via the production of these mediators. The fact that epidermal TNF‐α and IL‐23 appear also in non‐lesional HS seems to prove these cytokines as excellent therapeutic targets.