Ashley K. Clark

Paraneoplastic Pemphigus and Autoimmune Blistering Diseases Associated with Neoplasm: Characteristics, Diagnosis, Associated Neoplasms, Proposed Pathogenesis, Treatment.

Autoimmune paraneoplastic and neoplasm-associated skin syndromes are characterized by autoimmune-mediated cutaneous lesions in the presence of a neoplasm. The identification of these syndromes provides information about the underlying tumor, systemic symptoms, and debilitating complications. The recognition of these syndromes is particularly helpful in cases of skin lesions presenting as the first sign of the malignancy, and the underlying malignancy can be treated in a timely manner. Autoimmune paraneoplastic and neoplasm-associated bullous skin syndromes are characterized by blister formation due to an autoimmune response to components of the epidermis or basement membrane in the context of a neoplasm. The clinical manifestations, histopathology and immunopathology findings, target antigens, associated neoplasm, current diagnostic criteria, current understanding of pathogenesis, and treatment options for a selection of four diseases are reviewed. Paraneoplastic pemphigus manifests with clinically distinct painful mucosal erosions and polymorphic cutaneous lesions, and is often associated with lymphoproliferative neoplasm. In contrast, bullous pemphigoid associated with neoplasm presents with large tense subepidermal bullae of the skin, and mild mucosal involvement, but without unique clinical features. Mucous membrane pemphigoid associated with neoplasm is a disorder of chronic subepithelial blisters that evolve into erosions and ulcerations that heal with scarring, and involves stratified squamous mucosal surfaces. Linear IgA dermatosis associated with neoplasm is characterized by annularly grouped pruritic papules, vesicles, and bullae along the extensor surfaces of elbows, knees, and buttocks. Physicians should be aware that these autoimmune paraneoplastic and neoplasm-associated syndromes can manifest distinct or similar clinical features as compared with the non-neoplastic counterparts.

Edible Plants and Their Influence on the Gut Microbiome and Acne

Acne vulgaris affects most people at some point in their lives. Due to unclear etiology, likely with multiple factors, targeted and low-risk treatments have yet to be developed. In this review, we explore the multiple causes of acne and how plant-based foods and supplements can control these. The proposed causative factors include insulin resistance, sex hormone imbalances, inflammation and microbial dysbiosis. There is an emerging body of work on the human gut microbiome and how it mediates feedback between the foods we eat and our bodies. The gut microbiome is also an important mediator of inflammation in the gut and systemically. A low-glycemic load diet, one rich in plant fibers and low in processed foods, has been linked to an improvement in acne, possibly through gut changes or attenuation of insulin levels. Though there is much interest in the human microbiome, there is much more unknown, especially along the gut-skin axis. Collectively, the evidence suggests that approaches such as plant-based foods and supplements may be a viable alternative to the current first line standard of care for moderate acne, which typically includes antibiotics. Though patient compliance with major dietary changes is likely much lower than with medications, it is a treatment avenue that warrants further study and development.

New and emerging targeted systemic therapies: a new era for atopic dermatitis

Abstract Purpose: This is a review of emerging targeted, systemic therapies for atopic dermatitis (AD). The information presented aims to provide dermatologists with updated therapeutic options, stimulate academic interest, and spark future research. Material and methods: Extensive search of ClinicalTrials.gov, the National Eczema Association, and PubMed was performed for clinical trials examining the effect of emerging targeted, systemic therapies in patients with AD. Results were included if they demonstrated efficacy in reversing AD symptoms. Studies that did not demonstrate clinical benefit were excluded. Results: A number of emerging systemic agents targeting specific mediators involved in the pathogenesis of AD were found. These targets include IL-4, IL-13, IgE, B-cells, IL-5, IL-31, JAK-STAT, SYK, IL-6, PDE-4, IL-12, IL-17, IL-23, IL-22, H4R, NKR1, κOR, TSLP, PPAR-γ, and DGLA. Treatment of AD patients with these therapies has, in many cases, led to statistically significant improvements in clinical severity scores and patient-reported outcomes. Conclusions: While multiple agents have demonstrated efficacy, only dupilumab is currently approved for adults with AD. Large-scale, randomized, placebo-controlled, double-blind trials, especially in children, are needed. As we enter the dawn of targeted therapy for AD, a comprehensive clinical trial registry is needed to facilitate data pooling and comparison among international registries.

Targeted treatments for hidradenitis suppurativa: a review of the current literature and ongoing clinical trials

Abstract Purpose: Targeted, immune-modulating drugs are at the forefront of therapy for HS, and a comprehensive clinical trial registry is needed to facilitate data pooling and clinical efficacy comparison. Materials and methods: A systematic review of the ClinicalTrials.gov database was searched for planned, in-progress, completed, or terminated trials investigating the effect of targeted biologic therapies for hidradenitis suppurativa (HS). When results of RCTs were not available, case reports or series were included. Results: Inflammatory mediators that are targeted by biologic agents include tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), IL-17, IL-12, IL-23, phosphodiesterase 4 (PDE4), lymphocyte function-associated antigen 1 (LFA-1), and complement component 5a (C5a). Clinical efficacy was measured by reduction in Sartorius score, Hidradenitis Suppurativa Clinical Response (HiSCR), Dermatology Life Quality Index (DLQI), or pain Visual Analog Scale (VAS). TNF inhibitors (adalimumab, etanercept, and infliximab), IL-1 receptor antagonist (Anakinra), IL-17A inhibitor (secukinumab), IL-12/23 inhibitor (ustekinumab), and PDE4 inhibitor (apremilast) show promise due to statistically significant improvements in disease severity. Conclusions: Currently, adalimumab is the only FDA-approved biologic available for the treatment of HS. However, results from trials of other biologic agents targeting downstream mediators are promising. Large-scale, randomized, placebo-controlled trials in patients with skin of color, as well as weight-based dosing trials, are needed.

Natural Oils for Skin-Barrier Repair: Ancient Compounds Now Backed by Modern Science

Natural plant oils are commonly used as topical therapy worldwide. They are usually easily accessible and are relatively inexpensive options for skin care. Many natural oils possess specific compounds with antimicrobial, antioxidant, anti-inflammatory, and anti-itch properties, making them attractive alternative and complementary treatments for xerotic and inflammatory dermatoses associated with skin-barrier disruption. Unique characteristics of various oils are important when considering their use for topical skin care. Differing ratios of essential fatty acids are major determinants of the barrier repair benefits of natural oils. Oils with a higher linoleic acid to oleic acid ratio have better barrier repair potential, whereas oils with higher amounts of irritating oleic acid may be detrimental to skin-barrier function. Various extraction methods for oils exist, including cold pressing to make unrefined oils, heat and chemical distillation to make essential oils, and the addition of various chemicals to simulate a specific scent to make fragranced oils. The method of oil processing and refinement is an important component of selecting oil for skin care, and cold pressing is the preferred method of oil extraction as the heat- and chemical-free process preserves beneficial lipids and limits irritating byproducts. This review summarizes evidence on utility of natural plant-based oils in dermatology, particularly in repairing the natural skin-barrier function, with the focus on natural oils, including Olea europaea (olive oil), Helianthus annus (sunflower seed oil), Cocos nucifera (coconut oil), Simmondsia chinesis (jojoba oil), Avena sativa (oat oil), and Argania spinosa (argan oil).

The Endocannabinoid System and Its Role in Eczematous Dermatoses.

The skin serves as the foremost barrier between the internal body and the external world, providing crucial protection against pathogens and chemical, mechanical, and ultraviolet damages. The skin is a central player in the intricate network of immune, neurologic, and endocrine systems. The endocannabinoid system (ECS) includes an extensive network of bioactive lipid mediators and their receptors, functions to modulate appetite, pain, mood, and memory, and has recently been implicated in skin homeostasis. Disruption of ECS homeostasis is implicated in the pathogenesis of several prevalent skin conditions. In this review, we highlight the role of endocannabinoids in maintaining skin health and homeostasis and discuss evidence on the role of ECS in several eczematous dermatoses including atopic dermatitis, asteatotic eczema, irritant contact dermatitis, allergic contact dermatitis, and chronic pruritus. The compilation of evidence may spark directions for future investigations on how the ECS may be a therapeutic target for dermatologic conditions.

The Role of Polyphenols in Rosacea Treatment: A Systematic Review

OBJECTIVES Various treatment options are available for the management of rosacea symptoms such as facial erythema, telangiectasia, papules and pustules, burning, stinging, and itching. Botanical therapies are commonly used to treat the symptoms. The objective of this review is to evaluate the use of polyphenols in rosacea treatment. DESIGN PubMed, Embase, Biosis, Web of Knowledge, and Scopus databases were systematically searched for clinical studies evaluating polyphenols in the management of rosacea. RESULTS Of 814 citations, 6 met the inclusion criteria. The studies evaluated licochalcone (n = 2), silymarin (n = 2), Crysanthellum indicum extract (n = 1), and quassia extract (n = 1). The studies only evaluated topical formations of stated polyphenols. Main results were summarized. CONCLUSIONS There is evidence that polyphenols may be beneficial for the treatment of rosacea symptoms. Polyphenols appear to be most effective at reducing facial erythema and papule and pustule counts. However, studies included have significant methodological limitations and therefore large-scale, randomized, placebo-controlled trials are warranted to further assess the efficacy and safety of polyphenols in the treatment of rosacea.

Phytochemical and Botanical Therapies for Rosacea: A Systematic Review.

Botanical and cosmeceutical therapies are commonly used to treat symptoms of rosacea such as facial erythema, papules/pustule counts, and telangiectasia. These products may contain plant extracts, phytochemicals, and herbal formulations. The objective of this study was to review clinical studies evaluating the use of botanical agents for the treatment of rosacea. MEDLINE and Embase databases were searched for clinical studies evaluating botanical therapies for rosacea. Major results were summarized, and study methodology was analyzed. Several botanical therapies may be promising for rosacea symptoms, but few studies are methodologically rigorous. Several plant extract and phytochemicals effectively improved facial erythema and papule/pustule counts caused by rosacea. Many studies are not methodologically rigorous. Further research is critical, as many botanicals have been evaluated in only one study. Botanical agents may reduce facial erythema and effectively improve papule/pustule counts associated with rosacea. Although promising, further research in the area is imperative. Copyright

Circadian rhythm in atopic dermatitis—Pathophysiology and implications for chronotherapy

Circadian rhythm is a biological clock that controls a wide range of physiological functions throughout the body, including various skin functions. A 24‐h diurnal cycle, governed by an endogenous clock in the brain, largely controls cutaneous diurnal rhythm, which external factors, including temperature, humidity, diet, and stress, also modulate locally. Circadian rhythm influences cutaneous blood flow and properties of skin barrier function, such as transepidermal water loss and capacitance, and has important implications in atopic dermatitis (AD). This review explores how aberrations in circadian rhythm may play a role in the pathogenesis of AD and proposes implementation of chronotherapy to improve treatment outcomes in patients with AD.

Sweat mechanisms and dysfunctions in atopic dermatitis

Skin barrier dysfunction is inherent to atopic dermatitis (AD), causing dryness, irritation, and increased permeability to irritants, allergens and pathogens. Eccrine sweat functions as part of the skins protective barrier. Variations in sweat responses have been observed in patients with AD, and altered sweat composition and dynamics are under-recognized as important factors in the disease cycle. This review discusses the role that sweat plays in the pathogenesis of AD, examines evidence on abnormal sweat composition, secretion, and neuro-immune responses to sweat in atopic skin, and highlights the value of sweat management.