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.

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.

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.

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.

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.

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.

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.

Allergic contact dermatitis: epidemiology, molecular mechanisms, in vitro methods and regulatory aspects. Current knowledge assembled at an international workshop at BfR, Germany.

Contact allergies are complex diseases, and one of the important challenges for public health and immunology. The German 'Federal Institute for Risk Assessment' hosted an 'International Workshop on Contact Dermatitis'. The scope of the workshop was to discuss new discoveries and developments in the field of contact dermatitis. This included the epidemiology and molecular biology of contact allergy, as well as the development of new in vitro methods. Furthermore, it considered regulatory aspects aiming to reduce exposure to contact sensitisers. An estimated 15-20% of the general population suffers from contact allergy. Workplace exposure, age, sex, use of consumer products and genetic predispositions were identified as the most important risk factors. Research highlights included: advances in understanding of immune responses to contact sensitisers, the importance of autoxidation or enzyme-mediated oxidation for the activation of chemicals, the mechanisms through which hapten-protein conjugates are formed and the development of novel in vitro strategies for the identification of skin-sensitising chemicals. Dendritic cell cultures and structure-activity relationships are being developed to identify potential contact allergens. However, the local lymph node assay (LLNA) presently remains the validated method of choice for hazard identification and characterisation. At the workshop the use of the LLNA for regulatory purposes and for quantitative risk assessment was also discussed.

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.

Evaluation of incidental thyroid nodules in patients with primary melanoma.

AIM: Literature data have suggested an increase of incidental thyroid nodules in patients with malignancies, including melanoma. METHODS: The ultrasound findings of 168 consecutive melanoma patients were revisited in order to evaluate the presence of incidental thyroid nodules and the results were compared with clinical features, Breslow thickness and the rate of malignancy of incidental thyroid nodules. RESULTS: We observed that: 1) incidental thyroid nodules are more frequent in patients affected by melanoma (60.6%) than in the healthy population; 2) no statistically significant difference were found in thyroid involvement on the basis of gender and age; 3) incidental thyroid nodules frequency is increased in patients with thinner melanoma and this increase is more evident if we consider melanoma in situ and female patients; 4) it was not detected malignant incidental thyroid nodules. CONCLUSION: The data revealed a high frequency of incidental thyroid nodules in patients with melanoma, suggesting that it is necessary to study this association in a larger group of patients, also including age/gender matched controls.

Pragmatic approach to the clinical work-up of patients with putative allergic disease to metallic orthopaedic implants before and after surgery.

Allergic complications following insertion of metallic orthopaedic implants include allergic dermatitis reactions but also extracutaneous complications. As metal-allergic patients and/or surgeons may ask dermatologists and allergologists for advice prior to planned orthopaedic implant surgery, and as surgeons may refer patients with complications following total joint arthroplasty for diagnostic work-up, there is a continuous need for updated guidelines. This review presents published evidence for patch testing prior to surgery and proposes tentative diagnostic criteria which clinicians can rely on in the work-up of patients with putative allergic complications following surgery. Few studies have investigated whether subjects with metal contact allergy have increased risk of developing complications following orthopaedic implant insertion. Metal allergy might in a minority increase the risk of complications caused by a delayed-type hypersensitivity reaction. At present, we do not know how to identify the subgroups of metal contact allergic patients with a potentially increased risk of complications following insertion of a metal implant. We recommend that clinicians should refrain from routine patch testing prior to surgery unless the patient has already had implant surgery with complications suspected to be allergic or has a history of clinical metal intolerance of sufficient magnitude to be of concern to the patient or a health provider. The clinical work-up of a patient suspected of having an allergic reaction to a metal implant should include patch testing and possibly in vitro testing. We propose diagnostic criteria for allergic dermatitis reactions as well as noneczematous complications caused by metal implants.

Contact urticaria to cosmetic and industrial dyes.

Contact urticaria (CU) defines the weal-and-flare reaction that occurs after external cutaneous contact with a causative agent. These reactions often cause discomfort for patients, affect their quality of life, and in severe cases may be life-threatening. Some dyes are known to be urticariogens. Many people have daily exposure to these urticariogens, because of the widespread use of dyes, for example in textiles, cosmetics and foods. We reviewed industrial and cosmetic dyes such as hair dyes, basic blue 99 dye, patent blue dyes, henna, red dyes, curcumin and reactive dyes, which can potentially cause CU. Overall, the reported cases of CU lacked appropriate controls. Hair-dye constituents such as preservatives and intensifiers may play an important role as causative agents of CU. We recommend appropriate protection guidelines to reduce the incidence of CU in high-risk groups such as hairdressers, dye-factory workers or workers in dye-related industries.