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Dermatology: Advances on Pathophysiology and Therapies

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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 (31 October 2023) | Viewed by 20765

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Special Issue Editors

Prof. Dr. Montserrat Fernández-Guarino

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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. Asunción Ballester-Martinez

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Guest Editor

1. Servicio de Dermatología, Hospital Ramon y Cajal Madrid, Madrid, Spain
2. Instituto Ramón y Cajal de Investigación Sanitaria, IRYCIS, Madrid, Spain
Interests: pemphigus; pemphigoid; bullous dermatosis; dermatitis herpetiformis; linear Ig A dermatosis; psoriasis; hidrosadenitis; lymphomas

Dr. Andrés González-García

E-Mail Website
Guest Editor

1. Servicio de Dermatología, Hospital Ramon y Cajal Madrid, Madrid, Spain
2. Instituto Ramón y Cajal de Investigación Sanitaria, IRYCIS, Madrid, Spain
Interests: complex patient in dermatology; autoimmune diseases; autoinflammatory syndromes; neutrophilic dermatosis; dermatologic manifestations in patient with systemic diseases

Special Issue Information

Dear Colleagues,

Dermatology has deeply changed in the last decade. Nowadays subspecialisation is needed for the management of inflammatory and complex dermatosis as being updated in all fields of dermatology is hard. Furthermore, new target therapies are emerging along with the discovering of new paths and pathogenic mechanisms. Therefore, interaction with other medical specialities 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 get physicians ahead 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 the literature review. We believe it would be very useful and a reference, and thus, we invite physicians working in this novel concept to share their experience and submit their work for publication in the International Journal of Molecular Science. We hope to develop and amazing issue representing the modern era in medical dermatology.

Prof. Dr. Montserrat Fernández-Guarino
Dr. Asunción Ballester-Martinez
Dr. Andrés González-García
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

Related Special Issue

Dermatology: Advances on Pathophysiology and Therapies 2.0 in International Journal of Molecular Sciences (2 articles)

Published Papers (11 papers)

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Research

Jump to: Review

13 pages, 1330 KiB

Open AccessArticle

Predictive Performances of Blood-Count-Derived Inflammatory Markers for Liver Fibrosis Severity in Psoriasis Vulgaris

by Oana Mirela Tiucă, Silviu Horia Morariu, Claudia Raluca Mariean, Robert Aurelian Tiucă, Alin Codrut Nicolescu and Ovidiu Simion Cotoi

Int. J. Mol. Sci. 2023, 24(23), 16898; https://doi.org/10.3390/ijms242316898 - 29 Nov 2023

Cited by 2 | Viewed by 938

Abstract

Psoriasis is an immune-mediated, chronic disorder that significantly alters patients’ quality of life and predisposes them to a higher risk of comorbidities, including liver fibrosis. Various non-invasive tests (NITs) have been validated to assess liver fibrosis severity, while blood-count-derived inflammatory markers have been proven to be reliable in reflecting inflammatory status in psoriatic disease. The fibrosis-4 (FIB-4) index became part of the newest guideline for monitoring psoriasis patients undergoing systemic treatment. Patients with psoriasis vulgaris and fulfilling inclusion criteria were enrolled in this study, aiming to assess for the first time in the literature whether such inflammatory markers are useful in predicting liver fibrosis. Based on internationally validated FIB-4 index values, patients were divided into two study groups: a low risk of significant fibrosis (LR-SF) and a high risk of significant fibrosis (HR-SF). Patients from HR-SF were significantly older and had higher values of the monocyte-to-lymphocyte ratio (MLR) (p < 0.001), which further significantly correlated with fibrosis severity (p < 0.001). Platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), platelet-to-white blood cell ratio (PWR), and aggregate index of systemic inflammations (AISI) significantly correlated negatively with liver fibrosis (p < 0.001). PWR proved to be the most reliable inflammatory predictor of fibrosis severity (AUC = 0.657). MLR, PWR, and AISI were independent inflammatory markers in multivariate analysis (p < 0.001), while the AST to platelet ratio index (APRI) and AST to ALT ratio (AAR) can be used as additional NITs for significant liver fibrosis (p < 0.001). In limited-resources settings, blood-count-derived inflammatory markers such as MLR, PWR, and AISI, respectively, and hepatic indexes APRI and AAR prove to be of particular help in predicting significant liver fibrosis. Full article

(This article belongs to the Special Issue Dermatology: Advances on Pathophysiology and Therapies)

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20 pages, 5772 KiB

Open AccessArticle

Comprehensive Physicochemical Characterization, In Vitro Membrane Permeation, and In Vitro Human Skin Cell Culture of a Novel TOPK Inhibitor, HI-TOPK-032

by Basanth Babu Eedara, Bhagyashree Manivannan, Wafaa Alabsi, Bo Sun, Clara Curiel-Lewandrowski, Tianshun Zhang, Ann M. Bode and Heidi M. Mansour

Int. J. Mol. Sci. 2023, 24(21), 15515; https://doi.org/10.3390/ijms242115515 - 24 Oct 2023

Viewed by 987

Abstract

Nonmelanoma skin cancers (NMSC) are the most common skin cancers, and about 5.4 million people are diagnosed each year in the United States. A newly developed T-lymphokine-activated killer cell-originated protein kinase (TOPK) inhibitor, HI-TOPK-032, is effective in suppressing colon cancer cell growth, inducing the apoptosis of colon cancer cells and ultraviolet (UV) light-induced squamous cell carcinoma (SCC). This study aimed to investigate the physicochemical properties, permeation behavior, and cytotoxicity potential of HI-TOPK-032 prior to the development of a suitable topical formulation for targeted skin drug delivery. Techniques such as scanning electron microscopy (SEM), energy-dispersive X-ray (EDX) spectroscopy, differential scanning calorimetry (DSC), hot-stage microscopy (HSM), X-ray powder diffraction (XRPD), Karl Fisher (KF) coulometric titration, Raman spectrometry, confocal Raman microscopy (CRM), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and Fourier transform infrared microscopy were used to characterize HI-TOPK-032. The dose effect of HI-TOPK-032 on in vitro cell viability was evaluated using a 2D cell culture of the human skin keratinocyte cell line (HaCaT) and primary normal human epidermal keratinocytes (NHEKs). Transepithelial electrical resistance (TEER) at the air–liquid interface as a function of dose and time was measured on the HaCAT human skin cell line. The membrane permeation behavior of HI-TOPK-032 was tested using the Strat-M^® synthetic biomimetic membrane with an in vitro Franz cell diffusion system. The physicochemical evaluation results confirmed the amorphous nature of the drug and the homogeneity of the sample with all characteristic chemical peaks. The in vitro cell viability assay results confirmed 100% cell viability up to 10 µM of HI-TOPK-032. Further, a rapid, specific, precise, and validated reverse phase-high performance liquid chromatography (RP-HPLC) method for the quantitative estimation of HI-TOPK-032 was developed. This is the first systematic and comprehensive characterization of HI-TOPK-032 and a report of these findings. Full article

(This article belongs to the Special Issue Dermatology: Advances on Pathophysiology and Therapies)

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12 pages, 703 KiB

Open AccessArticle

Value of the Lymphocyte Transformation Test for the Diagnosis of Drug-Induced Hypersensitivity Reactions in Hospitalized Patients with Severe COVID-19

by Carlos Fernández-Lozano, Emilio Solano Solares, Isabel Elías-Sáenz, Isabel Pérez-Allegue, Monserrat Fernández-Guarino, Diego Fernández-Nieto, Laura Díaz Montalvo, David González-de-Olano, Ana de Andrés, Javier Martínez-Botas and Belén de la Hoz Caballer

Int. J. Mol. Sci. 2023, 24(14), 11543; https://doi.org/10.3390/ijms241411543 - 17 Jul 2023

Viewed by 1330

Abstract

In the first wave of COVID-19, up to 20% of patients had skin lesions with variable characteristics. There is no clear evidence of the involvement of the SARS-CoV-2 virus in all cases; some of these lesions may be secondary to drug hypersensitivity. To analyze the possible cause of the skin lesions, we performed a complete allergology study on 11 patients. One year after recovery from COVID-19, we performed a lymphocyte transformation test (LTT) and Th1/Th2 cytokine secretion assays for PBMCs. We included five nonallergic patients treated with the same drugs without lesions. Except for one patient who had an immediate reaction to azithromycin, all patients had a positive LTT result for at least one of the drugs tested (azithromycin, clavulanic acid, hydroxychloroquine, lopinavir, and ritonavir). None of the nonallergic patients had a positive LTT result. We found mixed Th1/Th2 cytokine secretion (IL-4, IL-5, IL-13, and IFN-γ) in patients with skin lesions corresponding to mixed drug hypersensitivity type IVa and IVb. In all cases, we identified a candidate drug as the culprit for skin lesions during SARS-CoV-2 infection, although only three patients had a positive drug challenge. Therefore, it would be reasonable to recommend avoiding the drug in question in all cases. Full article

(This article belongs to the Special Issue Dermatology: Advances on Pathophysiology and Therapies)

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13 pages, 2045 KiB

Open AccessArticle

Anti-Fibrotic Effects of RF Electric Currents

by María Luisa Hernández-Bule, Elena Toledano-Macías, Luis Alfonso Pérez-González, María Antonia Martínez-Pascual and Montserrat Fernández-Guarino

Int. J. Mol. Sci. 2023, 24(13), 10986; https://doi.org/10.3390/ijms241310986 - 1 Jul 2023

Cited by 1 | Viewed by 1487

Abstract

Hypertrophic scars and keloids are two different manifestations of excessive dermal fibrosis and are caused by an alteration in the normal wound-healing process. Treatment with radiofrequency (RF)-based therapies has proven to be useful in reducing hypertrophic scars. In this study, the effect of one of these radiofrequency therapies, Capacitive Resistive Electrical Transfer Therapy (CRET) on biomarkers of skin fibrosis was investigated. For this, in cultures of human myofibroblasts treated with CRET therapy or sham-treated, proliferation (XTT Assay), apoptosis (TUNEL Assay), and cell migration (Wound Closure Assay) were analyzed. Furthermore, in these cultures the expression and/or localization of extracellular matrix proteins such as α-SMA, Col I, Col III (immunofluorescence), metalloproteinases MMP1 and MMP9, MAP kinase ERK1/2, and the transcription factor NFκB were also investigated (immunoblot). The results have revealed that CRET decreases the expression of extracellular matrix proteins, modifies the expression of the metalloproteinase MMP9, and reduces the activation of NFκB with respect to controls, suggesting that this therapy could be useful for the treatment of fibrotic pathologies. Full article

(This article belongs to the Special Issue Dermatology: Advances on Pathophysiology and Therapies)

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18 pages, 5925 KiB

Open AccessArticle

Innovative Rocuronium Bromide Topical Formulation for Targeted Skin Drug Delivery: Design, Comprehensive Characterization, In Vitro 2D/3D Human Cell Culture and Permeation

by Victor H. Ruiz, David Encinas-Basurto, Bo Sun, Basanth Babu Eedara, Eunmiri Roh, Neftali Ortega Alarcon, Clara Curiel-Lewandrowski, Ann M. Bode and Heidi M. Mansour

Int. J. Mol. Sci. 2023, 24(10), 8776; https://doi.org/10.3390/ijms24108776 - 15 May 2023

Cited by 1 | Viewed by 1664

Abstract

Cutaneous squamous cell carcinoma (cSCC) is the second-most common type of non-melanoma skin cancer and is linked to long-term exposure to ultraviolet (UV) radiation from the sun. Rocuronium bromide (RocBr) is an FDA-approved drug that targets p53-related protein kinase (PRPK) that inhibits the development of UV-induced cSCC. This study aimed to investigate the physicochemical properties and in vitro behavior of RocBr. Techniques such as thermal analysis, electron microscopy, spectroscopy and in vitro assays were used to characterize RocBr. A topical oil/water emulsion lotion formulation of RocBr was successfully developed and evaluated. The in vitro permeation behavior of RocBr from its lotion formulation was quantified with Strat-M^® synthetic biomimetic membrane and EpiDerm™ 3D human skin tissue. Significant membrane retention of RocBr drug was evident and more retention was obtained with the lotion formulation compared with the solution. This is the first systematic and comprehensive study to report these findings. Full article

(This article belongs to the Special Issue Dermatology: Advances on Pathophysiology and Therapies)

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Review

Jump to: Research

27 pages, 645 KiB

Open AccessReview

Vitiligo: Pathogenesis and New and Emerging Treatments

by Javier Perez-Bootello, Ruth Cova-Martin, Jorge Naharro-Rodriguez and Gonzalo Segurado-Miravalles

Int. J. Mol. Sci. 2023, 24(24), 17306; https://doi.org/10.3390/ijms242417306 - 9 Dec 2023

Cited by 1 | Viewed by 2084

Abstract

Vitiligo is a complex disease with a multifactorial nature and a high impact on the quality of life of patients. Although there are multiple therapeutic alternatives, there is currently no fully effective treatment for this disease. In the current era, multiple drugs are being developed for the treatment of autoimmune diseases. This review assesses the available evidence on the pathogenesis of vitiligo, and a comprehensive review of treatments available for vitiligo now and in the near future is provided. This qualitative analysis spans 116 articles. We reviewed the mechanism of action, efficacy and safety data of phototherapy, afamelanotide, cyclosporine, phosphodiesterase 4 inhibitors, trichloroacetic acid, basic fibroblast growth factor, tumor necrosis factor (TNF) inhibitors, secukinumab, pseudocatalase and janus kinase (JAK) inhibitors. At the moment, there is no clearly outstanding option or fully satisfactory treatment for vitiligo, so it is necessary to keep up the development of new drugs as well as the publication of long-term effectiveness and safety data for existing treatments. Full article

(This article belongs to the Special Issue Dermatology: Advances on Pathophysiology and Therapies)

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35 pages, 6385 KiB

Open AccessReview

From Molecular Insights to Clinical Perspectives in Drug-Associated Bullous Pemphigoid

by Belen de Nicolas-Ruanes, Asuncion Ballester-Martinez, Emilio Garcia-Mouronte, Emilio Berna-Rico, Carlos Azcarraga-Llobet and Montserrat Fernandez-Guarino

Int. J. Mol. Sci. 2023, 24(23), 16786; https://doi.org/10.3390/ijms242316786 - 26 Nov 2023

Cited by 1 | Viewed by 1333

Abstract

Bullous pemphigoid (BP), the most common autoimmune blistering disease, is characterized by the presence of autoantibodies targeting BP180 and BP230 in the basement membrane zone. This leads to the activation of complement-dependent and independent pathways, resulting in proteolytic cleavage at the dermoepidermal junction and an eosinophilic inflammatory response. While numerous drugs have been associated with BP in the literature, causality and pathogenic mechanisms remain elusive in most cases. Dipeptidyl peptidase 4 inhibitors (DPP4i), in particular, are the most frequently reported drugs related to BP and, therefore, have been extensively investigated. They can potentially trigger BP through the impaired proteolytic degradation of BP180, combined with immune dysregulation. DPP4i-associated BP can be categorized into true drug-induced BP and drug-triggered BP, with the latter resembling classic BP. Antineoplastic immunotherapy is increasingly associated with BP, with both B and T cells involved. Other drugs, including biologics, diuretics and cardiovascular and neuropsychiatric agents, present weaker evidence and poorly understood pathogenic mechanisms. Further research is needed due to the growing incidence of BP and the increasing identification of new potential triggers. Full article

(This article belongs to the Special Issue Dermatology: Advances on Pathophysiology and Therapies)

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19 pages, 368 KiB

Open AccessReview

Treatment Strategies in Neutrophilic Dermatoses: A Comprehensive Review

by Grisell Starita-Fajardo, David Lucena-López, María Asunción Ballester-Martínez, Montserrat Fernández-Guarino and Andrés González-García

Int. J. Mol. Sci. 2023, 24(21), 15622; https://doi.org/10.3390/ijms242115622 - 26 Oct 2023

Viewed by 905

Abstract

Neutrophilic dermatoses (NDs) are a group of noninfectious disorders characterized by the presence of a sterile neutrophilic infiltrate without vasculitis histopathology. Their physiopathology is not fully understood. The association between neutrophilic dermatoses and autoinflammatory diseases has led some authors to propose that both are part of the same spectrum of diseases. The classification of NDs depends on clinical and histopathological features. This review focuses on the recent developments of treatments in these pathologies. Full article

(This article belongs to the Special Issue Dermatology: Advances on Pathophysiology and Therapies)

20 pages, 1040 KiB

Open AccessReview

Imiquimod as Local Immunotherapy in the Management of Premalignant Cutaneous Conditions and Skin Cancer

by Emilio Garcia-Mouronte, Emilio Berna-Rico, Belen de Nicolas-Ruanes, Carlos Azcarraga-Llobet, Luis Alonso-Martinez de Salinas and Sonia Bea-Ardebol

Int. J. Mol. Sci. 2023, 24(13), 10835; https://doi.org/10.3390/ijms241310835 - 29 Jun 2023

Cited by 1 | Viewed by 1699

Abstract

Cutaneous cancers are, by far, the most common malignant neoplasms of the human being. Due to the great array of clinical conditions, their worldwide increasing incidence and the steady ageing of the population, non-invasive treatments modalities that show a good clinical response, a proper benefit–risk ratio and cosmetic results are becoming increasingly important in the clinical setting. Imiquimod is a topically applied immunomodulator which is often used in the management of several premalignant and malignant cutaneous disorders. This article is a review of the current literature on its mechanism of action, pharmacokinetics, and therapeutical effects. Full article

(This article belongs to the Special Issue Dermatology: Advances on Pathophysiology and Therapies)

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26 pages, 788 KiB

Open AccessReview

Genetic Influence on Treatment Response in Psoriasis: New Insights into Personalized Medicine

by Emilio Berna-Rico, Javier Perez-Bootello, Carlota Abbad-Jaime de Aragon and Alvaro Gonzalez-Cantero

Int. J. Mol. Sci. 2023, 24(12), 9850; https://doi.org/10.3390/ijms24129850 - 7 Jun 2023

Cited by 8 | Viewed by 1954

Abstract

Psoriasis is a chronic inflammatory disease with an established genetic background. The HLA-Cw*06 allele and different polymorphisms in genes involved in inflammatory responses and keratinocyte proliferation have been associated with the development of the disease. Despite the effectiveness and safety of psoriasis treatment, a significant percentage of patients still do not achieve adequate disease control. Pharmacogenetic and pharmacogenomic studies on how genetic variations affect drug efficacy and toxicity could provide important clues in this respect. This comprehensive review assessed the available evidence for the role that those different genetic variations may play in the response to psoriasis treatment. One hundred fourteen articles were included in this qualitative synthesis. VDR gene polymorphisms may influence the response to topical vitamin D analogs and phototherapy. Variations affecting the ABC transporter seem to play a role in methotrexate and cyclosporine outcomes. Several single-nucleotide polymorphisms affecting different genes are involved with anti-TNF-α response modulation (TNF-α, TNFRSF1A, TNFRSF1B, TNFAIP3, FCGR2A, FCGR3A, IL-17F, IL-17R, and IL-23R, among others) with conflicting results. HLA-Cw*06 has been the most extensively studied allele, although it has only been robustly related to the response to ustekinumab. However, further research is needed to firmly establish the usefulness of these genetic biomarkers in clinical practice. Full article

(This article belongs to the Special Issue Dermatology: Advances on Pathophysiology and Therapies)

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17 pages, 1639 KiB

Open AccessReview

The Role of Physical Therapies in Wound Healing and Assisted Scarring

by Montserrat Fernández-Guarino, Stefano Bacci, Luis Alfonso Pérez González, Mariano Bermejo-Martínez, Almudena Cecilia-Matilla and Maria Luisa Hernández-Bule

Int. J. Mol. Sci. 2023, 24(8), 7487; https://doi.org/10.3390/ijms24087487 - 19 Apr 2023

Cited by 14 | Viewed by 5090

Abstract

Wound healing (WH) is a complex multistep process in which a failure could lead to a chronic wound (CW). CW is a major health problem and includes leg venous ulcers, diabetic foot ulcers, and pressure ulcers. CW is difficult to treat and affects vulnerable and pluripathological patients. On the other hand, excessive scarring leads to keloids and hypertrophic scars causing disfiguration and sometimes itchiness and pain. Treatment of WH includes the cleaning and careful handling of injured tissue, early treatment and prevention of infection, and promotion of healing. Treatment of underlying conditions and the use of special dressings promote healing. The patient at risk and risk areas should avoid injury as much as possible. This review aims to summarize the role of physical therapies as complementary treatments in WH and scarring. The article proposes a translational view, opening the opportunity to develop these therapies in an optimal way in clinical management, as many of them are emerging. The role of laser, photobiomodulation, photodynamic therapy, electrical stimulation, ultrasound therapy, and others are highlighted in a practical and comprehensive approach. Full article

(This article belongs to the Special Issue Dermatology: Advances on Pathophysiology and Therapies)

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