Patch Testing With Nickel, Cobalt, and Chromium in Patients With Suspected Allergic Contact Dermatitis.

Background: Allergic contact dermatitis is frequently caused by metals, including multiple metals simultaneously. Objectives: To assess characteristics and associations of positive and clinically relevant patch test (PT) reactions with solitary and concurrent metal sensitization. Methods: A retrospective analysis of PT results for nickel, cobalt, and/or chromium from the North American Contact Dermatitis Group between 2001 and 2018 (n = 43,522). Results: 18.0% had a positive/allergic reaction to nickel sulfate hexahydrate, 7.3% to cobalt chloride hexahydrate, and 3.0% to potassium dichromate. 87.9% patients had a currently relevant reaction to 0, 9.4% to 1, and 2.7% to multiple metals tested. Patients with 1 versus no currently relevant reactions to metal were more likely to have a primary dermatitis site of trunk, feet, and ears; patients with currently relevant reactions to multiple metals had more dermatitis affecting the trunk and ears. Metal sources varied by co-reacting metal, especially for patients with cobalt and chromium allergy. Jewelry was the most commonly identified source of nickel and cobalt for both solitary and concurrent metal allergy. Conclusions: Sensitization to multiple metals occurred in 6% of patients. Allergen sources varied between patients with sensitivity to 1 metal versus those who had concurrent sensitivity to cobalt and/or chromium.

Medical school dermatology education: a scoping review.

Dermatological diseases are widespread and have a significant impact on the quality of life of patients; however, access to appropriate care is often limited. Improved early training during medical school represents a potential upstream solution. This scoping review explores dermatology education during medical school, with a focus on identifying the factors associated with optimizing the preparation of future physicians to provide care for patients with skin disease. A literature search was conducted using online databases (Embase, MEDLINE, CINAHL and Scopus) to identify relevant studies. The Joanna Briggs Institute methodological framework for scoping reviews was used, including quantitative and qualitative data analysis following a grounded theory approach. From 1490 articles identified, 376 articles were included. Most studies were from the USA (46.3%), UK (16.2%), Germany (6.4%) and Canada (5.6%). Only 46.8% were published as original articles, with a relatively large proportion either as letters (29.2%) or abstracts (12.2%). Literature was grouped into three themes: teaching content, delivery and assessment. Core learning objectives were country dependent; however, a common thread was the importance of skin cancer teaching and recognition that diversity and cultural competence need greater fostering. Various methods of delivery and assessment were identified, including computer-aided and online, audiovisual, clinical immersion, didactic, simulation and peer-led approaches. The advantages and disadvantages of each need to be weighed when deciding which is most appropriate for a given learning outcome. The broader teaching-learning ecosystem is influenced by (i) community health needs and medical school resources, and (ii) the student and their ability to learn and perform. Efforts to optimize dermatology education may use this review to further investigate and adapt teaching according to local needs and context.

"Normal" TEWL-how can it be defined? A systematic review.

Trans-epidermal water loss (TEWL), the total non-eccrine sweat water evaporating from a given area of epidermis over time, is a measurement of skin barrier integrity. Skin diseases (e.g., psoriasis and atopic dermatitis) often result in transient increases in TEWL, so, knowledge of "normal" TEWL values may be used to predict disease progression in dermatological settings. Variables such as age, race and anatomic location have been suggested to affect TEWL, but current regulatory agencies have failed to control for additional variables of interest. Thus, this review summarizes variables that may cause TEWL variation. A comprehensive literature search was performed using Embase, PubMed and Web of Science to find human studies that provided data on variables affecting TEWL. 31 studies, analysing 22 affecting TEWL, were identified. Variables causing increased TEWL were mask-use (n = 1), dry eye disease (n = 1), chronic venous disease (n = 1), coronary artery disease (n = 1), age (infants vs adults) (n = 4), nourishment in infants (n = 1), stress within individuals (n = 2), Body Mass Index (n = 2), bathing versus showering (n = 2) and scratching/friction (n = 1). Variables with decreases in TEWL were genetic variability with SNPs on chromosome 9q34.3 (n = 1) and cancer-cachexia (n = 1). We summarized 12 variables that impact TEWL and are not typically controlled for in experimental settings. Therefore, defining normal TEWL may currently be problematic. Thus, regulatory agencies should provide stricter guidelines on proper measurement of TEWL to minimize human introduced TEWL variation, and we should continue to examine factors impacting individual skin integrity.

Unbearable transepidermal water loss (TEWL) experimental variability: why?

Despite the wide breadth of research, much disparity exists in transepidermal water loss (TEWL) research data-possibly due to uncontrolled experimental variables. We determined whether such experimental variables significantly impact TEWL studies and cause this disparity. An initial literature search regarding TEWL was performed to determine potential confounding variables. A subsequent search procured relevant and representative studies investigating the impact of these variables on TEWL. Variables, such as age, anatomic site, and temperature, impact TEWL and should be controlled for in TEWL studies. Other variables, such as smoking and menstrual cycle, have inconclusive results or do not provide sufficient data breadth to make a conclusion regarding its effect, if such an effect exists, on TEWL metrics. Therefore, these variables require further research to determine their potential impact on TEWL. Matching for as many experimental variables as possible may reduce the disparity in TEWL data/conclusions.

Effect of soak and smear on [14C]-hydrocortisone in vitro human skin percutaneous penetration.

INTRODUCTION: 'Soak and smear' method, water soaking to induce skin hydration followed by topical corticoids application suggests effectiveness in clinical dermatological practice. We investigate one possible mechanism of soaking times effect on drug partitioning and diffusion rates in skin and its proposed efficacy. METHODS: Utilizing an in vitro flow-through diffusion system to evaluate efficacy of the 'soak and smear' method following 0.5, 8, and 20 min water soaking and [14C]-hydrocortisone topical application on human skin to probe the possibility of percutaneous penetration enhancement. RESULTS: In water-soak groups, more [14C]-hydrocortisone was absorbed and retained in stratum corneum and epidermis, whereas, in the control (no soak) more was in the deep skin-dermis and receptor fluid. These differences between water-soak groups and the control are statistically significant (p < .05). CONCLUSION: Effect of 'soak and smear' on skin absorption and penetration depends on interaction of individual drug's physicochemical property, stratum corneum hydration, and stratum corneum-epidermoid barrier status. Water soaking (≤ 20 min) induced skin hydration increases [14C]-hydrocortisone absorption and retention into the upper skin layer but not deep layers. This could support the proposed hypothesis of clinical dermatological treatment of hydrocortisone to local skin inflammations should the epidermis be found to be a key target for atopic dermatitis therapy.

Patch Testing During Immunosuppressive Therapy: A Systematic Review.

ABSTRACT: Patch testing, used in the assessment of allergic contact dermatitis, is ideally avoided in patients receiving immunosuppressive therapy because of concerns with reductions in accuracy; however, this is not well characterized in the literature. This systematic review summarizes patch testing results in patients receiving immunosuppressive therapy. We identified 16 studies, comprising 195 patients with dermatitis or psoriasis, who were patch tested while receiving immunosuppressants. Of these, 7 studies, comprising 85 patients with dermatitis, patch tests were performed before and during immunosuppression. Overall, 67.9% (n = 19) of the dermatitis patients receiving dupilumab maintained positive reactions to an allergen that previously graded as a 2+/3+ reaction. Several immunosuppressants were also associated with positive patch test results for various allergens. These include dupilumab, cyclosporine, and low-dose prednisone (≤10 mg/d) for dermatitis, and tumor necrosis factor α inhibitors, ustekinumab, and methotrexate for psoriasis. Ideally, it is preferable to patch test when patients are not receiving oral immunosuppressants or immunomodulators. However, clinicians may choose to assess the risks and benefits of patch testing for each patient given the impact of allergic contact dermatitis on patient quality of life.

Effect of Palmitic Acid Conjugation on Physicochemical Properties of Peptide KTTKS: A Preformulation Study.

Lys-Thr-Thr-Lys-Ser (KTTKS) minimally crosses the skin because of hydrophilicity; therefore, its palmitoyl derivative, palmitoyl-KTTKS (Pal-KTTKS), is used in cosmetic products. In spite of this, there is insuffi cient information on its physicochemical properties and the effects of palmitoylation on such properties. The aim of this study was to investigate these properties. Such information would help appropriate formulation development. KTTKS and Pal-KTTKS were synthesized and characterized for ultra violet (UV) absorption, structure [X-ray diffraction (XRD)], morphology (electron microscopy), birefringence (polarized light microscopy), partitioning,solubility, thermal behavior (melting, thermogravimetric analysis, and differential scanning calorimetry), surface activity, critical micelle concentration (CMC, by tensiometry), and stability. KTTKS and Pal-KTTKS decomposed at about 154 and 150°C, respectively, and did not show a melting point before decomposition. The maximum UV absorbance of peptides was less than 200 nm. Both peptides showed birefringence, irregular flake morphologies, and hygroscopicity. KTTKS was freely soluble in water at room temperature (logP = -1.6 ± 0.15), indicating its hydrophilic nature. logP of Pal-KTTKS was calculated to be about 3.7, indicating a lipophilic compound. Pal-KTTKS showed surface activity with a CMC value of 0.024 ± 0.004 mM (19.25 ± 2.9 mg/L),whereas KTTKS did not show such surface activity. Palmitoylation demonstrated sharp peaks in the XRD pattern of KTTKS. KTTKS and Pal-KTTKS differ mainly in terms of chemical properties and show some similarity in physical properties. These results can be used for formulation developments.

Occupationally Related Nickel Reactions: A Retrospective Analysis of the North American Contact Dermatitis Group Data 1998-2016.

BACKGROUND: The epidemiology of nickel allergy in occupational settings is not well understood. OBJECTIVE: The aim of the study was to characterize occupationally related nickel allergy (ORNA). METHODS: This is a retrospective cross-sectional analysis of 44,378 patients patch tested by the North American Contact Dermatitis Group from 1998 to 2016. Characteristics of individuals with ORNA were compared with those with non-ORNA (NORNA). RESULTS: A total of 7928 (18.2%) individuals were positive to nickel sulfate 2.5%. Two hundred sixty-eight (3.4%) had ORNA. As compared with NORNA, ORNA was statistically associated with the male sex (41.0% vs 12.9%, P < 0.001), a diagnosis of irritant contact dermatitis (22.4% vs 12.0%, P < 0.001), and no history of eczema (81.7% vs 75.7%, P = 0.0217). The most common sites of ORNA dermatitis were hand (39.9%) and arm (18.1%), which were significantly more common than in NORNA (P < 0.0001). Sixteen industry categories and 22 occupation categories were identified for ORNA; the most common industries were durable goods manufacturing (24.6%) and personal services (15.7%), and the most frequent occupations were hairdressers/cosmetologists/barbers (14.3%), machine operators (9.3%), and health care workers (7.1%). Overall 30% of ORNA occupations were in metalworking. Of 215 ORNA sources identified, instruments/phones/other equipment (16.3%), vehicles/machinery (15.8%), and tools (15.3%) were the most common. CONCLUSIONS: Occupational nickel allergy is distinct from nonoccupational nickel allergy.

Dermatotoxicology of microneedles (MNs) in man.

Developed within the last few decades, microneedles (MNs) have only recently seen wide-scale use among the general population, especially in the area of cosmetics. With the FDA only starting to regulate microneedling devices and the many new microneedling products that enter the modern global market, it is of utmost importance to establish the safety profile and reasonable expectations of the microneedling practice and its products. In our review of current literature, the authors searched the keyword "microneedle" with the following terms: "safety", "side effect", "toxicology", "adverse effect", "adverse event", "infection", "dermatitis", "granuloma", "scarring", and "hyperpigmentation". Despite wide-scale implementation of MNs, we are likely only beginning to understand the potential of MNs as a medical and consumer product, and we should, therefore, be aware of any potential adverse events associated with the product.

Skin toxicity of topically applied nanoparticles.

Nowadays, nanoproducts have found numerous applications, allowing them to enter the human body in different ways. Skin is a major body organ that acts as the first-line barrier between the internal organs and external environment. Although the inhalation and ingestion of nanoparticles is more dangerous compared with skin exposure, there are noteworthy information gaps in skin exposure to nanoparticles that need much attention. Despite the few reviews in the literature on the cytotoxic effects of nanoparticles, no research has reviewed the clinical side effects of nanoparticles following topical admonition, including skin inflammation, skin cancer and genetic toxicity.

Epidemiology of nickel sensitivity: Retrospective cross-sectional analysis of North American Contact Dermatitis Group data 1994-2014.

BACKGROUND: Nickel is a common allergen. OBJECTIVE: To examine the epidemiology of nickel sensitivity in North America. METHODS: Retrospective, cross-sectional analysis of 44,097 patients patch tested by the North American Contact Dermatitis Group from 1994 to 2014. Nickel sensitivity was defined as a positive patch test for nickel. We evaluated the frequency of nickel sensitivity and patient demographics. For each positive reaction to nickel, we tabulated clinical relevance, occupational relatedness, and exposure sources. RESULTS: The average frequency of nickel sensitivity was 17.5% (1994-2014). Nickel sensitivity significantly increased over time (from 14.3% in 1994-1996 to 20.1% in 2013-2014 [P < .0001]). Nickel-sensitive patients were significantly more likely to be female, young, nonwhite, and atopic (have eczema and asthma) and/or have dermatitis affecting the face, scalp, ears, neck, arm, or trunk (P values ≤ .0474). Overall, 55.5% of reactions were currently clinically relevant; this percentage significantly increased over time (from 44.1% in 1994-1996 to 51.6% in 2013-2014 [P < .0001]). The rate of occupational relatedness was 3.7% overall, with a significant decrease over time (from 7.9% in 1994-1996 to 1.9% in 2013-2014 [P < .0001]). Jewelry was the most common source of nickel contact. LIMITATIONS: Tertiary referral population. CONCLUSIONS: Nickel allergy is of substantial public health importance in North America. The frequency of nickel sensitivity in patients referred for patch testing has significantly increased over a 20-year period.

Epidemiology of pediatric nickel sensitivity: Retrospective review of North American Contact Dermatitis Group (NACDG) data 1994-2014.

BACKGROUND: Nickel is a common allergen responsible for allergic contact dermatitis. OBJECTIVE: To characterize nickel sensitivity in children and compare pediatric cohorts (≤5, 6-12, and 13-18 years). METHODS: Retrospective, cross-sectional analysis of 1894 pediatric patients patch tested by the North American Contact Dermatitis Group from 1994 to 2014. We evaluated demographics, rates of reaction to nickel, strength of nickel reactions, and nickel allergy sources. RESULTS: The frequency of nickel sensitivity was 23.7%. Children with nickel sensitivity were significantly less likely to be male (P < .0001; relative risk, 0.63; 95% confidence interval, 0.52-0.75) or have a history of allergic rhinitis (P = .0017; relative risk, 0.74; 95% confidence interval, 0.61-0.90) compared with those who were not nickel sensitive. In the nickel-sensitive cohort, the relative proportion of boys declined with age (44.8% for age ≤5, 36.6% for age 6-12, and 22.6% for age 13-18 years). The most common body site distribution for all age groups sensitive to nickel was scattered/generalized, indicating widespread dermatitis. Jewelry was the most common source associated with nickel sensitivity (36.4%). LIMITATIONS: As a cross-sectional study, no long-term follow-up was available. CONCLUSIONS: Nickel sensitivity in children was common; the frequency was significantly higher in girls than in boys. Overall, sensitivity decreased with age. The most common source of nickel was jewelry.

Ultraviolet A Enhances Cathepsin L Expression and Activity via JNK Pathway in Human Dermal Fibroblasts.

BACKGROUND: Cathepsin L (CatL) is a cysteine protease with strong matrix degradation activity that contributes to photoaging. Mannose phosphate-independent sorting pathways mediate ultraviolet A (UVA)-induced alternate trafficking of CatL. Little is known about signaling pathways involved in the regulation of UVA-induced CatL expression and activity. This study aims to investigate whether a single UVA irradiation affects CatL expression and activity and whether mitogen-activated protein kinase (MAPK)/activator protein-1 (AP-1) pathway is involved in the regulation of UVA-induced CatL expression and activity in human dermal fibroblasts (HDFs). METHODS: Primary HDFs were exposed to UVA. Cell proliferation was determined by a cell counting kit. UVA-induced CatL production and activity were studied with quantitative real-time reverse transcription polymerase chain reaction (RT-PCR), Western blotting, and fluorimetric assay in cell lysates collected on three consecutive days after irradiation. Time courses of UVA-activated JNK and p38MAPK signaling were examined by Western blotting. Effects of MAPK inhibitors and knockdown of Jun and Fos on UVA-induced CatL expression and activity were investigated by RT-PCR, Western blotting, and fluorimetric assay. Data were analyzed by one-way analysis of variance. RESULTS: UVA significantly increased CatL gene expression, protein abundance, and enzymatic activity for three consecutive days after irradiation (F = 83.11, 56.14, and 71.19, respectively; all P < 0.05). Further investigation demonstrated phosphorylation of JNK and p38MAPK activated by UVA. Importantly, inactivation of JNK pathway significantly decreased UVA-induced CatL expression and activity, which were not affected by p38MAPK inhibition. Moreover, knockdown of Jun and Fos significantly attenuated basal and UVA-induced CatL expression and activity. CONCLUSIONS: UVA enhances CatL production and activity in HDFs, probably by activating JNK and downstreaming AP-1. These findings provide a new possible molecular approach for antiphotoaging therapy.

Proposed ICDRG Classification of the Clinical Presentation of Contact Allergy.

The International Contact Dermatitis Research Group proposes a classification for the clinical presentation of contact allergy. The classification is based primarily on the mode of clinical presentation. The categories are direct exposure/contact dermatitis, mimicking or exacerbation of preexisting eczema, multifactorial dermatitis including allergic contact dermatitis, by proxy, mimicking angioedema, airborne contact dermatitis, photo-induced contact dermatitis, systemic contact dermatitis, noneczematous contact dermatitis, contact urticaria, protein contact dermatitis, respiratory/mucosal symptoms, oral contact dermatitis, erythroderma/exfoliative dermatitis, minor forms of presentation, and extracutaneous manifestations.

Guidelines for the use of local anesthesia in office-based dermatologic surgery.

There are an increasing number and variety of dermatologic surgical procedures performed safely in the office setting. This evidence-based guideline addresses important clinical questions that arise regarding the use and safety of local anesthesia for dermatologic office-based procedures. In addition to recommendations for dermatologists, this guideline also takes into account patient preferences while optimizing their safety and quality of care. The clinical recommendations presented here are based on the best evidence available as well as expert opinion.

Percutaneous penetration and pharmacodynamics: Wash-in and wash-off of sunscreen and insect repellent.

Increased awareness of skin cancer and mosquito-transmitted diseases has increased use of insect repellents and sunscreens. The challenge in setting recommendations for use and reapplication, especially when used concomitantly, lies in finding the balance between applying a durable product effective in withstanding natural and physical factors such as water, sweat, temperature and abrasion, while limiting percutaneous absorption and decreasing risk of potential dermal and systemic toxicity. Inorganic sunscreens show no or little percutaneous absorption or toxic effects in comparison to organic sunscreens, which show varying levels of dermal penetration and cutaneous adverse effects. An alternative to N,N-diethyl-m-toluamide (DEET), the traditional gold standard compound in insect repellents, picaridin appears as efficacious, has lower risk of toxicity, and when used simultaneously with sunscreen may decrease percutaneous absorption of both compounds. Conversely, combined use of DEET and sunscreen results in significantly higher absorption of both compounds. It is important to increase consumer awareness of "washing in" of various compounds leading to increased risk of toxicity, as well as differences in reapplication need due to "washing off" caused by water, sweat and abrasion. Although much remains to be studied, to maximize efficacy and decrease toxicity, contemporary research tools, including dermatopharmokinetics, should aid these prospective advances.

Low-Molecular-Weight Hydrophilic and Lipophilic Antioxidants in Nonmelanoma Skin Carcinomas and Adjacent Normal-Looking Skin.

Low-molecular-weight antioxidants are some of the most efficient agents of the skin defense mechanism against environmental factors, such as cosmic rays, smoke, and pollutants. The total skin concentrations of hydrophilic ascorbic and uric acids, as well as lipophilic α-tocopherol, ß-carotene, and ubiquinol-10 antioxidants were determined by an HPLC-EC detector from 18 biopsies of human nonmelanoma skin carcinomas and 18 biopsies from skin areas adjacent to carcinomas. No significant differences in the concentrations of lipophilic antioxidants in both carcinomas and normal-looking skin areas adjacent to carcinomas were observed. On the contrary, ascorbic and uric acid concentrations were found to be 18 and 36% lower in carcinomas than in normal-looking skin areas, respectively. No statistical significance was observed between antioxidant concentrations and age, sex, phototype, profession, site of tumor, frequency, and time of UV light exposure either. Accordingly the antioxidant concentrations in both cancerous skin and adjacent normal-looking areas were found to be much higher than in normal skin, in contrast to literature data.

Cutaneous Delayed-Type Hypersensitivity to Surfactants.

BACKGROUND: Repeated and prolonged use of surfactants can cause irritant as well as allergic contact dermatitis. OBJECTIVE: This study reports the frequency of positive patch test results to surfactants tested on the North American Contact Dermatitis Group screening series including cocamidopropyl betaine (CAPB), amidoamine (AA), dimethylaminopropylamine (DMAPA), oleamidopropyl dimethylamine (OPD), and cocamide diethanolamide (CDEA), and correlations of positive reactions between CAPB and the other surfactants. METHODS: This was a retrospective analysis of 10 877 patients patch tested between 2009 and 2014 to the surfactants CAPB, AA, DMAPA, OPD, and CDEA. Frequencies of positive reactions to these surfactants were calculated, and trends of reactivity between the surfactants analyzed. CONCLUSIONS: The OPD had the highest rate of positive patch reactions (2.3%) followed by DMAPA (1.7%), and CAPB (1.4%). The AA and CDEA had the lowest rate of positive reactions (0.8%). There was a high degree of overlap in positive patch tests between the surfactants. The CDEA was the least likely to coreact with another surfactant.

Role of sebaceous glands in inflammatory dermatoses.

Skin is an important interface between the host and its environment. Inflammatory dermatoses often have disrupted skin barrier function, rendering patients more susceptible to allergenic triggers leading to an exaggerated immune response. The skin surface lipid film, an important component of the skin barrier, comprises a mixture of keratinocyte and sebaceous gland-derived lipids. Recent evidence demonstrated that defective keratinocyte lipid synthesis predisposes for the development of atopic dermatitis. However, the important role of sebaceous gland-derived lipids in skin inflammatory diseases may be underrecognized. This overview focuses on the importance of the contribution of sebaceous glands to barrier function. Sebaceous gland alteration may play a role in the pathogenesis of common skin diseases including acne vulgaris, atopic dermatitis, psoriasis, rosacea, and seborrheic dermatitis.