The Role of Inhalant Allergens on the Clinical Manifestations of Atopic Dermatitis.

BACKGROUND: Inhalant allergens provide a source of environmental factors that contribute to the development of clinical symptoms in patients with atopic dermatitis (AD). OBJECTIVE: To review the relationship between inhalant allergens and AD. METHODS: A literature review was conducted using three databases: PubMed/MEDLINE, ClinicalKey, and Web of Science. Search terms, including "atopic dermatitis," "atopic eczema," and "eczema," were used in combination with "inhalant allergen," "inhaled allergen," and "aeroallergen" to identify relevant published manuscripts that highlight the relationship between AD and exposures to inhalant allergens. RESULTS: Fifteen articles were suitable for review. The studies included in the review investigated the effect of inhalant allergens on the clinical manifestations of AD through bronchial provocation, direct skin contact, and allergen sensitization. CONCLUSION: There is a significant relationship between exposures to inhalant allergens and AD. Inhalant allergens may aggravate AD symptoms by either bronchial provocation or direct skin contact. Sensitization of inhalant allergens, mainly house dust mites, follows a specific age-related pattern.

CT109-SN-38, a Novel Antibody-drug Conjugate with Dual Specificity for CEACAM5 and 6, Elicits Potent Killing of Pancreatic Cancer Cells.

BACKGROUND: CEACAM5 and CEACAM6 are glycosylphosphatidylinositol (GPI)- linked members of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family, which are frequently upregulated in epithelial cancers where they contribute to invasion, metastasis, immune evasion, and resistance to anoikis. CT109 is a novel antibody with dual specificity to both CEACAM5 and 6. OBJECTIVE: In this study, we aimed to perform the preclinical characterization of CT109 and antibody- drug conjugate (ADCs) derivatives of CT109, focusing on CT109-SN-38. METHODS: CT109's cognate epitope was characterized by scanning mutagenesis. CT109 specificity and internalization kinetics were assessed by immunoblot and flow cytometry, respectively. Cognate antigen expression prevalence in colorectal cancer and normal tissue arrays was determined by immunohistochemistry. CT109 conjugations were generated by the reaction of reduced CT109 cysteines with maleimide-functionalized payload linkers. In vitro cytotoxic activity of CT109 ADCs was characterized on antigen-positive and negative pancreatic ductal adenocarcinoma cell (PDAC) lines using a luminometric viability assay. In vivo efficacy of CT109-SN-38 was assessed on a PDAC tumor xenograft model at 10 and 25 mg/kg concentrations. RESULTS: CT109 showed to bind a glycoepitope centered on N309. CT109 is internalized in the CEACAM5+/CEACAM6+ double-positive PDAC line, BxPC-3, with a t1/2 of 2.3 hours. CT109 ADCs elicit a dose and antigen-dependent cytotoxic effect, with CT109-SN-38 exhibiting an IC50 value of 21 nM in BxPC-3 cells. In a BxPC-3 tumor xenograft model, CT109-SN-38 reduced tumor growth and induced regression in 3/10 mice at 25 mg/kg concentration. CONCLUSIONS: These data suggest that further preclinical and clinical development of CT109-SN-38 is warranted.

Cardiometabolic multimorbidity is common among patients with psoriasis and is associated with poorer outcomes compared to those without comorbidity.

BACKGROUND: Associations between cardiometabolic multimorbidity and response to therapy in psoriasis are unknown. OBJECTIVE: Determine the associations of multimorbidity with response to biologic treatment in psoriasis patients. METHODS: CorEvitas Psoriasis Registry participants who initiated biologic therapy and had 6-month follow-up were stratified by 0, 1, 2+ comorbidities (diabetes, hypertension, hyperlipidemia). Adjusted odds ratios (95% CIs) were calculated overall and separately by biologic class (TNFi, IL-17i, IL-12/23i + IL-23i), to assess the likelihood of achieving response for the 1 and 2+ groups vs. 0. RESULTS: Of 2,923 patients, 49.5%, 24.7% and 25.8% reported 0, 1 and 2+ comorbidities, respectively. Overall, likelihood of PASI75 was 18% (OR = 0.82; 95%CI: 0.67, 1.00) and 23% (OR = 0.77; 95%CI: 0.63, 0.96) lower in those with 1 and 2+ comorbidities, respectively, vs. 0. In those who initiated IL-17i, odds of PASI75 and PAS90 were 34% (OR = 0.66; 95%CI: 0.48-0.91) and 35% (OR = 0.65; 95%CI: 0.47-0.91) lower in the 2+ multimorbidity cohort. No significant associations were found among users of TNFi or IL-12/23i + IL-23i groups in the multimorbidity group. LIMITATIONS: Patients may not be representative of all psoriasis patients. CONCLUSION: Multimorbidity in psoriasis may decrease the likelihood of achieving treatment response to biologic therapy and should be considered when discussing treatment expectations with patients.

Comorbid obesity and history of diabetes are independently associated with poorer treatment response to biologics at 6 months: A prospective analysis in Corrona Psoriasis Registry.

BACKGROUND: Psoriasis is associated with comorbid systemic metabolic disease. OBJECTIVE: To assess possible associations of comorbid obesity, history of diabetes, hypertension, and hyperlipidemia with response to biologic treatment at 6 months among patients in CorEvitas' Psoriasis Registry. METHODS: Participants included 2924 patients initiating biologic therapy (tumour necrosis factor inhibitors [TNFi], interleukin [IL]-17i, IL-12/23i, or IL-23i) with baseline and 6-month follow-up visits available. Logistic regressions resulted in adjusted odd ratios (OR) and 95% confidence intervals (CI) for achievement of response in select outcomes for those with obesity and history of diabetes, hypertension, and hyperlipidemia relative to those without each. RESULTS: Overall, obesity reduced by 25% to 30% odds of achieving PASI75 (OR, 0.75; 95% CI, 0.64-0.88) and PASI90 (OR, 0.70; 95% CI, 0.59-0.81). History of diabetes reduced odds of achieving PASI75 by 31% (OR, 0.69; 95% CI, 0.56-0.85) and PASI90 by 21% (OR, 0.79; 95% CI, 0.63-0.98). Obesity was associated with lower response to TNFi and IL-17i classes. Independent of obesity, diabetes was associated with poorer outcomes when on IL-17i therapy and hypertension, to a lesser extent, when on the TNFi class. No significant associations were found in the hyperlipidemia group. LIMITATIONS: The study assessed only short-term effectiveness and small sample sizes limited the power to detect differences. CONCLUSION: Assessment of comorbid disease burden is important for improved likelihoods of achieving treatment response with biologics.

Psoriasis Severity, Comorbidities, and Treatment Response Differ among Geographic Regions in the United States.

Little is known about how psoriatic disease characteristics and treatment outcomes differ geographically in the United States. Our aim was to explore real-world, geographic variations in the use of biologic classes and outcomes within the Corrona Psoriasis Registry. Patient demographics and disease characteristics were assessed at biologic initiation and at 6 months. Logistic regressions were conducted to evaluate the odds of achieving targeted outcomes for seven United States geographic regions. We examined 737 biologic initiations among 717 patients. IL-17 inhibitors were used most frequently (45%), followed by IL-12‒IL-23 and IL-23 inhibitors (38%) and TNF inhibitors (17%). The proportions of patients with obesity (body mass index > 30) and very severe psoriasis (body surface area > 20) were greatest in the East South Central and West South Central regions. After adjusting for age, sex, race, body mass index, and baseline body surface area, decreased odds of achieving 75% improvement in PASI at 6 months were observed among patients in the East South Central (OR = 0.47, 95% confidence interval = 0.28-0.79, P = 0.004), West South Central (OR = 0.43, 95% confidence interval = 0.22-0.87, P = 0.019), and Pacific (OR = 0.49, 95% confidence interval = 0.28-0.84, P = 0.010) regions compared with those observed among patients in the Northeast. The East South Central and West South Central regions may have the greatest frequencies of very severe disease burden and, along with the Pacific region, may be less likely to achieve targeted response within 6 months of initiating biologic therapy.

Sun-protection Behaviors Among Active Members of the United States Lifesaving Association.

BACKGROUND: Ultraviolet radiation exposure is the most prominent modifible risk factor for developing both melanoma and non-melanoma skin cancers. OBJECTIVE: We sought to elucidate sun-protective behaviors among active members of the United States Lifesaving Association (USLA), a nationwide nonprofit organization comprising beach lifeguards, and to identify positive and negative predictors of sun protective behaviors. METHODS: This was a pilot, cross-sectional survey study. All USLA lifeguards aged 18 years or older were invited to complete a 19-item survey. Data were collected anonymously at the 2018 USLA National Lifeguard Championships in Virginia Beach, Virginia. Participant characteristics and sun-protective behaviors (e.g., hat, sunglasses, protective clothing, sunscreen, and seeking shade) were surveyed. A composite score (0-10 points) was created based on sun-protective behaviors. Simple linear regression models were fit to assess the relationship between lifeguard characteristics and the sun-behavior composite score and a multiple linear regression model was used to assess their overall positive or negative effect on composite scores. RESULTS: A total of 215 USLA lifeguards completed the survey study; of these, 64.2% were male and the average age was 34.2 years. The most common sun-protective behavior was wearing sunglasses (85%), followed by applying sunscreen (65%), wearing a hat (46.7%), seeking shade (38.6%), and wearing protective clothing (34.0%). The overall average composite score was 7.5±1.9 points. In the multiple linear regression model, female sex (ß=-0.85; p=0.0012), desiring a tan (ß=-1.26; p=0.0008), and working more summer daytime hours (ß=-0.49; p=0.049) negatively impacted composite scores. CONCLUSIONS: USLA beach lifeguards are subject to sun-exposure patterns and practiced sun-protective behaviors that potentially place them at higher risk for skin cancer.

Management of psoriasis in patients with inflammatory bowel disease: From the Medical Board of the National Psoriasis Foundation.

BACKGROUND: There is a significant association between psoriasis and inflammatory bowel disease (IBD). Many treatments for psoriasis and psoriatic arthritis are also used for IBD. OBJECTIVE: To assess therapeutic options for patients with psoriasis and concurrent IBD. METHODS: A systematic literature search was performed for clinical studies of biologic and systemic psoriasis medications in psoriasis, psoriatic arthritis, ulcerative colitis, and Crohn's disease, for the period from January 1, 1947, to February 14, 2017. Randomized, controlled, double-blinded studies were selected if available. If not, the next highest level of available evidence was selected. RESULTS: Of the 2282 articles identified, 132 were selected. Infliximab and adalimumab have demonstrated efficacy in psoriasis, psoriatic arthritis, ulcerative; colitis, and Crohn's disease. Ustekinumab has demonstrated efficacy in psoriasis, psoriatic arthritis, and Crohn's disease. Certolizumab has demonstrated efficacy in psoriatic arthritis and Crohn's disease. Etanercept, secukinumab, brodalumab, and ixekizumab have demonstrated efficacy in psoriasis and psoriatic arthritis but may exacerbate or induce IBD. Guselkumab has demonstrated efficacy in psoriasis. LIMITATIONS: There are no known clinical trials of treatment specifically for concurrent psoriasis and IBD. CONCLUSIONS: Infliximab and adalimumab have demonstrated efficacy in psoriasis, psoriatic arthritis, ulcerative colitis, and Crohn's disease; other agents have demonstrated efficacy for some, but not all, of these indications.

From Bench to Bedside: The Hampton University Skin of Color Research Institute 2015 Skin of Color Symposium.

The Hampton University Skin of Color Research Institute Skin of Color Symposium 2015: From Bench to Bedside was held in Williamsburg, Virginia at the Williamsburg Lodge, November 13-15, 2015. The conference was designed to promote, develop, and advance the education, knowledge, and research of cutaneous disorders disproportionately affecting people of racial and ethnic minority groups. Centered on the theme of "From Bench to Bedside", the symposium provided a program featuring a diverse panel of nationally recognized physician-scientists, basic scientists, and clinicians who updated attendees on the latest research advances across multiple relevant disciplines, including public health, basic science, and the clinical diagnosis and management of select complex and rare dermatologic conditions. Featured sessions included recent advances in vitiligo, disorders of hyperpigmentation, keloids, central centripetal cicatricial alopecia, and cutaneous lupus. We expect that the scientific sessions and interactive panel discussions, combined with the synergistic environment that has characterized this conference, will spur the formation of new collaborations and scientific discovery and, ultimately, will culminate in novel treatments for dermatologic disorders disproportionately affecting individuals with skin of color.

Diversity in Dermatology Residency Programs.

Given the change in our population to one that is more racially and ethnically diverse, the topic of diversity in dermatology residency programs has gained attention. In a field that has become highly competitive, diversity is lagging behind. What are the reasons for this? The existing diversity among medical school matriculants is reflective of the applicant pool, and although modest, there has been an increase in applications and acceptances from minority populations. However, these proportions do not carry through to the population applying to dermatology residency. Making sense of this and planning how to recruit a more diverse applicant pool will improve the quality and cultural competency of future dermatologists.

The Role of Neighborhood Characteristics in Late Stage Melanoma Diagnosis among Hispanic Men in California, Texas, and Florida, 1996-2012.

BACKGROUND: Hispanics diagnosed with cutaneous melanoma are more likely to present at advanced stages but the reasons for this are unknown. We identify census tracts at high risk for late stage melanoma diagnosis (LSMD) and examine the contextual predictors of LSMD in California, Texas, and Florida. METHODS: We conducted a cross-sectional study using geocoded state cancer registry data. Using hierarchical multilevel logistic regression models we estimated ORs and 95% confidence intervals for the impact of socioeconomic, Hispanic ethnic concentration, index of dissimilarity, and health resource availability measures on LSMD. RESULTS: We identified 12,493 cases. In California, late stage cases were significantly more likely to reside within census tracts composed mostly of Hispanics and immigrants. In Texas, LSMD was associated with residence in areas of socioeconomic deprivation and a higher proportion of immigrants. In Florida, living in areas of low education attainment, high levels of poverty, and a high percentage of Hispanic residents was significantly associated with LSMD. Residential segregation did not independently affect LSMD. CONCLUSION: The influence of contextual predictors on LSMD varied in magnitude and strength by state, highlighting both the cosegregation of social adversity and poverty and the complexity of their interactions.

Discriminating the hemolytic risk of blood type A plasmas using the complement hemolysis using human erythrocytes (CHUHE) assay.

BACKGROUND: The agglutination-based cross-matching method is sensitive for antibody binding to red blood cells but is only partially predictive of complement-mediated hemolysis, which is important in many acute hemolytic transfusion reactions. Here, we describe complement hemolysis using human erythrocytes (CHUHE) assays that directly evaluate complement-mediated hemolysis between individual serum-plasma and red blood cell combinations. The CHUHE assay is used to evaluate correlations between agglutination titers and complement-mediated hemolysis as well as the hemolytic potential of plasma from type A blood donors. STUDY DESIGN AND METHODS: Plasma or serum from each type A blood donor was incubated with AB or B red blood cells in the CHUHE assay and measured for free hemoglobin release. RESULTS: CHUHE assays for serum or plasma demonstrate a wide, dynamic range and high sensitivity for complement-mediated hemolysis for individual serum/plasma and red blood cell combinations. CHUHE results suggest that agglutination assays alone are only moderately predictive of complement-mediated hemolysis. CHUHE results also suggest that plasma from particular type A blood donors produce minimal complement-mediated hemolysis, whereas plasma from other type A blood donors produce moderate to high-level complement-mediated hemolysis, depending on the red blood cell donor. CONCLUSION: The current results indicate that the CHUHE assay can be used to assess complement-mediated hemolysis for plasma or serum from a type A blood donor, providing additional risk discrimination over agglutination titers alone.

Keloids and Hypertrophic Scars: A Spectrum of Clinical Challenges.

Since their earliest description, keloids and hypertrophic scars have beleaguered patients and clinicians alike. These scars can be aesthetically disfiguring, functionally debilitating, emotionally distressing, and psychologically damaging, culminating in a significant burden for patients. Our current understanding of keloid pathophysiology has grown and continues to advance while molecular biology, genetics, and technology provide ever-deepening insight into the nature of wound healing and the pathologic perturbations thereof. Greater understanding will lead to the development and application of refined therapeutic modalities. This article provides an overview of our current understanding of keloids, highlighting clinical characteristics and diagnostic criteria while providing a comprehensive summary of the many therapeutic modalities available. The proposed mechanism, application, adverse events, and reported efficacy of each modality is evaluated, and current recommendations are summarized.