Immune checkpoint inhibitor (ICI) therapies carry the risk of major immune-related adverse events (irAEs). Among the most severe irAEs is epidermal necrosis that may clinically mimic Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN). The aim of this study was to provide a summary of the clinical and histological features of ICI-associated epidermal necrosis, with a special focus on factors associated with fatal outcomes in cases of extensive disease. A total of 98 cases, 2 new cases and 96 reported on PubMed and in the literature, of ICI-associated epidermal necrosis were assessed. Development of epidermal necrosis occurred between 1 day and 3 years after starting ICI therapy, with an average onset of 13.8 weeks for patients with limited (< 30% BSA) and 11.3 weeks for those with extensive (≥ 30% BSA) involvement, and a median onset of 5.8 weeks and 4 weeks respectively. A preceding rash was seen in 52 cases and was more common in extensive cases. Mucosal involvement was only reported in 65% of extensive cases but was significantly associated with fatal reactions. Co-administration of cytotoxic chemotherapy was associated with more extensive disease. Recovery was observed in 96% and 65% of those with limited and extensive involvement respectively and no specific therapy was associated with improved survival. Young age was significantly associated with poor outcomes in extensive disease, the average age of surviving patients was 64.5 years old versus 55.1 years old for deceased patients, p < 0.01. Both superficial perivascular and interface/lichenoid inflammatory infiltrates were commonly seen. These findings suggest that ICI-associated epidermal necrosis should be considered a distinct clinical entity from drug-induced SJS/TEN.

Atopic dermatitis, also known as atopic eczema, is a chronic inflammatory skin disease characterized by red pruritic skin lesions, xerosis, ichthyosis, and skin pain. Among the social impacts of atopic dermatitis are difficulties and detachment in relationships and social stigmatization. Additionally, atopic dermatitis is known to cause sleep disturbance, anxiety, hyperactivity, and depression. Although the pathological process behind atopic dermatitis is not fully known, it appears to be a combination of epidermal barrier dysfunction and immune dysregulation. Skin is the largest organ of the human body which acts as a mechanical barrier to toxins and UV light and a natural barrier against water loss. Both functions face significant challenges due to atopic dermatitis. The list of factors that can potentially trigger or contribute to atopic dermatitis is extensive, ranging from genetic factors, family history, dietary choices, immune triggers, and environmental factors. Consequently, prevention, early clinical diagnosis, and effective treatment may be the only resolutions to combat this burdensome disease. Ensuring safe and targeted drug delivery to the skin layers, without reaching the systemic circulation is a promising option raised by nano-delivery systems in dermatology. In this review, we explored the current understanding and approaches of atopic dermatitis and outlined a range of the most recent therapeutics and dosage forms brought by nanotechnology. This review was conducted using PubMed, Google Scholar, and ScienceDirect databases.

Transdermal drug administration has grown in popularity in the pharmaceutical research community due to its potential to improve drug bioavailability, compliance among patients, and therapeutic effectiveness. To overcome the substantial barrier posed by the stratum corneum (SC) and promote drug absorption within the skin, various physical penetration augmentation approaches have been devised. This review article delves into popular physical penetration augmentation techniques, which include sonophoresis, iontophoresis, magnetophoresis, thermophoresis, needle-free injection, and microneedles (MNs) Sonophoresis is a technique that uses low-frequency ultrasonic waves to break the skin\'s barrier characteristics, therefore improving drug transport and distribution. In contrast, iontophoresis uses an applied electric current to push charged molecules of drugs inside the skin, effectively enhancing medication absorption. Magnetophoresis uses magnetic fields to drive drug carriers into the dermis, a technology that has shown promise in aiding targeted medication delivery. Thermophoresis is the regulated heating of the skin in order to improve drug absorption, particularly with thermally sensitive drug carriers. Needle-free injection technologies, such as jet injectors (JIs) and microprojection arrays, offer another option by producing temporary small pore sizes in the skin, facilitating painless and effective drug delivery. MNs are a painless, minimally invasive method, easy to self-administration, as well as high drug bioavailability. This study focuses on the underlying processes, current breakthroughs, and limitations connected with all of these approaches, with an emphasis on their applicability in diverse therapeutic areas. Finally, a thorough knowledge of these physical enhancement approaches and their incorporation into pharmaceutical research has the potential to revolutionize drug delivery, providing more efficient and secure treatment choices for a wide range of health-related diseases.

Skin perceives and reacts to external mechanical forces to create resistance against the external environment. Excessive or inappropriate stimuli of pressure may lead to cellular alterations of the skin and the development of both benign and malignant skin disorders. We conducted a comprehensive literature review to delve into the pressure-induced and aggravated skin disorders and their underlying pressure-related mechanisms. Dysregulated mechanical responses of the skin give rise to local inflammation, ischemia, necrosis, proliferation, hyperkeratosis, impaired regeneration, atrophy, or other injurious reactions, resulting in various disease entities. The use of personal devices, activities, occupations, weight bearing, and even unintentional object contact and postures are potential scenarios that account for the development of pressure-related skin disorders. The spectrum of these skin disorders may involve the epidermis (keratinocytes and melanocytes), hair follicles, eccrine glands, nail apparatuses, dermis (fibroblasts, mast cells, and vasculature), subcutis, and fascia. Clarifying the clinical context of each patient and recognizing how pressure at the cellular and tissue levels leads to skin lesions can enhance our comprehension of pressure-related skin disorders to attain better management.

The stratum corneum (SC)-the outermost layer of the epidermis-is the principal permeability and protective barrier of the skin. Different components of the SC, including corneocytes, natural moisturizing factor, a variety of enzymes and their inhibitors, antimicrobial peptides and lipids, work interactively to maintain barrier function. The main barrier properties of the SC are the limitation of water loss and the prevention of infection and contact with potentially harmful exogenous factors. Although the SC functions consistently as a protective barrier throughout the body, variations in functions and morphology occur across body sites with age and skin type. Healthy SC function also depends on the interplay between the chemosensory barrier, the skin\'s microbiome and the innate immune system. Dysregulation of SC barrier function can lead to the development of skin disorders, such as dry, flaky or sensitive skin, but the complete underlying pathophysiology of these are not fully understood. This review provides insight into the current literature and emerging themes related to epidermal barrier changes that occur in the context of dry, flaky and sensitive skin. Additional studies are needed to further elucidate the underlying aetiology of dry, flaky and sensitive skin and to provide tailored treatment.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and presents a major public health problem worldwide. It is characterized by a recurrent and/or chronic course of inflammatory skin lesions with intense pruritus. Its pathophysiologic features include barrier dysfunction, aberrant immune cell infiltration, and alterations in the microbiome that are associated with genetic and environmental factors. There is a complex crosstalk between these components, which is primarily mediated by cytokines. Epidermal barrier dysfunction is the hallmark of AD and is caused by the disruption of proteins and lipids responsible for establishing the skin barrier. To better define the role of cytokines in stratum corneum lipid abnormalities related to AD, we conducted a systematic review of biomedical literature in PubMed from its inception to 5 September 2023. Consistent with the dominant TH2 skewness seen in AD, type 2 cytokines were featured prominently as possessing a central role in epidermal lipid alterations in AD skin. The cytokines associated with TH1 and TH17 were also identified to affect barrier lipids. Considering the broad cytokine dysregulation observed in AD pathophysiology, understanding the role of each of these in lipid abnormalities and barrier dysfunction will help in developing therapeutics to best achieve barrier homeostasis in AD patients.

BACKGROUND: Dermatological conditions, especially when severe, can lead to sleep disturbances that affect a patient\'s quality of life. However, limited research exists on the efficacy of treatments for improving sleep parameters in skin conditions.
OBJECTIVE: The objective was to perform a systematic review of the literature on dermatological conditions and the treatments available for improving sleep parameters.
METHODS: A literature review was performed using the PubMed, Ovid MEDLINE, Embase, Cochrane, and ClinicalTrials.gov databases from 1945 to 2021. After filtering based on our exclusion criteria, studies were graded using the SORT (Strength of Recommendation Taxonomy) algorithm, and only those receiving a grade of \"2\" or better were included.
RESULTS: In total, 25 treatment studies (n=11,025) assessing sleep parameters related to dermatological conditions were found. Dupilumab appeared to be the best-supported and most effective treatment for improving sleep in atopic dermatitis (AD) but had frequent adverse effects. Topical treatments for AD were mostly ineffective, but procedural treatments showed some promise. Treatments for other conditions appeared efficacious.
CONCLUSIONS: The evaluation of sleep parameter changes in dermatological treatments is predominantly restricted to AD. Systemic interventions such as dupilumab and procedural interventions were the most efficacious. Sleep changes in other dermatoses were limited by a paucity of available studies. The inclusion of a sleep assessment component to a broader range of dermatological treatment studies is warranted.

To improve wound healing or treatment of other skin diseases, and provide model cells for skin biology studies, in vitro differentiation of stem cells into keratinocyte-like cells (KLCs) is very desirable in regenerative medicine. This study examined the most recent advancements in in vitro differentiation of stem cells into KLCs, the effect of biofactors, procedures, and preparation for upcoming clinical cases. A range of stem cells with different origins could be differentiated into KLCs under appropriate conditions. The most effective ways of stem cell differentiation into keratinocytes were found to include the co-culture with primary epithelial cells and keratinocytes, and a cocktail of growth factors, cytokines, and small molecules. KLCs should also be supported by biomaterials for the extracellular matrix (ECM), which replicate the composition and functionality of the in vivo extracellular matrix (ECM) and, thus, support their phenotypic and functional characteristics. The detailed efficient characterization of different factors, and their combinations, could make it possible to find the significant inducers for stem cell differentiation into epidermal lineage. Moreover, it allows the development of chemically known media for directing multi-step differentiation procedures.In conclusion, the differentiation of stem cells to KLCs is feasible and KLCs were used in experimental, preclinical, and clinical trials. However, the translation of KLCs from in vitro investigational system to clinically valuable cells is challenging and extremely slow.

BACKGROUND: Post-inflammatory hyperpigmentation (PIH) is a common complication after laser surgeries. Recent studies applied epidermal growth factor (EGF) on the lasered area after laser surgery to decrease the incidence of PIH with controversial results. Therefore, a comprehensive literature review of randomized controlled trials (RCTs) was conducted to investigate the issue.
METHODS: Two reviewers independently searched the literatures, extracted, and analyzed the data. A total of seven RCTs involving 169 patients were included to evaluate the efficacy of EGF on recovery and PIH prevention after laser surgery.
RESULTS: The results show that the incidence of PIH in the EGF group was relatively lower than that in the control group, although the difference was not statistically significant (OR 0.64, 95% CI 0.33 ~ 1.25, p = 0.19). However, the EGF groups had a significant decrease in melanin index (MI) scores at the 1st month after the laser surgery when compared to the control groups (SMD -1.57, 95% CI -2.83 ~ -0.31, p = 0.01). In addition, the patients on the EGF side rated significantly higher satisfactory scores (SMD 0.49, 95% CI 0.22 ~ 0.76, p = 0.0004). There was no significant difference as regard to changes in MI at the 2nd week and 2nd month, erythema index (EI), and trans-epidermal water loss (TEWL) at days 3 and 7 after laser therapy, respectively.
CONCLUSIONS: The current meta-analysis found a limited temporary inhibitory effect of EGF-containing topical products on PIH with no significant effect on reducing post-laser erythema or promoting epidermal barrier repair. More studies are needed in the future due to the small sample size and marked intergroup heterogeneities.

Interface dermatitis or lichenoid interface dermatitis refers to a cutaneous inflammatory pattern in which keratinocyte cell death is the essential feature. These terms have evolved from the originally described lichenoid tissue reaction. These lesions are the basis for an important group of skin diseases in animals and people where cytotoxic T-cell-mediated epidermal damage is a major pathomechanism. Yet, for largely historical reasons these commonly used morphological diagnostic terms do not reflect the essential nature of the lesion. An emphasis on subsidiary lesions, such as the presence of a lichenoid band, and definitions based on anatomical features, such as location at the dermo-epidermal location, may cause confusion and even misdiagnosis. This review covers historical aspects of the terminology, including the origin of terms such as \"lichenoid.\" The types of cell death involved and the histopathologic lesions are described. Etiopathogenesis is discussed in terms of aberrations of immune/inflammatory mechanisms focusing on cutaneous lupus erythematosus, erythema multiforme, and Stevens-Johnson syndrome/toxic epidermal necrolysis. Mechanisms have most extensively been studied in humans and laboratory animals and the discussion is centered on these species. As interface dermatitis is firmly entrenched in dermatological parlance, rather than using \"cytotoxic\" as its substitute, the terminologies \"interface cytotoxic dermatitis\" and \"panepidermal cytotoxic dermatitis\" are recommended, based on location and extent of epithelium affected.