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.

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.

Transdermal estradiol and testosterone transfer in man: existence, models, and strategies for prevention.

BACKGROUND: Transdermal hormone application allows delivery of a clinically relevant hormone dose often with fewer systemic side effects than oral formulations. However, transdermal hormone transfer from a dosed individual to naïve interpersonal contact occurs and may cause significant hormone imbalance and adverse effects. METHODS: We reviewed PubMed, Medline, and Scopus articles from the years 1950 to 2010 for articles related to transdermal hormone transfer in the setting of in vivo and in vitro human and animal models. We used the following key words: transfer, transdermal, absorption, cutaneous, hormone, estradiol, and testosterone. Unpublished trials were reviewed on the US Food and Drug Administration (FDA) website for product approval. RESULTS: Data reflecting in vivo transfer of transdermal estradiol and testosterone in man is available from case reports, clinical trials, and FDA product information. While results clearly show that transfer can occur, methods for measuring the effect are not standardized and are thus difficult to compare among positive and negative studies. No in vitro human studies or animal models have been developed to specifically examine transfer potential of transdermal estradiol or testosterone. CONCLUSION: It is necessary to consider the mechanism behind transdermal hormone transfer and consider ways to enhance clinical benefits to the dosed individual while minimizing transfer to a naïve interpersonal contact. A detailed discussion of trial comparisons and future optimization methods may help enhance our understanding of the potential for transdermal hormone transfer and encourage development of newer formulations and/or application methods to minimize its occurrence.

Enhancing sunscreen efficacy in the 'real' world?

Sunscreens, used in the prevention of sunburn and skin cancer, have been commercialized since the 1930s. Their utilization is expanding, particularly in response to photoaging and an increase of skin cancer. However, failures occur in sunscreen use because their efficacy depends on the adequacy of application and utilization. This overview documents issues in sunscreen use and also discusses 2007 FDA-proposed rules to offer possible options for enhanced efficacy and communications to the consumer.

In vitro human topical bioactive drug transdermal absorption: estradiol.

Use of the percutaneous route may avoid some of the undesirable side effects that occur following oral administration in estrogen replacement therapy. At present, knowledge of estradiol transdermal properties relating to delivery of drugs in the skin is lacking. One reason is that in the existing transport models of estradiol, the skin is regarded as a single layer. This study revealed a significant difference of effects on estradiol delivery in the 3 sublayers of the skin and has caused us to believe that if we can obtain information about the transfer properties of estradiol in human skin (3 sublayers), we will not only increase our understanding of the estradiol biotransport mechanism, but also benefit clinical application. Accordingly, radioactive 17beta-estradiol was used to clarify the percutaneous absorption of estradiol into the 3 sublayers of the skin (stratum corneum, epidermis, and dermis) and to evaluate the effect of drugs delivered in each sublayer. Based on data thereby obtained, mathematical models were built to further obtain transport parameters (diffusivity, permeability, lag time, and partition coefficients) for the 3 layers of the skin.

Role of topical peptides in preventing or treating aged skin.

Ageing, a basic biological process seen in all living creatures, is not preventable. Surgical and topical modalities have been invented and substances were applied topically to alter the ageing process. Peptides and proteins, frequently used for this purpose, were categorized into four groups: signal peptides, enzyme-inhibitor peptides, neurotransmitter-inhibitor peptides and carrier peptides. We comprehensively review eligible studies -including controlled ex vivo or in vivo efficacy studies on any topical peptide or protein that has been administered to treat signs and symptoms of ageing.

Many common drugs in dermatology are light, temperature, or moisture-sensitive.

Photosensitivity is defined as responsiveness to light exposure. For many common dermatologic drugs, proper storage conditions are essential for maintaining drug activity. Degradation and loss of activity can occur with exposure to light, temperature, and/ or moisture. For example, ketoconazole degrades after 24 hours of light exposure. In this article storage guidelines for common dermatology drugs are provided. We suspect that drug degradation is common due to improper storage and that improved patient instruction regarding storage will reduce degradation and alleviate some of the danger associated with improper storage and usage patterns.

Chondrodermatitis nodularis chronica helicis in monozygotic twins.

Chondrodermatitis nodularis chronica helicis (CNCH) is a benign inflammatory nodule of the helix. Patients report severe tenderness upon pressure. Commonly seen in middle-aged men, there are no reports of this disease in twins. We report middle-aged male monozygotic twins who simultaneously developed CNCH. This suggests, but does not prove, the possibility of a hereditary factor in the pathogenesis of CNCH.

Intrinsic and extrinsic factors in skin ageing: a review.

As the proportion of the ageing population in industrialized countries continues to increase, the dermatological concerns of the aged grow in medical importance. Intrinsic structural changes occur as a natural consequence of ageing and are genetically determined. The rate of ageing is significantly different among different populations, as well as among different anatomical sites even within a single individual. The intrinsic rate of skin ageing in any individual can also be dramatically influenced by personal and environmental factors, particularly the amount of exposure to ultraviolet light. Photodamage, which considerably accelerates the visible ageing of skin, also greatly increases the risk of cutaneous neoplasms. As the population ages, dermatological focus must shift from ameliorating the cosmetic consequences of skin ageing to decreasing the genuine morbidity associated with problems of the ageing skin. A better understanding of both the intrinsic and extrinsic influences on the ageing of the skin, as well as distinguishing the retractable aspects of cutaneous ageing (primarily hormonal and lifestyle influences) from the irretractable (primarily intrinsic ageing), is crucial to this endeavour.

Gender differences of enzymatic activity and distribution of 17beta-hydroxysteroid dehydrogenase in human skin in vitro.

The interconversion of estrone (E1) and 17beta-estradiol (E2) is catalyzed by 17beta-hydroxysteroid dehydrogenase (17beta-HSD) in peripheral steroidogenic organs such as the skin. To investigate gender differences of activity and skin distribution of 17beta-HSD in human skin, enzymatic activity was measured in skin homogenates and skin horizontally sliced by 10 microm thickness in vitro. Reductive 17beta-HSD (E2 formation from E1) in female skin has a lower substrate affinity than in male skin; Km (Michaelis-Menten constant) of female and male skin is 11.8 +/- 6.5 and 2.0 +/- 2.0 microM, respectively. Female skin had a tendency to activate estrogen; Vmax (maximum rate) for E2 formation, 5.8 +/- 4.0 pmol/min/mg protein, is 1.7 times larger than E1 formation, 3.5 +/- 1.5 pmol/min/mg protein, and, on the other hand, male skin tends to deactivate estrogen; Vmax for E1 and E2 is 10.5 +/- 6.1 and 4.2 +/- 3.7 pmol/min/mg protein, respectively. The concentration of metabolite had a peak value at 80-120 microm from the skin surface. Therefore, these in vitro results suggest that the enzymatic activities of 17beta-HSDs have a gender difference in estrogen formation/metabolism and are distributed around the basement layer of the epidermis irrespective of sex. 17Beta-HSDs distributed around the basement epidermis may be effectively supplied with circulating estrogen from the papillary plexus to maintain the estrogen level in skin. This distribution pattern having a peak surrounding 100 microm from the skin surface indicates the importance for defense from noxae (e.g. detoxication) and maintenance of the internal environment (e.g. biosynthesis of hormones). Future studies should increase sample size and confirm these results by stricter statistical analysis.

In vitro model for decontamination of human skin: formaldehyde.

Decontamination of a chemical from skin is often an emergency measure. This study utilized an in vitro model to compare the decontamination capacity of three model decontaminant solutions (tap water, isotonic saline, and hypertonic saline). Human cadaver skin was dosed (approximately 0.25 microg on 3 cm(2) per skin) with radio-labeled [(14)C]-formaldehyde. After a defined exposure time (1, 3, and 30 min post-dosing, respectively), the surface skin was washed three times (4ml per time) with each solution. After washing, the skin was stripped with tape discs twice. Lastly, the wash solutions, strippings, receptor fluid, and remainder of skin were liquid scintillation analyzer counted to determine the amounts of formaldehyde. Additionally, an evaporation test at different exposure times (1min, 3min, 15min, 30min, and 60min, respectively) was conducted to monitor formaldehyde % evaporation. There were no statistical differences among these groups except isotonic saline, at 3min post-exposure (in wash solutions), showed a significantly difference (p<0.05) when compared to tap water. Formaldehyde % evaporation increased linearly with extending application times, and were 7.7%, 13.6%, 19.7%, 24.4%, and 35.9% (1min, 3min, 15min, 30min, and 60min, respectively). This data suggests that isotonic saline may be effective in removing formaldehyde from skin. However, results from this model need validation in vivo. The model may provide a facile and robust method of accelerating knowledge of decontamination mechanism and lead to enhanced efficacy.

Evaluation of the antioxidant capacity and preventive effects of a topical emulsion and its vehicle control on the skin response to UV exposure.

Supplying topical exogenous antioxidants to the skin may prevent or minimize free radical-induced damaging. This study determines antioxidative capacity of a topical skin care emulsion (an oil-in-water vitamin E-containing formulation) versus its vehicle on human skin that was exposed to ultraviolet radiation (UVR) by utilizing a photochemiluminescence device and biophysical methods. Ten healthy Caucasians (3 male and 7 female; mean age 47 +/- 10 years) were enrolled. In a randomized and double-blind manner, a pH-balanced vitamin E emulsion or its vehicle control was applied onto predesignated forearm prior to UVR exposure. Thirty minutes after application, these test sites were exposed to a UV light to induce the minimal erythema dose. One untreated site served as a blank control. Visual scoring and instrumental measurements were recorded at baseline and at 24 h and 48 h thereafter. At day 3, after completing instrumental measurements, each test site was stripped three times in a consecutive manner with a proprietary adhesive tape disc. These tapes were quantified for antioxidant capacity using a photochemiluminescence device. Vitamin E emulsion and vehicle control significantly (p < 0.05) suppressed visual scores when compared with blank control at day 2 and day 3 after UV exposure. However, vitamin E emulsion showed significantly (p < 0.05) lower visual scores when compared with vehicle control at day 2 and day 3 after UV exposure.Also,vitamin E emulsion and its vehicle control significantly (p < 0.05) diminished skin color measurement (a*) values when compared with blank control at day 2 and day 3 after UV exposure. At day 2 after UV exposure, only vitamin E emulsion significantly (p < 0.05) reduced skin blood flow volume when compared with blank control. Vitamin E emulsion and its vehicle control showed significant (p < 0.05) reduction of blood flow volume when compared with blank control at day 3 after UV exposure. Vitamin E emulsion and its vehicle control proved effective in preventing induction of erythema and reducing inflammatory damage caused by UV exposure. The effect of vitamin E emulsion exceeded that of an 'active control'.

Hydrating effects of a corticoid oil formulation and its vehicle on human skin.

Factors in the treatment of atopic dermatitis include restoring skin moisture and reducing inflammation. This study evaluated a corticoid oil formulation and its components with respect to their skin hydration potential. Ten healthy Caucasians were enrolled. Five test sites on the left and right forearm of each subject were tested: one site served as a normal skin control (without treatment), whereas four were wetted by spraying distilled water (approximately 0.1 ml) over a 3-cm2 skin surface area, and spraying was repeated every 5 min for a total of three applications. Five minutes after the final application, 0.2 ml of the corticoid oil formulation, moisturizing vehicle, and plain peanut oil were applied to each pre-designated site (3 cm2); one site was kept as a blank control (water saturation only). Thirty minutes later, test sites were gently wiped with paper tissues, and visual scoring, transepidermal water loss (TEWL), and capacitance were recorded and repeated at 2 and 3 h. The corticoid oil formulation, plain peanut oil, and moisturizing vehicle significantly increased skin hydration 30 min after each single application, with no statistically significant difference among the treatments at any point. The corticoid oil formulation and plain peanut oil slightly but not significantly elevated TEWL 30 min after application. The results support intuitive dermatologic judgment of advising patients to apply moisturizing medicaments after bathing.

Provocative use test of nickel coins in nickel-sensitized subjects and controls.

BACKGROUND: Consensus exists on levels of nickel release that are well tolerated in exposure to nickel-containing items in direct and continuous contact with skin (e.g. watches). The clinical relevance of nickel-containing coins eliciting nickel dermatitis associated with extensive occupational exposure (e.g. coins handled by cashiers) has not been determined. OBJECTIVES: To examine whether nickel-containing coins might be an elicitor of allergic contact dermatitis (ACD) in occupational settings with extensive exposure to coins (i.e. cashiers). METHODS: Eighteen subjects (10 nickel sensitized and eight non-nickel sensitized) completed this study after screening of history, physical examination and diagnostic patch testing (5% nickel sulphate). Each volunteer handled 10 coins (nickel-containing coins or non-nickel-containing coins) in a cross-over design at 5-min intervals (5 min handling followed by 5 min rest) for 8 h per day, for a total of 12 days excluding the weekend. One hand was gloved while the other was not during coin handling. Visual scoring and bioengineering measurements were recorded at each of four predetermined sites at baseline (day 1), end of day 5 and day 12 (last day of exposure). RESULTS: There were no statistical differences for either visual or bioengineering data comparing: (i) nickel-sensitized vs. non-nickel-sensitized subjects handling nickel-containing coins at day 1, day 5 and day 12; (ii) day 12 vs. day 1 (baseline) for nickel-sensitized subjects handling nickel-containing coins; (iii) handling of nickel-containing coins vs. non-nickel-containing coins by nickel-sensitized subjects at day 5 and day 12; (iv) gloved hand vs. ungloved hand of nickel-sensitized subjects handling nickel-containing coins at day 12. Limitations of the method and clinical extrapolation are detailed. CONCLUSIONS: Individuals handling these nickel-containing coins daily did not develop ACD, as judged by visual signs or bioengineering parameters.

Impact of ultraviolet radiation and ozone on the transepidermal water loss as a function of skin temperature in hairless mice.

Exposure to ultraviolet radiation or ozone leads to skin damage including oxidation of skin biomolecules, as well as to depletion of constitutive antioxidants. The highly organized stratum corneum forming the main barrier against most xenobiotics is particularly susceptible to such damage and possible barrier perturbation may be the consequence. Whereas ample evidence exists for an increased permeability for different solutes including water after exposure to ultraviolet radiation, such an effect has not yet been reported for ozone. This study reports on the effect of such oxidative stressors using the hairless mouse as the skin model and measuring temperature-controlled transepidermal water loss (TEWL) as an indicator for skin barrier integrity. First, a strong dependency of the TEWL on skin temperature was observed, an effect that was clearly more pronounced than that found in man. Given this temperature dependency in untreated animals, we proceeded to determine the effects of both ultraviolet radiation and ozone on TEWL over a relevant physiological skin temperature range. Solar-simulated ultraviolet radiation (0.75-3 minimal erythemal dose) resulted in a delayed and dose-dependent skin barrier disruption over the entire temperature range investigated. Conversely, daily ozone exposure at 2 ppm for 1 week, however, did not significantly alter TEWL up to 72 h after the last exposure. The results demonstrate a differential response of the epidermis to two environmental stressors associated with oxidative damage; they suggest that chronic ozone exposure at relevant environmental levels does not lead to a detectable skin barrier defect, while solar UV exposure was demonstrated to increase epidermal water loss. Furthermore, experimental evidence clearly suggests that future studies applying TEWL measurements in animal models should be performed under carefully controlled skin temperature conditions.

Estrogen and skin. An overview.

As the population of postmenopausal women increases, interest in the effects of estrogen grows. The influence of estrogen on several body systems has been well-documented; however, one area that has not been explored is the effects of estrogen on skin. Estrogen appears to aid in the prevention of skin aging in several ways. This reproductive hormone prevents a decrease in skin collagen in postmenopausal women; topical and systemic estrogen therapy can increase the skin collagen content and therefore maintain skin thickness. In addition, estrogen maintains skin moisture by increasing acid mucopolysaccharides and hyaluronic acid in the skin and possibly maintaining stratum corneum barrier function. Sebum levels are higher in postmenopausal women receiving hormone replacement therapy. Skin wrinkling also may benefit from estrogen as a result of the effects of the hormone on the elastic fibers and collagen. Outside of its influence on skin aging, it has been suggested that estrogen increases cutaneous wound healing by regulating the levels of a cytokine. In fact, topical estrogen has been found to accelerate and improve wound healing in elderly men and women. The role of estrogen in scarring is unclear but recent studies indicate that the lack of estrogen or the addition of tamoxifen may improve the quality of scarring. Unlike skin aging, the role of endogenous and exogenous estrogen in melanoma has not been well established.

In vitro permeation of nickel salts through human stratum corneum.

Allergic contact dermatitis due to nickel salts is common. It is therefore important to measure the permeation of these salts through the stratum corneum (SC), the primary rate-limiting domain in skin. An advanced diffusion system and analytical techniques now enable better measurement of the flux than was possible in earlier experiments. Human SC was prepared by trypsinization of dermatomed cadaver leg skin. The diffusion system included diffusion cells with a spiral line. Aqueous solutions of nickel salts (Ni(NO3)2, NiSO4, NiCl2 and Ni(-OOCCH3)2 at 1% Ni2+ concentration) were used as the donor solution (400 microL/cell). The receptor fluid, pure water, was collected up to 96 h after application of the donor solutions. Nickel concentrations in the donor and receptor fluid, as well as in the SC, were analysed using inductively coupled plasma mass spectrometry (ICP-MS) with a confidence limit of 0.5 ppb. Based on the total recovery of nickel from the experiments, about 98% of the dose remained in the donor solution, whereas 1% or less was retained in SC and less than 1% was found in the receptor fluid. Following an early surge, nickel permeates slowly across SC. The steady-state permeability coefficients of nickel were calculated from the flux data (approximately 5.2-8.5 x 10(-7) cm/h) with no significant difference among the salts. The results concur in principle with earlier studies conducted using the full-thickness human skin in vitro, and suggest that in vivo nickel ions may permeate simultaneously by routes of diffusion such as the shunt pathway, apart from slow transcellular/intercellular diffusion alone.

Human stratum corneum adsorption of nickel salts. Investigation of depth profiles by tape stripping in vivo.

Sequential adhesive tape stripping was implemented to characterize the penetration of nickel salts in human stratum corneum. Exposure areas of the salts in methanol applied open on arm and back skin in low volume were stripped 20 times to the level of the glistening layer at intervals of 30 min to 24 h post-dosing, and the strips analyzed for metal content by inductively coupled plasma-atomic emission spectroscopy. In the case of nickel chloride, sulfate, nitrate and acetate, material left on the skin surface, the depth-penetration profiles in the stratum corneum, and the dosage unaccounted for suggest the following conclusions: (a) Up to 24 h, most of the nickel dose applied remains on the skin surface or is adsorbed in the uppermost layers of the stratum corneum. (b) At higher concentrations, incomplete material recovery becomes discernible; within 24 h, nickel salts thus appear to penetrate beyond the stratum corneum to a minor degree, possibly via the skin shunts. (c) While the concentration gradients of nickel adsorbed vary with counter ion, anatomical site, dose and exposure time, for all variables tested the depth profiles converge to non-detectable levels (< 20 ppb) towards the level of the glistening layer. A notable exception is nickel as nitrate, for which levels continue at low but constant levels (1% of dose) beyond the third stratum corneum strip, indicative of intercellular diffusion. (d) Differences in material recovered suggest that the stratum corneum on the arm is more penetrable to nickel than stratum corneum on the back. (e) The counter ion in nickel salts plays a major part in their diffusion into the stratum corneum, suggestive of ion pairing. Overall, the data point to all three avenues of skin penetration by nickel: intracellular, intercellular, and transappendageal.