Targeting the gut‐skin axis—Probiotics as new tools for skin disorder management?

The existence of a gut‐skin axis is supported by increasing evidence, but its translational potential is not widely recognized. Studies linked inflammatory skin diseases to an imbalanced gut microbiome; hence, the modulation of the gut microbiota to improve skin condition seems to be a feasible approach. Today, there is a growing interest in natural products as alternatives to synthetic drugs. In this respect, oral probiotics could be a simple, safe and cheap modality in the therapeutic management of skin inflammation. Unfortunately, very few studies have looked into how probiotic supplementation influences inflammatory skin disorders. The result, though promising, are difficult to implement in clinical practice due to the heterogeneity of the applied supplemental regimen in the different studies. In this Viewpoint, we aim to encourage the conduction of more research in that direction to explore unambiguously the therapeutic potential of oral probiotics in dermatology. We focus on the most common inflammatory skin diseases (atopic dermatitis, psoriasis, rosacea, acne vulgaris) with an associated gut dysbiosis, but we also discuss some less common, but very serious skin pathologies (eg erythema nodosum, pyoderma gangrenosum, hidradenitis suppurativa) that are possibly linked to a disturbed gut flora composition. We dissect the possible mechanisms along the gut‐skin axis and highlight novel points where probiotics could interfere in this communication in the diseased state.     

What can we learn about skin of color in dermatopathology?

As the US population becomes increasingly diverse, more patients of color seek dermatologic care and often have concerns that are unique to their skin color. Therefore, it is critically important that the knowledge gap in skin of color dermatology be urgently addressed. In addition to addressing the clinical gap in recognizing dermatologic disease in patients of color, the role of dermatopathology in bridging this gap remains unaddressed. Given the impact that skin color can have on the presentation and subsequent management of dermatologic diseases, understanding the current knowledge of the unique structural and histologic characteristics in skin of color may help give us insight on the role skin color should play in histopathologic diagnosis. In this paper, we bring insights into the role dermatopathology plays in addressing our knowledge of cutaneous disease in patients with skin of color. After we highlight issues to consider, we can begin to identify gaps in knowledge that still exist within dermatopathology that need to be addressed to ensure patients of all backgrounds receive equitable dermatologic care.     

Melanomas arising from naevi and de novo melanomas — does origin matter?

BACKGROUND: It is widely accepted that some melanomas arise from pre-existing naevi, while others appear de novo. The proportions involved and the effect of melanoma origin on prognosis is unclear. OBJECTIVES: To determine whether melanomas reported by the patient to have developed from a pre-existing naevus are associated with a better or worse prognosis compared with those arising de novo when adjusted for confounding variables. METHODS: All patients attending a dedicated melanoma screening clinic between March 1997 and March 2002 were included. The distinction between melanoma arising without any pre-existing lesion (de novo) and those derived from a pre-existing lesion (naevus melanoma) was based on patient history. We categorized patients into three groups: those who gave a history of their lesion arising within a pre-existing naevus, those in whom the melanoma developed de novo and those in whom no conclusive history could be obtained. We compared prognostic indicators between the naevus and de novo melanoma groups. RESULTS: Of 8593 patients screened, 377 had a positive diagnosis of melanoma (in situ or invasive). Of these 42% had naevus melanomas, 34% new melanomas and 24% were uncertain. Patients presenting with a melanoma arising from a pre-existing naevus had a greater Breslow thickness despite presenting sooner than the de novo group, although no significant difference in thickness was found when other prognostic factors were controlled for. CONCLUSIONS: This prospective study shows that naevi that undergo malignant change may result in melanomas that are thicker and thus potentially have a worse prognosis than de novo melanomas. Although our results were not statistically significant when other risk factors were also taken into account, it is possible that a larger study would identify a significant association.     

Sarcoidosis: Are there differences in your skin of color patients?

The skin of color population is growing at an astronomical rate, making it critically important to recognize diseases, such as sarcoidosis, in patients with skin of color. Sarcoidosis is a multisystem, granulomatous disease, which manifests in a variety of organs and is found more frequently in Blacks as compared with Caucasians. In addition, Blacks have a poorer prognosis and often present with more advanced disease. Sarcoidal lesions can present with multiple morphologic features, some more common in patients with skin of color. We offer a review of the cutaneous presentations of sarcoid lesions in patients with skin of color, an overview of extracutaneous sarcoidosis, the cutaneous signs that may impact overall disease prognosis, and treatment options.     

Can we teach old drugs new tricks?—Repurposing of neuropharmacological drugs for inflammatory skin diseases

Despite the “hype” for monoclonal antibodies, the so‐called biologics, which added significant value to the therapeutic armamentarium of dermatologists and improved the life of many patients, but may exhibit significant adverse effects, the vast majority of dermatological patients suffering from atopic dermatitis or psoriasis is still treated topically. Thus, there is a huge need for locally applied, locally acting drugs for inflammatory skin diseases with better risk‐benefit profiles compared to topical corticosteroids or calcineurin inhibitors. Drug repositioning is a complex process, but offers advantages, in particular for indications with lower revenues. In this viewpoint, the neuroendocrine system of the skin is described as an attractive drug target because it contributes significantly to neutralizing external noxious agents prior to inducing immune or vascular changes leading to the clinical signs of skin inflammation, for example, itch and erythema. In addition, epidermis and dermis are accessible for topically applied products which may act locally without pharmacodynamically relevant systemic exposure limiting adverse events. Moreover, since numerous drugs have been evaluated for various CNS diseases, some failed and some approved, this resource should be exploited for repurposing as anti‐inflammatory drugs for topical application, for example, cannabidiol, fingolimod or asimadoline. Finally, a screening algorithm is shared which gives direct evidence of links between drug and inflammatory skin diseases.     

Is self-assessment of skin type a valid method for adolescents?

Self-assessed sun sensitivity (skin type) according to Fitzpatrick's classification has been reported to have drawbacks. Data from a cross-sectional study of tanning habits in Stockholm, Sweden, showed an underestimation of sun sensitivity among adolescents. Cautionary advice regarding sun and sun bed exposure, and sunscreen use versus skin type may have to be revised.     

How much skin protection cream is actually applied in the workplace? Determination of dose per skin surface area in nurses

Background. Skin protection creams (PCs) are used in the occupational setting to prevent irritant hand dermatitis. However, so far, the actual amounts of PC applied and the resulting dose per area unit on hands at work have not been a matter of systematic investigation. The quantities used in experimental studies investigating the efficacy of PCs range between 4 and 25 mg/cm². Objectives. To develop a practical and accurate method to analyse the actual consumed quantities of PCs at workplaces in relation to hand surface area. Methods. Thirty‐one hospital nurses without hand eczema were provided with a sample PC in special monitoring tubes with Medication Event Monitoring Systems (MEMS TrackCaps^®; Aardex Ltd, Zug, Switzerland), and used the product over 5 working days as usual. The consumption was calculated by weighing of the tubes and analysis of the application frequency, and related to the individual calculated hand surface area. Results. The mean PC dose applied was 0.97 ± 0.6 mg/cm². Conclusions. The amounts of PC applied by hospital nurses were significantly lower than the amounts that have been used in experimental studies. The method appears to be suitable for use in different in occupational settings. Further investigations are needed to gain realistic insights into consumers' attitudes regarding PCs.     

Population‐based surveys on the frequency of common skin diseases in adults—is there a risk of response bias?

Population-based surveys on the frequency of common skin diseases are important in determining the health needs of a community. As they rely on voluntary presentation, there is a risk of response bias which may compromise the quality of the data obtained. The aim was to determine in what way and to what degree response bias may occur in a population-based survey on the frequency of common skin diseases in adults. A follow-up study was conducted on 1043 out of 2500 adults who did not attend for examination as part of a randomized population-based survey on the frequency of common skin diseases amongst adults in Maryborough, Central Victoria, Australia. Nonrespondents were more likely to be at the extremes of age, retired, unemployed and less likely to report that they had a history of skin disease than the respondents. Subsequent examination of a sample of the nonrespondents revealed they were more likely to have skin cancers and Campbell de Morgan angiomas than the respondents. These differences cannot be fully explained on the basis of an age-related response bias alone. Response bias is a risk in population-based surveys of common skin diseases which rely on voluntary presentation. Some attempt should be made to sample the nonrespondents in these surveys to determine the nature and extent of any bias and to adjust for it, if necessary.     

Melanoma and nonmelanoma skin cancer chemoprevention: A role for nicotinamide?

Ultraviolet radiation (UVR) causes DNA damage in melanocytes by producing photolesions such as cyclobutane pyrimidine dimers and 8‐oxo‐7‐hydrodeoxyguanosine. The production of reactive oxygen species by UVR also induces inflammatory cytokines that, together with the inherent immunosuppressive properties of UVR, propagate carcinogenesis. Nicotinamide (Vitamin B₃) enhances DNA repair, modulates the inflammatory environment produced by UVR, and reduces UV‐induced immunosuppression. As nicotinamide reduces the incidence of actinic keratoses and nonmelanoma skin cancers in high‐risk individuals and enhances repair of DNA damage in melanocytes, it is a promising agent for the chemoprevention of melanoma in high‐risk populations.     

How does the type of vehicle influence the in vitro skin absorption and elimination kinetics of terpenes?

Terpenes are widely used in the topical dermal preparations, cosmetics and toiletries and also in the experimental dermopharmacy, as penetration enhancers. Terpenes do not need to penetrate into viable skin tissue and this event is not even desired. The aim of this study was to investigate skin absorption and elimination kinetics of two terpenes, namely linalool and terpinen-4-ol, incorporated in three different dermatological vehicles: oily solution, hydrogel and o/w emulsion. The preparations were applied onto the human skin in vitro, and after 1–4 h the content of terpenes in the stratum corneum layers and in the epidermis/dermis was determined using GC. Similarly, the amounts of terpenes in the skin were analysed during 4 h elimination process following 1 h absorption. The highest skin absorption was observed when terpenes were applied in hydrogel — their total content in the skin after 4 h was 385 and 705 μg/cm² for linalool and terpinen-4-ol, respectively. After 1 h of the elimination process about 10–20% drop of the total content of both terpenes in the skin was noted for all formulations. The skin penetration of both terpenes from the vehicles is increasing in the following order: emulsion < oily solution < hydrogel, while the elimination phase is relatively slower for terpenes applied in hydrogel.