Pyoderma Gangrenosum: The Impact of Treatment Non-adherence on Disease Progression.

Pyoderma gangrenosum (PG) is a rare, ulcerative, rapidly progressing, destructive, inflammatory cutaneous disease that is both diagnostically and therapeutically challenging. Due to the lack of standardized diagnostic criteria or conclusive guidelines for patient management, clinicians often find themselves without reliable tools for the daily management of PG patients. Additionally, the lack of strict therapeutic compliance in patients with this diagnosis might contribute to a catastrophic evolution of the condition. We report a case of ulcerative PG that is illustrative of the inherent challenges posed by patients frequently changing healthcare providers and treatment regimens, displaying inconsistency and non-adherence. Such behaviors can lead to the loss of disease control, particularly in the context of extensive or rapidly progressing PG, ultimately culminating in the development of mutilating forms of this disease.

Resveratrol and Its Derivatives in Inflammatory Skin Disorders-Atopic Dermatitis and Psoriasis: A Review.

Atopic dermatitis (AD) and psoriasis are inflammatory skin diseases whose prevalence has increased worldwide in recent decades. These disorders contribute to patients' decreased quality of life (QoL) and constitute a socioeconomic burden. New therapeutic options for AD and psoriasis based on natural compounds are being investigated. These include resveratrol (3,5,40-trihydroxystilbene) and its derivatives, which are produced by many plant species, including grapevines. Resveratrol has gained interest since the term "French Paradox", which refers to improved cardiovascular outcomes despite a high-fat diet in the French population, was introduced. Resveratrol and its derivatives have demonstrated various health benefits. In addition to anti-cancer, anti-aging, and antibacterial effects, there are also anti-inflammatory and antioxidant effects that can affect the molecular pathways of inflammatory skin disorders. A comprehensive understanding of these mechanisms may help develop new therapies. Numerous in vivo and in vitro studies have been conducted on the therapeutic properties of natural compounds. However, regarding resveratrol and its derivatives in treating AD and psoriasis, there are still many unexplained mechanisms and a need for clinical trials. Considering this, in this review, we discuss and summarize the most critical research on resveratrol and its derivatives in animal and cell models mimicking AD and psoriasis.

Secretome of human umbilical cord mesenchymal stem cell maintains skin homeostasis by regulating multiple skin physiological function.

Skin is the largest organ in the body and the first defense to resist various diseases and external stimuli that easily cause infection and inflammation. Aseptic inflammation, barrier damage, and foreign aid pressure induce the destruction and damage to the skin microenvironment. Subsequently, it destroys the skin's physiological function, leading to the maintenance and circulation of steady-state imbalance and aggravating the process of skin disorders. Our study evaluated the therapeutic potential of the secretome of human umbilical cord mesenchymal stem cells (UC-CM) for dermatological diseases in adult human skin cells, ex vivo skin tissue, and a 3D skin model. Our data suggested several advantages of UC-CM due to (1) their low cytotoxicity and sensitization properties; (2) their anti-inflammatory capacity for treating inflammatory chronic cutaneous diseases; (3) their enhanced capacity of the skin barrier for treating abnormal barrier metabolism; and (4) their positive impact on restoring skin homeostasis due to effective regulation ability of skin physiological function including cell apoptosis, detoxification, and anti-aging. We thus envisage that the possibility of harnessing the therapeutic potential of UC-CM might benefit patients suffering from inflammatory skin disorders such as atopic dermatitis, acne, and psoriasis.

Alterations of the Human Gut Microbiome in Patients With Hidradenitis Suppurativa: A Case-control Study and Review of the Literature.

Introduction: Hidradenitis suppurativa (HS) is a chronic and systemic inflammatory disease that extends beyond the skin. The role of gut microbiome (GM) alterations in the pathogenesis of inflammatory and autoimmune disorders is remarkable. Objectives: Based on the hypothesis that dysbiosis in the GM may trigger systemic inflammation in the pathogenesis of HS, this study aimed to investigate whether the GM is altered in HS patients compared with healthy subjects. Methods: In the present case-control study, fecal samples from 15 patients with HS and 15 age- and sex-matched healthy individuals were collected and analyzed using 16S rRNA-based metagenomic analysis, New Generation Sequencing (NGS). The V3 and V4-hypervariable regions of the bacterial 16S rDNA gene were amplified from all samples and sequenced by the Illumina MiSeq platform. Bioinformatics analyses were performed in QIIME2. Results: Shannon alpha diversity index showed significantly reduced diversity in HS patients (P = 0.048). Bray-Curtis Dissimilarity and Jaccard Distance revealed that the gut microbial composition of HS patients was significantly distinctive from that of controls (P = 0.01 and P = 0.007, respectively). The relative abundance of unclassified Clostridiales, unclassified Firmicutes, and Fusicatenibacter in HS was significantly lower than that in controls (P = 0.005, P = 0.029, and P = 0.046, respectively). Conclusions: This study indicated that significant alterations in the GM of HS patients could play a critical role in the pathogenesis of HS and might be a trigger for systemic inflammation. Increased understanding of the pathogenesis of HS will shed light on the new potential therapeutic targets and novel treatment options.

Ischemia-Modified Albumin-A Potential New Marker of Oxidative Stress in Dermatological Diseases.

There is growing evidence that oxidative stress is involved in the pathogenesis of numerous conditions, including dermatological diseases. Various markers are available to assess oxidative stress, but none of these can be considered the ideal marker. Recent studies have shown that ischemia-modified albumin (IMA) is not only an indicator of ischemia, but also a marker of oxidative stress. We have conducted a narrative review to evaluate the role of IMA in dermatological diseases. We have identified 24 original articles that evaluated IMA in skin disorders (psoriasis, acne vulgaris, hidradenitis suppurativa, urticaria, vitiligo and Behcet's disease) and hair disorders (alopecia areata, androgenetic alopecia and telogen effluvium). The results of the studies analyzed reveal that IMA may be considered a new marker of oxidative stress in dermatological diseases and offer new insights into the pathogenesis of these disorders and the theoretical basis for the development of new, effective, targeted therapies. To the best of our knowledge, this is the first review that gathers up data on the role of IMA in dermatological diseases.

Near-infrared photoimmunotherapy for the treatment of skin disorders.

INTRODUCTION: Near-Infrared Photoimmunotherapy (NIR-PIT) is a novel molecularly targeted phototherapy. This technique is based on a conjugate of a near-infrared photo-inducible molecule (antibody-photon absorber conjugate, APC) and a monoclonal antibody that targets a tumor-specific antigen. To date, this novel approach has been successfully applied to several types of cancer. AREAS COVERED: The authors discuss the possible use of NIR-PIT for the management of skin diseases, with special attention given to squamous cell carcinomas, advanced melanomas, and primary cutaneous lymphomas. EXPERT OPINION: NIR-PIT may be an attractive strategy for the treatment of skin disorders. The main advantage of NIR-PIT therapy is its low toxicity to healthy tissues. Cutaneous lymphocyte antigen is a potential molecular target for NIR-PIT for both cutaneous T-cell lymphomas and inflammatory skin disorders.

T-cell subsets in the skin and their role in inflammatory skin disorders.

T lymphocytes (T cells) are major players of the adaptive immune response. Naive T cells are primed in the presence of cytokines, leading to polarization into distinct T-cell subsets with specific functions. These subsets are classified based on their T-cell receptor profile, expression of transcription factors, surface cytokine and chemokine receptors, and their cytokine production, which together determine their specific function. This review provides an overview of the various T-cell subsets and their function in several inflammatory skin disorders ranging from allergic inflammation to skin tumors. Moreover, we highlight similarities of T-cell responses across different skin disorders, demonstrating the presence of similar and opposing functions for the different T-cell subsets. Finally, we discuss the effects of currently available and promising therapeutic approaches to harness T cells in inflammatory skin diseases for which efficacy next to unwanted side effects provide new insights into the pathophysiology of skin disorders.

Cutaneous manifestations related to the COVID-19 pandemic: a review article.

BACKGROUND: Skin lesions are either caused by COVID-19 disease or they can be due to other driving forces related to the COVID-19 pandemic. AIM: Considering the fact that the reported data in different articles for the type and prevalence of skin manifestations related to the COVID-19 pandemic are inconsistent, we have described the mechanism and type of skin lesions related to the COVID-19 pandemic. METHODS: In this review article, we have searched the Medline database (PubMed) for the combination of the following key terms "Dermatological Manifestation", "cutaneous Manifestation", "Skin Manifestation", "COVID-19", "SARS-CoV-2". RESULTS: The prevalence of skin manifestations related to COVID-19 ranged from 0.2% to 20%. The majority of these skin lesions are maculopapular eruptions. The skin presentations related to the COVID-19 pandemic are described below. Traumatic skin conditions such as dermatitis in individuals, especially those with allergies, might initiate secondary to over-washing or rinsing with inappropriate detergents. Also, inappropriate use of personal protective equipment (mask-gloves-shield) can trigger skin lesions on the face and hands or aggravate the lesions of acne, seborrhoeic dermatitis, eczema, etc. Furthermore, cutaneous adverse drug reactions may occur during hospitalization or outpatient treatment of COVID-19 patients. Also, psychocutaneous disorders due to acute stress can trigger or deteriorate several skin manifestations. Moreover, COVID-19 prevalence and course may be changed in patients with autoimmune or chronic inflammatory underlying skin disorders such as psoriasis, lupus erythematosus, pemphigus, scleroderma who are on immunosuppressive or biological medications to control their disorders. CONCLUSION: Due to the various dimensions of skin organ involvement and the large population affected, long-term skin conditions following this pandemic can be a lot more problematic than it appears. Serious preventive measures and medical supports are necessary to avoid skin disorders from becoming permanent or even chronic.

Mast Cells in the Skin: Defenders of Integrity or Offenders in Inflammation?

Mast cells (MCs) are best-known as key effector cells of immediate-type allergic reactions that may even culminate in life-threatening anaphylactic shock syndromes. However, strategically positioned at the host-environment interfaces and equipped with a plethora of receptors, MCs also play an important role in the first-line defense against pathogens. Their main characteristic, the huge amount of preformed proinflammatory mediators embedded in secretory granules, allows for a rapid response and initiation of further immune effector cell recruitment. The same mechanism, however, may account for detrimental overshooting responses. MCs are not only detrimental in MC-driven diseases but also responsible for disease exacerbation in other inflammatory disorders. Focusing on the skin as the largest immune organ, we herein review both beneficial and detrimental functions of skin MCs, from skin barrier integrity via host defense mechanisms to MC-driven inflammatory skin disorders. Moreover, we emphasize the importance of IgE-independent pathways of MC activation and their role in sustained chronic skin inflammation and disease exacerbation.

Neoplastic and inflammatory skin disorders and serum levels of polychlorinated biphenyls in a population living in a highly polluted area.

BACKGROUND: Although polychlorinated biphenyls (PCBs) have been classified as human carcinogens for their association with melanoma, few data are available for other skin lesions. OBJECTIVES: To investigate the prevalence of skin disorders in a highly PCB polluted area in northern Italy, with locally produced food as the main source of human contamination, and evaluate the association between skin lesions and PCB serum levels, taking account of possible confounders. MATERIALS & METHODS: Thirty-three PCB congeners were quantitatively assessed and a total of 189 subjects were equally divided into three groups using the tertiles of total PCB serum concentrations. All subjects underwent a clinical examination and were interviewed on their risk factors and history of skin diseases. RESULTS: No statistically significant difference was found in the prevalence of skin cancer, nevi, pigmentary disorders as well as inflammatory and infectious skin diseases among the three PCB exposure groups. It should be noted that the use of questionnaires to assess subjects' past sun exposure and photoprotection is intrinsically flawed due to random error. CONCLUSION: Our study does not support the hypothesis that chronic PCB exposure, through the ingestion of contaminated food, determines an increased risk of developing skin diseases.

A Molecular Perspective on the Potential Benefits of Metformin for the Treatment of Inflammatory Skin Disorders.

Due to its anti-hyperglycemic effect, metformin is the first-line medication for the treatment of type 2 diabetes, particularly in people who are obese. However, metformin is a drug with a very wide range of pharmacological properties and reports of its therapeutic effect on diseases including inflammation and cancer are increasing. Numerous research groups have reported that metformin has beneficial effects on a variety of inflammatory skin disorders including psoriasis, acanthosis nigricans, acne, hidradenitis suppurativa, and allergic contact dermatitis. According to these reports, in addition to the well-known action of metformin, that is, its anti-hyperglycemic effect, NF-kB inhibition and the resulting alteration to the cytokine network may be the potential targets of metformin. Its anti-hyperandrogenism effect has also been confirmed as the major action of metformin in some inflammatory skin diseases. Moreover, novel regulatory mechanisms, including autophagy and antioxidant processes, have been suggested as promising mechanisms of action for metformin in inflammatory skin disorders.

Extracellular vesicles in Inflammatory Skin Disorders: from Pathophysiology to Treatment.

Extracellular vesicles (EVs), naturally secreted by almost all known cell types into extracellular space, can transfer their bioactive cargos of nucleic acids and proteins to recipient cells, mediating cell-cell communication. Thus, they participate in many pathogenic processes including immune regulation, cell proliferation and differentiation, cell death, angiogenesis, among others. Cumulative evidence has shown the important regulatory effects of EVs on the initiation and progression of inflammation, autoimmunity, and cancer. In dermatology, recent studies indicate that EVs play key immunomodulatory roles in inflammatory skin disorders, including psoriasis, atopic dermatitis, lichen planus, bullous pemphigoid, systemic lupus erythematosus, and wound healing. Importantly, EVs can be used as biomarkers of pathophysiological states and/or therapeutic agents, both as carriers of drugs or even as a drug by themselves. In this review, we will summarize current research advances of EVs from different cells and their implications in inflammatory skin disorders, and further discuss their future applications, updated techniques, and challenges in clinical translational medicine.

Targeting the cutaneous lymphocyte antigen (CLA) in inflammatory and neoplastic skin conditions.

Introduction: The cutaneous lymphocyte antigen interacts with E-selectin on endothelial cells and is expressed on 15% of circulating T-cells. Skin-homing T-cells express the cutaneous lymphocyte antigen and play a role in local cutaneous immunity in inflammatory reactions and neoplastic conditions.Areas covered: Lymphocyte extravasation is the essential para-physiological mechanism enabling immune surveillance of tissues for tumors as well as effector cell recruitment to inflammatory sites.The authors focused on skin inflammatory disorders, on cutaneous lymphoproliferative disease, and on other skin malignancies.Expert opinion: Interfering with leukocyte extravasation has been regarded as an attractive strategy in skin disorders, in the past for inflammatory conditions and more recently for cutaneous T-cell lymphomas. Therapeutic blocking of skin-homing interactions has been attempted in psoriasis and atopic dermatitis and has been achieved in the treatment of cutaneous T-cell lymphomas. Cutaneous lymphocyte antigen is a potential molecular target for both systemic and skin-directed therapy for cutaneous T-cell lymphomas.

Alternative uses of dermoscopy in daily clinical practice: An update.

Dermoscopy is a noninvasive diagnostic tool that is currently being used for neoplastic skin lesions, several inflammatory and infectious diseases, and skin appendage disorders. As the clinical applications of dermoscopy beyond pigmented lesions are constantly increasing, the aim of this article is to provide an update on this topic. This comprehensive review substantiates how several diseases may show peculiar dermoscopy features so as to enhance the diagnosis and avoid (in selected cases) unnecessary histologic confirmation. In other cases, dermoscopy features may be shared with other conditions, with the advantage of narrowing down the differential diagnosis by ruling out those dermatoses with similar clinical aspect but different dermoscopic presentation.

In vivo blood flow imaging of inflammatory human skin induced by tape stripping using optical microangiography.

Vasculature response is a hallmark for most inflammatory skin disorders. Tape stripping on human skin causes a minor inflammation which leads to changes in microvasculature. In this study, optical microangiography (OMAG), noninvasive volumetric microvasculature in vivo imaging method, has been used to track the vascular responses after tape stripping. Vessel density has been quantified and used to correlate with the degree of skin irritation. The proved capability of OMAG technique in visualizing the microvasculature network under inflamed skin condition can play an important role in clinical trials of treatment and diagnosis of inflammatory skin disorders.