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Dermatology: Advances in Pathophysiology and Therapies (2nd Edition)
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Dermatology: Advances in Pathophysiology and Therapies (2nd Edition)

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (20 April 2025) | Viewed by 20136

Special Issue Editors

Prof. Dr. Montserrat Fernández-Guarino

E-Mail Website
Guest Editor
1. Servicio de Dermatología, Head of Hospitalization and Emergencies in Dermatology, Hospital Ramon y Cajal Madrid, Madrid, Spain
2. Instituto Ramón y Cajal de Investigación Sanitaria, IRYCIS, Madrid, Spain
Interests: cutaneous drug reactions; cutaneous lymphoma; dermatological emergencies; severe dermatological patient; erythroderma; cutaneous vasculitis; graft versus host disease; phototherapy; photobiology
Special Issues, Collections and Topics in MDPI journals
Dr. Belén De la Hoz

E-Mail Website
Guest Editor
Head, Allergy Department, University Ramón y Cajal Hospital, Carretera de Colmenar Km. 9, 100, 28034 Madrid, Spain
Interests: skin disease; dermatology
Dr. Javier Martínez-Botas

E-Mail Website
Guest Editor
Biochemistry-Research Department, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria, Carretera de Colmenar Km 9, 28034 Madrid, Spain
Interests: allergy; epitope mapping; microarray; lipid metabolism; cholesterol

Special Issue Information

Dear Colleagues,

Dermatology has undergone profound alterations over the last decade. Today, subspecialisation is needed for the management of inflammatory and complex dermatosis as remaining updated in all fields of dermatology is difficult. Furthermore, new target therapies are emerging along with the discovery of new paths and pathogenic mechanisms. Therefore, interaction with other medical specialties and multidisciplinary management is mandatory.

The new times in dermatology need to be open minded and innovative in hospital practise. Coordination between researchers, diagnosis and possible therapies undoubtedly will advance the work of physicians and benefit patients.

In this Special Issue, entitled “Dermatology: Advances on Pathophysiology and Therapies”, we aim to present this reality and a review of our experience working in coordination, adding a review of the relevant literature. We believe that would be a very useful reference and, thus, we invite physicians working in the field of this novel concept to share their experience and submit their work for publication in the International Journal of Molecular Science. We hope to develop an amazing Issue capable of representing the modern era in medical dermatology.

Prof. Dr. Montserrat Fernández-Guarino
Dr. Belén De la Hoz
Dr. Javier Martínez-Botas
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • immunodermatology
  • cutaneous lymphoma
  • cutaneous drug reaction
  • erythroderma
  • psoriasis
  • atopic dermatitis
  • eczematous reactions
  • cutaneous manifestation of systemic diseases
  • cutaneous vasculitis

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Related Special Issue

Published Papers (8 papers)

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Research

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15 pages, 5585 KiB  
Article
Effect of Combination of Blue and Red Light with Terbinafine on Cell Viability and Reactive Oxygen Species in Human Keratinocytes: Potential Implications for Cutaneous Mycosis
by Luis Alfonso Pérez González, María Antonia Martínez-Pascual, Elena Toledano-Macías, Rosa Cristina Jara-Laguna, Montserrat Fernández-Guarino and María Luisa Hernández-Bule
Int. J. Mol. Sci. 2024, 25(22), 12145; https://doi.org/10.3390/ijms252212145 - 12 Nov 2024
Viewed by 972
Abstract
Cutaneous mycoses are common infections whose treatment has become more complex due to increasing antifungal resistance and the need for prolonged therapies, hindering patient adherence and increasing the incidence of adverse effects. Consequently, the use of physical therapies, especially photodynamic therapy (PDT), has [...] Read more.
Cutaneous mycoses are common infections whose treatment has become more complex due to increasing antifungal resistance and the need for prolonged therapies, hindering patient adherence and increasing the incidence of adverse effects. Consequently, the use of physical therapies, especially photodynamic therapy (PDT), has increased for the treatment of onychomycosis due to its antimicrobial capacity being mediated by the production of reactive oxygen species. This study investigates the in vitro effect of applying blue light (448 nm) or red light (645 nm), alone or together with terbinafine, on the viability of human keratinocytes and the production of reactive oxygen species. The combination of terbinafine and blue light significantly increases ROS production and caspase-3 expression, while red light together with terbinafine increases catalase, superoxide dismutase (SOD) and PPARγ expression, which reduces the amount of ROS in the cultures. The effect of both treatments could be useful in clinical practice to improve the response of cutaneous mycoses to pharmacological treatment, reduce their toxicity and shorten their duration. Full article
(This article belongs to the Special Issue Dermatology: Advances in Pathophysiology and Therapies (2nd Edition))
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11 pages, 2819 KiB  
Communication
Rare Filaggrin Variants Are Associated with Pustular Skin Diseases in Asians
by Luca Lo Piccolo, Wasinee Wongkummool, Phatcharida Jantaree, Teerada Daroontum, Suteeraporn Chaowattanapanit, Charoen Choonhakarn, Warayuwadee Amornpinyo, Romanee Chaiwarith, Salin Kiratikanon, Rujira Rujiwetpongstorn, Napatra Tovanabutra, Siri Chiewchanvit, Chumpol Ngamphiw, Worrachet Intachai, Piranit Kantaputra and Mati Chuamanochan
Int. J. Mol. Sci. 2024, 25(12), 6466; https://doi.org/10.3390/ijms25126466 - 12 Jun 2024
Viewed by 1292
Abstract
Reactive pustular eruptions (RPEs) can manifest in a variety of conditions, including pustular psoriasis (PP) and adult-onset immunodeficiency syndrome due to anti-interferon-γ autoantibody (AOID). These RPEs can be attributed to different causes, one of which is genetic factors. However, the genetic basis for [...] Read more.
Reactive pustular eruptions (RPEs) can manifest in a variety of conditions, including pustular psoriasis (PP) and adult-onset immunodeficiency syndrome due to anti-interferon-γ autoantibody (AOID). These RPEs can be attributed to different causes, one of which is genetic factors. However, the genetic basis for pustular skin diseases remains poorly understood. In our study, we conducted whole-exome sequencing on a cohort of 17 AOID patients with pustular reactions (AOID-PR) and 24 PP patients. We found that 76% and 58% of the AOID-PR and PP patients, respectively, carried rare genetic variations within the filaggrin (FLG) gene family. A total of 12 out of 21 SNPs on FLG had previously received clinical classifications, with only p.Ser2706Ter classified as pathogenic. In contrast, none of the FLG3 SNPs identified in this study had prior clinical classifications. Overall, these variations had not been previously documented in cases of pustular disorders, and two of them were entirely novel discoveries. Immunohistochemical analysis of skin biopsies revealed that FLG variants like p.Ser860Trp, p.Gly3903Ter, p.Gly2440Glu, and p.Glu2133Asp caused reductions in FLG levels similar to the pathogenic FLG p.Ser2706Ter. These results highlight rare FLG variants as potential novel genetic risk factors contributing to pustule formation in both AOID and PP. Full article
(This article belongs to the Special Issue Dermatology: Advances in Pathophysiology and Therapies (2nd Edition))
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Review

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16 pages, 1454 KiB  
Review
Managing a Burning Face: Clinical Manifestations and Therapeutic Approaches for Neurogenic Rosacea
by Gabriel Aedo, Marco Chahuán, Elsa Gatica, Isabel Herrera, Luis Felipe Parada, Alvaro Seguel, Nigel P. Murray, Sócrates Aedo and Diego Aragón-Caqueo
Int. J. Mol. Sci. 2025, 26(5), 2366; https://doi.org/10.3390/ijms26052366 - 6 Mar 2025
Viewed by 1641
Abstract
Rosacea is a common chronic inflammatory condition primarily affecting middle-aged women. It presents with flushing, erythema, telangiectasia, papules, pustules, phymatous changes, and ocular involvement. Although typically grouped into four subtypes—erythematotelangiectatic, papulopustular, ocular, and phymatous—overlapping features often favor a phenotypic diagnostic approach. Neurogenic rosacea [...] Read more.
Rosacea is a common chronic inflammatory condition primarily affecting middle-aged women. It presents with flushing, erythema, telangiectasia, papules, pustules, phymatous changes, and ocular involvement. Although typically grouped into four subtypes—erythematotelangiectatic, papulopustular, ocular, and phymatous—overlapping features often favor a phenotypic diagnostic approach. Neurogenic rosacea (NR) has emerged as a distinct subgroup featuring distinguishing features such as peripheral facial erythema, severe burning and stinging sensations, and resistance to standard rosacea therapies. Recent insights into the pathophysiology of NR propose neural dysregulation as the main driver of the condition. Specifically, the activation of TRP channels at cutaneous sensory nerve endings in the dermis triggers the release of vasoactive peptides, driving neuroinflammation and resulting in burning and stinging. Additionally, there is a marked association with neuropsychiatric comorbidities, which would further mediate the pathogenesis of the condition. In line with this pathophysiological model, NR often fails to respond to conventional rosacea treatments. Instead, patients benefit more from antidepressants and neuroleptic agents that help modulate neuronal activity and alleviate symptoms. This review explores and summarizes the scientific evidence regarding the new insights on disease pathogenesis, clinical manifestations, and proposed treatments for NR. Full article
(This article belongs to the Special Issue Dermatology: Advances in Pathophysiology and Therapies (2nd Edition))
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39 pages, 3256 KiB  
Review
zDHHC-Mediated S-Palmitoylation in Skin Health and Its Targeting as a Treatment Perspective
by Farah A. Abdulrahman, King A. Benford, Gregory T. Lin, Andrew J. Maroun, Caleb Sammons, Darya N. Shirzad, Harrison Tsai, Vincent L. Van Brunt, Zack Jones, Jafet E. Marquez, Evan C. Ratkus, Abdulrahman K. Shehadeh, Hugo Abasto Valle, Dea Fejzo, Ashlynn E. Gilbert, Catherine A. McWee, Lexie F. Underwood, Ethny Indico, Brittany B. Rork and Meera Nanjundan
Int. J. Mol. Sci. 2025, 26(4), 1673; https://doi.org/10.3390/ijms26041673 - 15 Feb 2025
Viewed by 1680
Abstract
S-acylation, which includes S-palmitoylation, is the only known reversible lipid-based post-translational protein modification. S-palmitoylation is mediated by palmitoyl acyltransferases (PATs), a family of 23 enzymes commonly referred to as zDHHCs, which catalyze the addition of palmitate to cysteine residues on specific target proteins. [...] Read more.
S-acylation, which includes S-palmitoylation, is the only known reversible lipid-based post-translational protein modification. S-palmitoylation is mediated by palmitoyl acyltransferases (PATs), a family of 23 enzymes commonly referred to as zDHHCs, which catalyze the addition of palmitate to cysteine residues on specific target proteins. Aberrant S-palmitoylation events have been linked to the pathogenesis of multiple human diseases. While there have been advances in elucidating the molecular mechanisms underlying the pathogenesis of various skin conditions, there remain gaps in the knowledge, specifically with respect to the contribution of S-palmitoylation to the maintenance of skin barrier function. Towards this goal, we performed PubMed literature searches relevant to S-palmitoylation in skin to define current knowledge and areas that may benefit from further research studies. Furthermore, to identify alterations in gene products that are S-palmitoylated, we utilized bioinformatic tools such as SwissPalm and analyzed relevant data from publicly available databases such as cBioportal. Since the targeting of S-palmitoylated targets may offer an innovative treatment perspective, we surveyed small molecules inhibiting zDHHCs, including 2-bromopalmitate (2-BP) which is associated with off-target effects, and other targeting strategies. Collectively, our work aims to advance both basic and clinical research on skin barrier function with a focus on zDHHCs and relevant protein targets that may contribute to the pathogenesis of skin conditions such as atopic dermatitis, psoriasis, and skin cancers including melanoma. Full article
(This article belongs to the Special Issue Dermatology: Advances in Pathophysiology and Therapies (2nd Edition))
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30 pages, 3165 KiB  
Review
The RAGE Pathway in Skin Pathology Development: A Comprehensive Review of Its Role and Therapeutic Potential
by Marcin Radziszewski, Ryszard Galus, Krzysztof Łuszczyński, Sebastian Winiarski, Dariusz Wąsowski, Jacek Malejczyk, Paweł Włodarski and Aneta Ścieżyńska
Int. J. Mol. Sci. 2024, 25(24), 13570; https://doi.org/10.3390/ijms252413570 - 18 Dec 2024
Cited by 2 | Viewed by 1584
Abstract
The receptor for advanced glycation end-products (RAGE), a member of the immunoglobulin superfamily, is expressed in various cell types and mediates cellular responses to a wide range of ligands. The activation of RAGE triggers complex signaling pathways that drive inflammatory, oxidative, and proliferative [...] Read more.
The receptor for advanced glycation end-products (RAGE), a member of the immunoglobulin superfamily, is expressed in various cell types and mediates cellular responses to a wide range of ligands. The activation of RAGE triggers complex signaling pathways that drive inflammatory, oxidative, and proliferative responses, which are increasingly implicated in the pathogenesis of skin diseases. Despite its well-established roles in conditions such as diabetes, cancer, and chronic inflammation, the contribution of RAGE to skin pathologies remains underexplored. This review synthesizes current findings on RAGE’s involvement in the pathophysiology of skin diseases, including conditions such as psoriasis, atopic dermatitis, and lichen planus, focusing on its roles in inflammatory signaling, tissue remodeling, and skin cancer progression. Additionally, it examines RAGE-modulating treatments investigated in dermatological contexts, highlighting their potential as therapeutic options. Given RAGE’s significance in a variety of skin conditions, further research into its mediated pathways may uncover new opportunities for targeted interventions in skin-specific RAGE signaling. Full article
(This article belongs to the Special Issue Dermatology: Advances in Pathophysiology and Therapies (2nd Edition))
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35 pages, 20176 KiB  
Review
Skin Aging and the Upcoming Role of Ferroptosis in Geroscience
by Rita Rezzani, Gaia Favero, Giorgia Cominelli, Daniela Pinto and Fabio Rinaldi
Int. J. Mol. Sci. 2024, 25(15), 8238; https://doi.org/10.3390/ijms25158238 - 28 Jul 2024
Cited by 1 | Viewed by 2392
Abstract
The skin is considered the most important organ system in mammals, and as the population ages, it is important to consider skin aging and anti-aging therapeutic strategies. Exposure of the skin to various insults induces significant changes throughout our lives, differentiating the skin [...] Read more.
The skin is considered the most important organ system in mammals, and as the population ages, it is important to consider skin aging and anti-aging therapeutic strategies. Exposure of the skin to various insults induces significant changes throughout our lives, differentiating the skin of a young adult from that of an older adult. These changes are caused by a combination of intrinsic and extrinsic aging. We report the interactions between skin aging and its metabolism, showing that the network is due to several factors. For example, iron is an important nutrient for humans, but its level increases with aging, inducing deleterious effects on cellular functions. Recently, it was discovered that ferroptosis, or iron-dependent cell death, is linked to aging and skin diseases. The pursuit of new molecular targets for ferroptosis has recently attracted attention. Prevention of ferroptosis is an effective therapeutic strategy for the treatment of diseases, especially in old age. However, the pathological and biological mechanisms underlying ferroptosis are still not fully understood, especially in skin diseases such as melanoma and autoimmune diseases. Only a few basic studies on regulated cell death exist, and the challenge is to turn the studies into clinical applications. Full article
(This article belongs to the Special Issue Dermatology: Advances in Pathophysiology and Therapies (2nd Edition))
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16 pages, 1200 KiB  
Review
A Breakthrough in the Treatment of Necrobiosis Lipoidica? Update on Treatment, Etiopathogenesis, Diagnosis, and Clinical Presentation
by Maciej Naumowicz, Stefan Modzelewski, Angelika Macko, Bartosz Łuniewski, Anna Baran and Iwona Flisiak
Int. J. Mol. Sci. 2024, 25(6), 3482; https://doi.org/10.3390/ijms25063482 - 20 Mar 2024
Cited by 4 | Viewed by 5518
Abstract
Necrobiosis lipoidica (NL) is a rare granulomatous disease of a not fully understood etiopathogenesis. Classically, NL is associated with insulin-dependent diabetes mellitus. The disease often fails to respond to conventional treatments and adversely affects patients’ quality of life. First-line medications are usually topical [...] Read more.
Necrobiosis lipoidica (NL) is a rare granulomatous disease of a not fully understood etiopathogenesis. Classically, NL is associated with insulin-dependent diabetes mellitus. The disease often fails to respond to conventional treatments and adversely affects patients’ quality of life. First-line medications are usually topical corticosteroids, but patients respond to them with varying degrees of success. Other options include tacrolimus, phototherapy, cyclosporine, fumaric acid esters, and biologics (adalimumab, etanercept, and infliximab). Our review aims to present new therapeutic approaches potentially effective in patients with refractory lesions, describe the presumed etiopathogenesis, and provide diagnostic guidance for clinicians. The review concludes that Janus kinase inhibitors and biologics such as ustekinumab and secukinumab can be used effectively in patients with recalcitrant NL. Another promising treatment option is tapinarof (an aryl hydrocarbon receptor agonist). However, studies on larger groups of patients are still needed to evaluate the effectiveness of different therapeutic options and to define consistent treatment regimens for NL. It is advisable to improve the awareness of physicians of various specialties regarding necrobiosis lipoidica as lesions diagnosed earlier usually have a better response to treatment. Full article
(This article belongs to the Special Issue Dermatology: Advances in Pathophysiology and Therapies (2nd Edition))
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21 pages, 3425 KiB  
Review
Clinical and Real-World Effectiveness of Mogamulizumab: A Narrative Review
by Montserrat Fernández-Guarino, Pablo Ortiz, Fernando Gallardo and Mar Llamas-Velasco
Int. J. Mol. Sci. 2024, 25(4), 2203; https://doi.org/10.3390/ijms25042203 - 12 Feb 2024
Cited by 6 | Viewed by 4291
Abstract
Mogamulizumab (MOG) is an antibody targeting the CCR4 receptor, authorized for relapsed or refractory peripheral T-cell (PTCL) and cutaneous T-cell lymphomas (CTCL). Its adoption in guidelines and endorsement by FDA and EMA established it as a systemic treatment, especially for advanced disease stages [...] Read more.
Mogamulizumab (MOG) is an antibody targeting the CCR4 receptor, authorized for relapsed or refractory peripheral T-cell (PTCL) and cutaneous T-cell lymphomas (CTCL). Its adoption in guidelines and endorsement by FDA and EMA established it as a systemic treatment, especially for advanced disease stages due to its comparatively lower toxicity. Clinical trials and real-world evidence have underscored its efficacy in advanced CTCLs, including mycosis fungoides and Sézary syndrome; PTCLs; and adult T-cell leukemia/lymphoma (ATLL), showcasing positive outcomes. Notably, the drug has demonstrated significant response rates, disease stability, and extended periods of progression-free survival, suggesting its applicability in cases with multiple treatment lines. Its safety profile is generally manageable, with adverse events (AEs) primarily related to the skin, infusion-related reactions, drug eruptions, autoimmune diseases, and skin disorders. The latter seem to appear as CCR4 can promote the skin-specific homing of lymphocytes, and MOG is directed against this receptor. While combination with immunostimulatory agents like interferon alpha and interleukin 12 has shown promising results, caution is urged when combining with PD1 inhibitors due to the heightened risk of immune-mediated AEs. The introduction of MOG as a systemic treatment implies a significant advancement in managing these diseases, supported by its favorable safety profile and complementary mechanisms. Full article
(This article belongs to the Special Issue Dermatology: Advances in Pathophysiology and Therapies (2nd Edition))
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