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Previous observational studies have linked inflammatory skin diseases with mental health issues and neuroticism. However, the specific impact of neuroticism and its subclusters (i.e. worry, depressed affect, and sensitivity to environmental stress and adversity) on these conditions remains underexplored. In this work, we explored causal associations between common inflammatory skin diseases and neuroticism. We conducted a two-sample, bidirectional Mendelian randomization (MR) analysis using data from genome-wide association studies in psoriasis, atopic dermatitis, neuroticism and relevant genetic subclusters conducted on participants of European ancestry. Corrections for sample overlap were applied where necessary. We found that psoriasis was causally associated with increased levels of worry (odds ratio, 95% confidence intervals: 1.011, 1.006–1.016, P = 3.84 × 10–6) while none of the neuroticism subclusters showed significant association with psoriasis. Sensitivity analyses revealed considerable evidence of directional pleiotropy between psoriasis and neuroticism traits. Conversely, genetic liability to atopic dermatitis did not exhibit any significant association with neuroticism traits. Notably, genetically predicted worry was linked to an elevated risk of atopic dermatitis (odds ratio, 95% confidence intervals: 1.227, 1.067–1.41, P = 3.97 × 10–3). Correction for overlapping samples confirmed the robustness of these results. These findings suggest potential avenues for future interventions aimed at reducing stress and worry among patients with inflammatory skin conditions. [ABSTRACT FROM AUTHOR]

Secondary bacterial infections of common dermatoses such as atopic dermatitis, ectoparasitosis, and varicella zoster virus infections are frequent, with Staphylococcus aureus and Streptococcus pyogenes being the bacteria most involved. There are also Gram-negative infections secondary to common dermatoses such as foot dyshidrotic eczema and tinea pedis. Factors favoring secondary bacterial infections in atopic dermatitis, ectoparasitosis, and varicella zoster virus infections mainly include an epidermal barrier alteration as well as itch. Mite-bacteria interaction is also involved in scabies and some environmental factors can promote Gram-negative bacterial infections of the feet. Furthermore, the bacterial ecology of these superinfections may depend on the geographical origin of the patients, especially in ectoparasitosis. Bacterial superinfections can also have different clinical aspects depending on the underlying dermatoses. Subsequently, the choice of class, course, and duration of antibiotic treatment depends on the severity of the infection and the suspected bacteria, primarily targeting S. aureus. Prevention of these secondary bacterial infections depends first and foremost on the management of the underlying skin disorder. At the same time, educating the patient on maintaining good skin hygiene and reporting changes in the primary lesions is crucial. In the case of recurrent secondary infections, decolonization of S. aureus is deemed necessary, particularly in atopic dermatitis. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by itching and skin barrier dysfunction. Moderate to severe AD is often refractory to first-line topical treatments, and systemic immunosuppressants have been shown to be effective but have significant adverse effects. The paucity of basic treatments has contributed to the development of targeted topical and systemic immunotherapies based on the use of small molecules and biologic drugs which can directly interact with AD pathogenetic pathways. They represent a new era of therapeutic innovation. Additional new treatments are desirable since AD is a heterogeneous disease marked by different immunological phenotypes. This manuscript will review the mechanism of action, safety profile, and efficacy of promising new systemic immunological treatments for AD. Since moderate to severe AD can result in poor quality of life, the development of targeted and well-tolerated immunomodulators is a crucial purpose. The introduction of new pharmacological agents may offer new therapeutic options. However, there is the need to evaluate how "narrow-acting" agents, such as individual interleukin inhibitors, will perform under the safety and efficacy profiles compared with "broad-acting" agents, such as JAK inhibitors. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disease with a multifactorial etiology that affects up to 20% of children and up to 7% of adults in the USA. Annual costs are estimated to be greater than $5 billion as of 2015 and have likely increased since. Mild cases can be managed with emollients and topical steroids or non-steroidal medications; however, moderate-to-severe AD is much more difficult to control and typically requires systemic therapy. While historically treatment has involved topical and oral corticosteroids and other immunosuppressive medications, advances in our understanding of the complex pathophysiology of AD has allowed us to develop more precisely targeted therapies for the condition. Specifically, because of the high prevalence and burden on quality of life, many new immunologic therapies are emerging or in development to treat this condition. This article summarizes the existing, upcoming, and failed immunologic-based medications for atopic dermatitis. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review aims to deliver a comprehensive report of the most recent knowledge on diagnosing allergic dermatoses in skin of color (SOC) patients. Recent Findings: Allergic dermatoses can affect populations of all backgrounds. However, racial/ethnic variations in epidemiology, clinical features, and associated allergens have been reported. Nuances in the approach to diagnosis, including the assessment of erythema and interpretation of patch tests, are important considerations when treating patients with SOC. Summary: In this review, we outline various manifestations of allergic dermatoses in SOC with a focus on important clinical presentations and diagnostic tools, aiming to support clinicians in accurate recognition of diseases, thereby opening avenues to improve outcomes across diverse skin types. [ABSTRACT FROM AUTHOR]

The article discusses the American Academy of Dermatology Annual Meeting that was held in San Diego, U.S. from March 8-12, 2024. Topics discussed include the efficacy and safety of different treatments for skin conditions like hidradenitis suppurativa and psoriasis. Attendees included experts such as Kimball AB, Papp KA, and Bissonnette R, who presented research findings on treatments like remibrutinib, lutikizumab, sonelokimab, ESK-001, and JNJ-77242113.

Background: Atopic dermatitis is a chronic inflammatory disease characterized by increased itch, skin pain, poor sleep quality, and other symptoms that negatively affect patient quality of life. Upadacitinib, an oral selective Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 than JAK2, JAK3, or tyrosine kinase 2, is approved to treat moderate-to-severe atopic dermatitis. Objective: We aimed to evaluate the effect of upadacitinib on patient-reported outcomes over 52 weeks in adults and adolescents with moderate-to-severe atopic dermatitis. Methods: Data from two phase III monotherapy trials of upadacitinib (Measure Up 1, NCT03569293; Measure Up 2, NCT03607422) were integrated. Changes in pruritus, pain, other skin symptoms, sleep, quality of life, mental health, and patient impression were evaluated. Patient-reported outcome assessments included the Worst Pruritus Numerical Rating Scale, Patient-Oriented Eczema Measure, Dermatology Life Quality Index, Atopic Dermatitis Symptom Scale, Atopic Dermatitis Impact Scale, Hospital Anxiety and Depression Scale, SCORing Atopic Dermatitis index, Patient Global Impression of Severity, Patient Global Impression of Change, and Patient Global Impression of Treatment. Minimal clinically important differences, achievement of scores representing minimal disease burden, and the change from baseline were evaluated in patients who received upadacitinib through week 52 and in patients who received placebo through week 16. Results: This analysis included 1609 patients (upadacitinib 15 mg, N = 557; upadacitinib 30 mg, N = 567; placebo, N = 485). Baseline demographics and disease characteristics were generally similar across all arms. The proportion of patients treated with upadacitinib reporting improvements in itch increased rapidly by week 1, increased steadily through week 8, and was sustained through week 52. Patients receiving upadacitinib also experienced improvements in pain and other skin symptoms by week 1, which continued through week 16; improvements were maintained through week 52. Patient reports of improved sleep increased rapidly from baseline to week 1, increased steadily through week 32, and were sustained through week 52. Patients experienced quality-of-life improvements through week 8, which were maintained through week 52. By week 1, patients in both upadacitinib groups experienced rapid improvements in emotional state, and by week 12, patients also achieved meaningful improvements in anxiety and depression. Improvements in mental health continued steadily through week 32 and were maintained through week 52. Patients treated with upadacitinib 30 mg generally experienced improvements in patient-reported outcomes earlier than those treated with upadacitinib 15 mg. Through week 16, patients receiving upadacitinib experienced greater improvements versus those receiving placebo in all assessed patient-reported outcomes. Conclusions: Adults and adolescents with moderate-to-severe atopic dermatitis treated with once-daily upadacitinib 15 or 30 mg experienced early improvements in itch, pain, other skin symptoms, sleep, quality of life, and mental health that were sustained through week 52. Clinical Trial Registration: ClinicalTrials.gov identifiers NCT03569293 (13 August 2018) and NCT03607422 (27 July 2018). Plain Language Summary: Atopic dermatitis, or eczema, is a condition that causes painful itchy dry skin, which is burdensome for patients and has a negative impact on quality of life. These symptoms frequently lead to disruption of daily activities such as school and work, decreased self-confidence, social isolation, anxiety, depression, and sleep disturbance. Symptoms of atopic dermatitis, such as itch and sleep disturbance, can only be assessed by patients. Therefore, it is important to consider patients' perceptions of their symptoms and the related impact on their quality of life, especially when evaluating treatment benefits. Upadacitinib is an orally administered drug approved to treat moderate-to-severe atopic dermatitis. In two clinical trials (Measure Up 1 and Measure Up 2), we investigated how treatment with upadacitinib (15-mg or 30-mg dose) given once daily to adults and adolescents with moderate-to-severe atopic dermatitis would impact their symptoms and quality of life over a 1-year period. We measured changes over time in patients' assessments of itch, pain, other skin-related symptoms, sleep, daily activities, emotional state, mental health, and overall quality of life. Patients treated with upadacitinib experienced improvements in symptoms of atopic dermatitis and quality of life within the first 1–2 weeks of treatment. These improvements continued to steadily increase in the following weeks and lasted through 1 year of treatment. In conclusion, once-daily treatment with upadacitinib 15 or 30 mg led to early and lasting improvements in the well-being of patients with atopic dermatitis. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic, heterogeneous, inflammatory disease characterized by skin lesions, pruritus, and pain. Patients with moderate-to-severe AD experience chronic symptoms, intensified by unpredictable flares, and often have comorbidities and secondary complications, which can result in significant clinical burden that impacts the patient's overall quality of life. The complex interplay of immune dysregulation and skin barrier disruption drives AD pathogenesis, of which T-cell-dependent inflammation plays a critical role in patients with AD. Despite new targeted therapies, many patients with moderate-to-severe AD fail to achieve or sustain their individual treatment goals and/or may not be suitable for or tolerate these therapies. There remains a need for a novel, efficacious, well-tolerated therapeutic option that can deliver durable benefits across a heterogeneous AD patient population. Expression of OX40 [tumor necrosis factor receptor superfamily, member 4 (TNFRSF4)], a prominent T-cell co-stimulatory molecule, and its ligand [OX40L; tumor necrosis factor superfamily, member 4 (TNFSF4)] is increased in AD. As the OX40 pathway is critical for expansion, differentiation, and survival of effector and memory T cells, its targeting might be a promising therapeutic approach to provide sustained inhibition of pathogenic T cells and associated inflammation and broad disease control. Antibodies against OX40 [rocatinlimab (AMG 451/KHK4083) and telazorlimab (GBR 830)] or OX40L [amlitelimab (KY1005)] have shown promising results in early-phase clinical studies of moderate-to-severe AD, highlighting the importance of OX40 signaling as a new therapeutic target in AD. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD) is a chronic immuno-inflammatory skin disease. Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor approved for the treatment of mild to moderate AD. This post hoc analysis assesses the efficacy and safety of crisaborole in Chinese patients aged ≥ 2 years with mild to moderate AD. Methods: We evaluated the efficacy and safety of crisaborole in Chinese patients from the vehicle-controlled, phase 3 CrisADe CLEAR study. Patients were randomly assigned 2:1 to receive crisaborole or vehicle twice daily, respectively, for 28 days. The primary endpoint was percent change from baseline in Eczema Area and Severity Index (EASI) total score at day 29. Key secondary endpoints were improvement in Investigator's Static Global Assessment (ISGA), ISGA success, and change from baseline in weekly average Peak Pruritus Numerical Rating Scale (PP-NRS) score. Adverse events were documented. Results: Of 391 patients in the overall study, 237 were from China, 157 assigned to crisaborole and 80 assigned to vehicle. A greater reduction in percent change from baseline in EASI total score at day 29 was shown in the crisaborole vs. vehicle group (least squares mean [LSM]: −66.34 [95% (confidence interval) CI −71.55 to −61.12] vs. −50.18 [95% CI −58.02 to −42.34]). Response rates for achievement of ISGA improvement (43.2% [95% CI 35.4–51.1] vs. 33.4% [95% CI 22.5–44.2]) and ISGA success (31.7% [95% CI 24.3–39.0] vs. 21.5% [95% CI 12.1–30.9]) at day 29 were higher in the crisaborole vs. vehicle group. A greater reduction in change from baseline in weekly average PP-NRS score at week 4 was observed in the crisaborole vs. vehicle group (LSM: −1.98 [95% CI −2.34 to −1.62] vs. −1.08 [95% CI −1.63 to −0.53]). No new safety signals were observed. Conclusion: Crisaborole was effective and well tolerated in Chinese patients aged ≥ 2 years with mild to moderate AD. Trial Registration: ClinicalTrials.gov, NCT04360187. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin disease that is associated with anxiety and depression. Few studies have addressed interventions for symptoms of anxiety and depression in this population. To determine the efficacy of interventions for anxiety and depression in patients with AD. PubMed, MEDLINE, EMBASE, and PsycINFO were searched from inception to November 2023. English-language studies published in peer-reviewed journals evaluating the effect of interventions on anxiety and/or depression using validated assessment tools on patients with AD were included. Titles, abstracts, and articles were screened by at least two independent reviewers. Of 1410 references that resulted in the initial search, 17 studies were included. Fourteen of these studies are randomized controlled trials, while the other 3 studies are prospective controlled trials with pre and post-test designs. Data were extracted using a standardized extraction form, and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. To accommodate trials with multiple interventions (each compared to a control group), we conducted a mixed-effects meta-analysis with the trial as a random effect. Prespecified outcomes were changes in symptoms of anxiety and depression in patients with AD as evaluated using standardized assessment tools. Of the 17 studies included in this systematic review, 7 pharmacological intervention studies with 4723 participants examining 5 different medications were included in a meta-analysis. Of these studies, only 1 study evaluated medications prescribed to treat anxiety and/or depression; the rest evaluated medications prescribed to treat AD. Meta-analysis of all the pharmacological interventions resulted in significant improvement in anxiety, depression, and combined anxiety-depression scale scores (standardized mean difference [95% CI]: − 0.29 [− 0.49 to − 0.09], − 0.27 [− 0.45 to − 0.08], − 0.27 [− 0.45 to − 0.08]) respectively. The 10 non-pharmacological studies with 2058 participants showed general improvement in anxiety but not depression. A meta-analysis of the non-pharmacological interventions was not conducted due to variable approaches and limited data. Pharmacological interventions designed to improve AD were found to improve anxiety and depression in patients with moderate-severe disease. More comprehensive studies on non-pharmacological and pharmacological interventions that primarily target anxiety and depression are needed. [ABSTRACT FROM AUTHOR]

Introduction: Treatments for atopic dermatitis (AD) often fail to achieve lasting disease control. In the CrisADe CONTROL phase III study (ClinicalTrials.gov: NCT04040192), participants aged ≥ 3 months with mild to moderate AD treated with once-daily (QD) crisaborole, following initial treatment success with crisaborole twice daily (BID), had longer periods of flare-free maintenance, a higher number of flare-free days, and a lower number of flares compared with those who received vehicle. The study was an exploratory analysis of data on the maintenance of response per Investigator's Static Global Assessment (ISGA; ISGA score of 0 [clear] or 1 [almost clear]) during the CrisADe CONTROL study through week 52. Methods: Exploratory endpoints were the time to ISGA response during the open-label run-in period, and the maintenance of ISGA response and the severity and duration of flares during the double-blind maintenance period. Outcomes were stratified by age (participants aged 3 months to < 12 years and ≥ 12 years) and duration of crisaborole BID treatment (< 4 weeks or ≥ 4 weeks) during the open-label run-in period. Results: During the open-label run-in period, the median time to ISGA response was 41.5 days. From week 4 to week 52 of the double-blind maintenance period, the proportion of participants who maintained ISGA response was greater with crisaborole versus vehicle, and this difference was statistically significant up to week 36 (P < 0.05). Duration of flare periods during the maintenance period were 54.1 and 54.0 days for the vehicle and crisaborole-treated groups, respectively. Numerically fewer crisaborole-treated participants experienced a flare with an ISGA score of ≥ 2 compared with vehicle-treated participants (64.8% vs. 74.4%, respectively). Findings were comparable across most subgroups. Conclusions: Adult and pediatric participants with mild to moderate AD at baseline who had achieved responder criteria (treatment success) with crisaborole BID during the run-in period maintained response per ISGA with crisaborole QD during the double-blind maintenance period through week 52. Trial Registration: ClinicalTrials.gov: NCT04040192. Plain Language Summary: Atopic dermatitis is a skin disease that causes itchy, red, and dry patches of skin that can affect a person for a long time. Current treatments for atopic dermatitis often fail to keep the symptoms under control. Some creams and ointments applied to the skin (known as topical treatments) can ease the discomfort of atopic dermatitis. Crisaborole is a steroid-free ointment that has been shown to improve symptoms of atopic dermatitis in clinical studies. In a study called the CrisADe CONTROL trial, crisaborole was tested to see if it can keep atopic dermatitis symptoms under control. People who participated in the study were aged 3 months and older and they had mild-to-moderate atopic dermatitis. Participants were asked to use crisaborole on their itchy, red, and dry skin twice daily for 8 weeks. Patients were called "responders" if their symptoms became nearly clear or completely clear based on a doctor's assessment called the Investigator's Static Global Assessment, which rates atopic dermatitis between clear to severe. Some responders were asked to use crisaborole once daily for 52 weeks and another group of responders was asked to use a control (an ointment with no medicine) once daily for 52 weeks. Investigators looked at how long the skin remained nearly clear or completely clear during the 52 weeks. Results of this study showed that after initial treatment success with crisaborole twice daily, adult and pediatric participants who had mild-to-moderate atopic dermatitis were able to keep their skin nearly clear or completely clear with crisaborole once daily. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized clinically by pruritus, and pathophysiologically by immune dysregulation, and compromised skin barrier function. While topical therapies are currently the cornerstone of AD management, especially in mild disease, recent advancements in systemic treatments and a deeper understanding of similar skin diseases, such as psoriasis, have highlighted the importance of early intervention. In this commentary, we explore the potential benefits of early systemic intervention in AD, with pruritus determining such a decision. Building on this concept, we assume that, through the timely systemic treatment that targets the immune dysregulation present in AD, the progression of the disease could be modified, improving overall patient outcomes. Early systemic intervention may minimize systemic inflammation, halting the "atopic march" and disrupting the "itch–scratch" cycle. Managing pruritus at its root could prevent secondary complications and reduce the psychosocial burden of the disease. This paradigm shift fosters a collaborative healthcare approach that empowers patients with long-term disease control strategies. In conclusion, the safety and efficacy of novel systemic treatments offer a compelling scenario for early intervention in atopic dermatitis care. [ABSTRACT FROM AUTHOR]

There is a growing awareness among dermatology providers of ocular comorbidities in patients with the chronic inflammatory skin disease atopic dermatitis (AD). For example, the prevalence of ocular surface diseases (OSD) such as conjunctivitis is higher in patients with AD than in the general population, and the use of some AD treatments may be associated with OSD. In a recent review published in the Journal of the American Academy of Dermatology, dermatologists and ophthalmologists provided an overview of the different types, etiology, pathophysiology, and practical management of OSD associated with AD. This review included a suggested treatment algorithm that champions a partnership between dermatology providers and eye care providers for optimal screening, diagnosis, and care. In this podcast article, a dermatologist and ophthalmologist who were authors on this review are joined by a nurse practitioner moderator to discuss how these concepts can be adapted to clinical practice, inclusive of dermatologists, eye care providers, and relevant advanced practice providers. This podcast focuses on the authors' clinical experiences and highlights the key aspects of optimal care, including exploring additional questions to answer with future research. [ABSTRACT FROM AUTHOR]

Atopic dermatitis is one of the most common inflammatory skin diseases among children and adults. Over the last 5 years, the armamentarium for the treatment of this disease, with both topical and systemic drugs, has increased. Treat-to-target is basically the concept where a treatment goal and a time frame for that goal is set at initiation of a new treatment, and if the goals are not achieved in time, treatment will be adjusted. In clinical trials, treatment targets are based on scoring systems for disease severity as recommended by the Harmonizing Outcome Measure for Eczema (HOME) initiative, with the primary endpoint being a reduction of at least 75% of the baseline Eczema Area and Severity Index (EASI) score (EASI-75). The question, however, is if these are useful targets in real-world settings and how this should be implemented in everyday clinical practice. In rheumatology, setting a measurable target and a time frame for an instigated therapy has been shown to lead to more efficient and successful treatment. For atopic dermatitis, the instruments recommended by HOME form the core outcome measures for the treat-to-target frameworks published to date, which are based on expert consensus and Delphi processes. Although atopic dermatitis patients have a high risk of co-morbidities, including physical, psychological and socioeconomic, instruments to measure the severity of co-morbidities have not been included in these existing frameworks. In order to apply a treat-to-target strategy that is meaningful for both the patient and the doctor, validated tools for the measurement of treatment effect on co-morbidities exist and should be included in a shared decision-making process with the individual patient when choosing which targets to aim for and what should be considered treatment success. An obvious limitation for the implementation of a treat-to-target strategy in the clinical setting with atopic dermatitis is that retrieving the data needed is very time consuming. This could to some degree be mitigated by the use of electronic applications in which patients could report their outcomes. [ABSTRACT FROM AUTHOR]

Hormonal and immunologic changes during pregnancy can contribute to the development of different dermatoses, the most common of which is atopic eruption of pregnancy (AEP). Of atopic dermatitis (AD) cases during pregnancy, 80% are new-onset presentations, while 20% represent recurrences or exacerbations of preexisting disease. Evidence on the effects of previous AD on fertility is limited. Different factors influence women's desire to conceive in this setting, and it has been hypothesized that barrier defects and systemic inflammation could contribute to biologic infertility, although more data are needed. Clinical practice suggests a tendency toward undertreatment in pregnant woman due to concerns about potential effects on obstetric and fetal outcomes. However, pregnant women should be offered adequate and safe treatments, preferably on an individual basis. The aim of this review was to summarize the evidence on disease course in pregnant women with AD and the challenges associated with its diagnosis and management. We also review the current evidence on the use of conventional and novel systemic therapies for AD in this population. [ABSTRACT FROM AUTHOR]

For decades, topical corticosteroids have been the mainstay of treatment for mild-to-moderate inflammatory skin diseases, even though only short-term use is approved for these agents and systemic inflammation is not addressed. Increased understanding of the immunopathogenesis of these conditions, especially for psoriasis and atopic dermatitis, has facilitated the development of antibody-based drugs that neutralize single key cytokines or their associated receptors, such as interleukin (IL)-17A/F, IL-23, and IL-17RA in psoriasis and IL-13 and IL-4Rα in atopic dermatitis. However, oral therapy is still preferred by many patients owing to the ease of use and needle-free administration. Phosphodiesterase 4 (PDE4) inhibitors have been approved for both oral and topical use for inflammatory skin diseases. In this review, we present a summary of an emerging class of selective PDE4B/D inhibitors under clinical development and compare the differences in selectivity of this new generation of PDE4 inhibitors with the less selective currently approved PDE4 inhibitors. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a common inflammatory skin disease. Cognitive dysfunction was recently demonstrated to be increased in adults and children with AD. However, little is known about the longitudinal course of cognitive impairment in AD and its relationship with pruritus. To investigate the longitudinal course and predictors of cognitive impairment in AD a prospective dermatology practice-based study was performed using questionnaires and evaluation by a dermatologist (n = 210). Patients with ≥ 2 visits were included (mean follow-up time: 318 days). Cognitive function was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Cognitive Function 8-item Short-Form. At baseline, 20.85% of patients had PROMIS T scores ≤ 45, indicating cognitive impairment (CI). Among patients with CI at baseline, 34.09% had persistent CI, 47.72% had a fluctuating course, and 18.18% had sustained improvement of cognitive function. In repeated-measures regression models, cognitive function scores declined overtime in patients with worse AD severity [SCORing Atopic Dermatitis (SCORAD): p = 0.01, Atopic Dermatitis Severity Index: p = 0.001], increased itch (p = 0.01), skin pain (p = 0.001), and sleep disturbance (p = 0.001). In multivariable logistic regression models, persistent CI was associated with female gender and depressive symptoms [moderate-to-severe Patient Health Questionnaire-9 score (PHQ9)]. Latent class analysis identified two classes of cognitive dysfunction: normal cognition (77.23%), moderate dysfunction (16.21%) and severe impairment (6.55%). Black/African-American race (p = 0.02), moderate-to-severe SCORAD (p = 0.03), dermatology life quality index (p < 0.0001), PHQ9 (p < 0.0001), itch (p = 0.02) and skin pain (p < 0.0001) were more likely to experience moderate dysfunction or severe cognitive impairment. AD is associated with a heterogeneous longitudinal course of cognitive function in adults, with some patients experiencing persistent CI over time. [ABSTRACT FROM AUTHOR]

Little is known about the role nutritional factors play in the pathogenesis of chronic pruritic dermatoses (CPD). In this study, we analyzed nutritional deficiencies in CPD patients compared to matched controls. We conducted a population-based study from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2006. The main outcomes of the study were laboratory data on serum vitamin levels in participants who answered affirmatively to the questionnaires on CPD as well as matched healthy controls. We identified 877 cases of CPD among 9817 adults in the US aged 20 to 59 years. These findings revealed a slightly higher percentage of females with CPD. Low vitamin B6 (OR 0.697; 95% CI: 0.696–0.699, p = 0.025) and vitamin D (OR 0.794; 95% CI: 0.789–0.799, p = 0.037) levels were associated with a higher rate of CPD compared to healthy controls. Our study suggests that low levels of Vitamin B6 and Vitamin D inversely correlates with the presence of CPD. These vitamin deficiencies suggest further studies on the effect of vitamin supplementation may help in patients with CPD. [ABSTRACT FROM AUTHOR]

Climate change has a pervasive impact on health and is of clinical relevance to every organ system. Climate change-related factors impact the skin's capacity to maintain homeostasis, leading to a variety of cutaneous diseases. Stratospheric ozone depletion has led to increased risk of melanoma and keratinocyte carcinomas due to ultraviolet radiation exposure. Atopic dermatitis, psoriasis, pemphigus, acne vulgaris, melasma, and photoaging are all associated with rising levels of air pollution. Elevated temperatures due to global warming induce disruption of the skin microbiome, thereby impacting atopic dermatitis, acne vulgaris, and psoriasis, and high temperatures are associated with exacerbation of skin disease and increased risk of heat stroke. Extreme weather events due to climate change, including floods and wildfires, are of relevance to the dermatologist as these events are implicated in cutaneous injuries, skin infections, and acute worsening of inflammatory skin disorders. The health consequences as well as the economic and social burden of climate change fall most heavily on vulnerable and marginalized populations due to structural disparities. As dermatologists, understanding the interaction of climate change and skin health is essential to appropriately manage dermatologic disease and advocate for our patients. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic or chronically relapsing inflammatory skin disease which results from a complex, multifaceted interaction between environmental factors in genetically predisposed patients. Epidermal barrier impairment, alteration of the cutaneous microbiota, effect of external antigens, neurosensory dysfunction, and inflammatory and immune dysregulation all play a pivotal role in inducing and maintaining AD lesions. AD significantly impacts the patient's quality of life and general well-being and is often associated with anxiety and/or depressive symptoms. Classical treatment options include topical corticosteroids and calcineurin inhibitors, phototherapy, and systemic immunosuppression with oral corticosteroids, cyclosporine, methotrexate, and azathioprine in more severe cases. A turning point in facing AD was accomplished when the efficacy and safety of dupilumab, a monoclonal antibody targeting the interleukin (IL)-4 receptor α subunit, led to its approval for the treatment of moderate-to-severe or severe AD in children, adolescents, and adults. Subsequently, a more extensive understanding of AD etiology and pathogenesis has allowed the development of several topical and systemic novel therapy options. Most of these drugs are monoclonal antibodies which interfere with the type 2 inflammatory cascade, especially its key cytokines IL-4 and IL-13, or its downstream Janus kinase signaling pathway. However, considering the relevance of other subtypes of T helper (Th) cells, such as Th1 and Th22, and the important role of specific cytokines (IL-31) in generating pruritus, the horizon of potential therapeutic targets has widened extremely. In this review, we aim to present the most promising systemic agents currently under investigation and illustrate the most significant aspects of their efficacy, safety, and tolerability. [ABSTRACT FROM AUTHOR]

Objective and design: The hallmark of type 2 inflammation is eosinophilia and/or high IgE serum levels, mostly in atopic dermatitis. Nevertheless, many dermatoses may present similar findings. Our aim is to explore the biological and clinical spectrum of cutaneous manifestations involving tissue and/or systemic eosinophilia, and distinct serum levels of IgE, where atopic dermatitis or other primary allergic eczema, not always is the definitive diagnosis. Materials/methods: A total of 37 scientific papers were enrolled in this narrative review. Results: A diagnostic approach for patients with elevated serum IgE level and a list of conditions not related to atopic dermatitis that runs through inborn errors of immunity, inflammatory disorders, lung disorders, malignancy, infections/infestations are displayed. Regarding to peripheral eosinophilia, differential diagnosis is also explored and clinical patterns of skin diseases associated with tissue eosinophilia are listed, to facilitate our diagnosis. Conclusions: We should maintain a high level of suspicion about other differential diagnosis involving eosinophilia and IgE dysregulation, especially in patients very young (when innate errors of the immunity may present) and in middle to elderly patients classified as having atopic dermatitis, due to the possibility of cutaneous hematological malignancies, paraneoplasia or autoimmune blistering diseases. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is one of the leading burdens of skin disease in children globally. Meteorological factors are involved in the onset and development of AD. Several studies have examined the effects of meteorological factors on AD, but their results are inconsistent, and the understanding of the link between AD and meteorological factors remains inadequate. In this study, a total of 19,702 children aged 0 to 14 visited the outpatient clinic for AD from 2015 to 2019 in Lanzhou, China. A distributed lag nonlinear model (DLNM) applies to evaluate effects of meteorological factors on childhood AD in Lanzhou, China, and further explored age and gender differences. It was found that extremely high or low temperatures, extremely high diurnal temperature range (DTR), extremely low relative humidity (RH), and extremely high wind speed (WS) increased the risk of outpatient visits for childhood AD. Effects of extremely high DTR and extremely high WS were more intense, with maximum cumulative risks of 2.248 (95% CI 1.798, 2.811) and 3.834 (95% CI 3.086, 4.759) at lag 0–21, respectively. Furthermore, the combination of low temperature and low RH can also contribute to the higher risk of childhood AD. For extreme temperatures, children aged 7–14 years were more vulnerable. For extremely low RH, extremely high DTR and WS, boys and children aged 0–3 years were more vulnerable. Public health departments should strengthen publicity and education about how meteorological factors affect childhood AD and develop sex- and age-specific preventative measures. [ABSTRACT FROM AUTHOR]

Introduction: Upadacitinib, an oral, selective Janus kinase inhibitor, is approved in Japan for the treatment of moderate-to-severe atopic dermatitis (AD), a chronic inflammatory skin disease characterized by eczematous morphology and intense itch. Methods: Rising Up is an ongoing phase 3, randomized, multicenter study evaluating the long-term safety and efficacy of upadacitinib in Japan. Patients with moderate-to-severe AD were randomized 1:1:1 to topical corticosteroids plus upadacitinib 15 mg (UPA15), upadacitinib 30 mg (UPA30), or placebo at baseline; at week 16, placebo patients were rerandomized 1:1 to UPA15 or UPA30 (plus topical corticosteroids per investigator discretion). This 2-year interim analysis evaluated safety and efficacy through 112 weeks (data cutoff date: 11 August 2021). Adverse events (AEs), AEs of special interest (AESIs), and laboratory data were assessed. Efficacy assessments included ≥ 75% and ≥ 90% improvement from baseline in Eczema Area and Severity Index (EASI 75/90), achievement of clear or almost clear on the validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD 0/1), and ≥ 4-point improvement in the Worst Pruritus Numerical Rating Scale (WP-NRS). Results: A total of 272 patients were enrolled and 242 were ongoing at data cutoff (UPA15, n = 120; UPA30, n = 122). After 112 weeks of treatment, serious AEs, AEs leading to discontinuation, and most AESIs were generally infrequent, and rates were similar between the two upadacitinib groups. One event each of rectal cancer and cerebellar hemorrhage was reported in the UPA15 group; no thrombosis events were observed. The most common AEs included acne, nasopharyngitis, and herpes zoster. EASI 75, EASI 90, vIGA-AD 0/1, and WP-NRS response rates were maintained through week 112. Conclusion: UPA15 and UPA30 were well tolerated through 112 weeks of treatment with similar safety profiles to short-term studies and demonstrated durable long-term efficacy for the treatment of moderate-to-severe AD in adults and adolescents. Trial Registration: ClinicalTrials.gov identifier, NCT03661138. [ABSTRACT FROM AUTHOR]

Background: Stigma has been recently identified as a crucial factor associated with the psychosocial burden of those who have chronic skin diseases. The self-stigma experiences of children living with atopic dermatitis (AD) have yet to be fully investigated, and questions of how these children respond to public stigma and how AD symptoms further affect their self-stigma experiences remain unresolved. The current qualitative study aimed to (1) describe the main manifestations of self-stigma in children living with AD; (2) investigate factors that might influence their self-stigma experiences; and (3) explore the potential mechanisms underlying the impacts of AD on their psychosocial well-being from the self-stigma perspective. Methods: We performed a secondary analysis of the qualitative literal transcription data which were collected earlier by using the participatory, drawing-based qualitative interviews with 17 children aged 8–12 who were diagnosed with severe or moderate AD. Results: The qualitative findings indicated that the visible and invisible symptoms of AD and its management exerted unique influences on self-stigma in children living with AD, which manifested in cognitive, affective, and behavioral aspects and ultimately affected their psychosocial well-being. Conclusions: Findings of this study allowed us to advocate for eliminating public stigma of people with skin diseases and propose recommendations for helping children living with AD relieve their self-stigma. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is the most common inflammatory skin disease seen in children. It is a heterogeneous disorder, with a variety of associated manifestations and symptoms. Cases may range from mild to severe. As a result, a spectrum of prescription and nonprescription therapies may be utilized when managing this condition. This article provides an extensive overview of these therapies, with equal consideration provided to current, emerging, and alternative options used in the pediatric population. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease that is triggered by intense pruritus, impaired skin barrier function, and immune responses to allergenic substances. Break-through therapies for AD include molecular-targeted drugs and the effective management of severe symptoms of AD. However, patients with clinical improvements may continue scratching owing to the influence of psychological stress, which might lead to quick relapses of stressors and subsequent intensive scratching. New drugs may be ineffective because of such scratching behavior caused by stressors. Therefore, it may be useful to consider adjunctive treatment options that focus on external stressors as triggers of deterioration of AD. We hypothesized that improvement of psychological stress by relieving cervical muscle tension would reduce pruritus and atopic symptoms. Methods: Overall, 21 patients with moderate-to-severe AD were treated to relieve cervical muscular tension using Spineliner SA201, which assists in osteopathic manipulative treatment. We assessed the subjective and objective symptoms of AD, cervical muscle tension, which was evaluated using cervical range of motion (ROM), and psychological burden. Only moisturizers were applied topically during the study period, and no topical corticosteroid therapy was used. Results: Twenty patients who completed the treatment demonstrated improvement in the symptoms of AD: changes on the visual analog scale (VAS) for pruritus were −44.2%, Eczema Area and Severity Index (EASI) was −67.9%, thymus and activation-regulated chemokine (TARC) was −56.2%, Hospital Anxiety and Depression Scale (HADS) was −27.2%, sleep disturbance was −49.7%, and Dermatology Life Quality Index (DLQI) was −46.7%. Additionally, the cervical muscle tension improved significantly: changes in cervical ROM were 14.7%. Conclusions: Release of cervical muscle tension may improve psychological stress and have an effect on moderate-to-severe AD. Plain Language Summary: Atopic dermatitis is a chronic relapsing inflammatory skin disease triggered by intense pruritus, impaired skin barrier function, and immune responses. Standard dermatological therapies for patients with atopic dermatitis include topical glucocorticoid treatments. In some cases, scratching and inflammation could not be adequately controlled, a relapse could not be prevented after remission, and their efficacy is limited. Break-through therapies for atopic dermatitis include new molecular biological drugs, which have demonstrated significantly improved and effective management of severe atopic symptoms. However, patients with clinical improvements may continue scratching owing to psychological stress, which might lead to quick relapses of stressors and subsequent intensive scratching. New drugs may be ineffective owing to such scratching behavior caused by stressors. Therefore, it may be useful to consider adjunctive treatment options focusing on external stressors as triggers for worsening atopic dermatitis. We hypothesized that improvement of psychological stress by relieving cervical muscle tension would reduce pruritus and atopic symptoms. Overall, 21 patients with moderate-to-severe atopic dermatitis were treated to relieve cervical muscular tension using Spineliner SA201, which assists in osteopathic manipulative treatment. We assessed the subjective and objective atopic symptoms, cervical muscle tension, and psychological burden. Only moisturizers were applied topically during the study period, and no topical corticosteroid therapy was used. Twenty patients completed the treatment, atopic symptoms improved significantly, cervical muscular tension improved, and the psychological burden decreased with the treatment. Release of cervical muscle tension may improve psychological stress and affect moderate-to-severe atopic dermatitis. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin condition that can have tremendous impact on quality of life for affected children and adults. First-line therapy for acute management of AD includes topical therapies such as corticosteroids, calcineurin inhibitors, and, more recently, the phosphodiesterase inhibitor crisaborole. Topical agents have remained the mainstay therapy for decades; however, there has been a longstanding need for topical therapies with high efficacy and low risk of adverse effects with long-term use. Given the ongoing advances in understanding the pathogenesis of AD, there are novel targets for pharmacological intervention. We are now in an unprecedented time with more than 40 topical treatments in the pipeline for AD in addition to many developments and treatments on the horizon. This review summarizes selected therapeutic topical agents in later phases of development that target various aspects in the pathogenesis of AD such as Janus kinase inhibition (ruxolitinib and delgocitinib), phosphodiesterase-4 inhibition (roflumilast and difamilast), aryl hydrocarbon modulation (tapinarof), and modulation of the microbiome. We also review novel targeted therapies that are in early phase clinical trials, including AMTX-100, BEN-2293, and PRN473. Preliminary findings on efficacy and tolerability of most of these agents are promising, but further studies are warranted to evaluate the long-term safety and efficacy of these novel agents against the current standard of care. [ABSTRACT FROM AUTHOR]

Atopic dermatitis is a common skin disease characterized by loss of skin integrity. Risk and severity have been associated with genetic variation especially with respect to the filaggrin gene, suggesting the importance of skin barrier function in atopic dermatitis pathogenesis. The keratin protein plays a role in epithelial health but its relationship with disease severity would benefit from further exploration. In this study, we evaluate the association between common keratin 6 variants and severity of atopic dermatitis over time using a Bayesian generalized linear mixed model to account for repeated measures. We identify groups of variants within which individual variants have similar effects on skin repair. Further assessment of the biological mechanisms by which these contribute to repair of epidermis may inform treatment of atopic dermatitis. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a complex and multifactorial skin disease characterized by skin inflammation and intense pruritus. There are many commercially available treatments such as topical corticosteroids and immunosuppressants to treat of AD, but their effectiveness is limited, and frequent use of these treatments can cause serious side effects. Therefore, the development of new therapeutic agents is necessary for the treatment of AD. Hence, an alternative agent that was derived from natural products that are effective and safe for AD treatment was investigated using experimental models. The biological activity of euscaphic acid has anti-inflammatory, anticoagulant, and antioxidant effects. Despite the various biomedical properties of euscaphic acid, its therapeutic effects on AD have not been well studied. In this study, we investigated the effects of euscaphic acid on skin inflammation and pruritus in AD mouse model. The effects of euscaphic acid were investigated in activated human epidermal keratinocytes and leukemia T lymphoblast cell lines, and Dermatophagoides farina extract and 2,4-dinitrochlorobenzene-induced AD mouse model. Euscaphic acid ameliorated AD properties, such as the expression of inflammatory cytokines and activation of transcription factors. In addition, euscaphic acid reduced critical factors for pruritus such as immunoglobulin E hyperproduction, mast cell invasion, and interleukin-33 expression. Taken together, euscaphic acid could be a potent therapeutic agent for the treatment of AD. [ABSTRACT FROM AUTHOR]

Janus kinase (JAK) inhibitors are immunomodulatory agents with broad potential for use within dermatology. However, the US Food and Drug Administration has recently placed additional warning labels on JAK inhibitors given concern for an increased risk of major adverse cardiovascular events, malignancy, venous thromboembolism, and mortality. Here, we summarize recent efficacy and safety data of multiple JAK inhibitors including tofacitinib, upadacitinib, baricitinib, and abrocitinib. JAK inhibitors have high efficacy in treating psoriatic arthritis and atopic dermatitis, but carry an increased risk of venous thromboembolism and cardiovascular events relative to other approved treatments. Here, we provide current considerations on balancing the benefits of JAK inhibitors with potentially serious, but low-absolute risk, safety concerns. [ABSTRACT FROM AUTHOR]

The pathogenesis of atopic dermatitis (AD) and psoriasis (Ps) overlaps, particularly the activation of the immune response and tissue damage. Here, we evaluated galectin (Gal)-1 and Gal-3 levels, which are beta-galactoside-binding proteins with immunomodulatory functions and examined their effects on human keratinocytes stimulated with either interleukin (IL)-4 or IL-17A. Skin biopsies from AD, Ps, and control patients were evaluated using histological and immunohistochemical analyses. Six studies containing publicly available transcriptome data were individually analyzed using the GEO2R tool to detect Gal-1 and Gal-3 mRNA levels. In vitro, IL-4- or IL-17A-stimulated keratinocytes were treated with or without Gal-1 or Gal-3 to evaluate cytokine release and migration. Our findings showed different patterns of expression for Gal-1 and Gal-3 in AD and Ps skins. Densitometric analysis in skin samples showed a marked increase in the protein Gal-1 levels in Ps epidermis and in both AD and Ps dermis compared to controls. Protein and mRNA Gal-3 levels were downregulated in AD and Ps lesional skin compared with the control samples. In vitro, both galectins addition abrogated the release of IL-8 and RANTES in IL-17-stimulated keratinocytes after 24 h, whereas IL-6 release was downregulated by Gal-3 and Gal-1 in IL-4- and IL-17-stimulated cells, respectively. Administration of both galectins also increased the rate of keratinocyte migration under IL-4 or IL-17 stimulation conditions compared with untreated cells. Altogether, the immunoregulatory and migration effects of Gal-1 and Gal-3 on keratinocytes under inflammatory microenvironment make them interesting targets for future therapies in cutaneous diseases. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD) is one of the most common skin diseases, and it may be associated with skin cancer risk. However, there is a controversy pertaining to whether it implies a greater or decreased risk of skin cancers. We aimed to study the relationship between AD and skin cancer risk. Methods: PubMed and Embase databases from their inception to 4 August 2021 were systematically searched. Results: We evaluated 16 studies involving a total of 9,638,093 participants examining the contribution of AD to skin cancers. Random-effects model was applied to estimate the overall effect sizes. The pooled analysis of 16 studies indicated that AD was significantly associated with an overall increased risk of skin cancer. Subgroup pooled analyses showed that AD was statistically associated with an increased risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). With regard to cohort study, AD was statistically associated with an increased risk of nonmelanoma skin cancer (NMSC), BCC, and SCC, but not melanoma risk. Sensitivity analysis revealed that excluding each study in turn did not alter the overall combined results. No publication bias existed among the studies. Conclusion: It can be concluded that AD is associated with risk of skin cancers; however, this association still needs to be verified in well-designed, worldwide trials (especially prospective, non-Western studies). The mechanism of AD leading to skin cancer is not clear, and further research is needed to explore the possibility of a potential pathogenesis. [ABSTRACT FROM AUTHOR]

Selection of appropriate biomarker to identify inflammatory skin diseases is complicated by the involvement of thousands of differentially expressed genes (DEGs) across multiple cell types and organs. This study aimed to identify combinatorial biomarkers in inflammatory skin diseases. From one gene expression microarray profiling dataset, we performed bioinformatic analyses on dataset from lesional skin biopsies of patients with inflammatory skin diseases (atopic dermatitis [AD], contact eczema [KE], lichen planus [Li], psoriasis vulgaris [Pso]) and healthy controls to identify the involved pathways, predict upstream regulators, and potential measurable extracellular biomarkers. Overall, 434, 629, 581, and 738 DEGs were mapped in AD, KE, Li, and Pso, respectively; 238 identified DEGs were shared among four different inflammatory skin diseases. Bioinformatic analysis on four inflammatory skin diseases showed significant activation of pathways with known pathogenic relevance. Common upstream regulators, with upregulated predicted activity, identified were CNR1 and BMP4. We found the following common serum biomarkers: ACR, APOE, ASIP, CRISP1, DKK1, IL12B, IL9, MANF, MDK, NRTN, PCSK5, and VEGFC. Considerable differences of gene expression changes, involved pathways, upstream regulators, and biomarkers were found in different inflammatory skin diseases. Integrated bioinformatic analysis identified 12 potential common biomarkers of inflammatory skin diseases requiring further evaluation. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD) is a chronic, pruritic, inflammatory skin disease with rising prevalence. Topical corticosteroids (TCS) are recommended as first-line therapy for patients with AD in China; however, corticophobia is a widespread concern, which can manifest as noncompliance: in a previous Chinese study, almost all parents whose children had AD were very concerned about the side effects of TCS and, as a result, nearly half did not use it in the event of recurrence. We propose a TCS-sparing treatment algorithm for the management of infants, children, adolescents, and adults with mild-to-moderate AD, to guide clinical practice in China. Methods: A panel of eight experts in AD from China and one expert from Germany formed to develop a practical algorithm for the management of mild-to-moderate AD, focusing on pimecrolimus. Results: Irrespective of body location, all patients with mild AD (including acute flares) and infants with moderate AD should apply the topical calcineurin inhibitor (TCI) pimecrolimus twice daily to the affected area until symptoms disappear. For children, adolescents, and adults with moderate AD, pimecrolimus should be applied twice daily to sensitive skin areas, and a TCI (either pimecrolimus or tacrolimus) should be applied twice daily to other body locations. Short-term administration of TCS, followed by TCI twice daily, is recommended for most patients with moderate AD experiencing acute flares, regardless of lesion site. Emollients should be used regularly. Conclusions: The algorithm presented intends to simplify treatment of AD in China and guide clinical decision-making. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "OX40 in the Pathogenesis of Atopic Dermatitis-A New Therapeutic Target" which appeared in the previous issue of the periodical.

Introduction: Atopic dermatitis (AD) can affect multiple body regions and is especially burdensome when involving exposed skin areas. Rapid, effective treatment of AD across body regions remains an unmet need, particularly for difficult-to-treat areas such as the head and neck area. We investigated the temporal and regional patterns of clinical improvement in AD with the use of abrocitinib, an orally available Janus kinase 1 selective inhibitor under development for the treatment of moderate-to-severe AD. Methods: We performed a post hoc analysis of data from JADE COMPARE, a phase 3, multicenter, randomized, double-blind, double-dummy trial that evaluated the efficacy and safety of abrocitinib 200 mg once daily, abrocitinib 100 mg once daily, dupilumab 300 mg subcutaneous injection every 2 weeks, and placebo in adult patients with moderate-to-severe AD who were concomitantly receiving medicated topical therapy. Assessments included the Eczema Area and Severity Index (EASI) and SCORing Atopic Dermatitis (SCORAD) index. Results: With abrocitinib 200 mg, time to ≥ 75% improvement in EASI (EASI-75) occurred at a median of 29 days across body regions, including the head and neck region. With abrocitinib 100 mg, EASI-75 response was achieved at a median of 30–32 days for the trunk and lower limbs, and at 56–57 days for the head and neck region and upper limbs. With dupilumab, EASI-75 response was achieved at a median of 43 days for the trunk and 57 days for other regions. EASI body region scores significantly improved with abrocitinib 200 mg and 100 mg versus placebo at week 2 (p < 0.0001 for all comparisons). Improvements with abrocitinib were maintained up to week 16. Conclusions: Rapid and persistent improvement in AD across all body regions was observed with abrocitinib treatment. Abrocitinib may be useful in patients with AD that affects difficult-to-treat anatomical areas or who require a rapid response. Trial registration: Clinicaltrials.gov identifier: NCT03720470. Plain Language Summary: Atopic dermatitis (AD) is the most common form of eczema. It is a long-lasting skin disease that often affects multiple body regions. AD may decrease a person's quality of life, especially when it involves skin areas that are visible to others. Quick, effective treatment for AD across multiple body regions is needed, especially in areas that are difficult to treat and/or cosmetically important, such as the head and neck area. Abrocitinib is a medicine taken orally that is being developed to treat moderate-to-severe AD. Researchers analyzed data from a clinical study called JADE COMPARE (Clinicaltrials.gov identifier: NCT03720470). It evaluated the effectiveness and safety of abrocitinib 200 mg taken once daily, abrocitinib 100 mg taken once daily, and placebo (no study medication) plus medicated skin cream in adults with moderate-to-severe AD. Abrocitinib 200 mg and 100 mg significantly improved the extent and severity of AD as assessed by a measure called the Eczema Area and Severity Index (EASI) compared to placebo at week 2. Improvements were maintained for up to 16 weeks. With abrocitinib 200 mg, the time to ≥ 75% improvement in EASI (EASI-75) was approximately 29 days across body regions, including the head and neck region. With abrocitinib 100 mg, this EASI-75 response occurred at approximately 30 to 32 days for the trunk and legs and at 56 to 57 days for the head and neck region and arms. Abrocitinib may be effective in people with AD that affects difficult-to-treat parts of the body or in those who need a fast response. [ABSTRACT FROM AUTHOR]

Introduction: Inflammatory skin diseases are a significant burden on affected patients. Inflammation is caused by various stress factors to the epidermis resulting in, e.g., dryness, redness, and pruritus. Emollients are used in basic therapy to restore the natural skin barrier and relieve symptoms. A systematic review was performed to evaluate the efficacy and safety of ectoine-containing topical formulations in inflammatory skin diseases characterized by an impaired skin barrier. Methods: A systematic review was carried out in PubMed, the Cochrane Library, and Microsoft Academic up to October 2021. Inclusion criteria were ectoine-containing topical formulations (creams, emollients) used for (adjuvant) therapy of inflammatory skin diseases. Clinical studies of any design published in any language were included. Results: A total of 230 references were screened for eligibility, of which six were selected for inclusion in the review (five studies on atopic dermatitis and one study on prevention and management of retinoid dermatitis). The application of topical formulations containing 5.5–7.0% ectoine positively influenced skin dryness and, consequently, pruritus and dermatitis-specific scores in patients with atopic dermatitis. Especially in infants and children, who belong to the most frequently affected group, the formulations were well-tolerated when applied for up to 4 weeks. In studies where ectoine was used as an adjuvant therapy, application was associated with a decreased need for pharmacological therapy and also improved the effectiveness of, e.g., topical corticosteroids. In patients undergoing isotretinoin therapy, ectoine was as effective as dexpanthenol in reducing retinoid dermatitis or improving symptoms. Conclusion: Ectoine is an effective natural substance with an excellent tolerability and safety profile, representing a beneficial alternative as basic therapy or to increase the efficacy of the pharmacological treatment regimen for patients with inflammatory skin diseases, including infants and children. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease often requiring long-term treatment. Crisaborole significantly improved global AD signs and symptoms in 28-day phase 3 studies of patients aged ≥ 2 years with mild-to-moderate AD (Investigator's Static Global Assessment [ISGA] 2 or 3). A post hoc analysis of a long-term, open-label extension study was conducted to assess efficacy and safety trends of crisaborole in patients stratified by the number of initial consecutive crisaborole treatment cycles, defined as the number of treatment cycles completed before achievement of ISGA 0 (clear)/1 (almost clear). Methods: Patients completing phase 3 studies without drug-related safety issues that precluded further crisaborole treatment were analyzed. Patients with ISGA 0/1 at baseline (the end of a 28-day cycle) did not receive crisaborole for the next 28-day cycle (off-treatment), whereas patients with ISGA ≥ 2 received crisaborole for the next 28-day cycle (on-treatment). Patients were stratified by number of initial consecutive crisaborole treatment cycles. Efficacy was assessed by achievement and maintenance of ISGA 0/1, and safety was assessed by incidence of treatment-emergent adverse events (TEAEs) and treatment-related AEs (TRAEs). Results: Overall, 418 patients were included in exclusive cohorts based on number of consecutive on-treatment cycles (1 on-treatment cycle, n = 133; 2 consecutive on-treatment cycles, n = 106; 3 consecutive on-treatment cycles, n = 106; 4 consecutive on-treatment cycles, n = 73). After one to four initial consecutive on-treatment cycles, 77.6, 76.3, 59.4, and 43.1% of patients, respectively, achieved ISGA 0/1. Of these patients, 49.5, 37.8, 44.4, and 45.2%, respectively, maintained ISGA 0/1 at the end of a 28-day cycle off-treatment. Incidence of TRAEs was 4.5, 4.7, 3.8, and 1.4% for patients receiving one to four consecutive on-treatment cycles, respectively. One patient discontinued because of AEs. Conclusion: These results support the efficacious and safe continuous, long-term use of crisaborole for the management of mild-to-moderate AD. Trial Registration: ClinicalTrials.gov: NCT02118766, NCT02118792. Plain Language Summary: Eczema is a skin disease that often requires long-term treatment. Crisaborole ointment improved mild-to-moderate eczema after 28 days of continuous use in two phase 3 clinical trials that included patients aged ≥ 2 years. In the study reported here we tested whether eczema improved with continuous crisaborole use after one to four back-to-back treatment periods, or 28–112 days. Patients who completed either of the aforementioned phase 3 clinical trials were included in this study. Patients received crisaborole for the next 28-day period if they had eczema rashes. Patients with clear or almost clear skin did not receive crisaborole for 28 days. Our study included a total of 418 patients. After one to four treatment periods, 78, 76, 59, and 43% of patients, respectively, had clear or almost clear skin. Of these patients, 50, 38, 44, and 45% still had clear or almost clear skin after stopping treatment for 28 days. Fewer than one in 20 patients had side effects related to crisaborole after one to four treatment periods. The most common side effect at the application site that was related to crisaborole was pain, particularly stinging and burning. Up to one in 50 patients had application site pain. One patient stopped taking crisaborole because of side effects. In conclusion, these results suggest that long-term crisaborole use is effective and safe. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a relapsing or chronic heterogeneous inflammatory skin disorder with a substantial economic and social impact. AD is a multifactorial disease regulated by a diverse set of environmental and genetic determinants. The main factors involved in the pathogenesis of AD are epidermal barrier dysfunction, immune dysregulation, and dysbiosis. Current data have valued interleukin (IL)-13 as conceivably the crucial cytokine in the underlying inflammation of AD. Advances in understanding AD pathophysiology have driven the progress of targeted immunomodulatory treatments for the treatment of AD, including tralokinumab, a selective IL-13 inhibitor. A phase IIb clinical trial showed that a dosing regimen of 150 or 300 mg every 2 weeks effectively treated moderate-to-severe AD in adults with an acceptable tolerability profile. Phase III clinical trials demonstrated that results with tralokinumab in monotherapy were superior to those with placebo at 16 weeks of treatment. It was also well tolerated up to 52 weeks in the vast majority of patients. In addition, in association with topical corticosteroids, tralokinumab was well tolerated and effective and had a favorable risk–benefit profile. These data provide additional evidence that IL-13 is central to AD pathogenesis, suggesting that tralokinumab may be seen as an innovative option for the treatment of moderate-to-severe AD. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a highly prevalent chronic inflammatory skin disease that is characterized by intense pruritus, seriously affecting patients' quality of life. Its pathophysiology, which involves both the adaptive and innate immune responses as well as skin barrier defects, is still poorly understood. We recently identified a microRNA, miR-335, as a key driver of keratinocyte differentiation and cornification, which is essential for the establishment of a healthy skin barrier. However, expression of miR-335 is lost in AD, leading to barrier defect. We further demonstrated how belinostat, a histone deacetylase inhibitor, can effectively restore miR-335 and resolve the barrier defect in a dry skin model. Here, in this commentary, we highlight the role of belinostat in the treatment of AD and discuss the need for more research into crosstalk between epigenetic and non-coding RNA-based regulation, as well as possible therapeutic strategies targeting the epigenome. [ABSTRACT FROM AUTHOR]

Patients with certain inflammatory skin diseases have multiple risk factors for venous thromboembolism (VTE). The objective of the study was to determine whether atopic dermatitis (AD), psoriasis, pemphigus, pemphigoid and/or hidradenitis is associated with VTE in US adults. Data were analyzed from the 2002–2012 Nationwide Inpatient Sample, a representative cohort of US hospitalizations (N = 72,512,581 adults, including 1,389,292 with VTE). In multivariable logistic regression models including age, sex, insurance, household income and race/ethnicity, hospitalization for AD (adjusted odds ratio [95% confidence intervals] 1.22 [1.17–1.27]), pemphigus (1.96 [1.68–2.28]) and pemphigoid (1.64 [1.47–1.83]) was associated with VTE. These associations remained significant in virtually all patient subsets, including males and females, different age groups and those with and without long-term corticosteroid use. In particular, AD, pemphigus and pemphigoid were each associated with DVT and PE. VTE was associated with increased inpatient length of stay, cost of care and mortality across all the inflammatory skin diseases. HS and psoriasis were not consistently associated with VTE. AD, pemphigus and pemphigoid and some subsets of patients with HS were associated with higher odds of hospitalization for VTE. Patients with these inflammatory skin diseases may benefit from increased screening and prevention of VTE. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin disease influencing not only children but also adults. It is well-known that AD has a complex pathogenesis without effective therapy. Herein, we explored the function and mechanism of CYT387, a novel JAK2 inhibitor, on epidermal barrier damage. HaCaT cells exposed with high-concentration Ca2+ (1.8 mM) for 14 days were recruited for the model of keratinocytes (KC). The cell model of skin barrier damage was induced by IL-13, and KC markers such as filaggrin (FLG), loricrin (LOR), and involucrin (IVL) were detected to judge the success of the model. In this study, we found that miR-143 was lowly expressed whereas IL-13Rα1 was highly expressed in blood cells of patients with AD, indicating their negative correlation. Moreover, IL-13 treatment down-regulated miR-143 and up-regulated activated JAK2 and STAT3 phosphorylation, which was reversed by CYT387 administration. The dual-luciferase reporter assay verified that miR-143 could directly bind to 3′-UTR of IL-13Rα1, as well as STAT3. Furthermore, the function of CYT387 in the skin barrier damage induced by IL-13 was abolished by miR-143 inhibitor. Thus, CYT387 might alleviate IL-13-induced epidermal barrier damage via targeting IL-13Rα1 and STAT3 by miR-143 to repress inflammation. These findings revealed that the protective effects and the underlying mechanisms of CYT387 in AD, which provided evidence that miR-143 may be a novel therapeutic target for AD. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin disease with an estimated prevalence of 10–15% in children and 2–10% in adults. Clinically, there is notable phenotypic variability driven by a complex interaction between genetics, immune function, and the environment. Impairment of the skin barrier plays a significant role in the pathogenesis of AD. The apparent beneficial effect of sunlight in patients with atopic eczema is questioned due to its capacity to disrupt the skin barrier and generate free radicals that can damage proteins, lipids, and DNA. The sum of the external factors that an individual is exposed to throughout their lifetime is termed the exposome. Environmental factors such as sun exposure, temperature, and humidity contribute to both AD flares and regional prevalence variation. Literature on photoprotection in atopic dermatitis is very scarce. The use of adequate sunscreens in atopic dermatitis can ensure the level of photoprotection required to prevent skin photoaging and skin cancer and to mitigate skin barrier dysfunction, decrease inflammation, and neutralize facial redness. Herein we discuss and review the role of UV radiation and the exposome in the etiology of AD, as well as the role of adequate photoprotection. [ABSTRACT FROM AUTHOR]

Dr Anne-Claire Fougerousse is Head of Dermatology at the Bégin Hospital in Saint-Mandé, France, and scientific coordinator of a French network of dermatologists and allergists (ResoEczema). The focus of her work is to improve the care of adolescent and adult patients with atopic dermatitis (AD), a chronic, pruritic inflammatory skin disease that substantially impacts patient quality of life. In this interview, Dr Fougerousse provides an overview of the clinical presentation of adult patients with AD and describes available treatments. Today, topical agents like emollients and corticosteroids are the mainstay of AD therapy, and patients with lesions that are resistant to optimally administered topical treatment can also receive phototherapy or systemic therapy with ciclosporin. Dr Fougerousse discusses her hopes for the future of AD therapy with the recent development of biologicals like dupilumab, which may provide improvements in clinical outcomes and quality of life for patients with moderate-to-severe AD. In the next few years, the therapeutic arsenal for AD will likely expand to include more systemic therapies providing sustained symptom control. The real challenge will be to ensure that the maximum number of patients with AD achieve clinical benefits from these new treatments. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD) is a chronic, relapsing, inflammatory skin disease characterized by eczema and pruritus, and frequently impairs sleep quality. Although cyclosporine improves symptoms of AD, objective evaluation of sleep in patients with AD treated with cyclosporine has not been reported. This study was conducted to elucidate the effects of cyclosporine on sleep quality for patients with AD. Methods: Twelve patients with moderate-to-severe AD were recruited. Nocturnal sleep quality was evaluated for 7 days using a sleep analyzer, which patients wore at the waist before and after cyclosporine was administered at 2.0–4.0 mg/kg per day. Seven parameters of sleep quality were measured before and after cyclosporine administration for a period of 7 days for each patient. Results: The administration of cyclosporine significantly improved total sleep time in four cases, sleep latency in two cases, wake after sleep onset in six cases, number of awakenings in two cases, sleep efficiency in seven cases, number of awakenings for more than 8 min in three cases, and number of position changes recorded every 2 min in three cases. The mean values of sleep latency significantly decreased after cyclosporine administration (P = 0.023). The mean value of sleep efficiency significantly increased after the administration (P = 0.002). Conclusion: Cyclosporine improves sleep quality in patients with moderate-to-severe AD. [ABSTRACT FROM AUTHOR]

Introduction: Xerosis and pruritus are common manifestations of numerous dermatologic and systemic diseases. We evaluated the effectiveness of an emollient containing an Aquaphilus dolomiae extract (ADE-G1) for the management of pruritus and xerosis in patients of all age with a range of dermatologic and systemic diseases. Methods: This open-label, real-world study involved 5910 patients from 33 European, South American, Asian, and North and South African countries, who applied the product for 7 days twice daily to the face and body after the skin had been cleansed and dried. The physician assessed xerosis severity and patients assessed pruritus severity, the duration of itch, sleep quality, and the impact of their skin disease on their quality of life, using scales derived from the SCORing Atopic Dermatitis (SCORAD) index and questionnaires, at inclusion and after 7 days of use. Results: The 7-day care regimen resulted in 56% and 60% reductions in xerosis and pruritus severity, respectively, regardless of the underlying pathology (p < 0.0001), with the largest decreases observed for patients with ichthyosis for xerosis and for patients post scabies treatment for pruritus. The mean sleep disturbance and mean total Dermatology Life Quality Index (DLQI) scores were also reduced by 58% and 60% (p < 0.0001), respectively. The emollient was effective whether the product was used alone or in combination with topical or systemic treatments and was well tolerated. Conclusion: Our study shows that the 7-day regimen with the emollient was a universally effective treatment for pruritus and xerosis, regardless of the underlying pathology. [ABSTRACT FROM AUTHOR]

Chronic inflammatory skin diseases (CISD) represent a significant burden of skin disease in the United States, and a growing number of studies demonstrate that CISD are associated with multiple comorbidities. However, few studies examined multimorbidity in adults with CISD. We sought to determine whether hospitalized US adults with chronic inflammatory skin disorders have increased multi-morbidity and mortality risk. Data from the 2002–2012 Nationwide Inpatient Sample were analyzed, including a representative 20% sample of US hospitalizations. Charlson comorbidity index (CCI) and mean estimated 10-year survival were calculated. Multivariable linear regression models were constructed with CCI score and mean estimated 10-year survival as the dependent variables and chronic inflammatory skin diagnosis, age and sex as the independent variables. CCI scores were significantly higher in bullous pemphigoid (P = 0.0005) and dermatomyositis (P < 0.0001), lower in hidradenitis suppurativa (P < 0.0001), pemphigus (P < 0.0001), rosacea (P < 0.0001), and not significantly different in atopic dermatitis, alopecia areata, and lichen planus compared to psoriasis. Conversely, the mean estimated 10-year survival was higher in pemphigus (P = 0.0451), lichen planus (P = 0.0352), rosacea (P < 0.0001), lower in bullous pemphigoid and dermatomyositis (P < 0.0001), and similar in atopic dermatitis, alopecia areata, and hidradenitis suppurativa compared to psoriasis. Each CISD had a distinct profile of comorbidities when compared to psoriasis. Hospitalized adults with multiple CISD have increased multimorbidity and decreased 10-year survival. Further studies are needed to develop multidisciplinary strategies aimed at preventing and treating multimorbidity, especially modifiable cardiovascular factors in adults with CISD. [ABSTRACT FROM AUTHOR]

Epigenetics is the study of heritable changes in gene expression that do not originate from alternations in the DNA sequence. Epigenetic modifications include DNA methylation, histone modification, and gene silencing via the action of microRNAs. Epigenetic dysregulation has been implicated in many disease processes. In the field of dermatology, epigenetic regulation has been extensively explored as a pathologic mechanism in cutaneous T-cell lymphoma (CTCL), which has led to the successful development of epigenetic therapies for CTCL. In recent years, the potential role of epigenetic regulation in the pathogeneses of inflammatory skin diseases has gained greater appreciation. In particular, epigenetic changes in psoriasis and atopic dermatitis have been increasingly studied, with DNA methylation the most rigorously investigated to date. In this review, we provide an overview of DNA methylation in inflammatory skin diseases with an emphasis on psoriasis and atopic dermatitis. [ABSTRACT FROM AUTHOR]

Eosinophilic dermatoses encompass a broad spectrum of diseases of different etiologies hallmarked by eosinophilic infiltration of the skin and/or mucous membranes, with or without associated blood eosinophilia. The wide range of dermatological manifestations of this spectrum, including nodules and plaques, pustules, blisters, ulcers, and urticarial lesions, is reflected in a non-univocal classification system. We identified six groups of eosinophilic dermatoses based on the predominant anatomic level of involvement: (1) epidermal; (2) of the dermal–epidermal junction; (3) dermal; (4) of the hypodermis and muscle fascia; (5) of the pilosebaceous unit; and (6) vascular/perivascular. We review clinicopathologic features and management of diseases belonging to each group, particularly: (1) pemphigus herpetiformis and atopic dermatitis as prototypes of the epidermal group; (2) bullous pemphigoid as prototypic eosinophilic dermatosis of the dermal–epidermal junction; (3) eosinophilic cellulitis (Wells syndrome), hypereosinophilic syndromes, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome, eosinophilic dermatosis of hematologic malignancy and chronic spontaneous urticaria as paradigmatic dermal eosinophilic dermatoses; (4) eosinophilic fasciitis as an eosinophilic dermatosis with predominant involvement of the hypodermis and muscle fascia; (5) eosinophilic pustular folliculitis as a model of the pilosebaceous unit involvement; and (6) granuloma faciale, angiolymphoid hyperplasia with eosinophilia, and eosinophilic granulomatosis with polyangiitis, belonging to the vascular/perivascular group. [ABSTRACT FROM AUTHOR]