Emerging drugs for the treatment of atopic dermatitis: a focus on phase 2 and phase 3 trials.

INTRODUCTION: Atopic dermatitis (AD) is an inflammatory skin condition that affects millions of pediatric and adult patients with well-studied impact on morbidity and quality of life. Management occurs in a stepwise fashion beginning with preventative measures before immunomodulators are introduced. However, challenges remain in treatment of moderate-to-severe atopic dermatitis that is refractory to first- and second-line treatments and there are only few topical anti-inflammatory options, especially for pediatric patients. AREAS COVERED: New medications are required to address these gaps as lesions may persist despite treatment or patients may discontinue treatment due to actual or anticipated adverse effects of mainstay medications. Emerging research into the pathophysiology of AD and the immune system at large has provided opportunities for novel interventions aimed at stopping AD mechanisms at new checkpoints. Clinical trials for 36 agents currently in phase 2 or phase 3 are evaluated with particular focus on the studies for, B244, CBP-201, tapinarof, lebrikizumab, nemolizumab, amlitelimab, and rocatinlimab as they explore novel pathways and have some of the most promising results. EXPERT OPINION: These clinical trials contribute to the evolution of AD treatment toward greater precision based on salient pathways with a particular focus on moderate-to-severe AD to enhance efficacy and minimize adverse effects.

Mental Health Disparities among Pre-Clinical Medical Students at Saint Louis University during the COVID-19 Pandemic.

The COVID-19 pandemic disproportionately affected racial and ethnic minorities. Medical students were also particularly impacted as they coped with increased stressors due to delayed medical training and a high prevalence of mental health conditions. This study investigates mental health disparities of underrepresented in medicine (URM) students at the Saint Louis University School of Medicine (SLUSOM). An anonymous online survey was distributed to first- and second-year medical students at SLUSOM in February 2021. The survey queried demographic information, lifestyle factors, and pandemic-related and institutional concerns. Mental health was assessed via the Generalized Anxiety Disorder-7 (GAD-7) and the Patient Health Questionnaire-9 (PHQ-9). Statistical tests were run with SPSS, version 27. A convenience sample of 87 students responded to the survey. Students who were categorized as URM were significantly more likely to be at risk of major depressive disorder during the pandemic. Concern about a lack of financial support was significantly greater among students categorized as URM. Concerns regarding a lack of financial support, mental health support, and decreased quality of medical training significantly predicted PHQ-9 scores. Our findings revealed several key factors that may exacerbate mental health disparities among URM students during the pandemic. Providing adequate financial and academic resources for URMs may improve mental health outcomes for similar adverse events in the future.

Patients' and Caregivers' Preferences for Mental Health Care and Support in Atopic Dermatitis.

Background: Atopic dermatitis (AD) has large mental health impacts for patients and caregivers, yet their preferences regarding how to relieve these impacts are poorly understood. Objective: To understand patients' and caregivers' preferences for AD-related mental health care and support. Methods: We surveyed 279 adult AD patients and 154 caregivers of children with AD across 26 countries regarding their AD-related mental health burden, preferred strategies for improving AD-related mental health, and experiences with mental health care in AD. Results: Caregivers reported significantly worse overall mental health (P = 0.01) and anxiety (P = 0.03) than adult patients when controlling for AD severity. Among adult patients, 58% selected treating the AD, 51% managing itch, 44% wearing clothing to cover up skin, 43% avoiding social situations, and 41% spending time alone, as strategies they felt would improve their own AD-related mental health. Caregivers selected managing itch and treating the AD most frequently for both their own (76% and 75%, respectively) and their children's (75% and 61%) mental health. Adult patients were less satisfied with mental health care from mental health providers versus nonmental health providers (P < 0.001). Conclusions: Effective AD management is the preferred method for improving mental health among patients as well as caregivers, who may experience the greatest mental health impacts. Self-care strategies should be considered in a shared decision-making approach.

Fruitful or unfruitful: strawberry and tomato specific immunoglobulin E testing at a tertiary pediatric center.

Background: Suspected strawberry and tomato (S/T) food allergy (FA) can be evaluated using specific immunoglobulin E (sIgE) testing despite its low specificity and positive predictive value. Objective: This study aims to understand ordering patterns for S/T sIgE testing and identify relevant factors to clinical decision-making. Methods: We retrospectively reviewed 814 patients with sIgE testing available for strawberries (651), tomatoes (276), or both (113) from January 2012 to May 2022 at a tertiary pediatric hospital. Patient demographics, provider specialty, and reasons for testing were collected. Student's t-test and multiple regression analyses were performed to test the association between the S/T sIgE level and clinically relevant outcome (CRO) status. Fisher's exact test and general linear models were used to evaluate and compare potential predictive factors for CRO status. Results: Allergy and immunology, gastroenterology, and general pediatrics ordered most S/T sIgE testing. Testing was ordered most frequently for non-IgE-mediated gastrointestinal symptoms, mild possible IgE-mediated reactions, and eczema. Testing was most often ordered for infants and school-age children. Mean sIgE levels were higher for S/T tests resulting in a CRO when controlling for other predictor variables (p = 0.015; p = 0.002 for S/T, respectively). Only 2.2% and 5.4% of tests resulted in a CRO for S/T, and severe allergy was rare. Testing for non-IgE-mediated GI symptoms or eczema, or in non-atopic patients, yielded no CROs. Exposure and reaction history of present illness (ERH) was associated with CROs (p < 0.001; p = 0.04) with a high negative predictive value (99.5%; 100%) and low positive predictive value (11.5%; 15.0%). ERH (p < 0.001, η2 = 0.073; p = 0.009, η2 = 0.123) was a more significant predictor than the sIgE level (p = 0.002, η2 = 0.037; p = 0.212, η2 = 0.030) for CRO status. Conclusion: The diagnosis of S/T food allergy is made primarily based on clinical history. S/T sIgE testing for children and adolescents should be avoided for patients without an ERH and in the workup of non-IgE-mediated GI symptoms. Testing for eczema and non-atopic patients is likely low-yield.

Provision of Food Allergy Care in the United Kingdom and United States: Current Issues and Future Directions.

Food allergy (FA) is a growing issue worldwide. The United Kingdom and United States are high-income, industrialized countries with reported increases in FA prevalence over the past few decades. This review compares delivery of FA care in the United Kingdom and United States and each country's response to the heightened demand and disparities for FA services. In the United Kingdom, allergy specialists are scarce and general practitioners (GPs) provide most allergy care. Whereas the United States has more allergists per capita than the United Kingdom, there is still a shortage of allergy services owing to the greater reliance on specialist care for FA in America and wide geographic variation in access to allergist services. Currently, generalists in these countries lack the specialty training and equipment to diagnose and manage FA optimally. Moving forward, the United Kingdom aims to enhance training for GPs so they may provide better quality frontline allergy care. In addition, the United Kingdom is implementing a new tier of semi-specialized GPs and increasing cross-center collaboration through clinical networks. The United Kingdom and United States aim to increase the number of FA specialists, which is critical at a time of rapidly expanding management options for allergic and immunologic diseases requiring clinical expertise and shared decision-making to select appropriate therapies. While these countries aim to grow their supply of quality FA services actively, further efforts to build clinical networks and perhaps recruit international medical graduates and expand telehealth services are necessary to reduce disparities in access to care. For the United Kingdom in particular, increasing quality services will require additional support from the leadership of the centralized National Health Service, which remains challenging.

Genetic/Environmental Contributions and Immune Dysregulation in Children with Atopic Dermatitis.

Atopic dermatitis (AD) is one of the most common skin conditions in humans. AD affects up to 20% of children worldwide and results in morbidity for both patients and their caregivers. The basis of AD is an interplay between genetics and the environment characterized by immune dysregulation. A myriad of mutations that compromise the skin barrier and/or immune function have been linked to AD. Of these, filaggrin gene (FLG) mutations are the most evidenced. Many other mutations have been implicated in isolated studies that are often unreplicated, creating an archive of genes with potential but unconfirmed relevance to AD. Harnessing big data, polygenic risk scores (PRSs) and genome-wide association studies (GWAS) may provide a more practical strategy for identifying the genetic signatures of AD. Epigenetics may also play a role. Staphylococcus aureus is the most evidenced microbial contributor to AD. Cutaneous dysbiosis may result in over-colonization by pathogenic strains and aberrant skin immunity and inflammation. Aeroallergens, air pollution, and climate are other key environmental contributors to AD. The right climate and/or commensals may improve AD for some patients.

Aeroallergens in Atopic Dermatitis and Chronic Urticaria.

PURPOSE OF REVIEW: While aeroallergens are a well-established trigger of asthma and allergic rhinitis, their role in allergic skin diseases such as atopic dermatitis and chronic urticaria remains controversial. This paper reviews the pathophysiology and clinical evidence for aeroallergens in these allergic skin diseases and summarizes current strategies for evaluation and management. RECENT FINDINGS: Current evidence implicates aeroallergens as triggers of cutaneous reactions in atopic dermatitis. Direct skin contact is the likely route of trigger. Aeroallergens may also trigger chronic urticaria, though mechanistic studies are limited. These allergens may cross the skin barrier and directly trigger neurons to release substance P, resulting in mast cell degranulation and dumping of histamine and prostaglandin D2. Many studies link aeroallergen sensitization to chronic urticaria, and case reports suggest the utility of avoidance strategies. The role of aeroallergens as a trigger is clear in atopic dermatitis and becoming emergent in chronic urticaria. Skin prick testing or serum-specific immunoglobulin E testing may be used to determine sensitivities. Management at this time centers on avoidance, and further studies are necessary to evaluate the efficacy of aeroallergen immunotherapy for both conditions.

Medical student anxiety and depression in the COVID-19 Era: Unique needs of underrepresented students.

Background: The COVID-19 pandemic has caused significant morbidity, mortality, and mental health consequences. Few studies have examined the mental toll of COVID-19 on United States (US) medical students, who experience greater rates of depression and anxiety than the general population. Students who identify as underrepresented in medicine (URM) may experience even greater mental health adversities than non-URM peers. This study examines COVID-19's impact on preclinical medical student anxiety and depression and unique challenges disproportionately affecting URM students during the initial phase of the pandemic. Methods: Medical students at four US institutions completed an anonymous survey including the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) questionnaires for depression and anxiety. Participants provided information on demographics, past mental health difficulties, and concerns during the pandemic. Chi-square and Mann-Whitney U tests were performed using SPSS. Results: During the initial phase of the pandemic, URMs were 3.71 times more likely to be in the at-risk category on GAD-7 than non-URM peers. Before COVID-19, there was no significant difference between self-reported feelings or diagnoses of anxiety between groups. During the COVID-19 pandemic, there were significant differences in feelings of increased anxiety between URM (Mdn = 76) and non-URM (Mdn = 49) students, U = 702.5, P < 0.001, feelings of increased sadness between URM (Mdn = 49) and non-URM (Mdn = 34) students, U = 1036.5, P = 0.042, concern for new financial difficulty between URM (Mdn = 50) and non-URM students (Mdn = 7), U = 950.5, P = 0.012, and concern about lack of mental health support from their academic institution between URM (Mdn = 18) and non-URM students (Mdn = 9), U = 1083, P = 0.036 (one-tailed). Discussion: Large-scale crises such as COVID-19 may exacerbate mental health disparities between URM and non-URM students. Medical schools should consider increasing financial and mental health support for URM students in response to these significant adverse events.

New astroglial injury-defined biomarkers for neurotrauma assessment.

Traumatic brain injury (TBI) is an expanding public health epidemic with pathophysiology that is difficult to diagnose and thus treat. TBI biomarkers should assess patients across severities and reveal pathophysiology, but currently, their kinetics and specificity are unclear. No single ideal TBI biomarker exists. We identified new candidates from a TBI CSF proteome by selecting trauma-released, astrocyte-enriched proteins including aldolase C (ALDOC), its 38kD breakdown product (BDP), brain lipid binding protein (BLBP), astrocytic phosphoprotein (PEA15), glutamine synthetase (GS) and new 18-25kD-GFAP-BDPs. Their levels increased over four orders of magnitude in severe TBI CSF. First post-injury week, ALDOC levels were markedly high and stable. Short-lived BLBP and PEA15 related to injury progression. ALDOC, BLBP and PEA15 appeared hyper-acutely and were similarly robust in severe and mild TBI blood; 25kD-GFAP-BDP appeared overnight after TBI and was rarely present after mild TBI. Using a human culture trauma model, we investigated biomarker kinetics. Wounded (mechanoporated) astrocytes released ALDOC, BLBP and PEA15 acutely. Delayed cell death corresponded with GFAP release and proteolysis into small GFAP-BDPs. Associating biomarkers with cellular injury stages produced astroglial injury-defined (AID) biomarkers that facilitate TBI assessment, as neurological deficits are rooted not only in death of CNS cells, but also in their functional compromise.