Andrew F. Alexis

Practical management of acne for clinicians: An international consensus from the Global Alliance to Improve Outcomes in Acne

&NA; Scientific advances are continually improving the knowledge of acne and contributing to the refinement of treatment options; it is important for clinicians to regularly update their practice patterns to reflect current standards. The Global Alliance to Improve Outcomes in Acne is an international group of dermatologists with an interest in acne research and education that has been meeting regularly since 2001. As a group, we have continuously evaluated the literature on acne. This supplement focuses on providing relevant clinical guidance to health care practitioners managing patients with acne, with an emphasis on areas where the evidence base may be sparse or need interpretation for daily practice.

Expert Perspectives on Management of Moderate-to-Severe Atopic Dermatitis: A Multidisciplinary Consensus Addressing Current and Emerging Therapies

Atopic dermatitis (AD) is a common, chronic, relapsing, inflammatory skin disease that affects children and adults. Until recently, the only Food and Drug Administration-approved systemic treatment option for patients with moderate-to-severe AD was systemic steroids, which are not recommended by current guidelines and are commonly associated with disease rebound. Instead, clinicians choose from several off-label immunosuppressants, which can have serious adverse effects. A significant number of these patients go untreated. Research on the immunopathogenesis of AD has paved the way for new, targeted, systemic therapies for moderate-to-severe AD. In early 2017, the Food and Drug Administration approved dupilumab for adults with moderate-to-severe AD whose disease is not adequately controlled with topical therapies. Although the national guidelines can be very helpful to clinicians, the process for updating them does not allow for timely incorporation of novel therapies. A steering committee of AD experts, including dermatologists, allergists, and a patient advocacy group representative, developed recommendations on the basis of a literature review and expert opinion to help clinicians understand how new therapies fit into the current treatment paradigm and to provide practical recommendations for assessing AD severity, treatment response, and treatment failure.

Atopic dermatitis in diverse racial and ethnic groups-Variations in epidemiology, genetics, clinical presentation and treatment

Atopic dermatitis (AD) is a chronic inflammatory skin condition that affects diverse ethnic groups with varying prevalence. Despite a predominance of studies in individuals of European ancestry, AD has been found to occur more frequently in Asian and Black individuals than Whites. Therefore, an understanding of the unique clinical features of AD in diverse ethnic groups, as well as the differences in genetic polymorphisms that influence susceptibility to AD and response to current therapies, is paramount for management of an increasingly diverse patient population. In this article, we review key nuances in the epidemiology, pathophysiology, clinical presentation and treatment of AD in non‐White ethnic groups, which are largely underappreciated in the literature. We highlight the need for studies evaluating the tissue molecular and cellular phenotypes of AD in non‐White patients, as well as greater inclusion of minority groups in clinical trials, to develop targeted treatments for a multi‐ethnic population.

Skin Bleaching and Dermatologic Health of African and Afro-Caribbean Populations in the US: New Directions for Methodologically Rigorous, Multidisciplinary, and Culturally Sensitive Research

Skin-bleaching practices, such as using skin creams and soaps to achieve a lighter skin tone, are common throughout the world and are triggered by cosmetic reasons that oftentimes have deep historical, economic, sociocultural, and psychosocial roots. Exposure to chemicals in the bleaching products, notably, mercury (Hg), hydroquinone, and steroids, has been associated with a variety of adverse health effects, such as Hg poisoning and exogenous ochronosis. In New York City (NYC), skin care product use has been identified as an important route of Hg exposure, especially among Caribbean-born blacks and Dominicans. However, surprisingly sparse information is available on the epidemiology of the health impacts of skin-bleaching practices among these populations. We highlight the dearth of large-scale, comprehensive, community-based, clinical, and translational research in this area, especially the limited skin-bleaching-related research among non-White populations in the US. We offer five new research directions, including investigating the known and under-studied health consequences among populations for which the skin bleach practice is newly emerging at an alarming rate using innovative laboratory and statistical methods. We call for conducting methodologically rigorous, multidisciplinary, and culturally sensitive research in order to provide insights into the root and the epidemiological status of the practice and provide evidence of exposure-outcome associations, with an ultimate goal of developing potential intervention strategies to reduce the health burdens of skin-bleaching practice.

Postinflammatory Hyperpigmentation: Epidemiology, Clinical Presentation, Pathogenesis and Treatment

Postinflammatory hyperpigmentation (PIH) is a reactive hypermelanosis that develops following cutaneous inflammation. Common causes of PIH include intrinsic skin conditions (e.g., acne and eczema) as well as external insults to the skin, such as burn injuries and dermatologic procedures. PIH more commonly occurs in individuals with darker skin, for whom it is often a source of significant psychological distress. Several therapeutic modalities are available for the treatment of PIH, including topical agents, chemical peels, and energy-based devices. We review the epidemiology, clinical presentation, pathogenesis, and treatment of PIH.

Nail Issues in Diverse Populations

The nail unit is similar between ethnic groups, yet the greater number of activated and differentiated nail matrix melanocytes in darker skin types has important implications on nail appearance and pathogenesis of nail disorders. Longitudinal melanonychia (LM), the presence of a light brown to black linear streak within the nail plate, is more commonly observed in blacks, Asians, and Hispanics due to activation or proliferation of melanocytes within the distal nail matrix. Similarly, the relative frequency of nail apparatus melanoma (compared to other melanoma subtypes) is significantly higher in darker skin phototypes and the overall prognosis appears to be poorer than in whites. These conditions, in addition to other primary nail disorders, medication side effects, cultural practices, and environmental exposures that disproportionately affect certain ethnic groups, are important to consider when treating an increasingly multi-ethnic patient population.

Biologics and Small Molecule Agents in Allergic and Immunologic Skin Diseases

Purpose of ReviewBiologics and small molecules are key therapeutic options in the treatment of chronic immunologic and allergic skin conditions. By directly targeting innate and inflammatory responses within the skin, including pro-inflammatory cytokines and cellular signaling pathways, these new agents have the potential to counteract the inflammatory cascade responsible for various conditions, including psoriasis and atopic dermatitis. Over the past decade, groundbreaking research identifying key cytokines and receptors involved in the pathogenesis of these diseases has allowed for the development of highly efficacious biologics and small molecules that are associated with unprecedented rates of skin clearance and favorable adverse event profiles.Recent FindingsThis narrative review evaluates new and upcoming biologic and small molecule agents for the treatment of two allergic/immunologic skin diseases—atopic dermatitis and psoriasis. Numerous small molecules and biologics targeting TNF-α, IL-12/23, IL-17 and IL-17R, and IL-23 are commercially available for the treatment of psoriasis, and newer agents are in various stages of development. Currently, dupilumab, a monoclonal antibody that blocks IL-4R∝, is the only approved biologic for atopic dermatitis. Antibodies targeting IL-13 and IL-31 and small molecules that inhibit Janus kinase and pruritus-mediating receptors are currently being studied in clinical trials. Further investigations into the pathophysiology of atopic dermatitis will likely yield additional therapeutic options in the future.SummaryThis article reviews recent literature on small molecules and biologics for the treatment of atopic dermatitis and psoriasis.

Atopic dermatitis in African American patients is TH2/TH22-skewed with TH1/TH17 attenuation

BACKGROUND African Americans (AA) are disproportionately impacted by atopic dermatitis (AD), with increased prevalence and therapeutic challenges unique to this population. Molecular profiling data informing development of targeted therapeutics for AD are derived primarily from European American (EA) patients. These studies are absent in AA, hindering development of effective treatments for this population. OBJECTIVE We sought to characterize the global molecular profile of AD in the skin of AA patients as compared with that of EA AD and healthy controls. METHODS We performed RNA-Seq with reverse transcription polymerase chain reaction validation and immunohistochemistry studies in lesional and nonlesional skin of AA and EA AD patients vs healthy controls. RESULTS African American AD lesions were characterized by greater infiltration of dendritic cells (DCs) marked by the high-affinity immunoglobulin E (IgE) receptor (FcεR1+) compared with EA AD (P < .05). Both AD cohorts showed similarly robust up-regulation of Th2-related (CCL17/18/26) and Th22-related markers (interleukin [IL]-22, S100A8/9/12), but AA AD featured decreased expression of innate immune (tumor necrosis factor [TNF], IL-1β), Th1-related (interferon gamma [IFN-γ], MX1, IL-12RB1), and Th17-related markers (IL-23p19, IL-36G, CXCL1) vs EA AD (P < .05). The Th2 (IL-13) and Th22-related products (IL-22, S100A8/9/12) and serum IgE were significantly correlated with clinical severity (Scoring of Atopic Dermatitis [SCORAD]) in AA. Fillagrin (FLG) was exclusively down-regulated in EA AD, whereas loricrin (LOR) was down-regulated in both AD cohorts and negatively correlated with SCORAD in AA. CONCLUSION The molecular phenotype of AA AD skin is characterized by attenuated Th1 and Th17 but similar Th2/Th22-skewing to EA AD. Our data encourages a personalized medicine approach accounting for phenotype-specific characteristics in future development of targeted therapeutics and clinical trial design for AD.