Dermatologic Manifestations of Mitochondrial Dysfunction: A Review of the Literature.

Mitochondria are eukaryotic cellular organelles that function in energy metabolism, ROS production, and programmed cell death. Cutaneous epithelial and hair follicle dermal papilla cells are energy-rich cells that thereby may be affected by mitochondrial dysfunction and DNA mutation accumulation. In this review, we aimed to summarize the medical literature assessing dermatologic conditions and outcomes associated with mitochondrial dysfunction. A search of PubMed and Embase was performed with subsequent handsearching to retrieve additional relevant articles. Mitochondrial DNA (mtDNA) deletions, mutation accumulation, and damage are associated with phenotypic signs of cutaneous aging, hair loss, and impaired wound healing. In addition, several dermatologic conditions are associated with aberrant mitochondrial activity, such as systemic lupus erythematosus, psoriasis, vitiligo, and atopic dermatitis. Mouse model studies have better established causality between mitochondrial damage and dermatologic outcomes, with some depicting reversibility upon restoration of mitochondrial function. Mitochondrial function mediates a variety of dermatologic conditions, and mitochondrial components may be a promising target for therapeutic strategies.

Bacteriophages and the Microbiome in Dermatology: The Role of the Phageome and a Potential Therapeutic Strategy.

Bacteriophages, also known as phages, are viruses that selectively target and infect bacteria. In addition to bacterial dysbiosis, dermatologic conditions such as acne, psoriasis, and atopic dermatitis are characterized by a relative reduction in the abundance of phages and the overgrowth of the corresponding bacteria. Phages often exhibit high specificity for their targeted bacteria, making phage-replacement therapy a promising therapeutic strategy for the control of pathogenic bacteria in dermatologic disease. Novel therapeutic strategies regulating pathogenic bacteria are especially necessary in light of growing antibiotic resistance. In this review, we aimed to review the medical literature assessing phage dysbiosis and therapeutic trials in dermatology. Ultimately, studies have depicted promising results for the treatment of acne, psoriasis, and atopic dermatitis but are limited by low sample sizes and the omission of control groups in some trials. Additional work is necessary to validate the efficacy depicted in proof-of-concept trials and to further determine optimal treatment vehicles, administration mechanisms, and dosing schedules. This review provides the necessary framework for the assessment of phage efficacy in future trials.

Sneddon-Wilkinson disease following COVID-19 vaccination.

Sneddon-Wilkinson disease, also known as subcorneal pustular dermatosis (SPD), is a rare disease characterized by vesicles or pustules that may rapidly expand and coalesce. Idiopathic in nature, SPD's clinical presentation of "half-half" blisters, with half of each blister containing pus and half containing clear fluid, is characteristic of this disease. We describe a previously healthy 21-year-old man who developed acute pustular vesicular eruptions consistent with SPD eight days following the Moderna COVID-19 vaccination.

The effect of synthetic acetylhexapeptide-8 (AH8) on sebaceous function.

OBJECTIVE: This study aims to evaluate the in vitro and clinical effects of topical acetylhexapeptide-8 (AH8) on the appearance of oily skin. METHOD: In vitro SEB-1 human sebocyte cell lines were exposed to different concentrations of AH8, then the lipid content of the sebocytes was measured. For the randomized, controlled, split-face clinical study, participants received AH8 10% lotion formulated in Cetaphil Moisturizing Facial Lotion on one side of their face and the control vehicle lotion on the other side of their face. Facial oiliness was assessed by a trained physician using a three-point grading system, high-resolution digital photographs, and a sebumeter (SM815). Participants also filled out self-assessments of their skin oiliness. RESULTS: The in vitro experiments showed that sebocyte lipid content significantly decreased after AH8 treatment (p < 0.05 at 0.00005% AH8, p = 0.09 at 0.0005% AH8, p < 0.05 at 0.005% AH8, and p < 0.001 at 0.025% AH8). In the clinical study, participants trended towards a 10% reduction (p = 0.16) in sebum production after AH8 treatment in comparison to the vehicle treatment. CONCLUSION: AH8 inhibits the accumulation of lipids in sebocytes in vitro without altering cell proliferation or SREBP-1 expression. Topical AH8 trended towards decreased sebum production in human participants. The use of AH8 may serve as a promising agent to reduce sebocyte lipid production and the appearance of oily skin. RÉSUMÉ: Objectif Cette étude vise à évaluer les effets in vitro et cliniques de l'acétylhexapeptide-8 (AH8) topique sur l'aspect de la peau grasse. Méthode Des lignées cellulaires de sébocytes humains SEB-1 in vitro ont été exposées à différentes concentrations d'AH8, à la suite de quoi la teneur en lipides des sébocytes a été mesurée. Pour l'étude clinique randomisée, contrôlée, en hémi-visage, les participants ont reçu une lotion AH8 10 % formulée dans la lotion hydratante pour le visage Cetaphil d'un côté de leur visage et la lotion témoin de l'autre côté de leur visage. Le sébum du visage a été évalué par un médecin formé à l'aide d'un système de classification à trois points, de photographies numériques à haute résolution et d'un sébumètre (SM815). Les participants ont également rempli des auto-évaluations du sébum de leur peau. Résultats Les expériences in vitro ont montré que la teneur en lipides des sébocytes diminuait significativement après le traitement par AH8 (p < 0.05 à 0.00005 % AH8, p = 0.09 à 0.0005 % AH8, p < 0.001 à 0.025 % AH8). Dans l'étude clinique, les participants avaient tendance à voir leur production de sébum diminuer de 10 % (p = 0.16) après le traitement par AH8, par rapport au traitement par excipient. Conclusion L'AH8 inhibe l'accumulation de lipides dans les sébocytes in vitro sans altérer la prolifération cellulaire ou l'expression de SREBP-1. L'AH8 topique tendait à diminuer la production de sébum chez les participants humains. L'utilisation d'AH8 peut servir d'agent prometteur pour réduire la production de lipides sébocytaires et l'apparence de peau grasse.

The therapeutic potential of cannabinoids for integumentary wound management.

The increasing legalization of Cannabis for recreational and medicinal purposes in the United States has spurred renewed interest in the therapeutic potential of cannabinoids (CBs) for human disease. The skin has its own endocannabinoid system (eCS) which is a key regulator of various homeostatic processes, including those necessary for normal physiologic wound healing. Data on the use of CBs for wound healing are scarce. Compelling pre-clinical evidence supporting the therapeutic potential of CBs to improve wound healing by modulating key molecular pathways is herein reviewed. These findings merit further exploration in basic science, translational and clinical studies.

Health insurance relationship to sun protection practices and beliefs.

PURPOSE: Lower socioeconomic status is associated with decreased sun protection practices. This survey study investigated practices and beliefs surrounding sun protection based on health insurance. METHODS: 401 surveys were administered May to June 2019 at two dermatology clinics in Sacramento, California. 384 surveys by private insurance, Medi-Cal (California's Medicaid), and Medicare coverage were analyzed. RESULTS: Patients with Medi-Cal are twice as likely to rarely or never use sunscreen (OR=2.37; 95% CI 1.45-3.87; P<0.001) compared to those with private insurance. Patients with Medi-Cal or Medicare are less likely to use sunscreen (P<0.001), protective clothing (P=0.025), and sun avoidance (P=0.028). Medi-Cal patients more often used tanning beds (OR=4.90; 95% CI 1.30-18.50; P=0.019). Over half of patients with Medi-Cal agreed it is worth getting burned for a tan (54.6%, OR=2.54; 95% CI 1.41-4.62; P=0.0021). There were no significant differences in opinion that sunscreen is a hassle to apply or expensive. Groups did not differ significantly in ethnicities or skin type. CONCLUSION: Those with Medi-Cal are less likely to use all forms of sun protection and more likely to value tanning. Negative opinions of sunscreen and perceived knowledge and concern for skin cancer were similar, pointing to additional factors influencing these disparities.

Papulopustular rosacea during nivolumab therapy of metastatic squamous cell esophageal carcinoma.

We present a 76-year old man who developed papulopustular rosacea after receiving nivolumab treatment for his esophageal carcinoma, metastatic to the lungs. Nivolumab is an emerging cancer therapy whose immune-related adverse events are still not fully recognized and likely underreported. The treatment has been reported to cause a myriad of cutaneous immune-related adverse events. However, nivolumab-induced-papulopustular rosacea has been scarcely reported. Thus, this case presents a clinically important finding that physicians should be aware of when seeing patients on nivolumab therapy.

Anti-MDA-5 negative, anti-Ku positive clinically amyopathic dermatomyositis.

We present a patient with anti-MDA5 negative, anti-Ku positive clinically amyopathic dermatomyositis (CADM). A 61-year-old woman presented with a chief complaint of a 20-year history of a pruritic rash that was active on her face, chest, hands, legs, and back. A mildly scaly, erythematous, photo-distributed eruption along with slightly violaceous, scaly papules accentuated on the wrist, metacarpophalangeal joints, proximal interphalangeal and distal interphalangeal joints. Antibody profile was significant for positive ANA and anti-dsDNA, elevated anti-TIF-1gamma (RDL)/p155, and weakly positive anti Ku. Biopsy was consistent with dermatomyositis. Melanoma differentiation-associated gene 5 antibody (anti-MDA-5) has been identified as the most commonly associated autoantibody found in CADM and is associated with poor prognosis and a biomarker for the diagnosis of rapidly progressive interstitial lung disease. To our knowledge, our patient is the first case of negative anti-MDA-5 and anti-Ku positive CADM.

Patient perceptions about nutrition and skin health: a survey study characterizing patient opinions and information resources.

BACKGROUND: Numerous studies in the clinical literature have explored the link between nutrition and skin physiology. However, it is unclear whether patients visit their dermatologists with knowledge of these studies, and unknown where they obtain their skin health information. We characterized patient perceptions surrounding nutrition and skin, including what patients identified as aggravating and alleviating foods and their information sources. METHODS: We administered a questionnaire to 409 participants attending University of California (UC) Davis Dermatology and Pacific Skin Institute in Sacramento. This survey assessed their perception on the influence of nutrition. We stratified responses by diseases. RESULTS: Of the 409 respondents, 83% believed that nutrition affects skin health. Respondents with healthy skin were not more likely to agree than those with skin conditions in general (P=0.34). Those with skin conditions also more likely received their information from reputable sources, defined as physicians and scientific journals (P=0.02). Additionally, respondents who disagreed were more likely informed by reputable sources (P=0.002), but when online blogs were included as reputable, this relationship was less significant (P=0.046). CONCLUSIONS: As online resources become more accessible, it is important for providers to know about changing patient perspectives. Our findings may help improve how dermatologists counsel patients about nutrition.

Lichen planopilaris with significant post-inflammatory pigmentary alteration.

Lichen planopilaris is an uncommon dermatological manifestation of lichen planus of the scalp and results in cicatricial alopecia. We present a patient with lichen planopilaris and significant post-inflammatory pigmentary alteration, confirmed by histopathology. The patient's case represents a clinically important variation from an expected typical pattern of dyschromia at periphery of alopecic zones in lichen planopilaris.

Comparison of 2-Octylcyanoacrylate Versus 5-0 Fast-Absorbing Gut During Linear Wound Closures and the Effect on Wound Cosmesis.

BACKGROUND: Although the use of 2-octylcyanoacrylate (OCA) in cutaneous surgery offers increased efficiency, there is scant data comparing scar outcomes achieved with OCA versus 5-0 fast-absorbing gut suture (FG). OBJECTIVE: To compare scar cosmesis achieved with OCA versus FG for surgical wound closure. MATERIALS AND METHODS: A total of 44 patients with postoperative defects of at least 3 cm were included. Half of each wound was randomized to receive closure with either OCA or FG. At 3 months, patients and 2 blinded observers evaluated each scar using the Patient and Observer Scar Assessment Scale (POSAS). RESULTS: The total observer POSAS score (mean [SD]) for the side repaired with OCA (12.3 [4.72]) and the side that received FG (11.6 [4.36]) did not differ significantly (p = .40). There was no significant difference in the total patient POSAS scores between closure with OCA (14.9 [8.67]) and FG (14.6 [8.90]) (p = .70). Based on observer POSAS scores, scar pigmentation was significantly worse on the scar half repaired with OCA (1.98 [0.91]) compared with FG (1.79 [0.80]) (p = .05). CONCLUSION: With the exception of inferior scar pigmentation with OCA, there was no statistically significant difference in wound cosmesis after linear wound closure with OCA versus FG.

Laser hair reduction for hidradenitis suppurativa warrants insurance coverage.

Hidradenitis suppurativa is a chronic, painful disease that significantly reduces quality of life. Laser hair reduction is one modality that can be used in combination with other treatments to ameliorate the condition. We argue that insurance should provide coverage for this necessary service.

The role of hypothalamus-pituitary-adrenal (HPA)-like axis in inflammatory pilosebaceous disorders.

Skin is the largest peripheral endocrine organ and functions as a hormone target and endocrine gland. A cutaneous hypothalamus-pituitary-adrenal (HPA)-like axis enables the skin to respond to stress and regulates its steroidogenic activity. The pilosebaceous unit is a site for production and metabolism of a number of steroid hormones, including stress and sex hormones. This is an overview of the important role that the cutaneous HPA-like-axis plays in the pathogenesis and treatment of inflammatory pilosebaceous disorders, including acne, rosacea, seborrheic dermatitis, and hidradenitis suppurativa.

Use of 5-0 Fast Absorbing Gut versus 6-0 Fast Absorbing Gut during cutaneous wound closure on the head and neck: A randomized evaluator-blinded split-wound comparative effectiveness trial.

BACKGROUND: Absorbable suture material (Fast Absorbing Gut [FG], Ethicon, Somerville NJ) is often used for patient convenience; however, the optimal diameter of FG sutures is debatable. OBJECTIVE: To determine whether the use of 6-0 FG during repair of linear cutaneous surgery wounds on the head and neck improves scar cosmesis compared with the use of 5-0 FG. METHODS: This was a prospective, randomized, split-scar intervention in patients undergoing repair of linear cutaneous wounds on the head and neck. The scar was assessed 3 months after surgery via the Physician Observer Scar Assessment Scale (POSAS), a validated instrument. RESULTS: The difference in the sum of the POSAS component scores for 6-0 FG (12.03) compared with that for 5-0 FG (13.11) was not statistically significant (P = .26). Observer overall opinion was similar for both interventions, at 2.49 for 6-0 FG vs 2.64 for 5-0 FG (P = .54). The difference in the number of complications in the 5-0 FG group (15) vs the 6-0 FG group (10) was not statistically significant (P = .40). LIMITATIONS: Single-center study with wounds limited to the head and neck in white individuals, with a predominance of men. CONCLUSION: For linear repair of cutaneous wounds, 6-0 FG was not statistically different for cosmetic outcomes, scar width, and complications compared with 5-0 FG.

Dermal suture only versus layered closure: A randomized, split wound comparative effectiveness trial.

BACKGROUND: Layered closure of cutaneous wounds is a commonly used surgical practice. However, there are studies that suggest the additional layer of epidermal sutures might not be necessary. OBJECTIVE: To compare scar outcomes between the single-layer deep-dermal suture technique and the conventional layered suture technique for primary closure of cutaneous wounds. METHODS: A total of 49 patients were enrolled in a prospective, randomized, evaluator-blinded, split scar study to compare the conventional bilayered closure technique with the single-layer deep-dermal suturing technique for primary closure of wounds. The primary outcome measure was mean sum Patient and Observer Scar Assessment Scale (POSAS) score at 3 and 12 months. RESULTS: At the 3-month follow-up, there was a statistically significant difference in the mean total POSAS scores for both the blinded observer and patients, indicating a preference for the side with the standard layered closure. However, at the 12-month follow-up, this difference was lost, with the exception of scar color, which was significantly more noticeable on the wound side closed with only dermal sutures. LIMITATION: Single-center study. CONCLUSION: Three months after surgery, the layered closure technique resulted in a slightly better scar outcome than the single-layered closure containing only dermal sutures. At 12-months' follow-up, this difference diminished, with scars for both sides appearing similar.

Noninvasive profiling of sweat-derived lipid mediators for cutaneous research.

BACKGROUND AND OBJECTIVE: Recent increases in the use of noninvasive matrices for biomedical analysis has led to interest in the evaluation of sweat for both clinical and research applications. However, despite being one of the two main cutaneous secretions, until very recently, only one study actually analyzed sweat in the context of cutaneous disease. This review attempts to make the case for increased use of sweat in cutaneous research, and discusses lipid mediators as potential analytical targets in sweat. METHODS: Sweat composition and its relationship with the skin and systemic circulation are discussed, as are practical considerations for sweat sampling and analysis. Previous analyses of lipid mediators in skin biopsies are provided to show that lipid mediators can regulate cutaneous processes and disease pathways. Summaries of recent studies involving the analysis of sweat lipid mediators are provided to demonstrate the utility of sweat lipid mediator testing to support future cutaneous research studies. RESULTS: Sweat has the potential to reflect both local and systemic biochemical changes in response to disease or intervention, and two recent studies of sweat lipid mediators confirm this ability. Additionally, sweat lipid mediators appear to be temporally stable with individual variability comparable to other matrices, suggesting that these analytes could be useful biomarkers. CONCLUSIONS: Sweat metabolites may be capable of reporting changes in cutaneous biochemical pathways, thereby providing insight into the immunomodulatory biochemistry of the skin. Lipid mediator analysis of sweat appears to be a non invasive approach that could enhance existing cutaneous research and diagnostic methodologies.

Prospective randomized controlled pilot study on the effects of almond consumption on skin lipids and wrinkles.

OBJECTIVE: Almonds are a rich source of fatty acids and antioxidants, and their supplementation is known to significantly modulate serum lipids. The effects of almond on the skin's lipid barrier and the appearance of wrinkles have not yet been elucidated. The aim of this study was to investigate the effects of almond consumption on facial sebum production and wrinkles. METHODS: This was a prospective, investigator-blinded, randomized controlled trial in which subjects consumed 20% of their daily energy consumption in either almonds or a calorie-matched snack for 16 weeks. This study was completed at the UC Davis Dermatology clinic. Participants were a volunteer sample of generally healthy postmenopausal females with Fitzpatrick skin types 1 and 2. A facial photograph and image analysis system was used to obtain standardized photographs and information on wrinkle width and severity at 0, 8, and 16 weeks. Measurements of transepidermal water loss and sebum production were also completed at 0, 8, and 16 weeks. RESULTS: Fifty healthy postmenopausal females were recruited, 31 participants were enrolled, and 28 completed the study. Under photographic analysis, the almond group had significantly decreased wrinkle severity and width compared with the control group at 16 weeks (p < .02). Changes in skin barrier function were nonsignificant, measured by the transepidermal water loss (p = .65) between the almond and control groups relative to baseline after 16 weeks. No adverse effects were reported. CONCLUSION: Our study demonstrates that daily almond consumption may reduce wrinkle severity in postmenopausal females to potentially have natural antiaging benefits.

Treatment-resistant ulcerative necrobiosis lipoidica in a diabetic patient responsive to ustekinumab.

Necrobiosis lipoidica is a chronic granulomatous disease of unknown etiopathogenesis, which is often difficult to treat. While data from randomized controlled trials for the treatment of necrobiosis lipoidica is lacking, several treatments of varying efficacy for necrobiosis lipoidica have been reported in the scientific literature. We present a case of a 29-year-old female with uncontrolled diabetes and treatment-resistant necrobiosis lipoidica which was responsive to ustekinumab.

A review of next generation sequencing technologies used in the evaluation of the skin microbiome: what a time to be alive.

The role of the microbiome in healthy and disease states of the human body is progressively being found to extend beyond the gastrointestinal tract and into other organ systems such as the skin. Researching the microbiome thus has become paramount to understanding additional physiological and pathophysiological mechanisms that may be at play between microbes and their hosts. Cell cultures have traditionally been used to study the microbiome, but in our current day and age, advanced metagenomic techniques - such as 16S rRNA amplicon sequencing and whole metagenomic shotgun sequencing - are better able to classify the microorganisms making up the microbiome. Utilizing metagenomics alone, however, does not allow for the study of the more complex effects of the microbiome, such as changes in gene expression and metabolic byproducts. Thus, incorporation of other modalities such as metatranscriptomics, metaproteomics, and metabolomics are needed to further elucidate the extensive intricacies of the skin microbiome.

Quantification of ultraviolet (UV) radiation in the shade and in direct sunlight.

Ultraviolet (UV) radiation is associated with negative health effects, including sun damage and skin cancer. The purpose of this study is to compare the protective effects of the shade provided by a sun umbrella versus that provided by a tree. Sun sensors that register the level and dose of UV radiation were placed in the shade and in direct sunlight. Measurements were recorded every half hour between the hours of 12:30 p.m. and 3:00 p.m. in Sacramento, California. The results suggest that the level of UV radiation in the shade is not zero. The sensors located in tree shade indicated that over 5% of UV radiation was detected in the shade. The sensors located in sun-umbrella shade showed that greater than 17% of UV radiation reached the shade. The sun sensors used in our study collected UV radiation data relevant to UV index; however, they did not differentiate between UVA, UVB, visible, and infrared light. The amount of UV radiation detected in the shade is not zero, thus regular sunscreen use and other sun protective practices should be followed to reduce the risk of sun damage and skin cancer.