Field Cancerization Therapies for the Management of Actinic Keratosis: An Updated Review.

Field cancerization theory highlights that the skin surrounding actinic keratoses (AK) is also at increased risk for possible malignant transformation; thus, field-directed treatments may both reduce the risk of AK recurrence and potentially reduce the risk of development of cutaneous squamous cell carcinoma (cSCC). Photodynamic therapy (PDT) with either aminolevulinic acid (ALA) or methylaminolevulinate (MAL), as well as topical treatments such as 5-fluorouracil (5-FU), diclofenac gel, piroxicam, imiquimod, and ingenol mebutate, have all shown higher efficacy than vehicle treatments. PDT is widely recognized for its high efficacy; however, concerns for associated pain have driven new studies to begin using alternative illumination and pretreatment techniques, including lasers. Among topical treatments, a combination of 5-FU and salicylic acid (5-FU-SA) has shown to be the most effective but also causes the most adverse reactions. Tirbanibulin, a new topical agent approved for use in 2020, boasts a favorable safety profile in comparison with imiquimod, 5-FU, and diclofenac. Meanwhile, ingenol mebutate is no longer recommended for the treatment of AKs due to concerns for increased risk of cSCC development. Moving forward, an increasing number of studies push for standardization of outcome measures to better predict risk of future cSCC and use of more effective measures of cost to better guide patients. Here, we present an updated and comprehensive narrative review both confirming the efficacy of previously mentioned therapies as well as highlighting new approaches to PDT and discussing the use of lasers and novel topical treatments for treatment of AK.

The Skin Barrier and Moisturization: Function, Disruption, and Mechanisms of Repair.

BACKGROUND: The anatomic layers of the skin are well-defined, and a functional model of the skin barrier has recently been described. Barrier disruption plays a key role in several skin conditions, and moisturization is recommended as an initial treatment in conditions such as atopic dermatitis. This review aimed to analyze the skin barrier in the context of the function model, with a focus on the mechanisms by which moisturizers support each of the functional layers of the skin barrier to promote homeostasis and repair. SUMMARY: The skin barrier is comprised of four interdependent layers - physical, chemical, microbiologic, and immunologic - which maintain barrier structure and function. Moisturizers target disruption affecting each of these four layers through several mechanisms and were shown to improve transepidermal water loss in several studies. Occlusives, humectants, and emollients occlude the surface of the stratum corneum (SC), draw water from the dermis into the epidermis, and assimilate into the SC, respectively, in order to strengthen the physical skin barrier. Acidic moisturizers bolster the chemical skin barrier by supporting optimal enzymatic function, increasing ceramide production, and facilitating ideal conditions for commensal microorganisms. Regular moisturization may strengthen the immunologic skin barrier by reducing permeability and subsequent allergen penetration and sensitization. KEY MESSAGES: The physical, chemical, microbiologic, and immunologic layers of the skin barrier are each uniquely impacted in states of skin barrier disruption. Moisturizers target each of the layers of the skin barrier to maintain homeostasis and facilitate repair.

Combination Approaches to Hand Rejuvenation: A Review of the Literature and Discussion.

BACKGROUND: Various noninvasive/minimally invasive modalities for hand rejuvenation exist, and the efficacy and safety of these procedures as both monotherapy and same-day procedures is increasingly being studied. OBJECTIVE: To review data on the efficacy and safety of hand rejuvenation modalities and suggest a practical combination approach for these procedures. METHODS: The PubMed database was queried for peer-reviewed articles regarding hand rejuvenation techniques, including chemical peels, laser and light sources, sclerotherapy, autologous fat transfer, and injectable volumetric fillers. RESULTS: Chemical peels have been studied the least, with most studies evaluating the use of fillers and laser/light-based devices. Most studies reported overall good results with high patient satisfaction. Satisfaction rates were lower in laser/light-based treatments compared with other modalities. Transient erythema, edema, or pain after procedures was common; most studies did not report serious postprocedure complications. Importantly, there was no significant increase in adverse effects after same-day procedures. CONCLUSION: Using same-day procedures allows practitioners to address hand rejuvenation from different aspects, seems to improve outcomes, and reduces time spent in the office for patients. The authors suggest a practical framework for combining cosmetic approaches to achieve the most optimal outcome for hand rejuvenation.

Applications of bakuchiol in dermatology: Systematic review of the literature.

BACKGROUND: Bakuchiol (BAK), a meroterpene phenol abundant in the plant Psoralea corylifolia, is an emerging cosmeceutical agent with promising anti-aging, anti-inflammatory, and antibacterial properties. The trend for "clean" skincare products and search for anti-aging retinoid alternatives have poised BAK as a "must-have" ingredient in skincare. AIMS: Our aim was to review the data for the applications of BAK in dermatology. METHODS: This is a systematic review of PubMed. RESULTS: Thirty articles matched our search terms ["Bakuchiol" and "Dermatology"] or ["Bakuchiol" and "Skin"] of which one did not meet inclusion criteria, 16 were pre-clinical studies, seven clinical studies, three commentaries, two narrative reviews, and one report on adverse events. BAK has been mostly studied for its effects on photoaging, acne, and post-inflammatory hyperpigmentation (PIH), showing beneficial results comparable to those achieved by topical retinoids. While having no structural resemblance to retinoids, BAK can function as a retinol analog, through retinol-like regulation of gene expression. In in vivo studies, BAK was used alone or in combination with other products resulting in a significant reduction in photodamage, hyperpigmentation, wrinkle scores, and acne severity. Additionally, in vitro studies hinted at its anti-cancer properties by inhibiting epidermal growth factor induced neoplastic cell transformation. Also, demonstrated potential applications in psoriasis by normalizing keratinocyte activity and in pigmentary disorders through inhibition of melanogenesis. There was one adverse event case reported of contact dermatitis in the literature. CONCLUSIONS: Bakuchiol is a retinol alternative with anti-aging, antibacterial, and anti-inflammatory properties. Additional studies are warranted to better understand its applications in dermatology.

A new era of moisturizers.

BACKGROUND: Moisturizers traditionally function to replenish both the intercellular lipid lamella and natural moisturizing factors, and form a hydrolipid film on the skin surface to decrease transepidermal water loss and improve hydration. As we continue to identify epidermal lipid imbalance in patients with atopic dermatitis, we turn to the use of bioactive ingredients in moisturizers for improving barrier repair and function. METHODS: This review aims to explore the modern use of moisturizers in targeting various components of the skin barrier, dampening immune response, and restoring microbial balance. We conducted a balanced and comprehensive narrative review of the literature. Studies were identified by searching electronic databases (MEDLINE and PubMed), focusing on studies and trials regarding moisturizers that include endocannabinoids, bioactive lipids, anti-inflammatory agents, antioxidants, and microbiome modulators. Only articles published in English language were included. RESULTS: The aforementioned ingredients exert additional biological effects to improve skin function by upregulating lipid synthesis, decreasing neurosensory transmission of itch signals, reversing oxidative stress, decreasing inflammatory cell activity and cytokine release, and modulating skin microbiota. The shift from traditional moisturizers to those with bioactive ingredients, anti-inflammatory agents, and microbiome modulating effects opens a realm of possible therapeutic options for patients with barrier-defective cutaneous conditions. CONCLUSION: Focusing on the disrupted skin barrier as a target for both prevention and treatment and incorporating a combined strategy that utilizes the aforementioned agents to tackle barrier dysfunction from different angles remains a promising area for clinical impact in dermatology.

Field Cancerization Therapies for Management of Actinic Keratosis: A Narrative Review.

Actinic keratoses (AKs) are atypical, precancerous proliferations of keratinocytes that develop because of chronic exposure to ultraviolet (UV) radiation. Treatment of AK can be lesion-directed or field-directed. Field cancerization theory postulates that the skin surrounding AK is also at increased risk for possible malignant transformation since it has been exposed to the same chronic UV light. Field-directed therapies thus have the potential to address subclinical damage, reduce AK recurrence rates, and potentially reduce the risk of squamous cell carcinoma (SCC) development. Published clinical studies have found lesion clearance rates ranging from 81 to 91% for photodynamic therapy (PDT) with either aminolevulinic acid (ALA) or methylaminolevulinate (MAL). Clinical studies have also been published on various topical treatments. Complete clinical clearance (CCC) was significantly higher in patients treated with a combination of 5-fluorouracil and salicylic acid (5-FU-SA) than in the vehicle group across multiple studies, and CCC ranged between 46 and 48% following treatment with imiquimod. Additionally, treatment with diclofenac sodium (DFS) found reduction in lesion sizes to range from 67 to 75%. Reported results have been similar for another non-steroidal anti-inflammatory drug (NSAID), piroxicam, which has more cyclooxygenase (COX)-1 activity than DFS. Active treatments with ingenol mebutate were also significantly more effective than vehicle at clearing AK lesions. All treatments resulted in mild, localized skin reactions. PDT using conventional light sources was associated with increased severity of pain and/or discomfort, while PDT using daylight as the light source was associated with less pain and occasionally no pain at all. Though no widely accepted algorithm for the treatment of AKs exists, field-directed therapy can be particularly useful for treating photo-exposed areas containing multiple AKs. Additional research with more direct comparisons between these field-directed therapies will help clinicians determine the best therapeutic approach. Here, we provide a balanced and comprehensive narrative review of the literature, considering both light-based and topical therapies with a focus on their field-therapy aspects, and propose a therapeutic algorithm for selecting an appropriate treatment in the clinical setting.

Unusually extensive scalp ulcerations manifested in pemphigus erythematosus.

Senear-Usher Syndrome, or pemphigus erythematosus, is an autoimmune skin blistering disorder with an overlapping clinical presentation of pemphigus foliaceus and lupus erythematosus. Lesions typically involve the scalp, face, and upper chest or back. This case study focuses on a patient who presentedwith progressive scalp ulcers, hyperpigmentation, and eroded plaques with overlying hemorrhagic crust. Pemphigus erythematosus was diagnosedwith direct immunofluorescence, demonstrating immunoglobulin G and complement deposition both intercellularly and at the dermoepidermal junction. The patient is continuing treatment with systemicsteroids and steroid-sparing immunosuppressants.

Successful treatment of two individual cases of generalized granuloma annulare with amoxicillin/clavulanic acid and a combination of doxycycline and pentoxifylline.

Granuloma annulare is a benign inflammatory skin disease potentially related to a delayed hypersensitivity reaction to the dermis. Generalized granuloma annulare (GGA) manifests as diffuse skin-colored to erythematous annular or nummular plaques affecting at least the trunk and either upper or lower extremities, or both. GGA is resistant to many therapeutic modalities, making it difficult to treat. Different therapeutic approaches to GGA have been attempted but definitive treatment for this disease remains elusive. This article focuses on the use of amoxicillin/clavulanic acid and a combination of doxycycline and pentoxifylline therapy as treatment options for GGA in two patients with histopathology-proven interstitial GGA. Both amoxicillin/clavulanic acid and doxycycline inhibit bacterial cell growth, raising the possibility that a bacterial pathogenesis may be of significance in GGA. This is the first reported case of successful treatment of GGA with these regimens.

Essential roles of FoxM1 in Ras-induced liver cancer progression and in cancer cells with stem cell features.

BACKGROUND & AIMS: Overexpression of FoxM1 correlates with poor prognosis in hepatocellular carcinoma (HCC). Moreover, the Ras-signaling pathway is found to be ubiquitously activated in HCC through epigenetic silencing of the Ras-regulators. We investigated the roles of FoxM1 in Ras-driven HCC, and on HCC cells with stem-like features. METHODS: We employed a transgenic mouse model that expresses the oncogenic Ras in the liver. That strain was crossed with a strain that harbor floxed alleles of FoxM1 and the MxCre gene that allows conditional deletion of FoxM1. FoxM1 alleles were deleted after development of HCC, and the effects on the tumors were analyzed. Also, FoxM1 siRNA was used in human HCC cell lines to determine its role in the survival of the HCC cells with stem cell features. RESULTS: Ras-driven tumors overexpress FoxM1. Deletion of FoxM1 inhibits HCC progression. There was increased accumulation of reactive oxygen species (ROS) in the FoxM1 deleted HCC cells. Moreover, FoxM1 deletion caused a disproportionate loss of the CD44+ and EpCAM+ HCC cells in the tumors. We show that FoxM1 directly activates expression of CD44 in human HCC cells. Moreover, the human HCC cells with stem cell features are addicted to FoxM1 for ROS-regulation and survival. CONCLUSION: Our results provide genetic evidence for an essential role of FoxM1 in the progression of Ras-driven HCC. In addition, FoxM1 is required for the expression of CD44 in HCC cells. Moreover, FoxM1 plays a critical role in the survival of the HCC cells with stem cell features by regulating ROS.