Hand eczema in children referred for patch testing: North American Contact Dermatitis Group Data, 2000-2016.

BACKGROUND: Little is known about the aetiologies and relevant allergens in paediatric patients with hand eczema (HE). OBJECTIVES: To characterize the aetiologies and determine the proportion of positive and currently relevant allergens in children/adolescents (age < 18 years) with HE referred for patch testing. METHODS: A retrospective analysis (2000-2016) of North American Contact Dermatitis Group data was performed. RESULTS: Of 1634 paediatric patients, 237 (14·5%) had involvement of the hands. Final physician diagnoses included allergic contact dermatitis (49·4%), atopic dermatitis (37·1%) and irritant contact dermatitis (16·9%). In multivariable logistic regression models, employment was the only association with increased odds of any HE or primary HE. Children with HE vs. those without HE had similar proportions of positive patch tests (56·1% vs. 61·7%; χ2 -test, P = 0·11). The five most common currently relevant allergens were nickel, methylisothiazolinone, propylene glycol, decyl glucoside and lanolin. In multivariable logistic regression models of the top 20 relevant allergens, HE was associated with significantly higher odds of currently relevant reactions to lanolin, quaternium-15, Compositae mix, thiuram mix, 2-mercaptobenzathiazole and colophony. The allergens with the highest mean significance-prevalence index number were methylisothiazolinone, carba mix, thiuram mix, nickel and methylchloroisothiazolinone/methylisothiazolinone. CONCLUSIONS: Children with HE who were referred for patch testing had a high proportion of positive patch tests, which was similar to the proportion found in children without HE. Children with HE had a distinct and fairly narrow profile of currently relevant allergens.

Pathophysiology and management of sensitive skin: position paper from the special interest group on sensitive skin of the International Forum for the Study of Itch (IFSI).

The special interest group on sensitive skin of the International Forum for the Study of Itch previously defined sensitive skin as a syndrome defined by the occurrence of unpleasant sensations (stinging, burning, pain, pruritus and tingling sensations) in response to stimuli that normally should not provoke such sensations. This additional paper focuses on the pathophysiology and the management of sensitive skin. Sensitive skin is not an immunological disorder but is related to alterations of the skin nervous system. Skin barrier abnormalities are frequently associated, but there is no cause and direct relationship. Further studies are needed to better understand the pathophysiology of sensitive skin - as well as the inducing factors. Avoidance of possible triggering factors and the use of well-tolerated cosmetics, especially those containing inhibitors of unpleasant sensations, might be suggested for patients with sensitive skin. The role of psychosocial factors, such as stress or negative expectations, might be relevant for subgroups of patients. To date, there is no clinical trial supporting the use of topical or systemic drugs in sensitive skin. The published data are not sufficient to reach a consensus on sensitive skin management. In general, patients with sensitive skin require a personalized approach, taking into account various biomedical, neural and psychosocial factors affecting sensitive skin.

Inhibition of MMPs Cat G and downregulates the signaling of TGF-ß/Smad in chronic photodamaged human fibroblasts.

OBJECTIVE: To understand the action of Cathepsin G (Cat G) and matrix metalloproteases (MMPs) on the ß/Smad pathway of transforming growth factor ß (TGF-ß) in chronically photodamaged human fibroblasts. Cat G plays a significant role in the process of skin photoaging and in collagen synthesis and degradation which is induced by UV irradiation it could interact with TGF-ß/Smad signaling. No available studies have thoroughly explored its molecular mechanisms of photoaging regulation. PATIENTS AND METHODS: Fibroblasts were divided into 4 groups: (1) control, (2) UVA irradiation of 25 J/cm2, (3) UVA irradiation of 25 J/cm2 + MMPs inhibitor, and (4) 25 J/cm2 UVA irradiation + Cat G inhibitor. All treatments were repeated daily for 21 days. Western blot and ELISA was employed to detect Protein levels for Cat G, MMPs, and several smads. RESULTS: Compared to UVA-irradiated cells, the addition of MMPs inhibitor downregulated the expression of smad2, smad3, and smad4 as well as TGF-ß. The addition of Cat G inhibitor downregulated the expression of smad2, smad3, and smad4 as well as TGF-ß. These data suggest that TGF-ß/Smad signaling was decreased by inhibition of MMPs and Cat G decreased in chronically human fibroblasts which are photo-damaged. CONCLUSIONS: These results may help expand our knowledge of mechanisms mediating photoaging and is possibly instrumental to the exploration of novel anti-photoaging treatments.

Comparing touch senses of naïve and expert panels through treated hair swatches: which associated wordings correlate with hair physical properties?

OBJECTIVES: This study (i) compared the sense of touch between a naïve and expert panels, under visual or blind conditions, using differently treated hair swatches and (ii) explored possible common wordings used by both panels and their possible links with some physical properties of hairs. METHODS: Two sets of 15 hair swatches of Caucasian and Chinese origins were differently treated (bleached, permed, brushed, etc.) or organized (root-tip vs. tip-root). These were evaluated by tactile assessments by two panels (105 naïve consumers and 10 hair experts) under visual or blind conditions, in two geographical locations. A series of 17 defined antonym adjectives, as descriptors, allowed responses of each panel to being scored and their preference mappings to being defined on a like-dislike scale. Hair swatches were measured and assessed by various instrumental techniques (bending, diameter, cuticle cohesion, alignments of hair). RESULTS: Apart from a few overlaps, all 15 hair swatches were well differentiated by both panels which showed a global agreement, making experts reliable assessors. Only three descriptors among 17 correlated with some objective measurements. Tactile-visual assessments differ from those performed tactile blind in both panels. Agreements between both panels appear, however, closer under tactile-blind conditions. CONCLUSION: Trained hair experts were confirmed as reliable representatives of a larger and naïve cohort, viewed as consumers. Hair swatches were well differentiated by both panels, with comparable descriptor rankings.

The three moments of skin cream application: an evidence-based proposal for use of skin creams in the prevention of irritant contact dermatitis in the workplace.

Contact dermatitis is one of the most common occupational diseases, with serious impact on quality of life, lost days at work and a condition that may be chronically relapsing. Regular prophylactic skin cream application is widely acknowledged to be an effective prevention strategy against occupational contact dermatitis; however, compliance rates remain low. To present a simple programme for skin cream application in the workplace with focus on implementation to drive down the rate of occupational irritant contact dermatitis, an expert panel of eight international dermatologists combined personal experience with extensive literature review. The recommendations are based on clinical experience as supported by evidence-based data from interventional studies. The authors identified three moments for skin cream application in the work place: (i) before starting a work period; (ii) after washing hands; and (iii) after work. Affecting behaviour change requires systematic communications, monitoring and reporting, which is proposed through Kotter's principles of organizational change management. Measurement tools are provided in the appendix. Interventional data based on application of this proposal is required to demonstrate its effectiveness.

Skin absorption through atopic dermatitis skin: a systematic review.

Patients with atopic dermatitis (AD) have skin barrier impairment in both lesional and nonlesional skin. They are typically exposed daily to emollients and intermittently to topical anti-inflammatory medicaments, thereby increasing the risk of developing contact allergy and systemic exposure to chemical ingredients found in these topical preparations. We systematically searched for studies that investigated skin absorption of various penetrants, including medicaments, in patients with AD, but also in animals with experimentally-induced dermatitis. We identified 40 articles: 11 human studies examining model penetrants, 26 human studies examining AD drugs, and three animal studies. We conclude that patients with AD have almost twofold increased skin absorption compared with healthy controls. There is a need for well-designed epidemiological and dermatopharmacokinetic studies that examine to what extent AD causes patients to be systemically exposed to chemicals compared with nonatopic dermatitis.

Effect of ultrasound and heat on percutaneous absorption of l-ascorbic acid: human in vitro studies on Franz cell and Petri dish systems.

OBJECTIVE: Percutaneous absorption of l-ascorbic acid (LAA) is limited due to its high hydrophilicity and low stability. Here, we investigated the effect of post-dosing sonophoresis (329 kHz, 20 mW cm-2 ) and heat (36°C) on transdermal delivery of LAA. METHODS: Ultrasound/heat, heat and control treatments were applied on skin surface for 2 and 5 min after topical application of C14-labelled LAA aqueous solution. After 15 min post-exposure, radioactivity was measured in tape-striped stratum corneum (TS-SC), epidermis, dermis and receptor fluid. As Franz diffusion cell model may have different acoustic response than in vivo human tissues, a novel Petri dish model was developed and compared with Franz cell model on the effects of ultrasound/heat treatment on the skin permeability. RESULTS: Five-min ultrasound/heat treatment significantly accelerated skin absorption/penetration of LAA; 2-min treatment showed no enhancement effect on Franz diffusion cell model at the end of experiment. The use of Petri dish model significantly increased LAA concentrations in epidermis after 5 min of ultrasound/heat treatment, compared to the results of Franz cell model. CONCLUSION: Combination of ultrasound (329 kHz, 20 mW cm-2 ) and heat (36°C) significantly enhanced LAA transdermal penetration, when the time of treatment was sufficient (5 min). As Petri dish model was designed to simulate acoustic respond of dense human tissue to ultrasound, the difference between Franz cell and Petri dish models suggests that the enhancement effect of ultrasound/heat on skin penetration in vivo may be greater than that determined on in vitro Franz cell model.

Qualitative vs. quantitative atopic dermatitis criteria - in historical and present perspectives.

This review summarizes historical aspects, clinical expression and pathophysiology leading to coining of the terms atopy and atopic dermatitis, current diagnostic criteria and further explore the possibility of developing quantitative diagnostic criteria of atopic dermatitis (AD) based on the importance of atopic features - subjective, objective, and those derived from laboratory tests - the new partly promising AD biomarkers. 'Atopy', introduced in 1923, denoted 'the sense of a strange disease without a precise place in the body'. A decade later, Sulzberger and Hill, first defined 'atopic dermatitis'. The pioneering well-recognized criteria, 'Hanifin & Rajka' (Acta Derm Venereol, 92, 1980, 44), were developed empirically on 'clinical experience' and expert consensus. As opposed to the widely used, rather anamnestic 'UK Criteria' (1994), they have few formal validation studies, but appear to well embrace various atopic phenotypes. Pruritus, xerosis, typical morphology/distribution of dermatitis and tendency to a relapsing/chronic course are common basic features in AD criteria, whereas skin sensitivity, heredity and various ill-defined atopic stigmata also seem to comprise the atopic phenomenon. Specific pheno- and endotypes are now emerging potentially enabling us to better classify patients with AD, but the influence of these on the diagnosis of AD is so far unclear. Few diagnostic models use quantitative scoring systems to establish AD cases from normal population, which, however, may be useful to better study and manage this disease. Long-term prospective observational studies, from which few are available at this point, along with interventional studies, are a perquisite and will provide the best option to improve our understanding of its complex characteristics and etiology.

Pitfalls in clinical trials reveal need for well tolerated, more effective depigmenting agents.

OBJECTIVE: Examine clinical trials performed for depigmenting agents in order to determine the most effective and well-tolerated depigmenting agent. METHODS: We searched clinical trials, published and unpublished, performed for hydroquinone, ascorbic acid, azelaic acid, retinol and niacinamide in the period 2009 till present. Studies were examined based on participant information, design, duration, intervention, outcome measurements and statistical significance. RESULTS: Sixty-one studies were examined, 40 published and 21 unpublished. Design, outcome measures and intervention showed sources of bias were not avoided. Only 30% of published trials were double-blind, 27% used a placebo and 80% used subjective measurements for their results. Unpublished trials follow similar outcomes, however, did not provide any significant results. CONCLUSION: Based on these results, we are unable to recommend a safer, more effective depigmenting agent. Lack of thorough trials limits us from accepting depigmenting agent full evaluation. To accept a depigmenting agent, its duration must test for long-term safety, clinical trial must be double-blind and comparative, use participants of the correct skin type and measure outcomes objectively. In addition, lack of results for parallel unpublished studies leaves room for discussion. Efforts toward creating more effective formulations are welcomed.

Measurement, analysis and prediction of topical UV filter bioavailability.

The aim of the present study was to objectively quantify and predict bioavailability of three sunscreen agents (i.e., benzophenone-3, 2-ethylhexylsalicylate, and 2 ethylhexyl-4-methoxycinnamate) in epidermis treated by petrolatum and emulsion-based formulations for 7 and 30min on four human volunteers. Profiles of sunscreen agents through stratum corneum (SC), derived from the assessment of chemical amounts in SC layers collected by successive adhesive tape-stripping, were successfully fitted to Fick's second law of diffusion. Therefore, permeability coefficients of sunscreen agents were found lower with petrolatum than with emulsion based formulations confirming the crucial role of vehicle in topical delivery. Furthermore, the robustness of that methodology was confirmed by the linear relationship between the chemical absorption measured after 30min and that predicted from the 7-min exposure experiment. Interestingly, in this dermatopharmacokinetic method, the deconvolution of permeability coefficients in their respective partition coefficients and absorption constants allowed a better understanding of vehicle effects upon topical bioavailability mechanisms and bioequivalence of skin products.

Physiological effect of olfactory stimuli inhalation in humans: an overview.

The importance of odorants in human life has long been recognized. Literature contains different approaches of physiological and psychological effects of odorant compounds, fragrances and essential oils. This work discusses odorants inhalation effect, based on an overview of major studies in humans. Beneficial effect of fragrances is mainly related to human behaviour. Studies document odorants influence in sympathetic and parasympathetic nervous systems, and neurophysiological brain activity. Moreover, odours compounds can act on the neuroendocrine system, neurotransmitters and neuromodulators, influencing psychological behaviour as well as body function. Odorant inhalation modulates physiological pathways, and in some cases, results in skin function regulation. The mechanism is incompletely elucidated. These findings suggest that olfactory system plays a role in central nervous system function beyond that of smell. In this overview, it was observed that odour compounds influenced stress biomarkers, dehydroepiandrosterone, oxidative stress, estradiol, dopamine, cutaneous barrier, sebum secretion and cutaneous immune system in humans. Some can be related with skin function. As the skin is associated with an extensive biochemical cascade and has complex mechanisms, studies have far to go, as there are processes not yet investigated related to skin that may be affected through olfaction. Future researches are needed to further understand and describe the mechanisms of action of physiological effects in fragrance compounds.

Skin benefits with a novel emollient-treated menstrual pad.

Manufacturers of consumer products consistently seek to improve marketed products in terms of both safety and efficacy. The desire for continued improvement is seen even in well-established products such as catamenial products which have existed in some form for thousands of years. A recent innovation in the design of menstrual pads is the addition of a surface finish of emollient for the purpose of increasing comfort during wear. The present paper presents different evaluations of such an emollient-treated menstrual pad with a novel absorbent core. These investigations demonstrated product tolerability, defined the optimal formulation and concentration of the emollient-containing finish, and demonstrated successful transfer of the emollient to the relevant skin surface. In addition, enhancement of skin moisturization, associated with exposure to the emollient-treated pad, was demonstrated by several technologies: assessment of skin moisturization by Corneometer®, skin friction testing, and skin capacitance.

Sensitive skin: an overview.

Sensitive skin is a condition of subjective cutaneous hyper-reactivity to environmental factors. Subjects experiencing this condition report exaggerated reactions when their skin is in contact with cosmetics, soaps and sun screens, and they often report worsening after exposure to dry and cold climate. Although no sign of irritation is commonly detected, itching, burning, stinging and a tight sensation are constantly present. Generally substances that are not commonly considered irritants are involved in this abnormal response.Sensitive skin and subjective irritation are widespread but still far from being completely defined and understood. A correlation between sensitive skin and constitutional anomalies and/or other triggering factors such as occupational skin diseases or chronic exposure to irritants has been hypothesized. Recent findings suggest that higher sensitivity can be due to different mechanisms. Hyper-reactors may have a thinner stratum corneum with a reduced corneocyte area causing a higher transcutaneous penetration of water-soluble chemicals. Alterations in vanilloid receptors and changes in neuronal transmission have been described. Monitoring skin parameters such as barrier function, proclivity to irritation, corneocyte size and sensorial transmission can also be useful to identify regional differences in skin sensitivity.

Nail apparatus melanoma: is trauma a coincidence? Is this peculiar tumor a real acral melanoma?

Nail Apparatus Melanoma (NAM) is rare, particularly in Caucasians. Understanding its pathogenesis and collecting epidemiologic data may be difficult due to its location and the exiguity of the case series of this cancer. Cutaneous melanoma has been thought related to UV radiation, and NAM is considered an acral variant of melanoma, even if the nail presents a specific anatomy. Little is reported about pathogenesis, except reports suggesting traumatic injuries as a causal factor. UV exposure is debated in nail melanoma because of its structure. The nail is, in fact, a unique structure with sun-exposed and non exposed melanocytes. NAM arises from the nail melanocytes, located in the nail matrix, which is the germinative part of the nail and composed of a proximal and distal portion. The proximal nail matrix lays under the proximal nail fold that covers it and is non-sun exposed, while the distant nail matrix, clinically visible as the lunula, is sun-exposed, though lying underneath the nail plate. According to these anatomical data, NAM is a distinct melanoma type, and studies need to classify it as acral melanoma or as a particular type of melanoma with its own pathogenesis and prognostic criteria. This study investigates potential risk factors of NAM, emphasizing (i) trauma and (ii) UV exposure among our NAM patients.

Age-related percutaneous penetration part 2: effect of age on dermatopharmacokinetics and overview of transdermal products.

Transdermal drug delivery allows for a constant rate of drug administration and prolonged action, which can be beneficial to elderly patients who are often polymedicated. Several studies have compared dermatopharmacokinetics in the young and elderly with conflicting results. Despite the potential limitations of age-related changes in skin factors and cutaneous metabolism, marketed transdermal products generally do not report age-related differences in pharmacokinetics. This overview discusses the current data, summarizes marketed product findings and highlights the importance of further studies to evaluate age-related dermatopharmacokinetics.

Age-related percutaneous penetration part 1: skin factors.

Changes in the skin that occur in the elderly may put them at increased risk for altered percutaneous penetration from pharmacotherapy along with potential adverse effects. Skin factors that may have a role in age-related percutaneous penetration include blood flow, pH, skin thickness, hair and pore density, and the content and structure of proteins, glycosaminoglycans (GAGs), water, and lipids. Each factor is examined as a function of increasing age along with its potential impact on percutaneous penetration. Additionally, topical drugs that successfully overcome the barrier function of the skin can still fall victim to cutaneous metabolism, thereby producing metabolites that may have increased or decreased activity. This overview discusses the current data and highlights the importance of further studies to evaluate the impact of skin factors in age-related percutaneous penetration.