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Chuang CC, Braham-Chaouche L, Thomas R, Mnif T. Epidemiology and Burden of Pediatric Atopic Dermatitis in China. Dermatol Ther (Heidelb) 2025; 15:1319-1329. [PMID: 40244548 PMCID: PMC12092880 DOI: 10.1007/s13555-025-01403-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 03/27/2025] [Indexed: 04/18/2025] Open
Abstract
INTRODUCTION We aimed to estimate the prevalence, severity, and burden of pediatric atopic dermatitis (AD) in China. METHODS EPI-CARE China was a cross-sectional online survey that assessed AD in the general pediatric populations (aged 0.5‒17 years) between 21 March 2021 and 5 April 2021 in China. Diagnosis of AD prevalence was based on both International Study of Asthma and Allergies in Childhood criteria and self-reported or parent-reported physician confirmation of ever having had AD. Severity (mild, moderate, and severe) in the preceding week was assessed by patient global assessment. Health-related quality of life (HRQoL) was assessed using established dermatology patient-reported outcomes tools (Infant Dermatitis Quality of Life and Children's Dermatology Life Quality Index). Outcomes included type 2 inflammatory comorbidities and itch, skin pain, and sleep disturbance in the previous 24 h (numeric rating scale [NRS]: 0-10 [no symptoms-worst symptoms]), stratified by age group (aged ≤ 5 years, 6-11 years, and 12-17 years). RESULTS In 7148 patients, AD prevalence was 3.2% (≤ 5 years, 3.8%; 6-11 years, 4.1%; 12-17 years, 1.7%). Of these, 59.1% (≤ 5 years, 66.1%; 6-11 years, 60.1%; 12-17 years, 39.4%), 38.8% (≤ 5 years, 33.9%; 6-11 years, 38.0%; 12-17 years, 53.1%), and 2.0% (≤ 5 years, 0.0%; 6-11 years, 1.9%; 12-17 years, 7.5%) had mild, moderate, and severe AD, respectively. Patients with moderate AD reported greater impacts on HRQoL than patients with mild AD (too few patients with severe AD provided HRQoL data for comparison). Overall, 90.5% patients reported ≥ 1 atopic comorbid condition. The mean (SD) itch, skin pain, and sleep disturbance NRS values were 5.9 (2.4), 5.6 (2.6), and 5.9 (2.3), respectively. CONCLUSIONS These results demonstrate that AD is associated with substantial patient burden in pediatric patients in China.
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Affiliation(s)
| | | | - Ryan Thomas
- Regeneron Pharmaceuticals Inc, New York, NY, USA
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Indolfi C, Grella C, Klain A, Dinardo G, Colosimo S, Piatto D, Nespoli C, Perrotta A, Miraglia del Giudice M. Biomarkers in Atopic Dermatitis in Children: A Comprehensive Review. Life (Basel) 2025; 15:375. [PMID: 40141720 PMCID: PMC11943560 DOI: 10.3390/life15030375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2025] [Revised: 02/25/2025] [Accepted: 02/26/2025] [Indexed: 03/28/2025] Open
Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disorder with significant implications for patient quality of life and a well-documented association with the atopic march. Recent advancements in biomarker research have unveiled critical insights into AD pathogenesis, diagnosis, prognosis, and therapeutic monitoring. This comprehensive review evaluates the utility of emerging biomarkers, including cytokines, chemokines, genetic markers, and microbiome-related components, in understanding the disease mechanisms and stratifying patient care. The role of minimally invasive diagnostic techniques, such as tape stripping and RNA monitoring, is highlighted, offering innovative approaches to pediatric populations. Furthermore, this review explores the biomarkers that predict disease progression, therapeutic response, and comorbidities, including food allergies and asthma. Personalized treatment strategies based on endotype-specific biomarkers are discussed as a future direction for improving clinical outcomes. Despite promising findings, the integration of biomarkers into routine practice necessitates further validation through large-scale studies. This work underscores the transformative potential of biomarker-driven approaches in enhancing the management of AD in children and its associated conditions.
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Affiliation(s)
| | | | - Angela Klain
- Department of Woman, Child and General and Specialized Surgery, University of Campania ‘Luigi Vanvitelli’, 80138 Naples, Italy; (C.I.); (C.G.); (S.C.); (D.P.); (C.N.); (A.P.); (M.M.d.G.)
| | - Giulio Dinardo
- Department of Woman, Child and General and Specialized Surgery, University of Campania ‘Luigi Vanvitelli’, 80138 Naples, Italy; (C.I.); (C.G.); (S.C.); (D.P.); (C.N.); (A.P.); (M.M.d.G.)
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Sabancı Ş, Küçükkeleş H, Çelmeli F, Yavuz S. Evaluation of Meibography Findings and Ocular Surface Parameters in Children with Atopic Dermatitis Without Eye Complaints. CHILDREN (BASEL, SWITZERLAND) 2025; 12:150. [PMID: 40003252 PMCID: PMC11854708 DOI: 10.3390/children12020150] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/07/2025] [Revised: 01/23/2025] [Accepted: 01/24/2025] [Indexed: 02/27/2025]
Abstract
BACKGROUND/OBJECTIVES To evaluate the meibomian gland (MG) morphology and ocular surface parameters of children with atopic dermatitis (AD) without ocular symptoms. MATERIALS AND METHOD Forty-five eyes of 24 children with AD and 44 eyes of 27 healthy children were included in the study. Upper and lower eyelid meibography measurements were performed for all cases and the rate of MG loss and the amount of tortuosity were evaluated. A Schirmer 1 test, tear break-up time (TBUT) test, and corneal staining scoring (CSS) were applied to all cases. RESULTS MG loss in the upper eyelid was 15.51 ± 10.39% in the AD group, while it was 9.30 ± 5.30% in the control group (p = 0.002). MG loss in the lower eyelid was 15.79 ± 10.93% in the AD group, while it was 9.23 ± 6.90% in the control group (p = 0.002). The rate of tortuosity in 26-50% of the upper and lower eyelid MGs was significantly higher in the AD group than in the healthy control group (p = 0.002 and p = 0.007, respectively). The Schirmer 1 test values were 10.98 ± 3.89 in the AD group and 17.41 ± 3.73 in the healthy control group (p < 0.0001). The TBUT values were found to be 9.18 ± 1.99 in the AD group and 11.40 ± 1.82 in the healthy control group (p < 0.0001). The CSS result was found to be significantly higher in the AD group than in the control group (p = 0.001). CONCLUSIONS Significant MG loss was detected in patients with AD without eye complaints, which may cause the early deterioration of ocular surface parameters. We believe that close follow-up examinations of children with AD in terms of ocular surface complications may be necessary.
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Affiliation(s)
- Şenol Sabancı
- Department of Ophthalmology, University of Health Science, Antalya Education and Research Hospital, 07100 Antalya, Turkey;
| | - Hediye Küçükkeleş
- Department of Pediatric Allergy and Immunology, University of Health Science, Antalya Education and Research Hospital, 07100 Antalya, Turkey; (H.K.); (F.Ç.)
| | - Fatih Çelmeli
- Department of Pediatric Allergy and Immunology, University of Health Science, Antalya Education and Research Hospital, 07100 Antalya, Turkey; (H.K.); (F.Ç.)
| | - Sibel Yavuz
- Department of Ophthalmology, University of Health Science, Antalya Education and Research Hospital, 07100 Antalya, Turkey;
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Paraskevopoulos G, Opálka L, Kováčik A, Paraskevopoulou A, Panoutsopoulou E, Sagrafena I, Pullmannová P, Čáp R, Vávrová K. Lysosphingolipids in ceramide-deficient skin lipid models. J Lipid Res 2025; 66:100722. [PMID: 39653083 PMCID: PMC11743119 DOI: 10.1016/j.jlr.2024.100722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Revised: 11/20/2024] [Accepted: 12/05/2024] [Indexed: 12/31/2024] Open
Abstract
Ceramides are key components of the skin's permeability barrier. In atopic dermatitis, pathological hydrolysis of ceramide precursors - glucosylceramides and sphingomyelin - into lysosphingolipids, specifically glucosylsphingosine (GS) and sphingosine-phosphorylcholine (SPC), and free fatty acids (FFAs) has been proposed to contribute to impaired skin barrier function. This study investigated whether replacing ceramides with lysosphingolipids and FFAs in skin lipid barrier models would exacerbate barrier dysfunction. When applied topically to human stratum corneum sheets, SPC and GS increased water loss, decreased electrical impedance, and slightly disordered lipid chains. In lipid models containing isolated human stratum corneum ceramides, reducing ceramides by ≥ 30% significantly increased permeability to four markers, likely due to loss of long-periodicity phase (LPP) lamellae and phase separation within the lipid matrix, as revealed by X-ray diffraction and infrared spectroscopy. However, when the missing ceramides were replaced by lysosphingolipids and FFAs, no further increase in permeability was observed. Conversely, these molecules partially mitigated the negative effects of ceramide deficiency, particularly with 5%-10% SPC, which reduced permeability even compared to control with "healthy" lipid composition. These findings suggest that while ceramide deficiency is a key factor in skin barrier dysfunction, the presence of lysosphingolipids and FFAs does not aggravate lipid structural or functional damage, but may provide partial compensation, raising further questions about the behavior of lyso(sphingo)lipids in rigid multilamellar lipid environments, such as the stratum corneum, that warrant further investigation.
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Affiliation(s)
- Georgios Paraskevopoulos
- Skin Barrier Research Group, Charles University, Faculty of Pharmacy in Hradec Králové, Hradec Králové, Czech Republic
| | - Lukáš Opálka
- Skin Barrier Research Group, Charles University, Faculty of Pharmacy in Hradec Králové, Hradec Králové, Czech Republic
| | - Andrej Kováčik
- Skin Barrier Research Group, Charles University, Faculty of Pharmacy in Hradec Králové, Hradec Králové, Czech Republic
| | - Anna Paraskevopoulou
- Skin Barrier Research Group, Charles University, Faculty of Pharmacy in Hradec Králové, Hradec Králové, Czech Republic
| | - Eleni Panoutsopoulou
- Skin Barrier Research Group, Charles University, Faculty of Pharmacy in Hradec Králové, Hradec Králové, Czech Republic
| | - Irene Sagrafena
- Skin Barrier Research Group, Charles University, Faculty of Pharmacy in Hradec Králové, Hradec Králové, Czech Republic
| | - Petra Pullmannová
- Skin Barrier Research Group, Charles University, Faculty of Pharmacy in Hradec Králové, Hradec Králové, Czech Republic
| | - Robert Čáp
- Plastic Surgery Clinic, Sanatorium Sanus, Hradec Králové, Czech Republic
| | - Kateřina Vávrová
- Skin Barrier Research Group, Charles University, Faculty of Pharmacy in Hradec Králové, Hradec Králové, Czech Republic.
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Elahi N, Astaneh ME, Ai J, Rizwan M. Atopic dermatitis treatment: A comprehensive review of conventional and novel bioengineered approaches. Int J Biol Macromol 2024; 282:137083. [PMID: 39515724 DOI: 10.1016/j.ijbiomac.2024.137083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Revised: 10/08/2024] [Accepted: 10/28/2024] [Indexed: 11/16/2024]
Abstract
Atopic dermatitis (AD) remains a challenging condition, with conventional treatments often leading to adverse effects and limited efficacy. This review explores the diverse landscape of AD treatments, encompassing conventional methods, novel topical and systemic therapies, and emerging bioengineered strategies. While conventional drug administration often requires high dosages or frequent administration, leading to adverse effects, targeted biologics have shown promise. Phototherapy and wet wrap therapy, while helpful, have limitations. Given these factors, the need for modern and effective therapeutic strategies for AD is pressing. Complementary or alternative therapies have garnered significant attention in recent years as a compelling treatment for AD. Among these, functionalized biomaterials and textiles with physicochemical, nanotechnology-based characteristics, or bioengineered features are some of the most common typical adjuvant therapies. The multifunctional-engineered biomaterials, as a new generation of biomedical materials, and stem cells, seem to hold tremendous promise for the treatment of dermatological diseases like AD. Biomaterials have seen great success, especially in various medical fields, due to their unique and adaptable characteristics. These materials, including collagen, PCL, and PLGA, offer unique advantages, such as biocompatibility, biodegradability, controlled drug release, and enhanced drug retention.
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Affiliation(s)
- Narges Elahi
- Student Research Committee, Fasa University of Medical Sciences, Fasa, Iran; Department of Tissue Engineering, School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran.
| | - Mohammad Ebrahim Astaneh
- Student Research Committee, Fasa University of Medical Sciences, Fasa, Iran; Department of Tissue Engineering, School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran; Department of Anatomical Sciences, School of Medicine, Fasa University of Medical Sciences, Fasa, Iran
| | - Jafar Ai
- Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Muhammad Rizwan
- Department of Biomedical Engineering, The University of Texas Southwestern Medical center, Dallas, TX, USA
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Criado PR, Miot HA, Bueno-Filho R, Ianhez M, Criado RFJ, de Castro CCS. Update on the pathogenesis of atopic dermatitis. An Bras Dermatol 2024; 99:895-915. [PMID: 39138034 PMCID: PMC11551276 DOI: 10.1016/j.abd.2024.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Accepted: 06/18/2024] [Indexed: 08/15/2024] Open
Abstract
Atopic dermatitis is a chronic, recurrent, and multifactorial skin-mucosal manifestation resulting from the interaction between elements mainly associated with the skin barrier deficit, the homeostasis of the immune response, neurological aspects, and patterns of reactivity to environmental antigens, which are established in genetically predisposed individuals. In addition to the skin, atopic diathesis involves other organs such as the airways (upper and lower), eyes, digestive tract, and neuropsychiatric aspects, which inflict additional morbidity on the dermatological patient. The different phenotypes of the disease fundamentally depend on the participation of each of these factors, in different life circumstances, such as age groups, occupational exposure patterns, physical activity, pollution, genetic load, and climatic factors. A better understanding of the complexity of its pathogenesis allows not only the understanding of therapeutic targets but also how to identify preponderant elements that mediate disease activity in each circumstance, for selecting the best treatment strategies and mitigation of triggering factors. This narrative review presents an update on the pathogenesis of atopic dermatitis, especially aimed at understanding the clinical manifestations, the main disease phenotypes and the context of available therapeutic strategies.
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Affiliation(s)
- Paulo Ricardo Criado
- Centro Universitário Faculdade de Medicina do ABC, Santo André, SP, Brazil; Faculdade de Ciências Médicas de Santos (Centro Universitário Lusíada), Santos, SP, Brazil.
| | - Hélio Amante Miot
- Department of Dermatology, Faculdade de Medicina de Botucatu, Universidade do Estado de São Paulo, Botucatu, SP, Brazil
| | - Roberto Bueno-Filho
- Division of Dermatology, Department of Internal Medicine, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
| | - Mayra Ianhez
- Department of Dermatology, Hospital de Doenças Tropicais de Goiás, Goiânia, GO, Brazil
| | - Roberta Fachini Jardim Criado
- Centro Universitário Faculdade de Medicina do ABC, Santo André, SP, Brazil; Alergoskin Alergia e Dermatologia, UCARE Center and ADCARE, Santo André, SP, Brazil
| | - Caio César Silva de Castro
- Pontifícia Universidade Católica do Paraná, Curitiba, PR, Brazil; Hospital de Dermatologia Sanitária do Paraná, Curitiba, PR, Brazil
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Pretel-Lara C, Sanabria-de la Torre R, Arias-Santiago S, Montero-Vilchez T. Skin Barrier Function and Microtopography in Patients with Atopic Dermatitis. J Clin Med 2024; 13:5861. [PMID: 39407921 PMCID: PMC11477937 DOI: 10.3390/jcm13195861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 09/23/2024] [Accepted: 09/27/2024] [Indexed: 10/20/2024] Open
Abstract
Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease whose incidence is increasing. Skin barrier dysfunction plays an important role in this disease. It has been observed that AD patients have higher transepidermal water loss (TEWL) and lower stratum corneum hydration (SCH); however, there is little information about skin microtopography in this pathology. The objective of this study is to evaluate skin barrier dysfunction and structural changes in patients with AD. Methods: A cross-sectional study was conducted including patients with AD. Parameters of skin barrier function were measured (TEWL, temperature, erythema, pH, skin hydration, elasticity) and also other topographical parameters (scaliness, wrinkles, smoothness, surface, contrast, variance) in both healthy skin and flexural eczematous lesions. Results: A total of 32 patients with AD were included in the study. Flexural eczematous lesions had higher erythema (369.12 arbitrary unit (AU) vs. 223.89 AU, p < 0.001), higher TEWL (27.24 g/h/m2 vs. 13.51 g/h/m2, p < 0.001), lower SCH (20.3 AU vs. 31.88 AU, p < 0.001) and lower elasticity (0.56% vs. 0.65%, p = 0.05). Regarding topographic parameters, flexural eczematous lesions presented greater scaliness (5.57 SEsc vs. 0.29 SEsc, p = 0.02), greater smoothness (316.98 SEsm vs. 220.95 SEsm p < 0.001), more wrinkles (73.33 SEw vs. 62.15 SEw p = 0.03), greater surface area (836.14% vs. 696.31%. p < 0.001), greater contrast (2.02 AU vs. 1.31 AU p = 0.01), greater variance (6.22 AU vs. 4.96 AU p < 0.001) and a lower number of cells (105.5 vs. 132.5 p < 0.001) compared to unaffected healthy skin, reflecting a decrease in skin quality in AD patients. Conclusions: Both skin barrier function and skin topography are damaged in patients with AD, with differences between healthy skin and flexural eczema.
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Affiliation(s)
- Carlota Pretel-Lara
- Dermatology Department, School of Medicine, University of Granada, 18016 Granada, Spain or (C.P.-L.); or (T.M.-V.)
| | - Raquel Sanabria-de la Torre
- Instituto de Investigación Biosanitaria ibs GRANADA, 18012 Granada, Spain;
- Dermatology Department, Virgen de las Nieves University Hospital, 18014 Granada, Spain
- Department of Biochemistry, Molecular Biology III and Immunology, University of Granada, 18071 Granada, Spain
| | - Salvador Arias-Santiago
- Dermatology Department, School of Medicine, University of Granada, 18016 Granada, Spain or (C.P.-L.); or (T.M.-V.)
- Instituto de Investigación Biosanitaria ibs GRANADA, 18012 Granada, Spain;
- Dermatology Department, Virgen de las Nieves University Hospital, 18014 Granada, Spain
| | - Trinidad Montero-Vilchez
- Dermatology Department, School of Medicine, University of Granada, 18016 Granada, Spain or (C.P.-L.); or (T.M.-V.)
- Instituto de Investigación Biosanitaria ibs GRANADA, 18012 Granada, Spain;
- Dermatology Department, Virgen de las Nieves University Hospital, 18014 Granada, Spain
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Özdemіr E, Öksüz L. Effect of Staphylococcus aureus colonization and immune defects on the pathogenesis of atopic dermatitis. Arch Microbiol 2024; 206:410. [PMID: 39302484 DOI: 10.1007/s00203-024-04134-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2024] [Revised: 08/26/2024] [Accepted: 09/07/2024] [Indexed: 09/22/2024]
Abstract
Atopic dermatitis (AD) is a common and recurrent skin disease characterized by skin barrier dysfunction, inflammation and chronic pruritus, with wide heterogeneity in terms of age of onset, clinical course and persistence over the lifespan. Although the pathogenesis of the disease are unclear, epidermal barrier dysfunction, immune and microbial dysregulation, and environmental factors are known to be critical etiologies in AD pathology. The skin microbiota represents an ecosystem consisting of numerous microbial species that interact with each other as well as host epithelial cells and immune cells. Although the skin microbiota benefits the host by supporting the basic functions of the skin and preventing the colonization of pathogens, disruption of the microbial balance (dysbiosis) can cause skin diseases such as AD. Although AD is a dermatological disease, recent evidence has shown that changes in microbiota composition in the skin and intestine contribute to the pathogenesis of AD. Environmental factors that contribute to skin barrier dysfunction and microbial dysbiosis in AD include allergens, diet, irritants, air pollution, epigenetics and microbial exposure. Knowing the microbial combination of intestin, as well as the genetic and epigenetic determinants associated with the development of autoantibodies, may help elucidate the pathophysiology of the disease. The skin of patients with AD is characterized by microbial dysbiosis as a result of reduced microbial diversity and overgrowth of the pathogens such as Staphylococcus aureus. Recent studies have revealed the importance of building a strong immune response against microorganisms during childhood and new mechanisms of microbial community dynamics in modulating the skin microbiome. Numerous microorganisms are reported to modulate host response through communication with keratinocytes, specific immune cells and adipocytes to improve skin health and barrier function. This growing insight into bioactive substances in the skin microbiota has led to novel biotherapeutic approaches targeting the skin surface for the treatment of AD. This review will provide an updated overview of the skin microbiota in AD and its complex interaction with immune response mechanisms, as well as explore possible underlying mechanisms in the pathogenesis of AD and provide insights into new therapeutic developments for the treatment of AD. It also focuses on restoring skin microbial homeostasis, aiming to reduce inflammation by repairing the skin barrier.
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Affiliation(s)
- Evrim Özdemіr
- Department of Medical Microbiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
- Institute of Graduate Studies in Health Sciences, Istanbul University, Istanbul, Turkey.
| | - Lütfiye Öksüz
- Department of Medical Microbiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
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Ng SP, Bielfeldt S, Laing S, Danby S, Cork MJJ. Effects of a pH-Regulating Emollient Cream in Mild Atopic Dermatitis Patients with Moderate Localized Lesions. Skin Pharmacol Physiol 2024; 37:49-58. [PMID: 39197436 PMCID: PMC11488831 DOI: 10.1159/000541022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Accepted: 08/18/2024] [Indexed: 09/01/2024]
Abstract
INTRODUCTION Increased skin pH values in patients with atopic dermatitis (AD) contribute to poor antimicrobial and permeability barrier functions of the skin. In practice, the majority of topical preparations available for dry skin conditions do not provide sufficient pH and buffering capacity for maintaining optimum skin surface conditions. To address this issue, we tested a novel zinc lactobionate preparation to determine whether the regular application would lower skin surface pH, and in doing so improve the condition of lesional skin. METHODS The assessment for local severity of AD was done with the Scoring Atopic Dermatitis Index (SCORAD) and skin dryness was assessed by capacitance measurement. RESULTS The results showed that the test product lowered skin pH and improved AD skin lesions from moderate to mild during 2 weeks of application. In the treated area a lowered pH of about 0.85 units was found. Together with the lowering of pH, the local SCORAD significantly improved from 8.3 on average down to 4.0, while in the untreated area, only a slight improvement (from 8.2 to 6.4) was found. CONCLUSION Synergistic effects of the test product's pH lowering and emollient properties might explain the observed improvements in clinical signs of AD and further research against a comparator would allow the specific contribution of pH modulation to these improvements to be unambiguously isolated.
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Affiliation(s)
- Sue Phay Ng
- Hyphens Pharma Pte Ltd, Singapore, Singapore
| | | | | | - Simon Danby
- Sheffield Dermatology Research, The University of Sheffield Medical School, Sheffield, UK
| | - Michael J John Cork
- Sheffield Dermatology Research, The University of Sheffield Medical School, Sheffield, UK
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Brown M, Williams A, Chilcott RP, Brady B, Lenn J, Evans C, Allen L, McAuley WJ, Beebeejaun M, Haslinger J, Beuttel C, Vieira R, Guidali F, Miranda M. Topically Applied Therapies for the Treatment of Skin Disease: Past, Present, and Future. Pharmacol Rev 2024; 76:689-790. [PMID: 38914467 DOI: 10.1124/pharmrev.123.000549] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Revised: 05/31/2024] [Accepted: 06/03/2024] [Indexed: 06/26/2024] Open
Abstract
The purpose of this review is to summarize essential biological, pharmaceutical, and clinical aspects in the field of topically applied medicines that may help scientists when trying to develop new topical medicines. After a brief history of topical drug delivery, a review of the structure and function of the skin and routes of drug absorption and their limitations is provided. The most prevalent diseases and current topical treatment approaches are then detailed, the organization of which reflects the key disease categories of autoimmune and inflammatory diseases, microbial infections, skin cancers, and genetic skin diseases. The complexity of topical product development through to large-scale manufacturing along with recommended risk mitigation approaches are then highlighted. As such topical treatments are applied externally, patient preferences along with the challenges they invoke are then described, and finally the future of this field of drug delivery is discussed, with an emphasis on areas that are more likely to yield significant improvements over the topical medicines in current use or would expand the range of medicines and diseases treatable by this route of administration. SIGNIFICANCE STATEMENT: This review of the key aspects of the skin and its associated diseases and current treatments along with the intricacies of topical formulation development should be helpful in making judicious decisions about the development of new or improved topical medicines. These aspects include the choices of the active ingredients, formulations, the target patient population's preferences, limitations, and the future with regard to new skin diseases and topical medicine approaches.
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Affiliation(s)
- Marc Brown
- MLBT Investments and Consultancy, Aylesbury, United Kingdom (M.Br.); MedPharm Ltd, Guildford, United Kingdom (M.Br., B.B., C.E., J.H., F.G.); Reading School of Pharmacy, Reading, United Kingdom (A.W.); School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom (R.P.C., W.J.M.); MedPharm Ltd, Durham. North Carolina (J.L., L.A., C.B.); Medicine Development and Supply, GlaxoSmithKline R&D, Stevenage, United Kingdom (M.Be.); Department of Dermatology, CUF Tejo Hospital, Lisbon, Portugal (R.V.); Centro de Investigação Interdisciplinar Egas Moniz, Egas Moniz School of Health and Science, Monte de Caparica, Portugal (M.M.); and Department of Chemistry, Coimbra Chemistry Center, University of Coimbra, Coimbra, Portugal (M.M.)
| | - Adrian Williams
- MLBT Investments and Consultancy, Aylesbury, United Kingdom (M.Br.); MedPharm Ltd, Guildford, United Kingdom (M.Br., B.B., C.E., J.H., F.G.); Reading School of Pharmacy, Reading, United Kingdom (A.W.); School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom (R.P.C., W.J.M.); MedPharm Ltd, Durham. North Carolina (J.L., L.A., C.B.); Medicine Development and Supply, GlaxoSmithKline R&D, Stevenage, United Kingdom (M.Be.); Department of Dermatology, CUF Tejo Hospital, Lisbon, Portugal (R.V.); Centro de Investigação Interdisciplinar Egas Moniz, Egas Moniz School of Health and Science, Monte de Caparica, Portugal (M.M.); and Department of Chemistry, Coimbra Chemistry Center, University of Coimbra, Coimbra, Portugal (M.M.)
| | - Robert P Chilcott
- MLBT Investments and Consultancy, Aylesbury, United Kingdom (M.Br.); MedPharm Ltd, Guildford, United Kingdom (M.Br., B.B., C.E., J.H., F.G.); Reading School of Pharmacy, Reading, United Kingdom (A.W.); School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom (R.P.C., W.J.M.); MedPharm Ltd, Durham. North Carolina (J.L., L.A., C.B.); Medicine Development and Supply, GlaxoSmithKline R&D, Stevenage, United Kingdom (M.Be.); Department of Dermatology, CUF Tejo Hospital, Lisbon, Portugal (R.V.); Centro de Investigação Interdisciplinar Egas Moniz, Egas Moniz School of Health and Science, Monte de Caparica, Portugal (M.M.); and Department of Chemistry, Coimbra Chemistry Center, University of Coimbra, Coimbra, Portugal (M.M.)
| | - Brendan Brady
- MLBT Investments and Consultancy, Aylesbury, United Kingdom (M.Br.); MedPharm Ltd, Guildford, United Kingdom (M.Br., B.B., C.E., J.H., F.G.); Reading School of Pharmacy, Reading, United Kingdom (A.W.); School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom (R.P.C., W.J.M.); MedPharm Ltd, Durham. North Carolina (J.L., L.A., C.B.); Medicine Development and Supply, GlaxoSmithKline R&D, Stevenage, United Kingdom (M.Be.); Department of Dermatology, CUF Tejo Hospital, Lisbon, Portugal (R.V.); Centro de Investigação Interdisciplinar Egas Moniz, Egas Moniz School of Health and Science, Monte de Caparica, Portugal (M.M.); and Department of Chemistry, Coimbra Chemistry Center, University of Coimbra, Coimbra, Portugal (M.M.)
| | - Jon Lenn
- MLBT Investments and Consultancy, Aylesbury, United Kingdom (M.Br.); MedPharm Ltd, Guildford, United Kingdom (M.Br., B.B., C.E., J.H., F.G.); Reading School of Pharmacy, Reading, United Kingdom (A.W.); School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom (R.P.C., W.J.M.); MedPharm Ltd, Durham. North Carolina (J.L., L.A., C.B.); Medicine Development and Supply, GlaxoSmithKline R&D, Stevenage, United Kingdom (M.Be.); Department of Dermatology, CUF Tejo Hospital, Lisbon, Portugal (R.V.); Centro de Investigação Interdisciplinar Egas Moniz, Egas Moniz School of Health and Science, Monte de Caparica, Portugal (M.M.); and Department of Chemistry, Coimbra Chemistry Center, University of Coimbra, Coimbra, Portugal (M.M.)
| | - Charles Evans
- MLBT Investments and Consultancy, Aylesbury, United Kingdom (M.Br.); MedPharm Ltd, Guildford, United Kingdom (M.Br., B.B., C.E., J.H., F.G.); Reading School of Pharmacy, Reading, United Kingdom (A.W.); School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom (R.P.C., W.J.M.); MedPharm Ltd, Durham. North Carolina (J.L., L.A., C.B.); Medicine Development and Supply, GlaxoSmithKline R&D, Stevenage, United Kingdom (M.Be.); Department of Dermatology, CUF Tejo Hospital, Lisbon, Portugal (R.V.); Centro de Investigação Interdisciplinar Egas Moniz, Egas Moniz School of Health and Science, Monte de Caparica, Portugal (M.M.); and Department of Chemistry, Coimbra Chemistry Center, University of Coimbra, Coimbra, Portugal (M.M.)
| | - Lynn Allen
- MLBT Investments and Consultancy, Aylesbury, United Kingdom (M.Br.); MedPharm Ltd, Guildford, United Kingdom (M.Br., B.B., C.E., J.H., F.G.); Reading School of Pharmacy, Reading, United Kingdom (A.W.); School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom (R.P.C., W.J.M.); MedPharm Ltd, Durham. North Carolina (J.L., L.A., C.B.); Medicine Development and Supply, GlaxoSmithKline R&D, Stevenage, United Kingdom (M.Be.); Department of Dermatology, CUF Tejo Hospital, Lisbon, Portugal (R.V.); Centro de Investigação Interdisciplinar Egas Moniz, Egas Moniz School of Health and Science, Monte de Caparica, Portugal (M.M.); and Department of Chemistry, Coimbra Chemistry Center, University of Coimbra, Coimbra, Portugal (M.M.)
| | - William J McAuley
- MLBT Investments and Consultancy, Aylesbury, United Kingdom (M.Br.); MedPharm Ltd, Guildford, United Kingdom (M.Br., B.B., C.E., J.H., F.G.); Reading School of Pharmacy, Reading, United Kingdom (A.W.); School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom (R.P.C., W.J.M.); MedPharm Ltd, Durham. North Carolina (J.L., L.A., C.B.); Medicine Development and Supply, GlaxoSmithKline R&D, Stevenage, United Kingdom (M.Be.); Department of Dermatology, CUF Tejo Hospital, Lisbon, Portugal (R.V.); Centro de Investigação Interdisciplinar Egas Moniz, Egas Moniz School of Health and Science, Monte de Caparica, Portugal (M.M.); and Department of Chemistry, Coimbra Chemistry Center, University of Coimbra, Coimbra, Portugal (M.M.)
| | - Mubinah Beebeejaun
- MLBT Investments and Consultancy, Aylesbury, United Kingdom (M.Br.); MedPharm Ltd, Guildford, United Kingdom (M.Br., B.B., C.E., J.H., F.G.); Reading School of Pharmacy, Reading, United Kingdom (A.W.); School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom (R.P.C., W.J.M.); MedPharm Ltd, Durham. North Carolina (J.L., L.A., C.B.); Medicine Development and Supply, GlaxoSmithKline R&D, Stevenage, United Kingdom (M.Be.); Department of Dermatology, CUF Tejo Hospital, Lisbon, Portugal (R.V.); Centro de Investigação Interdisciplinar Egas Moniz, Egas Moniz School of Health and Science, Monte de Caparica, Portugal (M.M.); and Department of Chemistry, Coimbra Chemistry Center, University of Coimbra, Coimbra, Portugal (M.M.)
| | - Jasmin Haslinger
- MLBT Investments and Consultancy, Aylesbury, United Kingdom (M.Br.); MedPharm Ltd, Guildford, United Kingdom (M.Br., B.B., C.E., J.H., F.G.); Reading School of Pharmacy, Reading, United Kingdom (A.W.); School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom (R.P.C., W.J.M.); MedPharm Ltd, Durham. North Carolina (J.L., L.A., C.B.); Medicine Development and Supply, GlaxoSmithKline R&D, Stevenage, United Kingdom (M.Be.); Department of Dermatology, CUF Tejo Hospital, Lisbon, Portugal (R.V.); Centro de Investigação Interdisciplinar Egas Moniz, Egas Moniz School of Health and Science, Monte de Caparica, Portugal (M.M.); and Department of Chemistry, Coimbra Chemistry Center, University of Coimbra, Coimbra, Portugal (M.M.)
| | - Claire Beuttel
- MLBT Investments and Consultancy, Aylesbury, United Kingdom (M.Br.); MedPharm Ltd, Guildford, United Kingdom (M.Br., B.B., C.E., J.H., F.G.); Reading School of Pharmacy, Reading, United Kingdom (A.W.); School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom (R.P.C., W.J.M.); MedPharm Ltd, Durham. North Carolina (J.L., L.A., C.B.); Medicine Development and Supply, GlaxoSmithKline R&D, Stevenage, United Kingdom (M.Be.); Department of Dermatology, CUF Tejo Hospital, Lisbon, Portugal (R.V.); Centro de Investigação Interdisciplinar Egas Moniz, Egas Moniz School of Health and Science, Monte de Caparica, Portugal (M.M.); and Department of Chemistry, Coimbra Chemistry Center, University of Coimbra, Coimbra, Portugal (M.M.)
| | - Raquel Vieira
- MLBT Investments and Consultancy, Aylesbury, United Kingdom (M.Br.); MedPharm Ltd, Guildford, United Kingdom (M.Br., B.B., C.E., J.H., F.G.); Reading School of Pharmacy, Reading, United Kingdom (A.W.); School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom (R.P.C., W.J.M.); MedPharm Ltd, Durham. North Carolina (J.L., L.A., C.B.); Medicine Development and Supply, GlaxoSmithKline R&D, Stevenage, United Kingdom (M.Be.); Department of Dermatology, CUF Tejo Hospital, Lisbon, Portugal (R.V.); Centro de Investigação Interdisciplinar Egas Moniz, Egas Moniz School of Health and Science, Monte de Caparica, Portugal (M.M.); and Department of Chemistry, Coimbra Chemistry Center, University of Coimbra, Coimbra, Portugal (M.M.)
| | - Florencia Guidali
- MLBT Investments and Consultancy, Aylesbury, United Kingdom (M.Br.); MedPharm Ltd, Guildford, United Kingdom (M.Br., B.B., C.E., J.H., F.G.); Reading School of Pharmacy, Reading, United Kingdom (A.W.); School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom (R.P.C., W.J.M.); MedPharm Ltd, Durham. North Carolina (J.L., L.A., C.B.); Medicine Development and Supply, GlaxoSmithKline R&D, Stevenage, United Kingdom (M.Be.); Department of Dermatology, CUF Tejo Hospital, Lisbon, Portugal (R.V.); Centro de Investigação Interdisciplinar Egas Moniz, Egas Moniz School of Health and Science, Monte de Caparica, Portugal (M.M.); and Department of Chemistry, Coimbra Chemistry Center, University of Coimbra, Coimbra, Portugal (M.M.)
| | - Margarida Miranda
- MLBT Investments and Consultancy, Aylesbury, United Kingdom (M.Br.); MedPharm Ltd, Guildford, United Kingdom (M.Br., B.B., C.E., J.H., F.G.); Reading School of Pharmacy, Reading, United Kingdom (A.W.); School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom (R.P.C., W.J.M.); MedPharm Ltd, Durham. North Carolina (J.L., L.A., C.B.); Medicine Development and Supply, GlaxoSmithKline R&D, Stevenage, United Kingdom (M.Be.); Department of Dermatology, CUF Tejo Hospital, Lisbon, Portugal (R.V.); Centro de Investigação Interdisciplinar Egas Moniz, Egas Moniz School of Health and Science, Monte de Caparica, Portugal (M.M.); and Department of Chemistry, Coimbra Chemistry Center, University of Coimbra, Coimbra, Portugal (M.M.)
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11
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Zhang Y, Zhang B, Wang R, Chen X, Xiao H, Xu X. The causal relationship and potential mediators between plasma lipids and atopic dermatitis: a bidirectional two-sample, two-step mendelian randomization. Lipids Health Dis 2024; 23:191. [PMID: 38909247 PMCID: PMC11193249 DOI: 10.1186/s12944-024-02134-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Accepted: 05/06/2024] [Indexed: 06/24/2024] Open
Abstract
BACKGROUND Observational studies have indicated that the plasma lipid profiles of patients with atopic dermatitis show significant differences compared to healthy individuals. However, the causal relationship between these differences remains unclear due to the inherent limitations of observational studies. Our objective was to explore the causal effects between 179 plasma lipid species and atopic dermatitis, and to investigate whether circulating inflammatory proteins serve as mediators in this causal pathway. METHODS We utilized public genome-wide association studies data to perform a bidirectional two-sample, two-step mendelian randomization study. The inverse variance-weighted method was adopted as the primary analysis technique. MR-Egger and the weighted median were used as supplementary analysis methods. MR-PRESSO, Cochran's Q test, and MR-Egger intercept test were applied for sensitivity analyses to ensure the robustness of our findings. RESULTS The Mendelian randomization analysis revealed that levels of Phosphatidylcholine (PC) (18:1_20:4) (OR: 0.950, 95% CI: 0.929-0.972, p = 6.65 × 10- 6), Phosphatidylethanolamine (O-18:1_20:4) (OR: 0.938, 95% CI: 0.906-0.971, p = 2.79 × 10- 4), Triacylglycerol (TAG) (56:6) (OR: 0.937, 95% CI: 0.906-0.969, p = 1.48 × 10- 4) and TAG (56:8) (OR: 0.918, 95% CI: 0.876-0.961, p = 2.72 × 10- 4) were inversely correlated with the risk of atopic dermatitis. Conversely, PC (18:1_20:2) (OR: 1.053, 95% CI: 1.028-1.079, p = 2.11 × 10- 5) and PC (O-18:1_20:3) (OR: 1.086, 95% CI: 1.039-1.135, p = 2.47 × 10- 4) were positively correlated with the risk of atopic dermatitis. The results of the reverse directional Mendelian randomization analysis indicated that atopic dermatitis exerted no significant causal influence on 179 plasma lipid species. The level of circulating IL-18R1 was identified as a mediator for the increased risk of atopic dermatitis associated with higher levels of PC (18:1_20:2), accounting for a mediation proportion of 9.07%. CONCLUSION Our research suggests that plasma lipids can affect circulating inflammatory proteins and may serve as one of the pathogenic factors for atopic dermatitis. Targeting plasma lipid levels as a treatment for atopic dermatitis presents a potentially novel approach.
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Affiliation(s)
- Yuke Zhang
- Department of Plastic and Burn Surgery, West China Hospital, Sichuan University, No.37, Guoxue Alley, Chengdu, Sichuan, 610041, China
| | - Bohan Zhang
- Department of Plastic and Burn Surgery, West China Hospital, Sichuan University, No.37, Guoxue Alley, Chengdu, Sichuan, 610041, China
| | - Ru Wang
- Department of Plastic and Burn Surgery, West China Hospital, Sichuan University, No.37, Guoxue Alley, Chengdu, Sichuan, 610041, China
| | - Xinghan Chen
- Department of Plastic and Burn Surgery, West China Hospital, Sichuan University, No.37, Guoxue Alley, Chengdu, Sichuan, 610041, China
| | - Haitao Xiao
- Department of Plastic and Burn Surgery, West China Hospital, Sichuan University, No.37, Guoxue Alley, Chengdu, Sichuan, 610041, China.
| | - Xuewen Xu
- Department of Plastic and Burn Surgery, West China Hospital, Sichuan University, No.37, Guoxue Alley, Chengdu, Sichuan, 610041, China.
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12
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Chhajed M, Gunasekaran PK, Bhanudeep S, Saini L. Charcot-Marie-Tooth Disease Type 4C and Autosomal Dominant Heterozygous Ichthyosis Vulgaris, with Bilateral Hearing Loss: A Novel Association with Review of Literature. J Pediatr Genet 2024; 13:110-115. [PMID: 38721572 PMCID: PMC11076064 DOI: 10.1055/s-0042-1759780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2022] [Accepted: 11/08/2022] [Indexed: 12/23/2022]
Abstract
A 3-year-old boy, firstborn to nonconsanguineous parents, presented with motor development delay and floppiness of bilateral lower limbs since birth. No significant family history presented at time of check-up. He could stand with support, eat with a spoon without spillage, and speak in two-word sentences. There was no history suggestive of cranial nerve impairment. Examination revealed normal head circumference, dry, scaly skin lesions on the trunk, distal weakness with sluggish deep tendon reflexes in bilateral lower limbs, and a high stepping gait. Nerve conduction studies revealed demyelinating polyneuropathy. Brain stem-evoked response audiometry testing revealed auditory neuropathy. Clinical exome sequencing revealed a known pathogenic variant of 3325C > T in the SH3TC2 gene suggestive of Charcot-Marie-Tooth disease type 4C and ichthyosis vulgaris with a novel variant of 2218C > T in the FLG gene. We have reviewed the available literature for reported associations of Charcot-Marie-Tooth disease type 4C and ichthyosis vulgaris. This is probably the first reported association of Charcot-Marie-Tooth disease type 4C and ichthyosis vulgaris with bilateral hearing loss.
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Affiliation(s)
- Monika Chhajed
- Department of Pediatrics, Chaitanya Hospital, Chandigarh, India
| | | | | | - Lokesh Saini
- Department of Pediatrics, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
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13
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Zhao S, Luo Z, Wang Y, Gao X, Tao J, Cui Y, Chen A, Cai D, Ding Y, Gu H, Gu J, Ji C, Kang X, Lu Q, Lv C, Li M, Li W, Liu W, Li X, Li Y, Man X, Qiao J, Sun L, Shi Y, Wu W, Xia J, Xiao R, Yang B, Kuang Y, Chen Z, Fang J, Kang J, Yang M, Zhang M, Su J, Zhang X, Chen X. Expert Consensus on Big Data Collection of Skin and Appendage Disease Phenotypes in Chinese. PHENOMICS (CHAM, SWITZERLAND) 2024; 4:269-292. [PMID: 39398426 PMCID: PMC11466921 DOI: 10.1007/s43657-023-00142-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 10/24/2023] [Accepted: 10/31/2023] [Indexed: 10/15/2024]
Abstract
The collection of big data on skin and appendage phenotypes has revolutionized the field of personalized diagnosis and treatment by enabling the evaluation of individual characteristics and early detection of abnormalities. To establish a standardized system for collecting and measuring big data on phenotypes, a systematic categorization of measurement entries has been undertaken, accompanied by recommendations on measurement entries, environmental equipment requirements, and collection processes, tailored to the needs of different usage scenarios. Specific collection sites have also been recommended based on different index characteristics. A multi-center, multi-regional collaboration has been initiated to collect big date on phenotypes of healthy and diseased skin in the Chinese population. This data will be correlated with patient disease information, exploring the factors influencing skin phenotype, analyzing the phenotypic data features that can predict prognosis, and ultimately promoting the exploration of the pathophysiology and pathogenesis of skin diseases and therapeutic approaches. Non-invasive skin measurement robots are also in development. This consensus aims to provide a reference for the study of phenomics and the standardization of phenotypic measurements of skin and appendages in China.
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Affiliation(s)
- Shuang Zhao
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 410083 China
| | - Zhongling Luo
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 410083 China
| | - Ying Wang
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 410083 China
| | - Xinghua Gao
- Department of Dermatology, No. 1 Hospital of China Medical University and Key Laboratory of Immunodermatology, Ministry of Health and Ministry of Education, Shenyang, 110001 China
| | - Juan Tao
- Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, 430022 China
| | - Yong Cui
- Department of Dermatology, China-Japan Friendship Hospital, Beijing, 100000 China
| | - Aijun Chen
- Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016 China
| | - Daxing Cai
- Department of Dermatology, Qilu Hospital, Shandong University, Jinan, 250000 China
| | - Yan Ding
- Department of Dermatology, Hainan General Hospital, Haikou, 570102 China
| | - Heng Gu
- Institute of Dermatology, Chinese Academy of Medical Sciences, Nanjing, 210042 China
| | - Jianying Gu
- Department of Plastic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032 China
| | - Chao Ji
- Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350000 China
| | - Xiaojing Kang
- Department of Dermatology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830001 China
| | - Qianjin Lu
- Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210000 China
| | - Chengzhi Lv
- Department of Dermatology, Dalian Skin Disease Hospital, Liaoning, 116021 China
| | - Min Li
- Department of Dermatology, Dushu Lake Hospital Affiliated to Soochow University (Medical Center of Soochow University, Suzhou Dushu Lake Hospital), Suzhou, 215000 China
| | - Wei Li
- School of Aeronautics and Astronautics, Sichuan University, Chengdu, 610000 China
| | - Wei Liu
- Department of Dermatology, General Hospital of Air Force, Beijing, 100000 China
| | - Xia Li
- Department of Dermatology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025 China
| | - Yuzhen Li
- Department of Dermatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150000 China
| | - Xiaoyong Man
- Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000 China
| | - Jianjun Qiao
- Department of Dermatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000 China
| | - Liangdan Sun
- Department of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230000 China
| | - Yuling Shi
- Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, 200443 China
| | - Wenyu Wu
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, 200443 China
| | - Jianxin Xia
- Department of Dermatology, The Second Affiliated Hospital of JiLin University, Changchun, 130000 China
| | - Rong Xiao
- Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, 410083 China
| | - Bin Yang
- Dermatology Hospital, Southern Medical University, Guangzhou, 510091 China
| | - Yehong Kuang
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 410083 China
| | - Zeyu Chen
- School of Materials Science and Engineering, Central South University, Changsha, 410083 China
| | - Jingyue Fang
- School of Physics and Electronics, Central South University, Changsha, 410083 China
| | - Jian Kang
- Department of Dermatology, The Third Xiangya Hospital of Central South University, Changsha, 410083 China
| | - Minghui Yang
- College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083 China
| | - Mi Zhang
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 410083 China
| | - Juan Su
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 410083 China
| | - Xuejun Zhang
- Department of Dermatology, Dushu Lake Hospital Affiliated to Soochow University (Medical Center of Soochow University, Suzhou Dushu Lake Hospital), Suzhou, 215000 China
| | - Xiang Chen
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 410083 China
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14
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Williams SF, Wan H, Chittock J, Brown K, Wigley A, Cork MJ, Danby SG. Characterization of skin barrier defects using infrared spectroscopy in patients with atopic dermatitis. Clin Exp Dermatol 2024; 49:466-477. [PMID: 38011533 DOI: 10.1093/ced/llad416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Revised: 10/30/2023] [Accepted: 11/20/2023] [Indexed: 11/29/2023]
Abstract
BACKGROUND Atopic dermatitis (AD) is characterized by skin barrier defects that are often measured by biophysical tools that observe the functional properties of the stratum corneum (SC). OBJECTIVES To employ in vivo infrared spectroscopy alongside biophysical measurements to analyse changes in the chemical composition of the SC in relation to AD severity. METHODS We conducted an observational cross-sectional cohort study where attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy measurements were collected on the forearm alongside surface pH, capacitance, erythema and transepidermal water loss (TEWL), combined with tape stripping, in a cohort of 75 participants (55 patients with AD stratified by phenotypic severity and 20 healthy controls). Common FLG variant alleles were genotyped. RESULTS Reduced hydration, elevated TEWL and redness were all associated with greater AD severity. Spectral analysis showed a reduction in 1465 cm-1 (full width half maximum) and 1340 cm-1 peak areas, indicative of less orthorhombic lipid ordering and reduced carboxylate functional groups, which correlated with clinical severity (lipid structure r = -0.59, carboxylate peak area r = -0.50). CONCLUSIONS ATR-FTIR spectroscopy is a suitable tool for the characterization of structural skin barrier defects in AD and has potential as a clinical tool for directing individual treatment based on chemical structural deficiencies.
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Affiliation(s)
- Samuel F Williams
- Sheffield Dermatology Research, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield Medical School, Sheffield, UK
| | - Helen Wan
- Sheffield Dermatology Research, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield Medical School, Sheffield, UK
| | - John Chittock
- Sheffield Dermatology Research, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield Medical School, Sheffield, UK
| | - Kirsty Brown
- Sheffield Dermatology Research, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield Medical School, Sheffield, UK
| | - Andrew Wigley
- Sheffield Dermatology Research, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield Medical School, Sheffield, UK
| | - Michael J Cork
- Sheffield Dermatology Research, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield Medical School, Sheffield, UK
- Sheffield Children's NHS Foundation Trust, Sheffield Children's Hospital, Western Bank, Sheffield, UK
- Sheffield Teaching Hospitals NHS Foundation Trust, The Royal Hallamshire Hospital, Sheffield, UK
| | - Simon G Danby
- Sheffield Dermatology Research, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield Medical School, Sheffield, UK
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15
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Lu HF, Zhou YC, Yang LT, Zhou Q, Wang XJ, Qiu SQ, Cheng BH, Zeng XH. Involvement and repair of epithelial barrier dysfunction in allergic diseases. Front Immunol 2024; 15:1348272. [PMID: 38361946 PMCID: PMC10867171 DOI: 10.3389/fimmu.2024.1348272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2023] [Accepted: 01/15/2024] [Indexed: 02/17/2024] Open
Abstract
The epithelial barrier serves as a critical defense mechanism separating the human body from the external environment, fulfilling both physical and immune functions. This barrier plays a pivotal role in shielding the body from environmental risk factors such as allergens, pathogens, and pollutants. However, since the 19th century, the escalating threats posed by environmental pollution, global warming, heightened usage of industrial chemical products, and alterations in biodiversity have contributed to a noteworthy surge in allergic disease incidences. Notably, allergic diseases frequently exhibit dysfunction in the epithelial barrier. The proposed epithelial barrier hypothesis introduces a novel avenue for the prevention and treatment of allergic diseases. Despite increased attention to the role of barrier dysfunction in allergic disease development, numerous questions persist regarding the mechanisms underlying the disruption of normal barrier function. Consequently, this review aims to provide a comprehensive overview of the epithelial barrier's role in allergic diseases, encompassing influencing factors, assessment techniques, and repair methodologies. By doing so, it seeks to present innovative strategies for the prevention and treatment of allergic diseases.
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Affiliation(s)
- Hui-Fei Lu
- Department of Graduate and Scientific Research, Zhuhai Campus of Zunyi Medical University, Zhuhai, China
- Department of Otolaryngology, Longgang Otolaryngology Hospital & Shenzhen Key Laboratory of Otolaryngology, Institute of Otolaryngology Shenzhen, Shenzhen, China
| | - Yi-Chi Zhou
- Department of Gastroenterology, Beijing University of Chinese Medicine Shenzhen Hospital (Longgang), Shenzhen, China
| | - Li-Tao Yang
- Clinical Laboratory Department of The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People’s Hospital of Shenzhen, Shenzhen, China
| | - Qian Zhou
- Department of Graduate and Scientific Research, Zhuhai Campus of Zunyi Medical University, Zhuhai, China
| | - Xi-Jia Wang
- Department of Graduate and Scientific Research, Zhuhai Campus of Zunyi Medical University, Zhuhai, China
- Department of Otolaryngology, Longgang Otolaryngology Hospital & Shenzhen Key Laboratory of Otolaryngology, Institute of Otolaryngology Shenzhen, Shenzhen, China
| | - Shu-Qi Qiu
- Department of Otolaryngology, Longgang Otolaryngology Hospital & Shenzhen Key Laboratory of Otolaryngology, Institute of Otolaryngology Shenzhen, Shenzhen, China
| | - Bao-Hui Cheng
- Department of Otolaryngology, Longgang Otolaryngology Hospital & Shenzhen Key Laboratory of Otolaryngology, Institute of Otolaryngology Shenzhen, Shenzhen, China
| | - Xian-Hai Zeng
- Department of Graduate and Scientific Research, Zhuhai Campus of Zunyi Medical University, Zhuhai, China
- Department of Otolaryngology, Longgang Otolaryngology Hospital & Shenzhen Key Laboratory of Otolaryngology, Institute of Otolaryngology Shenzhen, Shenzhen, China
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Andrew PV, Pinnock A, Poyner A, Brown K, Chittock J, Kay LJ, Cork MJ, Danby SG. Maintenance of an Acidic Skin Surface with a Novel Zinc Lactobionate Emollient Preparation Improves Skin Barrier Function in Patients with Atopic Dermatitis. Dermatol Ther (Heidelb) 2024; 14:391-408. [PMID: 38175365 PMCID: PMC10891035 DOI: 10.1007/s13555-023-01084-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Accepted: 12/06/2023] [Indexed: 01/05/2024] Open
Abstract
INTRODUCTION The skin of patients with atopic dermatitis (AD) is characterised by elevated pH. As a central homeostatic regulator, an increased pH accelerates desquamation and suppresses lipid processing, resulting in diminished skin barrier function. The aim of this study was to determine whether a novel zinc lactobionate emollient cream can strengthen the skin barrier by lowering skin surface pH. METHODS A double-blind, forearm-controlled cohort study was undertaken in patients with AD. Participants applied the test cream to one forearm and a vehicle cream to the other (randomised allocation) twice daily for 56 days. Skin surface pH and barrier function (primary outcomes) were assessed at baseline and after 28 days and 56 days of treatment, amongst other tests. RESULTS A total of 23 adults with AD completed the study. During and after treatment, a sustained difference in skin surface pH was observed between areas treated with the test cream and vehicle (4.50 ± 0.38 versus 5.25 ± 0.54, respectively, p < 0.0001). This was associated with significantly reduced transepidermal water loss (TEWL) on the test cream treated areas compared with control (9.71 ± 2.47 versus 11.20 ± 3.62 g/m2/h, p = 0.0005). Improvements in skin barrier integrity, skin sensitivity to sodium lauryl sulphate, skin hydration, and chymotrypsin-like protease activity were all observed at sites treated with the test cream compared with the control. CONCLUSION Maintenance of an acidic skin surface pH and delivery of physiologic lipids are beneficial for skin health and may help improve AD control by reducing sensitivity to irritants and allergens.
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Affiliation(s)
- Paul V Andrew
- Sheffield Dermatology Research, Division of Clinical Medicine, School of Medicine and Population Health, The University of Sheffield, Beech Hill Road, Sheffield, UK.
| | - Abigail Pinnock
- Sheffield Dermatology Research, Division of Clinical Medicine, School of Medicine and Population Health, The University of Sheffield, Beech Hill Road, Sheffield, UK
| | - Anna Poyner
- Sheffield Dermatology Research, Division of Clinical Medicine, School of Medicine and Population Health, The University of Sheffield, Beech Hill Road, Sheffield, UK
| | - Kirsty Brown
- Sheffield Dermatology Research, Division of Clinical Medicine, School of Medicine and Population Health, The University of Sheffield, Beech Hill Road, Sheffield, UK
| | - John Chittock
- Sheffield Dermatology Research, Division of Clinical Medicine, School of Medicine and Population Health, The University of Sheffield, Beech Hill Road, Sheffield, UK
| | - Linda J Kay
- Sheffield Dermatology Research, Division of Clinical Medicine, School of Medicine and Population Health, The University of Sheffield, Beech Hill Road, Sheffield, UK
| | - Michael J Cork
- Sheffield Dermatology Research, Division of Clinical Medicine, School of Medicine and Population Health, The University of Sheffield, Beech Hill Road, Sheffield, UK
- Sheffield Teaching Hospitals NHS Foundation Trust, The Royal Hallamshire Hospital, Sheffield, UK
- Sheffield Children's NHS Foundation Trust, Sheffield Children's Hospital, Western Bank, Sheffield, UK
| | - Simon G Danby
- Sheffield Dermatology Research, Division of Clinical Medicine, School of Medicine and Population Health, The University of Sheffield, Beech Hill Road, Sheffield, UK
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17
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Edwards T, Felix K, Francois S, Cardwell L, Rice Z. Nonprescription Treatment Options. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1447:151-167. [PMID: 38724792 DOI: 10.1007/978-3-031-54513-9_14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/15/2024]
Abstract
The pathogenesis of atopic dermatitis (AD) is complex and multifactorial. However, recent advancements in the genetics and pathophysiology of AD suggest that epidermal barrier dysfunction is paramount in the development and progression of the condition (Boguniewicz M, Leung DYM, Immunol Rev 242(1):233-246, 2011). In addition to standard therapy for AD, there are a plethora of nonprescription treatment modalities which may be employed. Over-the-counter treatments for atopic dermatitis can come in the form of topical corticosteroids, moisturizers/emollients, and oral antihistamines. Though these treatments are beneficial, prescription treatments may be quicker acting and more efficacious in patients with moderate to severe disease or during flares. OTC agents are best used for maintenance between flares and to prevent progression of mild disease. Alternative and complementary treatments lack strong efficacy evidence. However, wet wraps, bleach baths, and other treatments appear to be promising when used in conjunction with conventional treatments. With the financial burden of atopic dermatitis ranging from 364 million to 3.8 billion dollars each year in the United States, we suspect this topic will gain further research attention.
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Affiliation(s)
- Taylor Edwards
- Ohio University Heritage College of Osteopathic Medicine, Athens, OH, USA
| | - Kayla Felix
- Department of Dermatology, Wake Forest University School of Medicine, Winston Salem, NC, USA
| | - Sandy Francois
- Department of Dermatology, Emory School of Medicine, Atlanta, GA, USA
| | - Leah Cardwell
- Department of Dermatology, Wake Forest University School of Medicine, Winston Salem, NC, USA
| | - Zakiyyah Rice
- Department of Dermatology, Emory School of Medicine, Atlanta, GA, USA.
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18
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Dessì A, Di Maria C, Pintus R, Fanos V, Bosco A. Lipidomics and Metabolomics in Infant Atopic Dermatitis: What's the Correlation with Early Nutrition? Curr Pediatr Rev 2024; 20:510-524. [PMID: 37055903 DOI: 10.2174/1573396320666230411093122] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 02/22/2023] [Accepted: 03/02/2023] [Indexed: 04/15/2023]
Abstract
To date, the complex picture of atopic dermatitis (AD) has not yet been fully clarified, despite the important prevalence of this disease in the pediatric population (20%) and the possibility of persistence into adulthood, with important implications for the quality of life of those affected, as well as significant social and financial costs. The most recent scientific evidence suggests a new interpretation of AD, highlighting the important role of the environment, particularly that of nutrition in the early stages of development. In fact, the new indications seem to point out the harmful effect of elimination diets, except in rare cases, the uselessness of chrono-insertions during complementary feeding and some benefits, albeit weak, of breastfeeding in those at greater risk. In this context, metabolomics and lipidomics can be necessary for a more in-depth knowledge of the complex metabolic network underlying this pathology. In fact, an alteration of the metabolic contents in children with AD has been highlighted, especially in correlation to the intestinal microbiota. While preliminary lipidomic studies showed the usefulness of a more in-depth knowledge of the alterations of the skin barrier to improve the development of baby skin care products. Therefore, investigating the response of different allergic phenotypes could be useful for better patient management and understanding, thus providing an early intervention on dysbiosis necessary to regulate the immune response from the earliest stages of development.
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Affiliation(s)
- Angelica Dessì
- Department of Surgical Sciences, University of Cagliari and Neonatal Intensive Care Unit, AOU Cagliari, Cagliari, Italy
| | - Camilla Di Maria
- Department of Surgical Sciences, University of Cagliari and Neonatal Intensive Care Unit, AOU Cagliari, Cagliari, Italy
| | - Roberta Pintus
- Department of Surgical Sciences, University of Cagliari and Neonatal Intensive Care Unit, AOU Cagliari, Cagliari, Italy
| | - Vassilios Fanos
- Department of Surgical Sciences, University of Cagliari and Neonatal Intensive Care Unit, AOU Cagliari, Cagliari, Italy
| | - Alice Bosco
- Department of Surgical Sciences, University of Cagliari and Neonatal Intensive Care Unit, AOU Cagliari, Cagliari, Italy
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19
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Bouwstra JA, Nădăban A, Bras W, McCabe C, Bunge A, Gooris GS. The skin barrier: An extraordinary interface with an exceptional lipid organization. Prog Lipid Res 2023; 92:101252. [PMID: 37666282 PMCID: PMC10841493 DOI: 10.1016/j.plipres.2023.101252] [Citation(s) in RCA: 44] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Revised: 08/29/2023] [Accepted: 08/30/2023] [Indexed: 09/06/2023]
Abstract
The barrier function of the skin is primarily located in the stratum corneum (SC), the outermost layer of the skin. The SC is composed of dead cells with highly organized lipid lamellae in the intercellular space. As the lipid matrix forms the only continuous pathway, the lipids play an important role in the permeation of compounds through the SC. The main lipid classes are ceramides (CERs), cholesterol (CHOL) and free fatty acids (FFAs). Analysis of the SC lipid matrix is of crucial importance in understanding the skin barrier function, not only in healthy skin, but also in inflammatory skin diseases with an impaired skin barrier. In this review we provide i) a historical overview of the steps undertaken to obtain information on the lipid composition and organization in SC of healthy skin and inflammatory skin diseases, ii) information on the role CERs, CHOL and FFAs play in the lipid phase behavior of very complex lipid model systems and how this knowledge can be used to understand the deviation in lipid phase behavior in inflammatory skin diseases, iii) knowledge on the role of both, CER subclasses and chain length distribution, on lipid organization and lipid membrane permeability in complex and simple model systems with synthetic CERs, CHOL and FFAs, iv) similarity in lipid phase behavior in SC of different species and complex model systems, and vi) future directions in modulating lipid composition that is expected to improve the skin barrier in inflammatory skin diseases.
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Affiliation(s)
- Joke A Bouwstra
- Division of Biotherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
| | - Andreea Nădăban
- Division of Biotherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands
| | - Wim Bras
- Chemical Sciences Division, Oak Ridge National Laboratory, One Bethel Valley Road, Oak Ridge, TN 37831, United States of America
| | - Clare McCabe
- School of Engineering & Physical Science, Heriot-Watt University, Edinburgh, Scotland, UK
| | - Annette Bunge
- Department of Chemical and Biological Engineering, Colorado School of Mines, Golden, CO 80401, United States of America
| | - Gerrit S Gooris
- Division of Biotherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands
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20
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Zhang Y, Gu H, Ye Y, Li Y, Gao X, Ken K, Huang X, Gao W, Chen H, Huang J, Wang L, Yan W. Trajectory of stratum corneum lipid subclasses in the first year of life and associations with atopic dermatitis: A prospective cohort study. Pediatr Allergy Immunol 2023; 34:e14045. [PMID: 38010004 DOI: 10.1111/pai.14045] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 09/20/2023] [Accepted: 10/20/2023] [Indexed: 11/29/2023]
Abstract
BACKGROUND Trajectories of stratum corneum (SC) lipid subclasses and their associations with infant atopic dermatitis (AD) are unclear. This study aimed to quantify the trajectories of 15 SC subclasses and carbon chain lengths and their associations with AD within 12 months. METHODS In total, 213 newborns were enrolled at birth with nonlesional skin samples collected from the inner forearm at birth, 42 days, 3, 6, and 12 months, respectively. Lesional skin samples were collected from 120 AD patients at clinic with the disease onset within the first year of life. Mass spectrometry was applied to assess relative contents of 12 ceramide (CER), three free fatty acid (FFA) subclasses, and average carbon chain length (CCL). AD incident within 1 year old was diagnosed by dermatologists according to UK criteria. RESULTS Sixty-four (30.0%) cases of ADs occurred in the cohort. All SC lipid subclasses and CCLs, but EOP varied significantly during the first year. AD infants showed lower NP but higher NS, NH, AP, hydroxy FFA, and CCL of FFAs compared with nonaffected infants. After normalization by age, the differences remained and were more pronounced in lesional skin of clinical AD infants compared with non-ADs. NS, NH, and CCL of FFAs in lesional skin of AD infants showed positive and significant correlations with the levels of transepidermal water loss at 3 month; some evidence supports a negative correlation for NP. CONCLUSIONS We provide an overview of developmental trajectories of 15 CER and FFA subclasses across the first year of healthy infants and a link between the imbalance of some subclasses with the development of AD.
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Affiliation(s)
- Yi Zhang
- Department of Clinical Epidemiology & Clinical Trial Unit, Children's Hospital of Fudan University & National Children Medical Center, Shanghai, China
| | - Hongjian Gu
- Department of Research & Development, Pigeon Maternal and Infant Skin Care Research Institute, Shanghai, China
| | - Ying Ye
- Department of Dermatology, Children's Hospital of Fudan University & National Children Medical Center, Shanghai, China
| | - Yun Li
- Shanghai Minhang Maternal and Children Health Care Hospital, Shanghai, China
| | - Xiaohua Gao
- Shanghai Minhang Maternal and Children Health Care Hospital, Shanghai, China
| | - Kaku Ken
- Department of Research & Development, Pigeon Maternal and Infant Skin Care Research Institute, Shanghai, China
| | - Xiangyuan Huang
- Department of Clinical Epidemiology & Clinical Trial Unit, Children's Hospital of Fudan University & National Children Medical Center, Shanghai, China
| | - Wei Gao
- Department of Dermatology, Children's Hospital of Fudan University & National Children Medical Center, Shanghai, China
| | - Hongyan Chen
- Department of Clinical Epidemiology & Clinical Trial Unit, Children's Hospital of Fudan University & National Children Medical Center, Shanghai, China
| | - Jun Huang
- Shanghai Minhang Maternal and Children Health Care Hospital, Shanghai, China
| | - Liuhui Wang
- Department of Dermatology, Children's Hospital of Fudan University & National Children Medical Center, Shanghai, China
| | - Weili Yan
- Department of Clinical Epidemiology & Clinical Trial Unit, Children's Hospital of Fudan University & National Children Medical Center, Shanghai, China
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21
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Fiskin E, Eraslan G, Alora-Palli MB, Leyva-Castillo JM, Kim S, Choe H, Lareau CA, Lau H, Finan EP, Teixeira-Soldano I, LaBere B, Chu A, Woods B, Chou J, Slyper M, Waldman J, Islam S, Schneider L, Phipatanakul W, Platt C, Rozenblatt-Rosen O, Delorey TM, Deguine J, Smith GP, Geha R, Regev A, Xavier R. Multi-modal skin atlas identifies a multicellular immune-stromal community associated with altered cornification and specific T cell expansion in atopic dermatitis. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.10.29.563503. [PMID: 37961084 PMCID: PMC10634929 DOI: 10.1101/2023.10.29.563503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2023]
Abstract
In healthy skin, a cutaneous immune system maintains the balance between tolerance towards innocuous environmental antigens and immune responses against pathological agents. In atopic dermatitis (AD), barrier and immune dysfunction result in chronic tissue inflammation. Our understanding of the skin tissue ecosystem in AD remains incomplete with regard to the hallmarks of pathological barrier formation, and cellular state and clonal composition of disease-promoting cells. Here, we generated a multi-modal cell census of 310,691 cells spanning 86 cell subsets from whole skin tissue of 19 adult individuals, including non-lesional and lesional skin from 11 AD patients, and integrated it with 396,321 cells from four studies into a comprehensive human skin cell atlas in health and disease. Reconstruction of human keratinocyte differentiation from basal to cornified layers revealed a disrupted cornification trajectory in AD. This disrupted epithelial differentiation was associated with signals from a unique immune and stromal multicellular community comprised of MMP12 + dendritic cells (DCs), mature migratory DCs, cycling ILCs, NK cells, inflammatory CCL19 + IL4I1 + fibroblasts, and clonally expanded IL13 + IL22 + IL26 + T cells with overlapping type 2 and type 17 characteristics. Cell subsets within this immune and stromal multicellular community were connected by multiple inter-cellular positive feedback loops predicted to impact community assembly and maintenance. AD GWAS gene expression was enriched both in disrupted cornified keratinocytes and in cell subsets from the lesional immune and stromal multicellular community including IL13 + IL22 + IL26 + T cells and ILCs, suggesting that epithelial or immune dysfunction in the context of the observed cellular communication network can initiate and then converge towards AD. Our work highlights specific, disease-associated cell subsets and interactions as potential targets in progression and resolution of chronic inflammation.
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22
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Quan VL, Erickson T, Daftary K, Chovatiya R. Atopic Dermatitis Across Shades of Skin. Am J Clin Dermatol 2023; 24:731-751. [PMID: 37336869 DOI: 10.1007/s40257-023-00797-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/23/2023] [Indexed: 06/21/2023]
Abstract
Atopic dermatitis (AD) is a chronic, heterogeneous inflammatory skin disease that is associated with immense patient burden globally. There is increasing appreciation of disparities among patients identified as having skin of color (SOC), which often refers to patients of non-White race or non-European ancestry, but can broadly include individuals from a number of different racial, ethnic, ancestral, and skin pigmentation groups based on definition. In this narrative review, we discuss key terminology as it relates to AD across shades of skin, including modern definitions of 'race', 'ethnicity', and 'SOC'. We then synthesize the current literature describing disparities in AD prevalence, disease recognition, and burden alongside current data regarding genetic and immunologic findings across SOC populations. In the context of these findings, we highlight key concomitant social determinants of health, including environmental factors, socioeconomic status, and access to care, for which race often serves as a proxy for true biological and genetic differences. Finally, we discuss future efforts to shift to a more inclusive understanding of AD to encompass all shades of skin, to ensure equitable representation of diverse populations in high impact research, and intensify efforts to address the critical upstream factors driving observed disparities.
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Affiliation(s)
- Victor L Quan
- Department of Dermatology, Feinberg School of Medicine, Northwestern University, 676 N St Clair St, Suite 1600, Chicago, IL, 60611, USA
| | - Taylor Erickson
- Department of Dermatology, Feinberg School of Medicine, Northwestern University, 676 N St Clair St, Suite 1600, Chicago, IL, 60611, USA
| | - Karishma Daftary
- Department of Dermatology, Feinberg School of Medicine, Northwestern University, 676 N St Clair St, Suite 1600, Chicago, IL, 60611, USA
| | - Raj Chovatiya
- Department of Dermatology, Feinberg School of Medicine, Northwestern University, 676 N St Clair St, Suite 1600, Chicago, IL, 60611, USA.
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23
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Rinnov MR, Halling AS, Gerner T, Ravn NH, Knudgaard MH, Trautner S, Goorden SMI, Ghauharali-van der Vlugt KJM, Stet FS, Skov L, Thomsen SF, Egeberg A, Rosted ALL, Petersen T, Jakasa I, Riethmüller C, Kezic S, Thyssen JP. Skin biomarkers predict development of atopic dermatitis in infancy. Allergy 2023; 78:791-802. [PMID: 36112082 DOI: 10.1111/all.15518] [Citation(s) in RCA: 51] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Revised: 07/14/2022] [Accepted: 08/08/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND There is currently no insight into biomarkers that can predict the onset of pediatric atopic dermatitis (AD). METHODS Nested in a prospective birth cohort study that examined the occurrence of physician-diagnosed AD in 300 children, 44 random children with onset of AD in the first year of life were matched on sex and season of birth with 44 children who did not develop AD. Natural moisturizing factor (NMF), corneocyte surface protrusions, cytokines, free sphingoid bases (SBs) of different chain lengths and their ceramides were analyzed from tape strips collected at 2 months of age before onset of AD using liquid chromatography, atomic force microscopy, multiplex immunoassay, and liquid chromatography mass spectrometry, respectively. RESULTS Significant alterations were observed for four lipid markers, with phytosphingosine ([P]) levels being significantly lower in children who developed AD compared with children who did not (median 240 pmol/mg vs. 540 pmol/mg, p < 0.001). The two groups of children differed in the relative amounts of SB of different chain lengths (C17, C18 and C20). Thymus- and activation-regulated chemokine (TARC/CCL17) was slightly higher in children who developed AD, whereas NMF and corneocyte surface texture were similar. AD severity assessed by the eczema area and severity index (EASI) at disease onset was 4.2 (2.0;7.2). [P] had the highest prediction accuracy among the biomarkers (75.6%), whereas the combination of 5 lipid ratios gave an accuracy of 89.4%. CONCLUSION This study showed that levels and SB chain length were altered in infants who later developed AD, and that TARC/CCL17 levels were higher.
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Affiliation(s)
- Maria Rasmussen Rinnov
- Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
| | - Anne-Sofie Halling
- Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.,Department of Dermatology and Venereology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Trine Gerner
- Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
| | - Nina Haarup Ravn
- Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
| | - Mette Hjorslev Knudgaard
- Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
| | - Simon Trautner
- Department of Neonatology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Susan M I Goorden
- Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Karen J M Ghauharali-van der Vlugt
- Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Femke S Stet
- Department of Dermatology and Venereology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Lone Skov
- Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
| | - Simon Francis Thomsen
- Department of Dermatology and Venereology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Alexander Egeberg
- Department of Dermatology and Venereology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Aske L L Rosted
- Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark
| | - Troels Petersen
- Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark
| | - Ivone Jakasa
- Laboratory for Analytical Chemistry, Department of Chemistry and Biochemistry, Faculty of Food Technology and Biotechnology, University of Zagreb, Zagreb, Croatia
| | | | - Sanja Kezic
- Amsterdam Public Health research institute, Department of Public and Occupational Health Amsterdam UMC, Department of Public and Occupational Health, University of Amsterdam, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands
| | - Jacob P Thyssen
- Department of Dermatology and Venereology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark
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24
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The dynamic balance of the skin microbiome across the lifespan. Biochem Soc Trans 2023; 51:71-86. [PMID: 36606709 PMCID: PMC9988004 DOI: 10.1042/bst20220216] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 12/02/2022] [Accepted: 12/05/2022] [Indexed: 01/07/2023]
Abstract
For decades research has centered on identifying the ideal balanced skin microbiome that prevents disease and on developing therapeutics to foster this balance. However, this single idealized balance may not exist. The skin microbiome changes across the lifespan. This is reflected in the dynamic shifts of the skin microbiome's diverse, inter-connected community of microorganisms with age. While there are core skin microbial taxa, the precise community composition for any individual person is determined by local skin physiology, genetics, microbe-host interactions, and microbe-microbe interactions. As a key interface with the environment, the skin surface and its appendages are also constantly exchanging microbes with close personal contacts and the environment. Hormone fluctuations and immune system maturation also drive age-dependent changes in skin physiology that support different microbial community structures over time. Here, we review recent insights into the factors that shape the skin microbiome throughout life. Collectively, the works summarized within this review highlight how, depending on where we are in lifespan, our skin supports robust microbial communities, while still maintaining microbial features unique to us. This review will also highlight how disruptions to this dynamic microbial balance can influence risk for dermatological diseases as well as impact lifelong health.
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25
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Hulme J. Staphylococcus Infection: Relapsing Atopic Dermatitis and Microbial Restoration. Antibiotics (Basel) 2023; 12:antibiotics12020222. [PMID: 36830133 PMCID: PMC9952585 DOI: 10.3390/antibiotics12020222] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 01/15/2023] [Accepted: 01/18/2023] [Indexed: 01/22/2023] Open
Abstract
Atopic Dermatitis (AD) skin is susceptible to Staphylococcus aureus (SA) infection, potentially exposing it to a plethora of toxins and virulent determinants, including Panton-Valentine leukocidin (PVL) (α-hemolysin (Hla) and phenol-soluble modulins (PSMs)), and superantigens. Depending on the degree of infection (superficial or invasive), clinical treatments may encompass permanganate (aq) and bleach solutions coupled with intravenous/oral antibiotics such as amoxicillin, vancomycin, doxycycline, clindamycin, daptomycin, telavancin, linezolid, or tigecycline. However, when the skin is significantly traumatized (sheathing of epidermal sections), an SA infection can rapidly ensue, impairing the immune system, and inducing local and systemic AD presentations in susceptible areas. Furthermore, when AD presents systemically, desensitization can be long (years) and intertwined with periods of relapse. In such circumstances, the identification of triggers (stress or infection) and severity of the flare need careful monitoring (preferably in real-time) so that tailored treatments targeting the underlying pathological mechanisms (SA toxins, elevated immunoglobulins, impaired healing) can be modified, permitting rapid resolution of symptoms.
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Affiliation(s)
- John Hulme
- Gachon Bio-Nano Institute, Gachon University, Seongnam-si 461-701, Republic of Korea
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26
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Menopause induces changes to the stratum corneum ceramide profile, which are prevented by hormone replacement therapy. Sci Rep 2022; 12:21715. [PMID: 36522440 PMCID: PMC9755298 DOI: 10.1038/s41598-022-26095-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Accepted: 12/09/2022] [Indexed: 12/23/2022] Open
Abstract
The menopause can lead to epidermal changes that are alleviated by hormone replacement therapy (HRT). We hypothesise that these changes could relate to altered ceramide production, and that oestrogen may have a role in keratinocyte ceramide metabolism. White Caucasian women were recruited into three groups: pre-menopausal (n = 7), post-menopausal (n = 11) and post-menopausal taking HRT (n = 10). Blood samples were assessed for hormone levels, transepidermal water loss was measured to assess skin barrier function, and stratum corneum lipids were sampled from photoprotected buttock skin. Ceramides and sphingomyelins were analysed by ultraperformance liquid chromatography with electrospray ionisation and tandem mass spectrometry. Post-menopausal stratum corneum contained lower levels of ceramides, with shorter average length; changes that were not evident in the HRT group. Serum oestradiol correlated with ceramide abundance and length. Ceramides had shorter sphingoid bases, indicating altered de novo ceramide biosynthesis. Additionally, post-menopausal women had higher sphingomyelin levels, suggesting a possible effect on the hydrolysis pathway. Treatment of primary human keratinocytes with oestradiol (10 nM) increased production of CER[NS] and CER[NDS] ceramides, confirming an effect of oestrogen on cutaneous ceramide metabolism. Taken together, these data show perturbed stratum corneum lipids post-menopause, and a role for oestrogen in ceramide production.
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Zouboulis CC, Coenye T, He L, Kabashima K, Kobayashi T, Niemann C, Nomura T, Oláh A, Picardo M, Quist SR, Sasano H, Schneider MR, Törőcsik D, Wong SY. Sebaceous immunobiology - skin homeostasis, pathophysiology, coordination of innate immunity and inflammatory response and disease associations. Front Immunol 2022; 13:1029818. [PMID: 36439142 PMCID: PMC9686445 DOI: 10.3389/fimmu.2022.1029818] [Citation(s) in RCA: 53] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Accepted: 10/17/2022] [Indexed: 08/01/2023] Open
Abstract
This review presents several aspects of the innovative concept of sebaceous immunobiology, which summarizes the numerous activities of the sebaceous gland including its classical physiological and pathophysiological tasks, namely sebum production and the development of seborrhea and acne. Sebaceous lipids, which represent 90% of the skin surface lipids in adolescents and adults, are markedly involved in the skin barrier function and perifollicular and dermal innate immune processes, leading to inflammatory skin diseases. Innovative experimental techniques using stem cell and sebocyte models have clarified the roles of distinct stem cells in sebaceous gland physiology and sebocyte function control mechanisms. The sebaceous gland represents an integral part of the pilosebaceous unit and its status is connected to hair follicle morphogenesis. Interestingly, professional inflammatory cells contribute to sebocyte differentiation and homeostasis, whereas the regulation of sebaceous gland function by immune cells is antigen-independent. Inflammation is involved in the very earliest differentiation changes of the pilosebaceous unit in acne. Sebocytes behave as potent immune regulators, integrating into the innate immune responses of the skin. Expressing inflammatory mediators, sebocytes also contribute to the polarization of cutaneous T cells towards the Th17 phenotype. In addition, the immune response of the perifollicular infiltrate depends on factors produced by the sebaceous glands, mostly sebaceous lipids. Human sebocytes in vitro express functional pattern recognition receptors, which are likely to interact with bacteria in acne pathogenesis. Sex steroids, peroxisome proliferator-activated receptor ligands, neuropeptides, endocannabinoids and a selective apoptotic process contribute to a complex regulation of sebocyte-induced immunological reaction in numerous acquired and congenital skin diseases, including hair diseases and atopic dermatitis.
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Affiliation(s)
- Christos C. Zouboulis
- Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodor Fontane and Faculty of Health Sciences Brandenburg, Dessau, Germany
| | - Tom Coenye
- Laboratory of Pharmaceutical Microbiology, Ghent University, Ghent, Belgium
| | - Li He
- Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Kenji Kabashima
- Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Tetsuro Kobayashi
- Laboratory for Innate Immune Systems, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Kanagawa, Japan
| | - Catherin Niemann
- Center for Molecular Medicine Cologne, CMMC Research Institute, University of Cologne, Cologne, Germany
- Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany
| | - Takashi Nomura
- Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Attila Oláh
- Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Mauro Picardo
- San Gallicano Dermatologic Institute, IRCCS, Rome, Italy
| | - Sven R. Quist
- Department of Dermatology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
| | - Hironobu Sasano
- Department of Pathology, Tohoku University School of Medicine, Sendai, Japan
| | - Marlon R. Schneider
- Institute of Veterinary Physiology, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany
| | - Daniel Törőcsik
- Department of Dermatology, Faculty of Medicine, University of Debrecen and ELKH-DE Allergology Research Group, Debrecen, Hungary
| | - Sunny Y. Wong
- Departments of Dermatology and Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, United States
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Sung B, Baek YY, Kim YM, You JC. Topical Administration of a Novel Acetylated Tetrapeptide Suppresses Vascular Permeability and Immune Responses and Alleviates Atopic Dermatitis in a Murine Model. Int J Mol Sci 2022; 23:ijms232113498. [PMID: 36362286 PMCID: PMC9658216 DOI: 10.3390/ijms232113498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 10/25/2022] [Accepted: 11/01/2022] [Indexed: 11/06/2022] Open
Abstract
Although the pathogenesis of atopic dermatitis (AD) remains to be fully deciphered, skin barrier abnormality and immune dysregulation are known to be involved. Recently, the vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) system has also been implicated in the pathogenesis of this multifactorial chronic inflammatory skin disorder. Previously, we showed that a novel tetrapeptide, N-acetyl-Arg-Leu-Tyr-Glu (Ac-RLYE), inhibits angiogenesis and vascular permeability effectively by selectively antagonizing VEGFR-2. The current study aimed to investigate the pharmacological effect of Ac-RLYE on AD in vitro and in vivo. The in vitro experiments demonstrated that Ac-RLYE inhibited VEGF-induced vascular permeability in endothelial cells. Moreover, in an in vivo animal model of AD, Ac-RLYE relieved AD-like symptoms such as ear thickness and dermatitis severity scores and infiltration of immune cells, including mast cells and eosinophils. Ac-RLYE inhibited IgE secretion, restored the skin barrier protein filaggrin level, and markedly downregulated gene expression of AD-related Th1, Th2, and Th17 cytokines. Collectively, these findings suggest that Ac-RLYE would be useful for the treatment of AD and associated inflammatory skin disorders.
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Affiliation(s)
- Bokyung Sung
- Avixgen Inc., 2477, Nambusunhwan-ro, Seocho-gu, Seoul 06725, Korea
| | - Yi-Yong Baek
- Avixgen Inc., 2477, Nambusunhwan-ro, Seocho-gu, Seoul 06725, Korea
| | - Young-Myeong Kim
- Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon 24341, Korea
| | - Ji Chang You
- Avixgen Inc., 2477, Nambusunhwan-ro, Seocho-gu, Seoul 06725, Korea
- National Research Laboratory for Molecular Virology, Department of Pathology, School of Medicine, The Catholic University of Korea, Seoul 06591, Korea
- Correspondence:
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Murashkin NN, Epishev RV, Ivanov RA, Materikin AI, Opryatin LA, Savelova AA, Nezhvedilova RY, Ambarchian ET, Fedorov DV, Rusakova LL. Innovations in Therapeutic Improvement of the Cutaneous Microbiome in Children with Atopic Dermatitis. CURRENT PEDIATRICS 2022. [DOI: 10.15690/vsp.v21i5.2449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Biofilm is the dominant form of skin microbiota organization that provides adhesion and preservation of microorganisms in the skin micro-environment. It is necessary to ensure epidermal barrier function and local immunomodulation. Staphylococcus aureus becomes the major colonizer of skin lesions in case of atopic dermatitis exacerbation, and it also can form the biofilms. S. aureus growth and biofilm formation due to other microbial commensals on the skin of patients with atopic dermatitis leads to chronic output of pro-inflammatory cytokines and later to abnormalities in healthy skin microbiome. The role of microbial biofilm in human’s health makes the skin microbiota an attractive target for therapeutic intervention in various skin diseases.
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Affiliation(s)
- N. N. Murashkin
- National Medical Research Center of Children’s Health; Sechenov First Moscow State Medical University; Central State Medical Academy of Department of Presidential Affairs
| | - R. V. Epishev
- National Medical Research Center of Children’s Health
| | - R. A. Ivanov
- National Medical Research Center of Children’s Health
| | | | | | | | | | - E. T. Ambarchian
- Pediatrics and Child Health Research Institute in Petrovsky National Research Centre of Surgery
| | - D. V. Fedorov
- National Medical Research Center of Children’s Health
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30
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Quadri M, Pellegrini C, Efimova T, Palazzo E. Editorial: New tools and molecular advances in hyperproliferative skin disorders. Front Med (Lausanne) 2022; 9:1002872. [PMID: 36035385 PMCID: PMC9403983 DOI: 10.3389/fmed.2022.1002872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Accepted: 07/28/2022] [Indexed: 11/21/2022] Open
Affiliation(s)
- Marika Quadri
- DermoLAB, Department of Surgical, Medical, Dental, and Morphological Science, University of Modena and Reggio Emilia, Modena, Italy
| | - Cristina Pellegrini
- Dermatology, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Tatiana Efimova
- Department of Anatomy and Cell Biology, The George Washington University School of Medicine and Health Sciences, Washington, DC, United States
- The George Washington Cancer Center, The George Washington University School of Medicine and Health Sciences, Washington, DC, United States
- Department of Dermatology, The George Washington University School of Medicine and Health Sciences, Washington, DC, United States
| | - Elisabetta Palazzo
- DermoLAB, Department of Surgical, Medical, Dental, and Morphological Science, University of Modena and Reggio Emilia, Modena, Italy
- *Correspondence: Elisabetta Palazzo
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31
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Gao JF, Tang L, Luo F, Zhang YY, Chen L, Ding H, Meng ZD. Nicotinamide mononucleotide ameliorates DNFB-induced atopic dermatitis-like symptoms in mice by blocking activation of ROS-mediated JAK2/STAT5 signaling pathway. Int Immunopharmacol 2022; 109:108812. [DOI: 10.1016/j.intimp.2022.108812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 04/24/2022] [Accepted: 04/26/2022] [Indexed: 11/28/2022]
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32
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Ma X, Ru Y, Luo Y, Kuai L, Chen QL, Bai Y, Liu YQ, Chen J, Luo Y, Song JK, Zhou M, Li B. Post-Translational Modifications in Atopic Dermatitis: Current Research and Clinical Relevance. Front Cell Dev Biol 2022; 10:942838. [PMID: 35874824 PMCID: PMC9301047 DOI: 10.3389/fcell.2022.942838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 06/16/2022] [Indexed: 11/20/2022] Open
Abstract
Atopic dermatitis (AD) is a chronic and relapsing cutaneous disorder characterized by compromised immune system, excessive inflammation, and skin barrier disruption. Post-translational modifications (PTMs) are covalent and enzymatic modifications of proteins after their translation, which have been reported to play roles in inflammatory and allergic diseases. However, less attention has been paid to the effect of PTMs on AD. This review summarized the knowledge of six major classes (including phosphorylation, acetylation, ubiquitination, SUMOylation, glycosylation, o-glycosylation, and glycation) of PTMs in AD pathogenesis and discussed the opportunities for disease management.
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Affiliation(s)
- Xin Ma
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Shanghai Skin Disease Hospital of Tongji University, Shanghai, China
| | - Yi Ru
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
| | - Ying Luo
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
| | - Le Kuai
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
| | - Qi-Long Chen
- Shanghai Skin Disease Hospital of Tongji University, Shanghai, China
| | - Yun Bai
- Shanghai Skin Disease Hospital of Tongji University, Shanghai, China
| | - Ye-Qiang Liu
- Shanghai Skin Disease Hospital of Tongji University, Shanghai, China
| | - Jia Chen
- Shanghai Skin Disease Hospital of Tongji University, Shanghai, China
| | - Yue Luo
- Shanghai Skin Disease Hospital of Tongji University, Shanghai, China
| | - Jian-Kun Song
- Shanghai Skin Disease Hospital of Tongji University, Shanghai, China
| | - Mi Zhou
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
- *Correspondence: Mi Zhou, ; Bin Li,
| | - Bin Li
- Shanghai Skin Disease Hospital of Tongji University, Shanghai, China
- Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
- *Correspondence: Mi Zhou, ; Bin Li,
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33
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Jazdarehee A, Lee J, Lewis R, Mukovozov I. Potential Mechanisms of the Sparing of Atopic Dermatitis in the Diaper Region: A Scoping Review. J Cutan Med Surg 2022; 26:398-403. [PMID: 35317630 PMCID: PMC9361425 DOI: 10.1177/12034754221088533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2021] [Revised: 02/14/2022] [Accepted: 02/19/2022] [Indexed: 11/18/2022]
Abstract
Atopic dermatitis (AD) is a chronic, inflammatory skin condition commonly affecting infants with notable sparing of the diaper region. Though sources anecdotally attribute this sparing to the physical barrier formed by the diaper and the subsequent retention of moisture, urine, sweat and feces, no studies have formally investigated the factors contributing to this sparing phenomenon. We performed a scoping literature review to investigate the factors involved in sparing of AD in the diaper region, namely humidity, scratching, urine, sweat, feces, and microbiome composition. A total of 130 papers met the inclusion criteria, and extracted data were analyzed in an iterative manner. Increased local humidity facilitates protective changes at the cellular level and offsets transepidermal water loss. Exposure to urea from both sweat and urine may contribute to improved moisturization of the skin through its natural humectant properties and ability to modulate gene expression. Introduction of flora in feces contributes to the generation of protective immune responses and outcompetes growth of pathogens such as Staphylococcus aureus. Finally, diapers physically prevent scratching, which directly interrupts the itch-scratch cycle classically implicated in AD. Our study reviews factors that may contribute to the sparing of AD in the diaper region in infants. A limitation to our findings is that the studies reviewed here explore the impacts of these factors on AD broadly, and not explicitly in the diaper region. Additional studies investigating this may further our understanding of AD pathogenesis and contribute to the development of effective therapeutics.
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Affiliation(s)
- Aria Jazdarehee
- Department of Medicine, University of British Columbia,
Vancouver, BC, Canada
| | - Jason Lee
- Department of Medicine, University of British Columbia,
Vancouver, BC, Canada
| | - Richard Lewis
- Department of Dermatology and Skin Science, University of
British Columbia, Vancouver, BC, Canada
- Kamloops Dermatology, Kamloops, BC, Canada
| | - Ilya Mukovozov
- Department of Dermatology and Skin Science, University of
British Columbia, Vancouver, BC, Canada
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34
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Dev K, Ho CJH, Bi R, Yew YW, S DU, Attia ABE, Moothanchery M, Guan STT, Olivo M. Machine Learning Assisted Handheld Confocal Raman Micro-Spectroscopy for Identification of Clinically Relevant Atopic Eczema Biomarkers. SENSORS 2022; 22:s22134674. [PMID: 35808168 PMCID: PMC9269422 DOI: 10.3390/s22134674] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Revised: 06/17/2022] [Accepted: 06/17/2022] [Indexed: 12/02/2022]
Abstract
Atopic dermatitis (AD) is a common chronic inflammatory skin dermatosis condition due to skin barrier dysfunction that causes itchy, red, swollen, and cracked skin. Currently, AD severity clinical scores are subjected to intra- and inter-observer differences. There is a need for an objective scoring method that is sensitive to skin barrier differences. The aim of this study was to evaluate the relevant skin chemical biomarkers in AD patients. We used confocal Raman micro-spectroscopy and advanced machine learning methods as means to classify eczema patients and healthy controls with sufficient sensitivity and specificity. Raman spectra at different skin depths were acquired from subjects’ lower volar forearm location using an in-house developed handheld confocal Raman micro-spectroscopy system. The Raman spectra corresponding to the skin surface from all the subjects were further analyzed through partial least squares discriminant analysis, a binary classification model allowing the classification between eczema and healthy subjects with a sensitivity and specificity of 0.94 and 0.85, respectively, using stratified K-fold (K = 10) cross-validation. The variable importance in the projection score from the partial least squares discriminant analysis classification model further elucidated the role of important stratum corneum proteins and lipids in distinguishing two subject groups.
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Affiliation(s)
- Kapil Dev
- Translational Biophotonics Lab, Institute of Bioengineering and Bioimaging, Agency for Science, Technology and Research (A*STAR), Singapore 138667, Singapore
| | - Chris Jun Hui Ho
- Translational Biophotonics Lab, Institute of Bioengineering and Bioimaging, Agency for Science, Technology and Research (A*STAR), Singapore 138667, Singapore
| | - Renzhe Bi
- Translational Biophotonics Lab, Institute of Bioengineering and Bioimaging, Agency for Science, Technology and Research (A*STAR), Singapore 138667, Singapore
| | - Yik Weng Yew
- National Skin Centre, Singapore 308205, Singapore
| | - Dinish U S
- Translational Biophotonics Lab, Institute of Bioengineering and Bioimaging, Agency for Science, Technology and Research (A*STAR), Singapore 138667, Singapore
| | - Amalina Binte Ebrahim Attia
- Translational Biophotonics Lab, Institute of Bioengineering and Bioimaging, Agency for Science, Technology and Research (A*STAR), Singapore 138667, Singapore
| | - Mohesh Moothanchery
- Translational Biophotonics Lab, Institute of Bioengineering and Bioimaging, Agency for Science, Technology and Research (A*STAR), Singapore 138667, Singapore
| | | | - Malini Olivo
- Translational Biophotonics Lab, Institute of Bioengineering and Bioimaging, Agency for Science, Technology and Research (A*STAR), Singapore 138667, Singapore
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35
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Prasannanjaneyulu V, Nene S, Jain H, Nooreen R, Otavi S, Chitlangya P, Srivastava S. Old drugs, new tricks: Emerging role of drug repurposing in the management of atopic dermatitis. Cytokine Growth Factor Rev 2022; 65:12-26. [PMID: 35550114 DOI: 10.1016/j.cytogfr.2022.04.007] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Accepted: 04/29/2022] [Indexed: 11/03/2022]
Abstract
Atopic dermatitis is a chronic recurring pruritic inflammatory skin disease manifested by increased pro-inflammatory mediators which lead to dry, thickened, cracked, scaly skin. The current treatment options for atopic dermatitis management comprise drawbacks and leave unmet effective clinical needs. So, the approach for repurposing existing drugs for atopic dermatitis management may potentially overcome these unmet needs. Diseases that share the common pathophysiological pathways with atopic dermatitis can serve as a foundation for the repurposing of drugs. Drugs used in the management of cancer, rheumatoid arthritis, and other immune-mediated diseases such as psoriasis are under investigation to know the potential in atopic dermatitis management by utilizing repurposing strategies for a novel therapeutic indication. This review mainly envisages the probable repurposing of drugs for the management of atopic dermatitis disease; the barriers and regulatory aspects involved in the repurposing of existing drugs.
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Affiliation(s)
- Velpula Prasannanjaneyulu
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India
| | - Shweta Nene
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India
| | - Harsha Jain
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India
| | - Rimsha Nooreen
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India
| | - Shivam Otavi
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India
| | - Palak Chitlangya
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India
| | - Saurabh Srivastava
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India.
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36
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Bieber T, Paller AS, Kabashima K, Feely M, Rueda MJ, Ross Terres JA, Wollenberg A. Atopic dermatitis: pathomechanisms and lessons learned from novel systemic therapeutic options. J Eur Acad Dermatol Venereol 2022; 36:1432-1449. [PMID: 35575442 DOI: 10.1111/jdv.18225] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 04/13/2022] [Indexed: 12/01/2022]
Abstract
Atopic dermatitis (AD) is a chronic, heterogenous, inflammatory skin disorder associated with a high skin-related health burden, typically starting in childhood and often persisting into adulthood. AD is characterized by a wide range of clinical phenotypes, reflecting multiple underlying pathophysiological mechanisms and interactions between genetics, immune system dysregulation, and environmental factors. In this review, we describe the diverse cellular and molecular mechanisms involved in AD, including the critical role of T cell-driven inflammation, primarily via T helper (Th) 2- and Th17-derived cytokines, many of which are mediated by the Janus kinase (JAK) signaling pathway. These local inflammatory processes interact with sensory neuronal pathways, contributing to the clinical manifestations of AD, including itch, pain, and sleep disturbance. The recent elucidation of the molecular pathways involved in AD has allowed treatment strategies to evolve from broad-acting systemic immunosuppressive therapies to more targeted agents, including JAK inhibitors and cytokine-specific biologic agents. Evidence from the clinical development of these targeted therapies has reinforced and expanded our understanding of the pathophysiological mechanisms underlying AD and holds promise for individualized treatment strategies tailored to specific AD subtypes.
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Affiliation(s)
- T Bieber
- Department of Dermatology and Allergy, University Medical Center, Bonn, Germany.,Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland
| | - A S Paller
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - K Kabashima
- Department Dermatology, Kyoto University School of Medicine, Kyoto, Japan
| | - M Feely
- Eli Lilly and Company, Indianapolis, IN, USA.,Department of Dermatology, Mount Sinai Hospital, New York, NY, USA
| | - M J Rueda
- Eli Lilly and Company, Indianapolis, IN, USA
| | | | - A Wollenberg
- Department of Dermatology and Allergy, University Hospital, Ludwig Maximillian University, Munich, Germany.,Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Department of Dermatology, Brussels, Belgium
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37
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Opálka L, Meyer JM, Ondrejčeková V, Svatošová L, Radner FPW, Vávrová K. ω-O-Acylceramides but not ω-hydroxy ceramides are required for healthy lamellar phase architecture of skin barrier lipids. J Lipid Res 2022; 63:100226. [PMID: 35568253 PMCID: PMC9192818 DOI: 10.1016/j.jlr.2022.100226] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Revised: 05/03/2022] [Accepted: 05/09/2022] [Indexed: 11/29/2022] Open
Abstract
Epidermal omega-O-acylceramides (ω-O-acylCers) are essential components of a competent skin barrier. These unusual sphingolipids with ultralong N-acyl chains contain linoleic acid esterified to the terminal hydroxyl of the N-acyl, the formation of which requires the transacylase activity of patatin-like phospholipase domain containing 1 (PNPLA1). In ichthyosis with dysfunctional PNPLA1, ω-O-acylCer levels are significantly decreased, and ω-hydroxylated Cers (ω-OHCers) accumulate. Here we explore the role of the linoleate moiety in ω-O-acylCers in the assembly of the skin lipid barrier. Ultrastructural studies of skin samples from neonatal Pnpla1+/+ and Pnpla1-/- mice showed that the linoleate moiety in ω-O-acylCers is essential for lamellar pairing in lamellar bodies, as well as for stratum corneum lipid assembly into the long periodicity lamellar phase (LPP). To further study the molecular details of ω-O-acylCer deficiency on skin barrier lipid assembly, we built in vitro lipid models composed of major stratum corneum lipid subclasses containing either ω-O-acylCer (healthy skin model), ω-OHCer (Pnpla1-/- model), or combination of the two. X-ray diffraction, infrared spectroscopy, and permeability studies indicated that ω-OHCers could not substitute for ω-O-acylCers, although in favorable conditions, they form a medium lamellar phase with a 10.8 nm-repeat distance and permeability barrier properties similar to LPP. In the absence of ω-O-acylCers, skin lipids were prone to separation into two phases with diminished barrier properties. The models combining ω-OHCers with ω-O-acylCers indicated that accumulation of ω-OHCers does not prevent ω-O-acylCer-driven lamellar stacking. These data suggest that ω-O-acylCer supplementation may be a viable therapeutic option in patients with PNPLA1 deficiency.
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Affiliation(s)
- Lukáš Opálka
- Charles University, Faculty of Pharmacy in Hradec Králové, Hradec Králové, Czech Republic
| | - Jason M Meyer
- Department of Dermatology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Veronika Ondrejčeková
- Charles University, Faculty of Pharmacy in Hradec Králové, Hradec Králové, Czech Republic
| | - Linda Svatošová
- Charles University, Faculty of Pharmacy in Hradec Králové, Hradec Králové, Czech Republic
| | - Franz P W Radner
- Institute of Molecular Biosciences, University of Graz, Graz, Austria
| | - Kateřina Vávrová
- Charles University, Faculty of Pharmacy in Hradec Králové, Hradec Králové, Czech Republic.
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Moosbrugger-Martinz V, Leprince C, Méchin MC, Simon M, Blunder S, Gruber R, Dubrac S. Revisiting the Roles of Filaggrin in Atopic Dermatitis. Int J Mol Sci 2022; 23:5318. [PMID: 35628125 PMCID: PMC9140947 DOI: 10.3390/ijms23105318] [Citation(s) in RCA: 57] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Revised: 05/03/2022] [Accepted: 05/06/2022] [Indexed: 12/31/2022] Open
Abstract
The discovery in 2006 that loss-of-function mutations in the filaggrin gene (FLG) cause ichthyosis vulgaris and can predispose to atopic dermatitis (AD) galvanized the dermatology research community and shed new light on a skin protein that was first identified in 1981. However, although outstanding work has uncovered several key functions of filaggrin in epidermal homeostasis, a comprehensive understanding of how filaggrin deficiency contributes to AD is still incomplete, including details of the upstream factors that lead to the reduced amounts of filaggrin, regardless of genotype. In this review, we re-evaluate data focusing on the roles of filaggrin in the epidermis, as well as in AD. Filaggrin is important for alignment of keratin intermediate filaments, control of keratinocyte shape, and maintenance of epidermal texture via production of water-retaining molecules. Moreover, filaggrin deficiency leads to cellular abnormalities in keratinocytes and induces subtle epidermal barrier impairment that is sufficient enough to facilitate the ingress of certain exogenous molecules into the epidermis. However, although FLG null mutations regulate skin moisture in non-lesional AD skin, filaggrin deficiency per se does not lead to the neutralization of skin surface pH or to excessive transepidermal water loss in atopic skin. Separating facts from chaff regarding the functions of filaggrin in the epidermis is necessary for the design efficacious therapies to treat dry and atopic skin.
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Affiliation(s)
- Verena Moosbrugger-Martinz
- Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, Anichstraße 35, 6020 Innsbruck, Austria; (V.M.-M.); (S.B.); (R.G.)
| | - Corinne Leprince
- Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), Toulouse University, CNRS UMR5051, Inserm UMR1291, UPS, 31059 Toulouse, France; (C.L.); (M.-C.M.); (M.S.)
| | - Marie-Claire Méchin
- Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), Toulouse University, CNRS UMR5051, Inserm UMR1291, UPS, 31059 Toulouse, France; (C.L.); (M.-C.M.); (M.S.)
| | - Michel Simon
- Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), Toulouse University, CNRS UMR5051, Inserm UMR1291, UPS, 31059 Toulouse, France; (C.L.); (M.-C.M.); (M.S.)
| | - Stefan Blunder
- Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, Anichstraße 35, 6020 Innsbruck, Austria; (V.M.-M.); (S.B.); (R.G.)
| | - Robert Gruber
- Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, Anichstraße 35, 6020 Innsbruck, Austria; (V.M.-M.); (S.B.); (R.G.)
| | - Sandrine Dubrac
- Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, Anichstraße 35, 6020 Innsbruck, Austria; (V.M.-M.); (S.B.); (R.G.)
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Rasool R, Shafi T, Bhat IA, Khursheed S, Manzoor S, Qadri Q, Shah ZA. Association of epidermal differentiation complex (EDC) genetic variants with House Dust Mite sensitization in Atopic Dermatitis patients. Immunobiology 2022; 227:152214. [DOI: 10.1016/j.imbio.2022.152214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 03/20/2022] [Accepted: 04/04/2022] [Indexed: 11/05/2022]
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Pavel P, Blunder S, Moosbrugger-Martinz V, Elias PM, Dubrac S. Atopic Dermatitis: The Fate of the Fat. Int J Mol Sci 2022; 23:2121. [PMID: 35216234 PMCID: PMC8880331 DOI: 10.3390/ijms23042121] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 02/09/2022] [Accepted: 02/11/2022] [Indexed: 12/12/2022] Open
Abstract
Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease in which dry and itchy skin may develop into skin lesions. AD has a strong genetic component, as children from parents with AD have a two-fold increased chance of developing the disease. Genetic risk loci and epigenetic modifications reported in AD mainly locate to genes involved in the immune response and epidermal barrier function. However, AD pathogenesis cannot be fully explained by (epi)genetic factors since environmental triggers such as stress, pollution, microbiota, climate, and allergens also play a crucial role. Alterations of the epidermal barrier in AD, observed at all stages of the disease and which precede the development of overt skin inflammation, manifest as: dry skin; epidermal ultrastructural abnormalities, notably anomalies of the lamellar body cargo system; and abnormal epidermal lipid composition, including shorter fatty acid moieties in several lipid classes, such as ceramides and free fatty acids. Thus, a compelling question is whether AD is primarily a lipid disorder evolving into a chronic inflammatory disease due to genetic susceptibility loci in immunogenic genes. In this review, we focus on lipid abnormalities observed in the epidermis and blood of AD patients and evaluate their primary role in eliciting an inflammatory response.
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Affiliation(s)
- Petra Pavel
- Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, A-6020 Innsbruck, Austria; (P.P.); (S.B.); (V.M.-M.)
| | - Stefan Blunder
- Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, A-6020 Innsbruck, Austria; (P.P.); (S.B.); (V.M.-M.)
| | - Verena Moosbrugger-Martinz
- Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, A-6020 Innsbruck, Austria; (P.P.); (S.B.); (V.M.-M.)
| | - Peter M. Elias
- Department of Dermatology, University of California, San Francisco, CA 94115, USA;
| | - Sandrine Dubrac
- Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, A-6020 Innsbruck, Austria; (P.P.); (S.B.); (V.M.-M.)
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Nowicka D, Chilicka K, Dzieńdziora-Urbińska I. Host-Microbe Interaction on the Skin and Its Role in the Pathogenesis and Treatment of Atopic Dermatitis. Pathogens 2022; 11:pathogens11010071. [PMID: 35056019 PMCID: PMC8779626 DOI: 10.3390/pathogens11010071] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 01/04/2022] [Accepted: 01/04/2022] [Indexed: 12/12/2022] Open
Abstract
Atopic dermatitis (AD) is a condition with a complex and unclear aetiology. Possible causes of AD encompass alterations in the structure and function of the epidermal barrier, disturbances in the skin microbiome, immune factors, allergens, bacterial and fungal infections as well as environmental and genetic factors. In patients with AD, acute skin lesions are colonized by a greater number of bacteria and fungi than chronic lesions, clinically unchanged atopic skin and the skin of healthy people. Mechanisms promoting skin colonization by pathogens include complex interplay among several factors. Apart from disturbances of the skin microbiome, increased adhesion in atopic skin, defects of innate immune response resulting in the lack of or restriction of growth of microorganisms also contribute to susceptibility to the skin colonization of and infections, especially with Staphylococcus aureus. This review of the literature attempts to identify factors that are involved in the pathogenesis of AD-related bacterial and fungal skin colonization. Studies on the microbiome, commensal microorganisms and the role of skin microorganisms in maintaining healthy skin bring additional insight into the treatment and prevention of AD. In the light of presented mechanisms, reduction in colonization may become both causative and symptomatic treatment in AD.
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Affiliation(s)
- Danuta Nowicka
- Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, 50-368 Wrocław, Poland
- Correspondence:
| | - Karolina Chilicka
- Department of Health Sciences, University of Opole, 45-040 Opole, Poland; (K.C.); (I.D.-U.)
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Danby SG, Andrew PV, Kay LJ, Pinnock A, Chittock J, Brown K, Williams SF, Cork MJ. Enhancement of stratum corneum lipid structure improves skin barrier function and protects against irritation in adults with dry, eczema-prone, skin. Br J Dermatol 2021; 186:875-886. [PMID: 34921679 PMCID: PMC9321855 DOI: 10.1111/bjd.20955] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 11/08/2021] [Accepted: 12/11/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND The skin of atopic dermatitis (AD) patients is characterised by abnormal stratum corneum (SC) lipid levels. Consequently, the lamellar matrices are disrupted and skin barrier function is diminished, increasing skin sensitivity to irritants and allergens. OBJECTIVE To determine whether a cream containing ceramides, triglycerides and cholesterol in a multi-vesicular emulsion can reinforce the skin barrier, and protect against skin irritation. METHODS A randomized observer-blind intrasubject-controlled study in 34 adults with dry, eczema-prone, skin was conducted. Each participant underwent 4 weeks treatment with the test cream on one forearm and lower leg and a reference emollient cream on the other. Skin properties were determined before and after treatment. Lipid structure was assessed by FTIR spectroscopy using a novel interface. RESULTS Skin barrier integrity was greater at sites treated with the Test cream (effect size -161.9 area-under-the-TEWL-curve, 95% CI -205.5, -118.3), and skin sensitivity to sodium lauryl sulfate reduced (-0.5 points [97.57% CI -1.00, -0.25] visual redness and -15.34 g/m2 /h [95% CI -20.28, -10.40] TEWL) compared to the reference. Sites treated with the test cream displayed enhanced lipid chain ordering, which was significantly associated with skin barrier integrity (r0.606). Compared to the reference, treatment with the Test cream increased hydration (8.61 capacitance units, 95% CI 6.61 to 10.60) and decreased signs of dryness. CONCLUSION The Test cream facilitates skin barrier restoration and protects the skin from dryness and irritation. Compared to a commonly prescribed emollient in the UK, the Test cream is highly suited to the management of dry, sensitive, skin.
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Affiliation(s)
- Simon G Danby
- Sheffield Dermatology Research, Dept. Infection, Immunity & Cardiovascular Disease, University of Sheffield Medical School, Sheffield, UK
| | - Paul V Andrew
- Sheffield Dermatology Research, Dept. Infection, Immunity & Cardiovascular Disease, University of Sheffield Medical School, Sheffield, UK
| | - Linda J Kay
- Sheffield Dermatology Research, Dept. Infection, Immunity & Cardiovascular Disease, University of Sheffield Medical School, Sheffield, UK
| | - Abigail Pinnock
- Sheffield Dermatology Research, Dept. Infection, Immunity & Cardiovascular Disease, University of Sheffield Medical School, Sheffield, UK
| | - John Chittock
- Sheffield Dermatology Research, Dept. Infection, Immunity & Cardiovascular Disease, University of Sheffield Medical School, Sheffield, UK
| | - Kirsty Brown
- Sheffield Dermatology Research, Dept. Infection, Immunity & Cardiovascular Disease, University of Sheffield Medical School, Sheffield, UK
| | - Samuel F Williams
- Sheffield Dermatology Research, Dept. Infection, Immunity & Cardiovascular Disease, University of Sheffield Medical School, Sheffield, UK
| | - Michael J Cork
- Sheffield Dermatology Research, Dept. Infection, Immunity & Cardiovascular Disease, University of Sheffield Medical School, Sheffield, UK.,Sheffield Children's NHS Foundation Trust, Sheffield Children's Hospital, Western Bank, Sheffield, UK.,Sheffield Teaching Hospitals NHS Foundation Trust, The Royal Hallamshire Hospital, Sheffield, UK
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Ferrucci S, Romagnuolo M, Maronese CA, Germiniasi F, Tavecchio S, Angileri L, Casazza G, Marzano AV, Genovese G. Skin barrier status during dupilumab treatment in patients with severe atopic dermatitis. Ther Adv Chronic Dis 2021; 12:20406223211058332. [PMID: 34900210 PMCID: PMC8655442 DOI: 10.1177/20406223211058332] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Accepted: 10/20/2021] [Indexed: 12/02/2022] Open
Abstract
Background: Atopic dermatitis (AD) is a common chronic-relapsing inflammatory skin disease hallmarked by epidermal barrier dysfunction, increased transepidermal water loss (TEWL) and decreased skin hydration. Recent findings on the T helper 2 (Th2)-driven pathogenesis of AD have led to the development of dupilumab, a monoclonal antibody directed against interleukin-4 and interleukin-13 that has been demonstrated to be effective in the treatment of moderate-to-severe AD. The effect of dupilumab on skin barrier dysfunction, however, has not yet been adequately investigated. Objectives: The primary endpoint of this study was to assess the status of the skin barrier in nonlesional skin of patients with severe AD treated with dupilumab, by evaluating the association between the relative variation of TEWL and the achievement of a 75% reduction of EASI (EASI75) over time. Methods: TEWL was measured below the antecubital fossae by means of the Vapometer® at baseline, at week 4 (T4), at week 16 (T16) and at week 32 after dupilumab starting. EASI and NRS-itch were measured at the same time points. Results: Seventy-eight patients with severe AD treated with dupilumab were enrolled. Median TEWL relative variation respect to baseline was significantly higher in patients who achieved EASI75 as compared with those who did not achieve EASI75 at T16 and at T32, but not at T4. Conclusion: During dupilumab treatment, TEWL on nonlesional skin tends to significantly improve 4 months after treatment initiation and could be a good tool for monitoring response to therapy.
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Affiliation(s)
- Silvia Ferrucci
- Dermatology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Maurizio Romagnuolo
- Dermatology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Carlo Alberto Maronese
- Dermatology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Francesca Germiniasi
- Dermatology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Simona Tavecchio
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Luisa Angileri
- Dermatology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Giovanni Casazza
- Dipartimento di Scienze Biomediche e Cliniche 'L. Sacco', Università degli Studi di Milano, Milan, Italy
| | - Angelo Valerio Marzano
- Dermatology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Pace 9, 20122 Milan, Italy. Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Giovanni Genovese
- Dermatology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
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Ghezzi M, Pozzi E, Abbattista L, Lonoce L, Zuccotti GV, D’Auria E. Barrier Impairment and Type 2 Inflammation in Allergic Diseases: The Pediatric Perspective. CHILDREN (BASEL, SWITZERLAND) 2021; 8:1165. [PMID: 34943362 PMCID: PMC8700706 DOI: 10.3390/children8121165] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 11/30/2021] [Accepted: 11/30/2021] [Indexed: 01/02/2023]
Abstract
Allergic diseases represent a global burden. Although the patho-physiological mechanisms are still poorly understood, epithelial barrier dysfunction and Th2 inflammatory response play a pivotal role. Barrier dysfunction, characterized by a loss of differentiation, reduced junctional integrity, and altered innate defence, underpins the pathogenesis of allergic diseases. Epithelial barrier impairment may be a potential therapeutic target for new treatment strategies Up now, monoclonal antibodies and new molecules targeting specific pathways of the immune response have been developed, and others are under investigation, both for adult and paediatric populations, which are affected by atopic dermatitis (AD), asthma, allergic rhinitis (AR), chronic rhinosinusitis with nasal polyps (CRSwNP), or eosinophilic esophagitis (EoE). In children affected by severe asthma biologics targeting IgE, IL-5 and against IL-4 and IL-13 receptors are already available, and they have also been applied in CRSwNP. In severe AD Dupilumab, a biologic which inhibits both IL-4 and IL-13, the most important cytokines involved in inflammation response, has been approved for treatment of patients over 12 years. While a biological approach has already shown great efficacy on the treatment of severe atopic conditions, early intervention to restore epithelial barrier integrity, and function may prevent the inflammatory response and the development of the atopic march.
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Affiliation(s)
- Michele Ghezzi
- Allergology and Pneumology Unit, V. Buzzi Children’s Hospital, 20154 Milan, Italy;
| | - Elena Pozzi
- Department of Pediatrics, V. Buzzi Children’s Hospital, 20154 Milan, Italy; (E.P.); (L.A.); (L.L.); (G.V.Z.)
| | - Luisa Abbattista
- Department of Pediatrics, V. Buzzi Children’s Hospital, 20154 Milan, Italy; (E.P.); (L.A.); (L.L.); (G.V.Z.)
| | - Luisa Lonoce
- Department of Pediatrics, V. Buzzi Children’s Hospital, 20154 Milan, Italy; (E.P.); (L.A.); (L.L.); (G.V.Z.)
| | - Gian Vincenzo Zuccotti
- Department of Pediatrics, V. Buzzi Children’s Hospital, 20154 Milan, Italy; (E.P.); (L.A.); (L.L.); (G.V.Z.)
- Department of Biomedical and Clinical Science “L. Sacco”, University of Milan, 20157 Milan, Italy
| | - Enza D’Auria
- Allergology and Pneumology Unit, V. Buzzi Children’s Hospital, 20154 Milan, Italy;
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Fan P, Yang Y, Liu T, Lu X, Huang H, Chen L, Kuang Y. Anti-atopic effect of Viola yedoensis ethanol extract against 2,4-dinitrochlorobenzene-induced atopic dermatitis-like skin dysfunction. JOURNAL OF ETHNOPHARMACOLOGY 2021; 280:114474. [PMID: 34332065 DOI: 10.1016/j.jep.2021.114474] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Revised: 07/02/2021] [Accepted: 07/28/2021] [Indexed: 06/13/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Viola yedoensis Makiho (VY, Violaceae) is a well-known medicinal herb in Chinese medicine, which is traditionally used to treat inflammation-related disorders, including allergic skin reactions. Although studies have uncovered its anti-inflammatory effects and corresponding bioactive constituents, the exact mechanism of action is still unclear in treating allergic skin reactions. OBJECTIVE Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by severe pruritus, dry, edema and inflamed skin. It affects people's quality of life seriously and causes huge economic losses to society. This study proposes VY as a possible remedy for atopic dermatitis since its traditional usage and superior anti-inflammatory effects. MATERIALS AND METHODS Atopic dermatitis-like skin lesion was induced by topical application of 2,4-dinitrochlorobenzene (DNCB) in ICR mice. After treatment with Viola yedoensis Makiho ethanol extract (VYE) or dexamethasone (positive control) for 3 weeks, skin pathological observation and the molecular biological index were performed for therapeutic evaluation, including visual inspection in the change of the stimulated skin, scar formation, pathological morphology by hematoxylin and eosin (HE) staining, the measurement of interleukin IL-1β, IL-6 and tumor necrosis factor-alpha (TNF-α) levels in serum as well as spleen index. The expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) were analyzed by western blot. The ratio of CD4+/CD8+ T lymphocyte in the spleen was detected by flow cytometry. Meanwhile, immunohistochemistry staining for CD68 identified the number of activated macrophages in skin lesions. Additionally, a reliable ultrahigh-performance liquid chromatography coupled with a Q exactive hybrid quadrupole-orbitrap mass spectrometry (UHPLC-Q-Orbitrap-MS) method was established for the systematic identification and characterization of main components in VYE. RESULTS VYE alleviated DNCB-stimulated AD-like lesions symptoms as evidenced by a significant decrease in hypertrophy, hyperkeratosis, and infiltration of inflammatory cells in dorsal skin. The levels of IL-1β, IL-6, and TNF-α in serum were suppressed in mice treated with VYE as compared to the DNCB-induced model group. Also, the administration of VYE reduced the ratio of CD4+/CD8+ T lymphocyte in the spleen and the number of activated macrophages stimulated by DNCB. Besides, the expression of iNOS and COX-2 were down-regulated in the dorsal skin. CONCLUSIONS VYE showed therapeutic effects on atopic dermatitis in DNCB-induced AD-like lesion mouse models by inhibiting the T cell-mediated allergic immune response. Our results indicated that VY could act as a potential remedy for atopic dermatitis.
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Affiliation(s)
- Pinglong Fan
- National Engineering Research Center for Modernization of Traditional Chinese Medicine- Hakka Medical Resources Branch, School of Pharmacy, Gannan Medical University, Ganzhou, 341000, People's Republic of China
| | - Yanling Yang
- National Engineering Research Center for Modernization of Traditional Chinese Medicine- Hakka Medical Resources Branch, School of Pharmacy, Gannan Medical University, Ganzhou, 341000, People's Republic of China
| | - Tao Liu
- Jiangxi Gannan Haixin Pharmaceutical Co., Ltd, Ganzhou, 341000, People's Republic of China
| | - Xiaolu Lu
- National Engineering Research Center for Modernization of Traditional Chinese Medicine- Hakka Medical Resources Branch, School of Pharmacy, Gannan Medical University, Ganzhou, 341000, People's Republic of China
| | - Hao Huang
- National Engineering Research Center for Modernization of Traditional Chinese Medicine- Hakka Medical Resources Branch, School of Pharmacy, Gannan Medical University, Ganzhou, 341000, People's Republic of China
| | - Lei Chen
- National Engineering Research Center for Modernization of Traditional Chinese Medicine- Hakka Medical Resources Branch, School of Pharmacy, Gannan Medical University, Ganzhou, 341000, People's Republic of China.
| | - Ying Kuang
- National Engineering Research Center for Modernization of Traditional Chinese Medicine- Hakka Medical Resources Branch, School of Pharmacy, Gannan Medical University, Ganzhou, 341000, People's Republic of China.
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Asada N, Morita R, Kamiji R, Kuwajima M, Komorisono M, Yamamura T, Ono N, Kanaya S, Yoshikawa S. Evaluation of intercellular lipid lamellae in the stratum corneum by polarized microscopy. Skin Res Technol 2021; 28:391-401. [PMID: 34751451 PMCID: PMC9907717 DOI: 10.1111/srt.13109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Accepted: 09/25/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND Intercellular lipids contain a lamellar structure that glows in polarized images. It could be expected that the intercellular lipid content be estimated from the luminance values calculated from polarized images of stratum corneum strips. Therefore, we attempted to develop a method for simple and rapid evaluation of the intercellular lipid content through a procedure. Herein, we demonstrated a relationship between the luminance value and the amount of ceramides, one of the main components of intercellular lipids. MATERIALS AND METHODS The stratum corneum was collected from the forearm using slides with a pure rubber-based adhesive, which did not produce unnecessary luminescence under polarizing conditions. Images were analyzed using luminance indices. The positive secondary ion peak images were obtained using the time of flight-secondary ion mass spectrometry; the polarized and brightfield images were obtained using a polarized microscope. The ceramide and protein amount was measured by high-performance liquid chromatography and bicinchoninic acid protein assay after microscope imaging. Images and quantitative values were used to construct evaluation models based on a convolutional neural network (CNN). RESULTS There was a correlation between the highlighted areas of the polarized image to overlap with the area where ceramide-derived peak was detected. Evaluation of the CNN-based model of the polarized images predicted the amount of ceramides per unit of stratum corneum. CONCLUSION The method proposed in the study enabled a large number of specimens to provide a simple, rapid, and efficient evaluation of the intercellular lipid content.
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Affiliation(s)
- Naoki Asada
- KOBAYASHI Pharmaceutical, Co. Ltd., Ibaraki, Japan.,Department of Science and Technology, NARA Institute of Science and Technology, Ikoma, Japan
| | - Ryo Morita
- KOBAYASHI Pharmaceutical, Co. Ltd., Ibaraki, Japan
| | - Rikae Kamiji
- KOBAYASHI Pharmaceutical, Co. Ltd., Ibaraki, Japan
| | | | | | | | - Naoaki Ono
- Department of Science and Technology, NARA Institute of Science and Technology, Ikoma, Japan.,Data Science Center, NARA Institute of Science and Technology, Ikoma, Japan
| | - Shigehiko Kanaya
- Department of Science and Technology, NARA Institute of Science and Technology, Ikoma, Japan
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Hassoun D, Malard O, Barbarot S, Magnan A, Colas L. Type 2 immunity-driven diseases: Towards a multidisciplinary approach. Clin Exp Allergy 2021; 51:1538-1552. [PMID: 34617355 PMCID: PMC9292742 DOI: 10.1111/cea.14029] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 08/23/2021] [Accepted: 09/08/2021] [Indexed: 12/31/2022]
Abstract
Asthma, atopic dermatitis and chronic rhinoconjunctivitis are highly heterogeneous. However, epidemiologic associations exist between phenotypic groups of patients. Atopic march is one such association but is not the only common point. Indeed, beyond such phenotypes, hallmarks of type 2 immunity have been found in these diseases involving immune dysregulation as well as environmental triggers and epithelial dysfunction. From the canonical Th2 cytokines (IL-4, IL-5, IL-13), new cellular and molecular actors arise, from the epithelium's alarmins to new innate immune cells. Their interactions are now better understood across the different environmental barriers, and slight differences appeared. In parallel, the development of type 2-targeting biotherapies not only raised hope to treat those diseases but also raised new questions regarding their true pathophysiological involvement. Here, we review the place of type 2 immunity in the different phenotypes of asthma, chronic rhinitis, chronic rhinosinusitis and atopic dermatitis, highlighting nuances between them. New hypotheses rising from the use of biotherapies will be discussed along with the uncertainties and unmet needs of this field.
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Affiliation(s)
- Dorian Hassoun
- CHU Nantes, CNRS, INSERM, l'institut du Thorax, Université de Nantes, Nantes, France
| | - Olivier Malard
- Department of Otorhinolaryngology and Head and Neck Surgery, Nantes University Hospital, Nantes, France
| | - Sébastien Barbarot
- Department of Dermatology, CHU Nantes, UMR 1280 PhAN, INRA, Nantes Université, Nantes, France
| | - Antoine Magnan
- INRAe UMR_S 0892, Hôpital Foch, Université de Versailles Saint-Quentin, Paris Saclay, France
| | - Luc Colas
- Plateforme Transversale d'Allergologie et d'Immunologie Clinique, Institut du Thorax, CHU de Nantes, Nantes, France.,INSERM, CHU Nantes, Centre de Recherche en Transplantation et Immunologie UMR1064, Nantes Université, ITUN, Nantes, France
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Schneider S, Li L, Zink A. The New Era of Biologics in Atopic Dermatitis: A Review. Dermatol Pract Concept 2021; 11:e2021144. [PMID: 35024236 DOI: 10.5826/dpc.1104a144] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/19/2021] [Indexed: 12/24/2022] Open
Abstract
Atopic dermatitis (AD) is a prevalent inflammatory skin disorder affecting all age and ethnic groups. The age-dependent varying appearance and extent of pruritic lesions are accompanied by distinct individual suffering, highlighting the importance of effective treatment options. Over the past years systemic drugs have considerably extended therapeutic approaches of patients with moderate to severe AD, in particular new biologics, most notably dupilumab has appeared as major breakthrough. In addition to monoclonal blockade of IL-4 and IL-13 pathway, more cytokines have been found to play a substantial role in AD pathogenesis, presenting potential targets for new therapy options.
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Affiliation(s)
- Simon Schneider
- Technical University of Munich, School of Medicine, Department of Dermatology and Allergy, Munich, Germany
| | - Linda Li
- Technical University of Munich, School of Medicine, Department of Dermatology and Allergy, Munich, Germany
| | - Alexander Zink
- Technical University of Munich, School of Medicine, Department of Dermatology and Allergy, Munich, Germany.,Division of Dermatology and Venereology, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden
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Fujii M. The Pathogenic and Therapeutic Implications of Ceramide Abnormalities in Atopic Dermatitis. Cells 2021; 10:2386. [PMID: 34572035 PMCID: PMC8468445 DOI: 10.3390/cells10092386] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 09/05/2021] [Accepted: 09/07/2021] [Indexed: 11/16/2022] Open
Abstract
Ceramides play an essential role in forming a permeability barrier in the skin. Atopic dermatitis (AD) is a common chronic skin disease associated with skin barrier dysfunction and immunological abnormalities. In patients with AD, the amount and composition of ceramides in the stratum corneum are altered. This suggests that ceramide abnormalities are involved in the pathogenesis of AD. The mechanism underlying lipid abnormalities in AD has not yet been fully elucidated, but the involvement of Th2 and Th1 cytokines is implicated. Ceramide-dominant emollients have beneficial effects on skin barrier function; thus, they have been approved as an adjunctive barrier repair agent for AD. This review summarizes the current understanding of the mechanisms of ceramide abnormalities in AD. Furthermore, the potential therapeutic approaches for correcting ceramide abnormalities in AD are discussed.
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Affiliation(s)
- Masanori Fujii
- Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan
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Holvoet S, Nutten S, Dupuis L, Donnicola D, Bourdeau T, Hughes-Formella B, Simon D, Simon HU, Carvalho RS, Spergel JM, Koletzko S, Blanchard C. Partially Hydrolysed Whey-Based Infant Formula Improves Skin Barrier Function. Nutrients 2021; 13:nu13093113. [PMID: 34578990 PMCID: PMC8472312 DOI: 10.3390/nu13093113] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 08/24/2021] [Accepted: 09/01/2021] [Indexed: 12/25/2022] Open
Abstract
Specific partially hydrolysed whey-based infant formulas (pHF-W) have been shown to decrease the risk of atopic dermatitis (AD) in infants. Historically, AD has been associated primarily with milk allergy; however, defective skin barrier function can be a primary cause of AD. We aimed to ascertain whether oral supplementation with pHF-W can improve skin barrier function. The effect of pHF-W was assessed on transepidermal water loss (TEWL) and antibody productions in mice epicutaneously exposed to Aspergillus fumigatus. Human primary keratinocytes were stimulated in vitro, and the expression of genes related to skin barrier function was measured. Supplementation with pHF-W in neonatal mice led to a significant decrease in TEWL and total IgE, but not in allergen-specific antibody levels. The whey hydrolysate was sufficient to decrease both TEWL and total IgE. Aquaporin-3 gene expression, linked with skin hydration, was modulated in the skin of mice and human primary keratinocytes following protein hydrolysate exposure. Skin barrier improvement may be an additional mechanism by which pHF-W may potentially reduce the risk of AD development in infants. Further human studies are warranted to confirm the clinical efficacy of these observations.
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Affiliation(s)
- Sébastien Holvoet
- Department of Gastrointestinal Health, Nestlé Institute of Health Sciences, Nestlé Research, Société des Produits Nestlé S.A., Vers-chez-les-Blanc, 1000 Lausanne, Switzerland; (S.H.); (S.N.); (D.D.); (T.B.)
| | - Sophie Nutten
- Department of Gastrointestinal Health, Nestlé Institute of Health Sciences, Nestlé Research, Société des Produits Nestlé S.A., Vers-chez-les-Blanc, 1000 Lausanne, Switzerland; (S.H.); (S.N.); (D.D.); (T.B.)
| | - Lénaïck Dupuis
- Biostatistics and Data Management, Clinical Research Unit, Nestlé Research, Société des Produits Nestlé S.A., Vers-chez-les-Blanc, 1000 Lausanne, Switzerland;
| | - Dominique Donnicola
- Department of Gastrointestinal Health, Nestlé Institute of Health Sciences, Nestlé Research, Société des Produits Nestlé S.A., Vers-chez-les-Blanc, 1000 Lausanne, Switzerland; (S.H.); (S.N.); (D.D.); (T.B.)
| | - Tristan Bourdeau
- Department of Gastrointestinal Health, Nestlé Institute of Health Sciences, Nestlé Research, Société des Produits Nestlé S.A., Vers-chez-les-Blanc, 1000 Lausanne, Switzerland; (S.H.); (S.N.); (D.D.); (T.B.)
| | | | - Dagmar Simon
- Department of Dermatology, Inselspital, Bern University Hospital, 3010 Bern, Switzerland;
| | - Hans-Uwe Simon
- Institute of Pharmacology, University of Bern, 3012 Bern, Switzerland;
- Department of Clinical Immunology and Allergology, Sechenov University, 119991 Moscow, Russia
- Laboratory of Molecular Immunology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia
- Institute of Biochemistry, Medical School Brandenburg, 16816 Neuruppin, Germany
| | | | - Jonathan M. Spergel
- Department of Pediatrics, Children’s Hospital of Philadelphia, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA 19104, USA;
| | - Sibylle Koletzko
- Department of Pediatrics, Dr. von Hauner Children’s Hospital and University Hospital, LMU Munich, 80337 Munich, Germany;
- Department of Pediatrics, Gastroenterology and Nutrition, School of Medicine Collegium Medicum, University of Warmia and Mazury, 10-719 Olsztyn, Poland
| | - Carine Blanchard
- Department of Gastrointestinal Health, Nestlé Institute of Health Sciences, Nestlé Research, Société des Produits Nestlé S.A., Vers-chez-les-Blanc, 1000 Lausanne, Switzerland; (S.H.); (S.N.); (D.D.); (T.B.)
- Correspondence: ; Tel.: +41-21-785-87-56
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