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Sexual and gender minority (SGM) individuals include, but are not limited to, those who identify as lesbian, gay, bisexual, transgender, and queer (LGBTQ). LGBTQ individuals are considered a marginalized and at-risk population, facing significant health care inequities when compared with heterosexual and cisgendered (ie, "gender-conforming") populations. They are more likely than heterosexual and cisgendered individuals to experience discrimination, bias, and dissatisfaction with the medical system. This article provides a broad overview of systemic inequalities confronting SGM patients.

Transgender individuals may transition to their identified gender through social, hormonal, and procedural methods by using a multidisciplinary team of health care providers, including dermatologists. In this review, we discuss the medical and aesthetic dermatologic needs related to the transitioning of transgender patients and provide therapeutic and procedural recommendations. In addition to routine cutaneous conditions, dermatologists may need to treat hormonal therapy–related complications. Acumen for genital dermatology and familiarity with gender reassignment surgery is important for the dermatologist caring for a transgender patient. From a structural standpoint, transgender beauty poses a unique aesthetic task. We identify key differences in the facial structure and physique of males versus those of females. Dermatologists may have a tremendous impact on the lives of transgender individuals who seek to realize their gender identity.

Ingredients found in the nail cosmetic industry, including but not limited to methacrylate and acrylate monomers, formaldehyde, and toluene sulfonamide-formaldehyde resin, can incite allergic contact dermatitis. An eczematous outbreak presents on areas surrounding the nail plate and may spread through contact transfer of the allergen, commonly to the face and neck. Even components that were originally deemed nonsensitizing, such as the ubiquitous cyanoacrylate adhesive family, have been found to be allergenic. They do not, however, cross-react with methacrylates and acrylates. Alternative options for individuals with allergic contact dermatitis reactions to these ingredients can be avoidance of these procedures or use of products that are "3, 4, 5 free" in which the common allergens dibutyl phthalate, toluene, and formaldehyde are absent. In cases where strengthening of the nail is the sole purpose, nail wraps or preformed nails can be applied for non-cyanoacrylate-sensitive individuals.

Background: Atopic dermatitis (AD) is classified as extrinsic and intrinsic, representing approximately 80% and 20% of patients with the disease, respectively. Although sharing a similar clinical phenotype, only extrinsic AD is characterized by high serum IgE levels. Because most patients with AD exhibit high IgE levels, an ‘‘allergic’’/IgE-mediated disease pathogenesis was hypothesized. However, current models associate AD with T-cell activation, particularly TH2/TH22 polarization, and epidermal barrier defects. Objective: We sought to define whether both variants share a common pathogenesis. Methods: We stratified 51 patients with severe AD into extrinsic AD (n 5 42) and intrinsic AD (n 5 9) groups (with similar mean disease activity/SCORAD scores) and analyzed the molecular and cellular skin pathology of lesional and nonlesional intrinsic AD and extrinsic AD by using gene expression (real-time PCR) and immunohistochemistry. Results: A significant correlation between IgE levels and SCORAD scores (r 5 0.76, P

Current atopic dermatitis (AD) models link epidermal abnormalities in lesional skin to cytokine activation. However, there is evolving evidence of systemic immune activation and detectable abnormalities in nonlesional skin. Because some of the best single correlations with severity (Scoring of AD, or SCORAD) are detected not only in lesional but also nonlesional skin and blood, more complex biomarker models of AD are needed. We thus performed extensive biomarker measures in these compartments using univariate and multivariate approaches to correlate disease biomarkers with SCORAD and with a combined hyperplasia score [thickness and keratin 16 (K16) mRNA] at baseline and after cyclosporine A treatment in 25 moderate to severe AD patients. Increases in serum cytokines and chemokines (IL-13, IL-22, CCL17) were found in AD versus healthy individuals and were reduced with treatment. SCORAD correlated with immune (IL-13, IL-22) and epidermal (thickness, K16) measures in lesional and, even more strongly, in nonlesional AD. Serum cytokines also had higher correlations with nonlesional markers at baseline and with treatment. Multivariate U statistics improved baseline and treatment-response SCORAD correlations. Nonlesional models showed the strongest correlations, with further improvement upon integration of serum markers. Even better correlations were obtained between biomarkers and the hyperplasia score. Larger cohorts are needed to confirm these preliminary data.

Background Atopic dermatitis (AD) is the most common inflammatory disease. The prevalence of allergic contact dermatitis to allergens (eg, fragrance) is higher in patients with AD, despite a trend toward weaker clinical allergic contact dermatitis reactions. The role of the AD skin phenotype in modulating allergic sensitization to common sensitizers has not been evaluated. Objective We sought to investigate whether patients with AD have altered tissue immune responses on allergen challenge. Methods Gene expression and immunohistochemistry studies were performed on biopsy specimens from 10 patients with AD and 14 patients without AD patch tested with common contact allergens (nickel, fragrance, and rubber). Results Although 1085 differentially expressed genes (DEGs) were commonly modulated in patch-tested skin from patients with AD and patients without AD versus control skin, 1185 DEGs were uniquely altered in skin from patients without AD, and only 246 DEGs were altered in skin from patients with AD. Although many inflammatory products (ie, matrix metalloproteinase 12/matrix metalloproteinase 1/S100A9) were upregulated in both groups, higher-magnitude changes and upregulation of interferon responses were evident only in the non-AD group. Stratification by allergen showed decreased expression of immune, T H 1-subset, and T H 2-subset genes in nickel-related AD responses, with increased T H 17/IL-23 skewing. Rubber/fragrance showed similar trends of lesser magnitude. Negative regulators showed higher expression in patients with AD. Conclusions Through contact sensitization, our study offers new insights into AD. Allergic immune reactions were globally attenuated and differentially polarized in patients with AD, with significant decreases in levels of T H 1 products, some increases in levels of T H 17 products, and inconsistent upregulation in levels of T H 2 products. The overall hyporesponsiveness in skin from patients with background AD might be explained by baseline immune abnormalities, such as increased T H 2, T H 17, and negative regulator levels compared with those seen in non-AD skin.

Background Allergic contact dermatitis (ACD) is the most common occupational disease. Although murine contact hypersensitivity provides a framework for understanding ACD, it carries important differences from its human counterpart. Unlike the contact hypersensitivity model, which is induced by potent sensitizers (ie, dinitrofluorobenzene), human ACD is induced by weak-to-moderate sensitizers (ie, nickel), which cannot induce reactions in mice. Distinct hapten-specific immune-polarizing responses to potent inducers were suggested in mice, with unclear relevance to human ACD. Objective We explored the possibility of distinct T-cell polarization responses in skin to common clinically relevant ACD allergens. Methods Gene-expression and cellular studies were performed on common allergens (ie, nickel, fragrance, and rubber) compared with petrolatum-occluded skin, using RT-PCR, gene arrays, and immunohistochemistry. Results Despite similar clinical reactions in all allergen groups, distinct immune polarizations characterized different allergens. Although the common ACD transcriptome consisted of 149 differentially expressed genes across all allergens versus petrolatum, a much larger gene set was uniquely altered by individual allergens. Nickel demonstrated the highest immune activation, with potent inductions of innate immunity, T H 1/T H 17 and a T H 22 component. Fragrance, and to a lesser extent rubber, demonstrated a strong T H 2 bias, some T H 22 polarization, and smaller T H 1/T H 17 contributions. Conclusions Our study offers new insights into the pathogenesis of ACD, expanding the understanding of T-cell activation and associated cytokines in allergen-reactive tissues. It is the first study that defines the common transcriptome of clinically relevant sensitizers in human skin and identifies unique pathways preferentially activated by different allergens, suggesting that ACD cannot be considered a single entity.

Nikhil Dhingra, BSa,b,c, Mayte Suarez-Farinas, PhDa,c, Judilyn Fuentes-Duculan, MDa, Julia K. Gittler, BAa,d, Avner Shemer, MDe, Assaf Raz, PhDf, Vincent A. Fischetti, PhDf, James G. Krueger, MD, PhDa, and Emma Guttman-Yassky, MD, PhDa,g Emma Guttman-Yassky: eguttman@rockefeller.edu aThe Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY bColumbia University College of Physicians & Surgeons, New York, NY cThe Center for Clinical and Translational Science, The Rockefeller University, New York, NY dAlbert Einstein College of Medicine, Bronx, NY eThe Department of Dermatology, Tel-Hashomer, Tel Aviv, Israel fThe Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, NY gThe Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY

Atopic dermatitis (AD) is a common inflammatory skin disease regulated by genetic and environmental factors. Both skin barrier defects and aberrant immune responses are believed to drive cutaneous inflammation in AD. Existing therapies rely largely on allergen avoidance, emollients and topical and systemic immune-suppressants, some with significant toxicity and transient efficacy; no specific targeted therapies are in clinical use today. As our specific understanding of the immune and molecular pathways that cause different subsets of AD increases, a variety of experimental agents, particularly biologic agents that target pathogenic molecules bring the promise of safe and effective therapeutics for long-term use.This paper discusses the molecular pathways characterizing AD, the contributions of barrier and immune abnormalities to its pathogenesis, and development of new treatments that target key molecules in these pathways. In this review, we will discuss a variety of biologic therapies that are in development or in clinical trials for AD, perhaps revolutionizing treatment of this disease.Biologic agents in moderate to severe AD offer promise for controlling a disease that currently lacks good and safe therapeutics posing a large unmet need. Unfortunately, existing treatments for AD aim to decrease cutaneous inflammation, but are not specific for the pathways driving this disease. An increasing understanding of the immune mechanisms underlying AD brings the promise of narrow targeted therapies as has occurred for psoriasis, another inflammatory skin disease, for which specific biologic agents have been demonstrated to both control the disease and prevent occurrence of new skin lesions. Although no biologic is yet approved for AD, these are exciting times for active therapeutic development in AD that might lead to revolutionary therapeutics for this disease.

Petrolatum is a common moisturizer often used in the prevention of skin infections after ambulatory surgeries and as a maintenance therapy of atopic dermatitis (AD). However, the molecular responses induced by petrolatum in the skin have never been assessed.We sought to define the cutaneous molecular and structural effects induced by petrolatum.Thirty-six healthy subjects and 13 patients with moderate AD (mean SCORAD score, 39) were studied by using RT-PCR, gene arrays, immunohistochemistry, and immunofluorescence performed on control skin, petrolatum-occluded skin, and skin occluded with a Finn chamber only.Significant upregulations of antimicrobial peptides (S100A8/fold change [FCH], 13.04; S100A9/FCH, 11.28; CCL20/FCH, 8.36; PI3 [elafin]/FCH, 15.40; lipocalin 2/FCH, 6.94, human β-defensin 2 [DEFB4A]/FCH, 4.96; P.001 for all) and innate immune genes (IL6, IL8, and IL1B; P.01) were observed in petrolatum-occluded skin compared with expression in both control and occluded-only skin. Application of petrolatum also induced expression of key barrier differentiation markers (filaggrin and loricrin), increased stratum corneum thickness, and significantly reduced T-cell infiltrates in the setting of "normal-appearing" or nonlesional AD skin, which is known to harbor barrier and immune defects.Petrolatum robustly modulates antimicrobials and epidermal differentiation barrier measures. These data shed light on the beneficial molecular responses of petrolatum in barrier-defective states, such as AD and postoperative wound care.

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by wet, oozing, erythematous, pruritic lesions in the acute stage and xerotic, lichenified plaques in the chronic stage. It frequently coexists with asthma and allergic rhinitis, sharing some mechanistic features with these diseases as part of the "atopic march." Controversy exists as to whether immune abnormalities, epidermal barrier defects, or both are the primary factors responsible for disease pathogenesis. In AD patients, there is often a coexisting irritant contact dermatitis (ICD) or allergic contact dermatitis (ACD) that is sometimes clinically difficult to distinguish from AD. ACD shares molecular mechanisms with AD, including increased cellular infiltrates and cytokine activation (Gittler et al., 2013). In this issue, Newell et al. (2013) used an experimental contact sensitization model with dinitrochlorobenzene (DNCB) to gain insight into the unique immune phenotype of AD patients.

BackgroundSevere atopic dermatitis (AD) has a high unmet need for effective and safe therapeutics. In early-phase trials, dupilumab, a fully human mAb targeting IL-4 receptor α, markedly improved disease activity, but the effect of IL-4/IL-13 blockade on AD at the molecular level has not been characterized.ObjectivesWe sought to evaluate dupilumab modulation of the AD molecular signature.MethodsWe performed transcriptomic analyses of pretreatment and posttreatment skin biopsy specimens from patients with moderate-to-severe AD treated weekly with 150 or 300 mg of dupilumab or placebo.ResultsExacerbation of the AD transcriptome was observed in placebo-treated patients. Dupilumab improved the AD signature in a dose-dependent manner. Expression of genes upregulated in AD lesions decreased in patients treated with dupilumab by 26% (95% CI, 21% to 32%) and 65% (95% CI, 60% to 71%) for treatment with 150 and 300 mg, respectively. Genes downregulated in AD lesions increased by 21% (95% CI, 16% to 27%) and 32% (95% CI, 26% to 37%) with dupilumab (150 and 300 mg, respectively). The molecular changes paralleled improvements in clinical scores. A dupilumab treatment signature of 821 probes (>2-fold change, P < .05) significantly modulated in the 300-mg dupilumab group at week 4 compared with baseline was identified in this sample set. Significant (P < .05) decreases in mRNA expression of genes related to hyperplasia (K16 and MKI67), T cells, and dendritic cells (CD1b and CD1c) and potent inhibition of TH2-associated chemokines (CCL17, CCL18, CCL22, and CCL26) were noted without significant modulation of TH1-associated genes (IFNG).ConclusionsThis is the first report showing rapid improvement of the AD molecular signature with targeted anti–IL-4 receptor α therapy. These data suggest that IL-4 and IL-13 drive a complex, TH2-centered inflammatory axis in patients with AD.