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Topical glucocorticosteroids (TCS) and emollients are the mainstay of treatment for atopic dermatitis (AD). In AD, TCS are used to relieve symptoms, manage acute flares and increase the intervals between flares. When they are used appropriately, they are both safe and effective. In cases of severe disease they may be combined with systemic therapies. The appropriate use of the correct TCS is important in optimising efficacy while at the same time limiting adverse effects. Important factors to consider before initiating TCS for AD are: potency, the delivery vehicle, the frequency of application, the duration of treatment, the patient's age and the body surface area to be treated. The correct application of a sufficiently strong TCS for long enough are requirements for optimal outcomes in the management of AD. In order to achieve this, it is necessary to have a basic understanding of the way in which TCS work, how to use them while maximising their benefits and minimising their well-known adverse effects. [ABSTRACT FROM AUTHOR]

Moisturisers improve the barrier function of the stratum corneum by providing it with water and lipids. They therefore form the cornerstone in atopic dermatitis therapy and should be included in management plans. They are important components of both active treatment, maintenance and the prevention of atopic dermatitis flares. A number of studies have shown that they reduce symptoms and signs of atopic dermatitis, including pruritus, erythema, fissuring and lichenification. It is important to recognise, though, that not all moisturisers are the same. As a result, the prescriber should be guided by clinical need, affordability, availability and informed patient choice. [ABSTRACT FROM AUTHOR]

Baricitinib previously demonstrated improvements in itch and sleep disturbance versus placebo in adults with moderate-to-severe atopic dermatitis (AD). Examine if itch and sleep improvements are associated with better quality of life (QoL) and productivity in patients with AD. Data were drawn from BREEZE-AD5 (NCT03435081). Itch and sleep improvement at Week 16 were defined using ≥4-point improvements in the Itch Numeric Rating Scale and ≥1.5 decreases in the number of nighttime awakenings since baseline, respectively. Patients with and without improvements were compared on Dermatology Life Quality Index (DLQI) and Work Productivity and Activity Impairment-AD scores. Changes from baseline were analyzed using ANCOVA with last observation carried forward. Proportions were analyzed using logistic regression with non-responder imputation. Greater proportions of patients with versus without itch improvement indicated no impact of AD on QoL (37.7 vs. 1.8%). Patients with itch improvement had greater decreases in work time impaired (−29.3 vs. −5.6%). More patients with versus without sleep improvement reported no effect of AD on QoL (25.5 vs. 1.1%); patients with better sleep experienced larger reductions in work time spent impaired (−33.3 vs. −6.1%). Patients with AD who experienced itch and sleep improvement had significantly better QoL and productivity. [ABSTRACT FROM AUTHOR]

Introduction: While the efficacy of dupilumab for the treatment of adults with moderate-to-severe atopic dermatitis (AD) has been demonstrated in several clinical trials, patients in such trials may not necessarily reflect the real-world clinical practice setting. This study evaluated the real-world effectiveness of dupilumab in adults with moderate-to-severe AD based on physician global assessment, percent body surface area affected, and patient-reported itch. Methods: From Modernizing Medicine's Electronic Medical Assistant dermatology-specific electronic medical records, adults (≥ 18 years) were identified with a diagnosis of AD and ≥ 1 dupilumab prescription (index event) between 1 April 2017 and 31 January 2019. Three cohorts were identified based on 3-month pre-index (1) Investigator Global Assessment (IGA) score ≥ 3, (2) an itch severity numerical rating scale (NRS) score ≥ 3, and (3) body surface area (BSA) affected ≥ 10%. Changes from pre-index on the outcome within each cohort were evaluated at 4 months post-index. Patients were also stratified for evaluation of outcomes by baseline demographic (sex, age) and prior AD treatments (topical therapy only or no treatment, any systemic therapy). Results: More than 70% of the 435 AD patients with baseline IGA score ≥ 3 improved to an IGA score of ≤ 2 at month 4 post-dupilumab initiation, including 42.8% who achieved IGA 0/1 (clear/minimal). Among 112 patients with a pre-index itch severity NRS ≥ 3, scores were reduced from mean (SD) 7.0 (2.4) pre-index to 2.8 (2.8) at month 4 (p < 0.0001); 70.5% of patients had a reduction ≥ 3 points. In the BSA cohort (n = 387), affected BSA was significantly reduced from a pre-index mean (SD) of 39.3% (26.1%) to 16.3% (21.2%) at month 4 (p < 0.0001). Significant improvements in IGA, itch NRS, and BSA were observed regardless of demographic (age and sex) or clinical characteristics such as treatment history (all p < 0.0001 compared with pre-index). Conclusions: Consistent with outcomes observed in clinical trials, patients treated with dupilumab in real-world clinical settings achieved clinically meaningful improvements in severity and extent of AD and severity of itch comparable to those reported in clinical trials at a similar time point. [ABSTRACT FROM AUTHOR]

The patient-oriented eczema measure: development and initial validation of a new tool for measuring atopic eczema severity from the patients' perspective. We wish to thank the caregivers, and their children with AD, who completed the survey. Figure 2 summarizes the association between AD severity and impact of AD on each decision domain. [Extracted from the article]

Millions of people globally suffer from allergic diseases, and the cases have been rising in the past decades. One of the major manifestations of allergic diseases is itch, which is an unpleasant symptom that triggers the urge to scratch and greatly affects the quality of life. Thus, research on how sensation of itch is detected/transmitted from the contact of the allergen to the nervous system is crucial in mitigating itch. Recent studies have attempted to elucidate the mechanisms of itch in allergic diseases. Here, we aim to review the endogenous mediators released from immune/nonimmune skin cells (that are indirectly involved in the propagation of itch) and the sensory neurons that express receptors for these itch mediators that are associated with direct transmission of itch in cutaneous allergic diseases. As the mechanisms for allergic itch become clearer, new therapeutic approaches to relieve itch are likely to be developed. Recent clinical trials are testing numerous compounds that target the endogenous mediators and their receptors. These studies provide the possibility of more effective itch treatment for allergic diseases. [ABSTRACT FROM AUTHOR]

Background and purpose: Glucosylsphingosine (GS), an endogenous sphingolipid, is highly accumulated in the epidermis of patients with atopic dermatitis (AD) due to abnormal ceramide metabolism. More importantly, GS can evoke scratching behaviours. However, the precise molecular mechanism by which GS induces pruritus has been elusive. Thus, the present study aimed to elucidate the molecular signalling pathway of GS, especially at the peripheral sensory neuronal levels. Experimental approach: Calcium imaging was used to investigate the responses of HEK293T cells or mouse dorsal root ganglion (DRG) neurons to application of GS. Scratching behaviour tests were also performed with wild‐type and Trpv4 knockout mice. Key results: GS activated DRG neurons in a manner involving both the 5‐HT2A receptor and TRPV4. Furthermore, GS‐induced responses were significantly suppressed by various inhibitors, including ketanserin (5‐HT2A receptor antagonist), YM254890 (Gαq/11 inhibitor), gallein (Gβγ complex inhibitor), U73122 (phospholipase C inhibitor), bisindolylmaleimide I (PKC inhibitor) and HC067047 (TRPV4 antagonist). Moreover, DRG neurons from Trpv4 knockout mice exhibited significantly reduced responses to GS. Additionally, GS‐evoked scratching behaviours were greatly decreased by pretreatment with inhibitors of either 5‐HT2A receptor or TRPV4. As expected, GS‐evoked scratching behaviour was also significantly decreased in Trpv4 knockout mice. Conclusion and implications: Overall, the present study provides evidence for a novel molecular signalling pathway for GS‐evoked pruritus, which utilizes both 5‐HT2A receptor and TRPV4 in mouse sensory neurons. Considering the high accumulation of GS in the epidermis of patients with AD, GS could be another pruritogen in patients with AD. [ABSTRACT FROM AUTHOR]

Prurigo nodularis (PN) is a debilitating chronic disease characterized by intense itching and excoriated hyperkeratotic nodules distributed on the trunk and extremities, especially the extensor surfaces. The pathophysiology includes complex and not yet well-understood mechanisms involving inflammation and dysregulation of the nervous system. Currently, there are no approved therapies by the Food and Drug Administration (FDA) and the few treatment approaches for this condition are often ineffective and related to severe side effects. An emerging therapeutic option is dupilumab, a monoclonal antibody for adults and adolescents with moderate-to-severe atopic dermatitis, that inhibits interleukin-4 receptor alpha subunit (IL4-Rα) and the signaling pathways activated by interleukin (IL)-4 and IL-13. These cytokines seem to be involved in the development and perpetuation of PN and other type-2 inflammation diseases. Data on this topic are limited, but the emergent positive effects of this drug, reported in the literature and summarized in this review, suggest that it can be a safe and efficient therapy in PN. [ABSTRACT FROM AUTHOR]

Introduction: Itch is a distressing atopic dermatitis (AD) symptom that impacts quality of life. With the emergence of multiple new agents for the treatment of AD, the ability and speed with which an agent reduces itch may factor in agent selection. Objective: In this study, the primary objective was to quantify the rate at which agents for AD provide itch reduction using the peak itch numerical rating scale (NRS) data from phase II and III clinical trials. Methods: A PubMed literature search was performed in February 2020 to find phase II and III randomized clinical trials for the treatment of AD published from 2014 to 2020. A TIMEACLIR-Itch value was calculated from NRS data to represent the time to meaningful itch reduction. Results: We find a shorter TIme to achieving a MEAningful CLInical Response for itch reduction (TIMEACLIR-Itch) for small molecule inhibitors when compared to biologic agents. We also observe that nemolizumab achieves TIMEACLIR-Itch more quickly than IL-4 or IL-4/13 agents. Conclusion: These findings support the role that IL-31 has in producing itch and the role Janus kinase inhibitors (JAKinibs) play in itch reduction. This comparison of TIMEACLIR-Itch for different treatments may help guide therapy and management for AD patients. [ABSTRACT FROM AUTHOR]

Dupilumab has been shown effective for prurigo nodularis (PN). However, precise data about efficacy of dupilumab as off-label use in PN is missing. We aggregated current evidence to assess efficacy of dupilumab in PN and to identify possible response predictors Five electronic databases were searched. Our primary outcome was improvement in pruritus measured by numerical rating scale (NRS). We collected data on NRS before (NRSpre) and after (NRSpost) the dupilumab therapy and designed two categorical variables: 'NRS_50' and 'NRS_100' defined as whether one patient reaches 50% and 100% reduction of the NRSpre. Secondary outcomes included: time until patient perceived any improvement (Time_First) and time until patient reported absence of pruritus (Time_Final). Data on 45 patients from eleven articles were analyzed. The NRSpre was 8.58 ± 1.89 and the NRSpost was 1.78 ± 2.29. Time_First was 10.15 ± 10.56 weeks, while Time_Final was 19.28 ± 13.71 weeks. 22/45 patients (48.88%) presented with complete resolution (NRS_100) and 37/45 patients (82.22%) had itch half dropped (NRS_50). Time_First was significantly longer in subjects that did not reach NRS_100 (13.13 ± 13.77) than in subjects that did (7.34 ± 7.86, p=.05). Time_First was significantly longer in atopic dermatitis (AD) patients (16.08 ± 16.18) than in subjects without AD (7.02 ± 5.69, p=.01). NRS_50 and NRS_100 presented with a significant association (p=.05) Dupilumab is an effective target-to-treat agent. In comparison with AD, the clinical response to dupilumab initiates later and, two months of therapy are required until significant itch relieves. Complete remission is rarely observed before 4 months of therapy. Notably, AD-related PN patients need longer treatment than non-AD related PN patients to find any relief. Two early signs of improvement are promising predictors of response to dupilumab: The Time_First and NRS_50. What's already known about this topic? Dupilumab has been shown to be an efficacious treatment for prurigo nodularis (PN) However, literature data on this topic are scattered. What does this study add? This work presents the largest cohort of PN patients treated with dupilumab. Our findings demonstrate dupilumab is a novel and effective choice In comparison with atopic dermatitis, the clinical response to dupilumab initiates later. Two months of therapy are required until the itch relieves. Complete remission is rarely observed before 4 months of therapy. Atopic dermatitis-related PN patients need more weeks of treatment than non-atopic dermatitis-related PN patients [ABSTRACT FROM AUTHOR]

Itch, skin pain, and sleep disturbance are burdensome symptoms in atopic dermatitis (AD) that negatively influence a patient's quality of life (QoL). To evaluate the impact of baricitinib on patient-reported outcomes (PROs) in adult patients with moderate-to-severe AD, and explore the association between improvement in key signs and symptoms of AD with improvements in QoL and patient's assessment of disease severity. Data were analyzed from two phase III monotherapy trials (BREEZE-AD1/BREEZE-AD2) in which patients were randomized 2:1:1:1 to once-daily placebo, baricitinib 1-mg, 2-mg, or 4-mg for 16 weeks and assessed using PRO measures. At week 16, baricitinib 4-mg and 2-mg significantly reduced itch severity (Itch Numeric Rating Scale (NRS) (BREEZE-AD1: percent change from baseline −36.6% and −29.4% vs. placebo (–12.0%), p≤.001 and p≤.05; BREEZE-AD2: −47.2% and −46.9% vs. placebo (–16.6%), p≤.001). Baricitinib significantly reduced SCORing AD (SCORAD) pruritus (4-mg in BREEZE-AD1 and 2-mg in BREEZE-AD2) and Patient Oriented Eczema Measure (POEM) itch (both doses). Improvements in skin pain severity and sleep disturbance were also observed. Improvements in AD symptoms showed higher correlations with patients' assessment of AD severity and QoL than improvements in skin inflammation. Baricitinib significantly improved symptoms in patients with moderate-to-severe AD. NCT03334396 (BREEZE-AD1) and NCT03334422 (BREEZE-AD2). [ABSTRACT FROM AUTHOR]

Introduction: As research continues, new drugs will no doubt be added to the current pool of treatments for moderate-to-severe atopic dermatitis (AD). This raises the need for studies to determine prescriber preferences for different pharmacological options and the factors that influence their choice of treatment. Here we aim to explore physician preferences in the systemic treatment of moderate-to-severe AD, identify the sociodemographic characteristics that can influence physician preferences, and evaluate their satisfaction with current AD therapies. Methods: A discrete-choice experiment (DCE) survey was administered to physicians treating patients with AD in Spain. Results were analyzed using a conditional logit model to estimate the relative importance of each attribute and the maximum risk accepted to achieve therapeutic benefit. Results: A total of 28 respondents completed the DCE survey (67.9% female, mean age 45.9 years). Participants identified objective clinical efficacy and risk of severe adverse events (AEs) as the most important attributes, followed by improvement in sleep and pruritus and faster onset of action from the start of the treatment. Respondents gave less importance to mode of administration and therapeutic benefit in other atopic conditions. Respondents were willing to accept an increased risk of severe AEs and mild-to-moderate AEs leading to treatment discontinuation due to intolerance in order to obtain improvements in efficacy, sleep, and pruritus, and long-term clinical benefit. Conclusion: Our findings can help prescribers choose the most appropriate systemic AD therapy. [ABSTRACT FROM AUTHOR]

Background: There is limited knowledge regarding prevalence and characteristics of atopic dermatitis (AD) among young adults in the general population. Objectives: To study AD among young adults in a Swedish population‐based birth cohort, with a particular focus on prevalence, sex differences including risk for AD at different ages, disease course and characteristics of AD at 24 years. Methods: The BAMSE cohort includes 4089 individuals who have been followed regularly from birth to age 24 years regarding AD and atopic diseases. For this study 3055 individuals who answered questions regarding AD at the 24‐year follow‐up were included. All were invited to a clinical examination including skin examination, evaluation by William's criteria and collection of blood for analysis of specific IgE, and 2264 individuals chose to participate. Results: At 24 years, the 12‐month prevalence of AD was 17.8% and more females than males had AD (20.5% vs. 14.8%), P < 0.0001. The point prevalence of ongoing AD at clinical examination was 8.0%. AD severity as assessed by Patient‐Oriented Eczema Measure (POEM) did not differ between sexes. The proportion of adult onset of AD was 16.9% (92 of 543), females 17.3% vs. males 16.4%. More females than males with AD at 24 years reported disturbed sleep due to itch (26.1% vs. 15.5%, P < 0.003). IgE sensitization was less common among females with AD than males with AD (61.3% vs. 79.6%, P < 0.0001). In addition, male sex (female sex being the reference) was associated with increased odds for AD the first year of life (OR: 1.31, 95% CI; 1.10–1.56), and decreased odds of AD in adolescence and young adulthood (OR: 0.66, 95% CI; 0.55–0.80). Conclusions: Atopic dermatitis is a common disease among young adults, and even though more females than males have AD at 24 years, adult onset of AD seems to be equally prevalent among both sexes in young adulthood. [ABSTRACT FROM AUTHOR]

Dupilumab is a monoclonal antibody against interleukins 4 and 13 currently FDA approved for the treatment of moderate to severe atopic dermatitis (AD) in adults and adolescents and severe AD in children aged 6–11 years. It is reported to be safe with the most common side effects described from clinical trials being conjunctivitis, nasopharyngitis and injection site reactions. Outside the clinical trial setting, there is insufficient data on the side effects of dupilumab in adults with AD, and much less among children and adolescents. The aim of this study was to analyze the spectrum of side effects in all patients receiving dupilumab for the treatment of AD and related conditions in a real‐world setting at a single tertiary referral center, and correlate any risk factors for the development of these side effects. A retrospective review of electronic medical records was conducted for all patients who had received dupilumab for a minimum of 2 months for the treatment of AD and related conditions in the department of dermatology at Rashid hospital, Dubai from February 2018 to November 2021. We analyzed the medical records of 128 patients who received dupilumab according to standard age‐related dosing. This included 78 adults (age range 18–81 years) and 50 children and adolescents (aged 6–17 years). There were 73 males and 55 females. The mean duration of dupilumab treatment was 14.9 months. The most common side effects encountered during dupilumab therapy were head and neck dermatitis in 25 (19.5%), conjunctivitis in 20 (15.6%), erythema, pruritus and peeling of skin in 14 (10.9%) and dryness of eyes in 10 (7.8%) patients, respectively. Overall, dupilumab was well‐tolerated in our patient population. Most of the side effects were mild and did not require discontinuation of dupilumab. These findings would enable dermatologists understand the side effects of dupilumab better, resulting in improved treatment plan decisions in clinical practice. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin disease that can significantly affect daily life by causing sleep disturbance due to extreme itching. In addition, if the symptoms of AD are severe, it can cause mental disorders such as ADHD and suicidal ideation. Corticosteroid preparations used for general treatment have good effects, but their use is limited due to side effects. Therefore, it is essential to minimize the side effects and study effective treatment methods. Dendrobium nobile Lindley (DNL) has been widely used for various diseases, but to the best of our knowledge, its effect on AD has not yet been proven. In this study, the inhibitory effect of DNL on AD was confirmed in a DNCB-induced Balb/c mouse. In addition, the inhibitory efficacy of inflammatory cytokines in TNF-α/IFN-γ-induced HaCaT cells and PMACI-induced HMC-1 cells was confirmed. The results demonstrated that DNL decreased IgE, IL-6, IL-4, scratching behavior, SCORAD index, infiltration of mast cells and eosinophils and decreased the thickness of the skin. Additionally, DNL inhibited the expression of cytokines and inhibited the MAPK and NF-κB signaling pathways. This suggests that DNL inhibits cytokine expression, protein signaling pathway, and immune cells, thereby improving AD symptoms in mice. [ABSTRACT FROM AUTHOR]

Summary: Pruritus is a hallmark of atopic dermatitis (AD), which affects disease severity and patient quality of life. In AD uncontrolled with first‐line topical therapies or in moderate to severe AD, systemic therapies are used; however, there is a paucity of head‐to‐head trials comparing the effectiveness of these therapies. The aim of this study was to compare the effectiveness of systemic therapies in relieving pruritus in moderate to severe AD in adults, using a meta‐analysis. The PubMed, EMBASE, Medline and CINAHL databases were searched from inception up to 31 May 2020 for randomized, placebo‐controlled trials investigating the effectiveness of systemic therapies on pruritus with moderate to severe AD in patients aged ≥ 16 years. In total, 26 studies (n = 5190 participants) were identified. Compared with placebo, there was a large and statistically significant (P < 0.001 for all) reduction in pruritus [standard mean difference (SMD); 95% CI] with dupilumab every 2 weeks (−0.88; −1.13 to −0.63), dupilumab every 2 weeks plus topical corticosteroids (−0.77; −0.91 to −0.62), dupilumab once weekly (−0.99; −1.29 to −0.68), dupilumab once weekly plus topical corticosteroids (−0.70; −0.81 to −0.59). There was also a large and statistically significant reduction with ciclosporin (−1.30; −2.34 to −0.26; P = 0.01) and a large, although not statistically significant reduction with azathioprine (−0.85; −2.07 to 0.35). There was a small reduction with both mepolizumab (−0.27; −0.89 to 0.35) and interferon‐γ (−0.31; −0.75 to 0.12). Of the investigational drugs, nemolizumab 2.0 mg/kg was the most effective (−8.13; −9.31 to −6.94). The majority of systemic therapies were superior to placebo in reducing pruritus. In particular, the dupilumab studies consistently showed large improvements in pruritus, while nemolizumab showed the strongest antipruritic effects. However, future head‐to‐head trials are required for conclusive evidence. [ABSTRACT FROM AUTHOR]

Tralokinumab (tralokinumab-ldrm) [Adbry™ (USA); Adtralza® (EU)], a human IgG4 monoclonal antibody that binds specifically to interleukin (IL)-13, is an effective and generally well tolerated treatment option for adult patients with moderate to severe atopic dermatitis who are candidates for systemic therapy. In pivotal phase III trials, subcutaneous tralokinumab improved the clinical signs and symptoms of atopic dermatitis as well as quality of life (QOL). In ECZTRA 1 and 2, tralokinumab monotherapy was superior to placebo in the first 16 weeks of treatment, with improvements in pruritus and sleep scores seen as early as week 1. Many patients who met the criteria for clinical response at week 16 maintained this response at week 52. Tralokinumab was also more effective than placebo when used in combination with 'as needed' topical corticosteroids (TCS) in ECZTRA 3 and 7; most tralokinumab recipients used no or very little amounts of TCS. In an open-label extension trial, tralokinumab provided consistent symptom control over the longer term (up to 2 years). The majority of adverse events with tralokinumab, including injection-site reactions and conjunctivitis, were of mild to moderate severity. The tolerability profile of tralokinumab longer term was consistent with that in the phase III trials. Plain Language Summary: Atopic dermatitis is an ongoing inflammatory skin condition that causes dryness, itching and redness. Standard first-line treatments include moisturizers and medical ointments that are applied directly to the skin. However, topical treatments often fail to adequately control symptoms in patients with moderate to severe disease. More recently, biological therapies have been developed that target the different inflammatory proteins involved in atopic dermatitis. Tralokinumab [Adbry™ (USA); Adtralza® (EU)] is a human monoclonal antibody that targets IL-13, a key protein involved in driving the signs and symptoms of atopic dermatitis. When given alone or together with topical corticosteroids, subcutaneous tralokinumab improves the signs and symptoms of atopic dermatitis in adults with moderate to severe disease and provides consistent long-term disease control. Patients treated with tralokinumab also report improvements in health-related quality of life. Adverse events seen with tralokinumab are generally mild or moderate in severity. Thus, subcutaneous tralokinumab offers a new effective and generally well-tolerated treatment option for adults with moderate to severe atopic dermatitis who require systemic therapy. [ABSTRACT FROM AUTHOR]

The article discusses atopic dermatitis, a common, chronic and often debilitating inflammatory skin disorder with a large burden of its diagnosis and management falling within primary care and new advancements and updates to management are significantly improving the outcomes for patients with this condition. Topics include phototherapy, new advanced therapies dupilumab and upadacitinib for the treatment of atopic dermatitis; and complications and psychological impact of atopic dermatitis.

Introduction: Pediatric atopic dermatitis (AD) leads to a considerable reduction in quality of life for patients and their families. Therapeutic options for pediatric patients with moderate-to-severe disease are limited and treatment is challenging. As little is understood about physician perceptions of pediatric AD in countries with emerging healthcare, we conducted a questionnaire-based study to identify treatment patterns and gaps. Methods: Physicians treating children (aged 6–11 years) and adolescents (aged 12–17 years) with AD in 11 emerging economy countries were interviewed regarding their beliefs and behaviors relating to the disease. Physicians gave an initial assessment of patient disease severity and control, which was then compared with patient records and pre-specified criteria to assess concordance and discordance between physician perception and recorded patient presentation. Results: A total of 574 physicians completed the study, with an assessment of 1719 patients. Only 51% of patients whose disease criteria matched 'severe disease' to pre-specified criteria and SCORing Atopic Dermatitis scores (SCORAD) were also initially identified by physicians as having severe disease. Patients with moderate-to-severe disease experienced flares for an average of 263 days in the preceding year. Ninety and 74% of patients experienced chronic flares and unpredictable flares, respectively. Control of flares could only be achieved within 7 days in 14% (n = 153) of patients. Most physicians listed elimination of skin symptoms as their primary treatment goal, and for moderate and severe cases, 59% and 33% of physicians reported that they were able to achieve this respectively. Nearly 24% and 40% of physicians were slightly dissatisfied with the treatment options for moderate disease and severe disease and severe disease, respectively. Conclusions: AD severity of children (aged 6–11 years) and adolescents (aged 12–17 years) appears to be underestimated by physicians in emerging economy countries. Practical, easy-to-use, and validated objective measures for assessment of disease severity and control, as well as effective use of novel therapies, are essential to ensure that patients are appropriately managed. Plain Language Summary: Atopic dermatitis (AD) is a common childhood disease that occurs in up to 30% of individuals under 18 years of age. Although most forms are mild, more severe disease forms of AD including symptoms such as pruritus, xerosis, lichenification, and excoriation of the skin can cause significant problems, such as lack of sleep, lack of productivity, poor self-image, and mental health disorders among patients. It also places a burden on patients' families, which affects home, school, and work life. In children with moderate-to-severe disease, treatment options are limited especially since doctors may not be keen to prescribe high-dose treatments to children such as potent and super-potent topical corticoid steroids and progress to systemic therapies. Relatively little is understood about how doctors determine whether the disease is mild, moderate, or severe and what they consider to be the best treatment options for patients. Therefore, we conducted a series of interviews with doctors in 11 countries with emerging healthcare to better understand their beliefs and behaviors about treating childhood AD. Our results indicated that doctors tended to underestimate the severity of a patient's disease. Additionally, 59% of doctors felt that they were able to successfully eliminate itching and skin syndrome frequently (that is, in 70% or more of their patients) in patients with moderate disease and 33% of doctors for their patients with severe disease. These results suggest that there are many unmet needs in the treatment of children and adolescents with AD in emerging economies, whose treatment could be further optimized. Improving how doctors measure the severity of a patient's disease should help them select the most appropriate and effective treatments for their patients. [ABSTRACT FROM AUTHOR]

Introduction: Emollients reduce the severity of dermatitis-associated symptoms. Antioxidant supplementation may be helpful to control inflammatory processes and consequential skin damage. The clinical performance and safety of an emollient medical device for topical treatment enriched with antioxidant ingredients in adults with mild-to-moderate dermatitis is presented in this manuscript. Methods: We performed a monocenter, open‐label, uncontrolled clinical trial. Participants applied the product twice a day for 28 days. No other medication or moisturizer was allowed. Changes in dermatitis severity were assessed at days 14 and 28 by study investigators. Subjects self-assessed pruritus, Dermatology Life Quality Index, and product satisfaction. At the end of the study, a global evaluation of the product was done both by patient-reported outcomes and investigators' evaluations. Results: Forty subjects were enrolled in the study (mean age 35 years). Treatment success was achieved in 87.5% of subjects (p < 0.0001) after 28 days. Mean Investigator's Global Assessment (IGA) and Eczema Area and Severity Index (EASI) scores decreased at days 14 and 28 (p < 0.0001). Subjects reported a reduction in pruritus severity and improvement of quality of life (p < 0.0001), along with satisfaction with the product. At the end of the study, skin condition improved in more than 90% of subjects. No safety issues were identified. Conclusion: The medical device studied for topical use in this clinical trial is considered safe and reduces pruritus in adults with atopic and contact dermatitis. [ABSTRACT FROM AUTHOR]

This prospective, 4‐week, placebo‐controlled, cross‐over study aimed to investigate the efficacy of 1% topical κ‐opioid agonist, asimadoline, in a model of canine atopic dermatitis (AD). Fourteen beagles were challenged with house dust mites every 3–4 days for a total of 9 challenges. Severity of dermatitis was assessed, and pruritus was monitored using GoPro HERO cameras. Pruritus scoring was evaluated at 10 time periods; baseline, 4 h post allergen challenge and the last day of the study on Day 28. Scoring was done blindly by personnel using BORIS software. A global subjective score was also given using a visual analogue scale (VAS). A 4‐week washout period occurred and dogs were crossed‐over, the study was repeated, and the results were analysed using combined data. Gel was applied once daily on inguinal area (0.6 ml/dog). ANOVA showed significant effect of time (p < 0.0001) and group (p = 0.0001) on dermatitis scores. Overall, no statistically significant effect on pruritus was found due to a crossing of scores on Day 17. Overtime the placebo scores increased while the active ingredient showed decrease after first 3 weeks. It is concluded that this approach is promising in dogs with AD and longer studies with more frequent application may be beneficial. [ABSTRACT FROM AUTHOR]

Of the 2677 patients who enrolled, 2207 patients completed treatment up to week 52, 1065 patients completed up to week 100, 557 patients completed up to week 148, 362 patients completed up to week 172 and 352 patients completed up to week 204. Of the 2677 patients who enrolled in the OLE, 2207 completed treatment up to week 52, 1065 patients completed up to week 100, 557 patients completed up to week 148, 362 patients completed up to week 172, and 352 patients completed up to week 204. Exposure-adjusted incidence rates of treatment-emergent adverse events (TEAEs) were lower in this OLE vs. the 300 mg qw plus TCS arm of the 1-year CHRONOS trial (167-5 patients per 100 patient-years vs. 322-4 patients per 100 patient-years). Following protocol amendments in June 2017 and January 2018, 114 patients and 272 patients re-entered the trial, respectively; 103 patients in the former group and 207 patients in the latter group had a treatment interruption of > 8 weeks between study week 148 and week 164. Overall, 38 patients discontinued administration of the drug; the main reasons for doing so were the improvement of AD (nine patients), economic issues (seven patients), adverse events (three patients), and lack of sufficient effectiveness (two patients). [Extracted from the article]

Summary: Background: Interleukin (IL)‐31 affects the inflammatory response, is involved in epidermal barrier disruption in atopic dermatitis (AD) and plays a key role in pruritus. Nemolizumab, a humanized monoclonal antibody against IL‐31 receptor A, reduced pruritus in patients with AD after a 16‐week administration period. Objectives: To examine the long‐term effectiveness and safety of nemolizumab in patients aged ≥ 13 years with AD and inadequately controlled moderate‐to‐severe pruritus. Methods: In two long‐term phase III studies, nemolizumab 60 mg every 4 weeks (Q4W) was administered subcutaneously, concomitantly with topical treatments. Study‐JP01 patients received double‐blind nemolizumab or placebo for 16 weeks, and then entered a 52‐week extension period in which all patients received nemolizumab (nemolizumab/nemolizumab and placebo/nemolizumab groups). Study‐JP02 patients received nemolizumab for 52 weeks. Both studies included an 8‐week follow‐up period. Results: Study‐JP01 nemolizumab/nemolizumab and placebo/nemolizumab, and Study‐JP02 nemolizumab groups comprised 143, 72 and 88 patients, respectively. In the nemolizumab/nemolizumab group, there were clinically meaningful improvements from the start of treatment to week 68 in the pruritus visual analogue scale (66% decrease) and Eczema Area and Severity Index (78% decrease). Quality of life (QoL) indicators improved after the first nemolizumab dose; improvements were maintained during the follow‐up period. The long‐term safety profile was consistent with previous studies, with no unexpected late‐onset adverse events. Conclusions: Nemolizumab 60 mg Q4W with concomitant topical treatments in patients with AD and inadequately controlled moderate‐to‐severe pruritus produced a continuous improvement in pruritus, signs of AD, and QoL for up to 68 weeks, with a favourable safety profile. [ABSTRACT FROM AUTHOR]

Background Currently, the genetically engineered drug dupilumab, which was recently registered in Russia and is planned for use, is widely used in the world for the treatment of atopic dermatitis.. Objective Possibility of use of the genetically engineered drug dupilumab for the treatment of atopic dermatitis among adult population. Methods To address the issues of treatment tactics in patients with atopic dermatitis, a 12-week placebo-controlled study of its effectiveness was carried out on two control groups of 45 people each, divided into three subgroups of 15 people (1 subgroup - placebo; subgroup 2 - dupilumab 300 mg subcutaneously 1 time in 2 weeks; subgroup 3 - dupilumab 200 mg subcutaneously 1 time per week). Evaluation of the effectiveness of the treatment of atopic dermatitis with the targeted drug dupilumab was carried out using the following scales: EASI, IGA, NRS, SCORAD, POEM, DLQI, HADS. Results The results of the study show a significant improvement in the symptoms and manifestations of atopic dermatitis according to the SCORAD, EASI-70 and POEM scales. All patients taking dupilumab showed cleansing of the skin, a decrease in the intensity of pain and skin itching, which contributes to an improvement in the quality of life of patients with atopic dermatitis (a decrease in the DLQI value from 12-14 to 6-7), as well as a decrease in the level of anxiety and stress. At the same time, the number of side effects that occur in patients taking dupilumab and placebo is comparable. Conclusion Based on the study and the results of earlier studies of the effectiveness of targeted therapy of atopic dermatitis with the genetically engineered drug dupilumab, it is possible to recommend a regimen for the use of this drug registered in the Russian Federation for the treatment of atopic dermatitis in the adult population: the initial dose of the drug is 600 mg, then 300 mg every 2 weeks with the regular use of moisturizers 2 times a day during the entire period of treatment. In the case of a protracted severe course of the disease, a weekly subcutaneous injection of the drug at a dose of 200-300 mg is possible. [ABSTRACT FROM AUTHOR]

This article discusses the use of dupilumab, a medication typically used to treat atopic dermatitis, in the treatment of dystrophic epidermolysis bullosa (DEB) in a pediatric patient. DEB is a rare genetic disease characterized by skin fragility and blistering. The patient in this case study experienced severe itching and skin lesions, which were not effectively managed with other medications. After starting treatment with dupilumab, the patient experienced a significant reduction in itching and improvement in skin lesions. This case suggests that dupilumab may be an effective and safe treatment option for pruritus in DEB patients. [Extracted from the article]

Itch is a complex symptom that is both common and burdensome in atopic dermatitis (AD). Yet, little is known about the longitudinal course of itch in AD. A prospective, dermatology practice-based study was performed of adults with AD (n = 463). Patients were assessed at baseline and approximately 6, 12, 18 and 24 months. Itch was assessed using Numeric Rating Scale (NRS) average and worst-itch scores, and frequency of itch in the past week. Repeated-measures regression models were constructed to examine itch over time. Overall, 31.5% and 22.5% had moderate (4–6) or severe (7–10) NRS average-itch scores; 27.4% and 36.4% had moderate (4–6) or severe (7–10) NRS worst-itch scores; 12.7% and 62.0% had itch from eczema 3–4 and ≥ 5 days in the past week; 27.4% and 45.1% reported sometimes and often/almost always having itch, respectively. Among patients with baseline moderate (4–6) or severe (7–10) NRS average-itch scores, 21.2% and 16.3% continued to have moderate or severe scores at ≥ 1 follow-up visits. In repeated-measures regression models, persistent NRS average-itch scores were associated with baseline NRS average-itch [adjusted β (95% CI): 0.75 (0.68, 0.82)] and food allergy [− 0.45 (− 0.84, − 0.07)]. Persistent NRS worst-itch was associated with baseline worst-itch NRS [0.73 (0.66, 0.80)] and Medicaid insurance [1.06 (0.17, 1.94)]. AD patients had a heterogeneous longitudinal course with fluctuating and complex overlapping patterns of average- and worst-itch intensity, and frequency. [ABSTRACT FROM AUTHOR]

In chronic pruritic diseases such as atopic dermatitis (AD), pruritus and skin lesions are exacerbated by scratching in clinical and experimental settings. TRPV1 is known to mediate itch and neurogenic inflammation, but the role of TRPV1 in itch‐associated scratching in AD is poorly understood. In this study, we examined the efficacy of cutting off nails and TRPV1 antagonist, ruthenium red (RR) in a murine model of AD induced by DNFB and further investigated the underlying mechanism. Nail clipping or RR could markedly ameliorate the general AD‐like symptoms as manifested by the reduced clinical severity of dermatitis, IgE and Th2‐related cytokine levels, and mast cell degranulation. Moreover, scratching behaviour, the levels of pruritogenic mediators, including HIS, TSLP, IL‐31 and SP, and skin pH and TEWL were all significantly decreased in nail clipping or RR‐treated mice, suggesting a reduction in itch‐associated scratching and skin barrier defects. Immunofluorescence staining and Western blot results revealed that antipruritic effect of nail clipping or RR in AD may be explained, at least in part, by the suppression of TRPV1 activation. In summary, these data show that TRPV1 mediates itch‐associated scratching and subsequent skin barrier defects, suggesting its potential as a therapeutic target in AD. [ABSTRACT FROM AUTHOR]

Background: Itching is considered to be a subjective symptom of the activation of neurosensory structures by different signal molecules and trigger factors. The signaling cascades responsible for it are closely linked to inflammatory processes. This explains why itching also occurs in many inflammatory diseases. One of these signaling cascades is mediated by Janus kinases (JAKs). Recently, it could be shown on a molecular level that Janus kinase 1 (JAK1) directly activates frontal cortex neurons and thus can cause chronic itching. Objectives: This study deals with the influence of different JAK inhibitors (JAKi) on the activity of chip-based neural networks of cultured frontal cortex neurons by investigating neurophysiological activity parameters. This in vitro model provides information on dose-dependent effects of model substances with different specificity regarding the inhibition of different JAKs. Methods: Tofacitinib (pan-JAKi), baricitinib (JAK1/2i), and upadacitinib (JAK1i) in a concentration range from 10 nmol/L to 50 μmol/L were tested in a microelectrode array neurochip culture system. Results: The results show that the inhibition of the neuronal activity of frontal cortex neurons increases with JAK1 selectivity and is dependent on concentration. Conclusion: These observations are supported by data from clinical studies in atopic dermatitis and psoriasis. The clinical relevance of these results must be proven by further clinical studies with subjective and objective parameters for itching. [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]

Atopic dermatitis (AD), driven by interleukins (IL‐4/IL‐13), is a chronic inflammatory skin disease characterized by intensive pruritus. However, it is unclear how immune signaling and sensory response pathways cross talk with each other. We differentiated itch sensory neuron‐like cells (ISNLCs) from iPSC lines. These ISNLCs displayed neural markers and action potentials and responded specifically to itch‐specific stimuli. These ISNLCs expressed receptors specific for IL‐4/IL‐13 and were activated directly by the two cytokines. We successfully innervated these ISNLCs into full thickness human skin constructs. These innervated skin grafts can be used in clinical applications such as wound healing. Moreover, the availability of such innervated skin models will be valuable to develop drugs to treat skin diseases such as AD. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD) is a heterogeneous inflammatory skin disease. A fresh look on the AD pathophysiology has focused on the skin barrier defect and immune dysfunctions. IL-17A and IL-19 seem to play role in AD pathogenesis. Aim: The aim was to investigate associations of SNPs of IL-17A (rs2275913) and IL-19 (rs22431188) with AD features, course and occurrence. Searching for prognostic panels composed of FLG (2282del4, R501X) mutations with IL-17A and IL-19 polymorphisms. Material and methods: Blood samples were collected from 239 patients with AD and 170 controls. Two SNPs, IL-17A and IL-19 and FLG null mutations were analyzed. PCR and RFLP restriction fragment length polymorphism analysis were used. SCORAD score to establish AD severity, VAS to estimate pruritus. Results: None polymorphisms of studied cytokines caused more frequent AD occurrence compared to controls. We found no associations between IL-17A and IL-19 gene polymorphisms and AD severity (respectively p = 0.954; p = 0.498), IgE level (p = 0.707; p = 0.584), VAS (p = 0.953; p = 0.478), concomitant asthma (p = 0.488, p = 0.764). The G/G genotype in IL-17A (rs2275913) occurrence with coexisting 2282del4 FLG gene mutation increased the AD frequency 9 times (p = 0.0266). Conclusions: The SNPs of IL-17A rs2275913 and IL-19 rs22431188 SNP seem not to have influence on AD course and occurrence while studied alone. The coexistence of GG genotype of IL-17A and 2282del4 FLG mutation may play a role as prognostic AD factor. [ABSTRACT FROM AUTHOR]

Introduction: Cutaneous T-cell lymphomas (CTCL) are malignant lymphoproliferative disorders accompanied by persistent pruritus. Pruritogenic role of interleukin-31 (IL-31) has been studied extensively and was proven in atopic dermatitis (AD), while its role in CTCL is still rather vague. Aim: To investigate IL-31 serum level along with IL-31, IL-31 receptor α (IL-31RA) and oncostatin M receptor β (OSMR) skin expression in CTCL and compare it to controls: AD and healthy volunteers. Material and methods: The level of IL-31 in serum was measured using ELISA, while IL-31 and receptors' expression in the skin were measured using immunohistochemistry and correlated with the stage of disease and pruritus severity. Results: Expression of IL-31 and IL-31 receptor in serum and skin were significantly higher in CTCL and AD in comparison to healthy controls. No significant correlation between the IL-31 serum level and pruritus severity in CTCL patients was found. There was also no correlation between IL-31/IL-31RA/OSMR expression in the skin and CTCL pruritus, while IL-31 and IL-31RA in CTCL skin negatively correlated with the stage of disease. Conclusions: Our data indicate that IL-31 does not play a crucial role in pruritus in CTCL but it is rather involved in the pathogenesis of the disease. It seems that IL-31 plays an essential role in the pruritus pathomechanism that is unique to AD. [ABSTRACT FROM AUTHOR]

Introduction: Baricitinib, an oral Janus kinase (JAK)1/JAK2 inhibitor, is indicated in the European Union and Japan for treatment of moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy. In the ongoing, placebo-controlled, phase 3 trial BREEZE-AD5, once-daily oral baricitinib 2-mg monotherapy improved disease in moderate-to-severe AD patients who had an inadequate response or intolerance to topical corticosteroids. This post-hoc analysis aimed to identify responders to baricitinib 2 mg, using a proposed clinical tailoring approach based on baseline body surface area (BSA) affected and early clinical improvement, in BREEZE-AD5. Methods: Classification and regression tree method was used to evaluate baseline predictors for the proportion of patients achieving ≥ 75% improvement in Eczema Area and Severity Index (EASI75) at week 16 among baricitinib 2-mg-treated patients. Two-by-two contingency tables evaluated the association between early response, defined as ≥ 50% improvement in BSA or ≥ 3-point improvement in Itch Numeric Rating Scale from baseline at weeks 4 or 8, and response at week 16 for the proportion of patients achieving EASI75, validated Investigator Global Assessment for AD (vIGA-AD) score of 0 or 1, or ≥ 4-point improvement in Itch (Itch ≥ 4), respectively. Missing data were imputed as non-responder. Results: At week 16, EASI75 and vIGA-AD (0,1) were achieved by 37.5% and 31.7% of baricitinib 2-mg-treated patients with baseline BSA 10–50% compared with 9.5% and 4.8% with BSA > 50%. Early response in skin inflammation or itch at week 4 was associated with corresponding EASI75, vIGA-AD (0,1), and Itch ≥ 4 of 55.4%, 48.2%, and 39.3% at week 16, while early response at week 8 was associated with 66.7%, 56.1%, and 42.1% of patients achieving these endpoints. Conclusion: Baseline BSA of 10–50% and early clinical improvement after 4 or 8 weeks of baricitinib 2-mg treatment may identify patients most likely to benefit from long-term baricitinib 2-mg therapy. Clinical Trial Registration: NCT03435081. Plain Language Summary: Baricitinib is a medication that helps a dysregulated immune system readjust. This leads to improvements in the inflammatory disease atopic dermatitis (AD). Baricitinib is approved for adults with moderate-to-severe AD in over 40 countries. In the ongoing study BREEZE-AD5, baricitinib 2 mg improved moderate-to-severe AD in patients who previously did not respond to or could not tolerate topical corticosteroids. Understanding which patients are likely to benefit most from a medication can improve patient experience with treatment. It can also ensure that only patients who are likely to benefit from a medication are exposed to it. This analysis aimed to identify patients who are most likely to benefit from baricitinib 2 mg in BREEZE-AD5, using an approach based on baseline body surface area (BSA) affected and early clinical improvement. We showed that patients with moderate-to-severe AD affecting between 10% and 50% of their BSA account for the majority of patients who respond to baricitinib 2 mg after 16 weeks of treatment. Clinical assessment of skin inflammation or itch in patients after 4–8 weeks of initiation of baricitinib 2-mg treatment further improved the ability to identify patients who are most likely to benefit from long-term therapy. This proposed clinical tailoring approach of baseline BSA of 10–50% and early clinical improvement after 4 or 8 weeks of baricitinib 2-mg treatment may allow for the treatment of patients who are most likely to respond to therapy, and rapid decision on discontinuation of treatment for those who are not likely to benefit from baricitinib 2 mg. [ABSTRACT FROM AUTHOR]

Background: Many patients with chronic itch and atopic dermatitis (AD) or psoriasis do not receive/use available medical and psychosocial treatments properly due to system, provider and/or patient factors. Objective: An educational website (ITCH‐RELIEF) to improve itch‐related quality of life (QoL) for adults with AD or psoriasis and chronic itch was developed and assessed. ITCH RELIEF stands for Interactive Toolbox of Comprehensive Health Resources to Enhance Living with Itch – Educational Facilitation (for Adults). Methods: Single‐arm pre‐ and post‐test design with 1‐month follow‐up (N = 137 at baseline). Results: There was statistically and clinically significant improvement in the primary outcome of itch‐related QoL impairment as assessed by the ItchyQoL from baseline [M = 78.9, 95% confidence interval (CI) = 75.9, 81.9] to follow up (M = 75.4, CI = 72.4, 78.5), P = 0.007, as well as statistically significant improvement in several itch‐related secondary outcomes (all Ps < 0.05). Conclusions: This study demonstrated initial effectiveness of an online intervention to improve itch‐related QoL among individuals with AD or psoriasis and chronic itch. Future studies should address limitations by randomizing more heterogeneous participants, utilizing a longer follow‐up and assessing medication use. [ABSTRACT FROM AUTHOR]

In the last decade, there has been an increase case of atopic dermatitis (AD) worldwide. AD is a type of disease with chronic inflammation of the skin characterized by mild to severe itching, recurrent, and mostly occurred in infancy and childhood. There were some substantial data of patients with AD that have been disturbed and less diverse skin and gut microbes than healthy individuals. In the skin microbiome, AD is known to possess a larger percentage of Staphylococcus aureus (S. aureus) than healthy individuals. In addition, the population of Staphylococcus aureus, Clostridium difficile, and Escherichia coli in the gastrointestinal tract of patients with AD is higher than normal individuals, whereas the population of Bifidobacteria, Bacteroidetes, and Bacteroides are experiencing a decrease. The AD will be prevented or treated if there is a balance in the skin and gut microbiome. It seems to underlie the benefit of probiotic in AD management. [ABSTRACT FROM AUTHOR]

Data from real-world use of new systemic treatments in atopic dermatitis (AD) is important for assessing safety and efficacy. The aim of this study is to describe the baseline characteristics of adult patients with moderate-to-severe AD enrolled in the Danish nationwide Severe and ChRonic Atopic dermatitis Treatment CoHort (SCRATCH) database, between October 2017 and August 2021. A total of 282 adult patients were included. Most (62%) were men, the median age at baseline was 43 years (interquartile range (IQR) 29-54 years), and median age at onset of AD was 1 year (IQR 0-6 years). The median Eczema Area and Severity Index at treatment initiation was 19.1 (IQR 11.9-25.7); median Patient Oriented Eczema Measure 21.0 (IQR 16.0-25.0); median Dermatology Life Quality Index 13.0 (IQR 7.0-19.0); and median itch and sleep numerical rating scale scores 8.0 (IQR 6.0-9.0) and 6.0 (IQR 4.0-8.0). Differences were found between the sexes. This registry will provide a source for future efficacy and safety studies. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is characterized by chronic, eczematous, severe pruritic skin lesions. The knowledge on the pathogenesis of AD is driving the development of new drugs. From the research results, it has been revealed that Th2 cell-mediated immunity, skin barrier dysfunction, and pruritus cause a vicious cycle of AD. On the other hand, the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway are one of the essential signaling pathways in various inflammatory diseases including AD. In particular, TSLP, IL-4, IL-13 and IL-22 occupy an important position for Th2 cell-mediated immune reaction. Moreover, experimentally pan-JAK inhibitor suppress the STAT3 activation and improved the skin barrier function. Furthermore TSLP, IL-4, IL-13 and IL-31 contribute a lot to chronic pruritus of AD, and transmitted via JAK-STAT pathway. Therefore, JAK inhibitors are promising candidates for the treatment of severe AD. Here we review clinical trials of topical dergocitinib; a pan-JAK inhibitor, ruxolitinib; a JAK1 and JAK2 inhibitor, and tofacitinib; a JAK1, JAK2, and JAK3 inhibitor and oral baricitinib; a JAK1 and JAK2 inhibitor, abrocitinib and upadacitinib; JAK1 inhibitor. Significant improvements in the symptoms were obtained by each drug with low frequency of adverse events. In particular, oral JAK inhibitors have the ability to improve the pruritus and skin symptoms quickly. Therefore, the emergence of these topical and oral JAK inhibitors would be regarded as an innovation in the treatment of atopic dermatitis. [ABSTRACT FROM AUTHOR]

Antihistamines are widely used drugs in pediatric population. First-generation antihistamines have been in use since last many years, though adequate data on their efficacy and safety in pediatric population is scarce. In contrast, second-generation antihistamines have been studied extensively in children and have a better safety profile with more receptor selectivity and less adverse effects. Pruritus has a significant impact on the quality of life in children and its management is of paramount importance. This article reviews the first and second-generation antihistamines in the light of recent advances in the understanding of their pharmacological properties and safety profile in children. An extensive literature search was done; all clinical trials, randomized double-blinded or single-blinded controlled trials, open-label studies, retrospective studies, reviews, case series, and case reports focusing on the use of antihistamines in pediatric age groups were screened. The selected articles were retrieved; the final manuscript was prepared, analyzed, and presented in a narrative fashion. [ABSTRACT FROM AUTHOR]

Introduction/Background Itch, scratch and poor sleep are often cited as key symptoms of Atopic Dermatitis (AD). Although approximately 10-41% of children and 7-48% of adults in the general population experience sleep disturbances, this figure climbs to 47-80% in children with AD and 33-90% in adults with AD (Bawany et al., 2021). While great effort has been done to characterize and validate nocturnal scratch and sleep, the relationship between the two remains poorly characterized. Objectives: We hypothesize that nocturnal scratch is the reason for the sleep disturbances in patients with AD. Literature suggests that these symptoms are linked, albeit not necessarily causal. Here we investigate the interaction between nocturnal scratch events and sleep disturbances in study participants with AD compared to a healthy cohort. Methods: Patients with AD (n=185) and without AD (n=40) aged between 2 to 75 years were recruited across three different studies. Study participants spent the night in a qualified sleep lab while being under observation with thermal videography and polysomnography (PSG). The thermal videography was annotated for both scratch and non-scratch movements by two trained annotators independently with any conflicts being resolved by an arbitrator. The PSG was scored by a credentialed technologist in 30-s epochs per revised American Academy of Sleep Medicine scoring guidelines. The study participants also wore a wrist-worn accelerometer on both the left and right wrists. Results: It was noted that sleep disturbances were associated with the observed scratch events, and that the temporal relationship between sleep disturbance and scratching seemed to differ between the AD and healthy cohorts. Surprisingly, however, it was also noted that within a few study participants with AD, scratch events occurred while the patient was in stable REM sleep, most often in the children with AD. Further investigation will provide additional information as to whether this was an artifact or in fact a true observation. We also present an overview of sleep, as well as nocturnal scratch and non-scratch movements in the AD and healthy cohorts, noting specifically how the behaviors differ between the groups, and over the course of the sleep opportunity, across sleep stages and sleep cycles, as well as their relationships to sleep disturbances. Conclusions: Nocturnal scratching is often associated with sleep disturbances in AD; however, the causality is not always clear. Moreover, in some cases scratching was observed during stable REM sleep in AD, an observation that requires further investigation. [ABSTRACT FROM AUTHOR]

Introduction Interleukin 25 (IL-25) is an alarmin that binds to its receptor composed of IL-17RA and IL-17RB and is known to induce the production of type 2 cytokines, leading to T helper type 2 (Th2) inflammatory responses. Atopic dermatitis (AD) is an autoimmune and chronic disorder that causes inflammation, dryness, redness and irritation of the skin. It is well-documented that upregulated IL-25 expression is tightly correlated with the disease severity of AD patients, suggesting that the IL-25 pathway is a potential therapeutic target of AD. SM17 is a humanized antibody of the IgG4/kappa isotype targeting the IL-25 pathway via specific binding to IL-17RB, a co-receptor for IL-25 expressed on the surface of ILC2 cells, dendritic Cells, fibroblast and epithelial cells. Therefore, we hypothesize that SM17 might serve as a potential therapeutic treatment for AD. Objectives: The current study aims at investigating if blockage of IL-25 pathway through SM17 administration could ameliorate AD associated inflammation, skin pathology and pruritus. Methods: To provide first evidence that SM17 could improve skin conditions, PBMCs from healthy individuals were pretreated with a cocktail of alarmins comprising IL-25, IL-33, and TSLP with or without SM17, and the mixture was co-cultured with the fully differentiated human keratinocyte cell line HaCaT in a transwell system for five days. Filaggrin level in HaCaT cells was used as an indicator for skin health. Beneficial effects of SM17 in AD was further tested in the 1-Fluoro-2,4-dinitrobenzene (DNFB) induced AD mouse model. DNFB and SM17 were administrated to the animals once per week and tissues were harvested after a month. Single cells were isolated from submental lymph nodes for ex-vivo culture while both dorsal skin and ear were collected for histological and biochemical analyses. In vivo efficacy of SM17 was further compared with upadacitinib, a JAK1 inhibitor currently approved by the FDA for the treatments of adults and adolescents aged 12+ years with moderate to severe AD, via behavioral, histological and biochemical analyses. Results: We first demonstrated that SM17 could potentially ameliorate the skin condition by upregulating the filaggrin levels in keratinocyte during Th2 inflammatory responses in vitro. In the DNFB induced AD mouse model, SM17 could improve the skin conditions in both ear and dorsal skin through attenuation of Th2 cytokine levels in submental lymph node and skin samples, and reduce infiltration of mast cell and eosinophil, while upregulating filaggrin expression in the skin layer. Weekly administration of SM17 provided similar efficacy as upadacitinib (5 doses/week) to suppress DNFB induced scratching behavior, thickening of skin and ear, and global induction of Th2 inflammatory responses in multiple tissues. Conclusions: In summary, these in vitro and in vivo data indicate that blockade of IL-25 pathway by SM17 could suppress Th2 mediated inflammatory response and ameliorate the AD pathology similar to that of upadacitinib, probably with a superior safety profile as demonstrated in our Phase I clinical trial (ClinicalTrials.gov Identifier: NCT05332834), where good safety profile and tolerability were observed with no reported cases of severe TEAE. We believe that SM17 could serve as a potential therapeutic treatment for AD in the future. [ABSTRACT FROM AUTHOR]

Our previous studies have shown that the Qingre Qushi (QRQS) formula can treat atopic dermatitis (AD), and its possible mechanism is related to the regulation of the IL-33/ST2 signaling pathway. However, the molecular mechanism of AD is complex, and various AD subtypes respond better to therapies aimed at distinct targets. This study aimed to investigate the multi-target mechanism of QRQS using experimental and network pharmacology studies. Flaky tail (FT) mice were treated with different concentrations of QRQS and cetirizine. The dermatitis score, scratching frequency, and histological evaluation were normatively evaluated. The levels of IgE and IgG1 in serum were tested using ELISAs. Using ELISA and RT-PCR, the expression of associated cytokines was determined. IL-17A-stimulated HaCaT cells were treated with QRQS to assess mRNA and protein expression. To elucidate the mechanism, a network pharmacology analysis based on active components derived from UPLC was conducted. Through molecular docking, we evaluated the binding affinity between the active constituents of QRQS and potential targets. Using UPLC, 177 active ingredients in QRQS were identified. Network pharmacology analysis showed that the anti-AD effect of the active ingredients was related to the IL-17 signaling pathway and its related targets. FT mice are characterized by Th17-dominated immune disorders. QRQS ameliorated AD-like symptoms and decreased dermatitis scores and scratching frequencies. After QRQS treatment, IL-17A expression was inhibited and IL-17 pathway-associated cytokines were downregulated. Along with changes in Th17-differentiation, QRQS suppressed the expression of IL-4, IL-13, and TNF-α. QRQS also decreased the expression of IL-6, IL-8, and COX-2 in HaCaT cells exposed to IL-17A. The anti-AD active doses are 3.86 g/kg/day in vivo and 100 μg/mL in vitro. QRQS has a multi-target immunoregulatory effect on AD and can improve the Th17-dominated inflammatory response by regulating the IL-17A signaling pathway. Quercetin, genistein, luteolin, and kaempferol are potential active ingredients. [Display omitted] [ABSTRACT FROM AUTHOR]

Phosphodiesterase 4 (PDE4) inhibitors are expected to exhibit efficacy against inflammatory diseases due to their broad pharmacological activity. The launched PDE4 inhibitors apremilast, crisaborole, and roflumilast have not exhibited sufficient inhibitory potential due to poor margins of effectiveness and tolerability. In this report, we describe the non-clinical efficacy, brain translocation, and vomit-inducing effects of ME3183 compared with apremilast. ME3183 showed extensive cytokine suppression in vitro studies using human peripheral blood mononuclear cells and T cells. ME3183 also significantly suppressed skin inflammation in a chronic oxazolone-induced dermatitis model and showed antipruritic effects in a substance P–induced mouse pruritus model. In these in vitro and in vivo studies, ME3183 also significantly suppressed cytokines, and focusing on tumor necrosis factor-α as a psoriasis-related cytokine and interleukin-4 as an atopic dermatitis–related cytokine, ME3183 potently inhibited both cytokines. ME3183 showed in vivo efficacy at lower doses than apremilast. The brain distribution of ME3183 was sufficiently low in mice and rats. The effective dose of ME3183 for emesis was similar to that of apremilast in ferrets. Given its high-potency inhibitory effects, ME3183 would have a wide margin of efficacy and tolerability. These wide margins demonstrate the effectiveness of ME3183 in treating many inflammatory diseases, such as psoriasis and atopic dermatitis. An on-going phase 2 trial is expected to further demonstrate the efficacy and safety of ME3183. [ABSTRACT FROM AUTHOR]

Aims/Purpose: Atopic Dermatitis (AD) is a common inflammatory skin disease that often begins in early childhood and may continue into adulthood. AD severity, and comorbid bronchial asthma and rhinitis have been associated with increased prevalence of Ocular Surface Diseases (OSD) in AD patients (1). OSD is common in the general population and symptoms from the ocular surface do not always lead to examination and diagnosis by healthcare professionals. The purpose of this study was to investigate the occurrence of self‐reported symptoms from the ocular surface in AD patients compared to the population without AD. Methods: A questionnaire study was conducted as a part of project FOREVER (Finding Ophthalmic Risk and Evaluating the Value of Eye exams and their predictive Reliability) to examine the relationship between eye and overall health in Danish citizens. Symptoms related to the ocular surface included tearing, blurred vision, red, itching, burning, gritty, and dry eyes. Logistic regression models were used to investigate associations between AD and the occurrence of symptoms related to the ocular surface. Results: 36874 people had completed the FOREVER questionnaire. 797, 3305 and 32 772 participants answered that they have current AD, previously had AD, and never had AD, respectively. 69% (550/797) and 67% (2201/3305) in the group with current AD and previous AD experienced one or more ocular surface symptoms compared to 60% (19 517/32 772) in the non‐AD group. The odds ratio of AD and ocular surface symptoms was 1.27 [1.09–1.48] (p < 0.01) and 1.17 [1.08–1.26] (p < 0.001) for current and previous AD when adjusting for age, sex, smoking status, and atopic comorbidities; bronchial asthma and rhinitis. Conclusions: Our study found that participants with AD from the FOREVER cohort reported a higher occurrence of OSD symptoms compared to participants who have never suffered from AD. This suggest that AD patients are at higher risk of developing OSD symptoms. Reference 1. Rønnstad ATM, Hansen PM, Halling AS, et al. Factors associated with ocular surface disease and severity in adults with atopic dermatitis: a nationwide survey. J Eur Acad Dermatol Venereol. 2022;36(4):592–601. [ABSTRACT FROM AUTHOR]

Previously, we have reported short term effectiveness and safety of dupilumab in Korea. In this study, we are trying to report the long-term effectiveness and safety of dupilumab in Korea. Ninety-nine patients with moderate to severe AD were analyzed. They were evaluated using Eczema Area and Severity Index (EASI), Numerical Rating Scale (NRS), Patient Oriented Eczema Measure (POEM), and Dermatology Quality of Life Index (DLQI) at baseline, week 16, 32 and 52. Efficacy outcomes showed higher improvement at 52 weeks compared with 16 weeks; high percentual reductions in EASI (88.1%), peak pruritus NRS (65.6%), POEM (67.2%), and DLQI (69.0%) compared to baseline. Proportion of patients achieving EASI 75 and 90 were 90.2% and 53.7%. POEM and DLQI had high correlation with clinical measured outcomes. In the analysis for the factors affecting achievement of EASI 90, female gender (OR 2.5), eosinophilia (OR 0.2) and elevated LDH (OR 0.07) were significantly associated. Most frequent adverse events included facial erythema (19.2%) and conjunctivitis (17.2%), which were mild/moderate and resolved during treatment. In conclusion, dupilumab treatment for 52 weeks in Korean patients with moderate-to-severe AD confirmed long term effectiveness and safety. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD), a predominantly type 2 inflammatory skin disease, affects approximately 2–5% of adults, with a high burden of disease. In moderate-to-severe AD, lesions can be extensive and pruritus intense with patients experiencing skin pain, sleep and mental health disturbances, and diminished quality of life (QoL). Methods: The objective of this study was to evaluate the efficacy of dupilumab for the treatment of AD from the patients' perspective using patient-reported outcome data from four clinical trials (CHRONOS, SOLO 1&2, and CAFÉ) in patients (N = 1553) receiving either the approved 300 mg q2w dupilumab with/without topical corticosteroids (TCS) dose or control (placebo or placebo + TCS). Patient Global Assessment of Disease Status (PGADS) was used to measure patients' well-being and Patient Global Assessment of Treatment Effect (PGATE) was used to measure treatment efficacy. Patients were asked "Considering all the ways in which your eczema affects you, indicate how well you are doing" to assess their perception of well-being and "How would you rate the way your eczema responded to the study medication?" to assess their perception of treatment effect. Possible responses for both metrics included poor, fair, good, very good, and excellent. Results: In all four studies, a significantly higher proportion of dupilumab-treated patients reported "Good"/"Very Good"/"Excellent" disease status from week 2 through study end versus control (CHRONOS, 52 weeks: 69.8% vs. 25.1%; SOLO 1&2, 16 weeks: 59.5% vs. 24.6%; CAFÉ, 16 weeks: 84.1% vs. 45.4%; all P < 0.0001), and significantly more dupilumab-treated patients reported "Good"/"Very Good"/"Excellent" treatment efficacy versus control (CHRONOS: 72.6% vs. 24.8%; SOLO 1&2: 65.0% vs. 21.1%; CAFÉ, 16 weeks: 85.0% vs. 36.1%; all P < 0.0001). Conclusion: Adult patients with AD perceived that dupilumab with/without concomitant TCS was highly efficacious and improved overall disease status and well-being as early as week 2 and throughout treatment periods up to 1 year. 54JKTqmo75hYgJCC19i13y Video Abstract (MP4 90521 kb) [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is a chronic, pruritic, immune‐mediated inflammatory disease. Developments in basic science and clinical research have increased our understanding of AD. Although pain as a symptom of AD is underemphasized in previous studies, multiple researchers address pain as a frequent burden of AD. However, the exact role of pain in AD is not fully understood. Aims: Our review aimed to summarize the current evidence focusing on characteristics, mechanism, and management of pain in AD. Materials & Methods: We conducted a thorough literature review in the PubMed database to figure out different aspects discussing pain in AD, including pain symptoms, burden, the relationship between pain and itch, mechanism, and pain management in AD. Results and Conclusion: AD patients affected by skin pain vary from 42.7%‐92.2% with remarkable intensity and heavy burden. Skin pain and itch interacted both in symptoms and mechanisms. Atopic skin with the impaired barrier, neurogenic inflammation mediators, peripheral and central sensitization of pain may possibly explain pain mechanism in AD. Future research is needed to clarify the commonality and disparity of pain and itch in AD in order to seek efficacious medications and treatment. [ABSTRACT FROM AUTHOR]

Glial cells are non-neuronal cells in the nervous system that are electrically nonexcitable and outnumber neurons in humans. Glial cells have attracted attention in recent years for their active involvement in the regulation of neuronal activity, suggesting their contribution to the pathogenesis and progression of neurological diseases. Studies have shown that astrocytes, a type of glial cell, are activated in the spinal cord in response to skin inflammation and contribute to the exacerbation of chronic itch. This review summarizes the current knowledge about the role of astrocytes and other glial cells in the modulation of itch processing and the mechanism of their activation under itch conditions. [ABSTRACT FROM AUTHOR]

Pruritus is a skin-specific sensation that is observed in various skin diseases, especially in inflammatory skin diseases such as atopic dermatitis, and is deeply involved in their pathogenesis. Pruritus also adversely affects patients' sleep and mental health, placing a heavy burden on daily life. As such, pruritus control is important to the maintenance of health. The mechanism of pruritus has recently been clarified and the discovery of various pruritus mediators, the identification of specific nerves that transmit pruritus and the accumulation of knowledge on pruritus perception have led to a better understanding of all aspects of pruritus generation, transmission and recognition. In the case of pruritus caused by dermatitis, immune cells infiltrating the skin secrete inflammatory cytokines, which also act on peripheral nerves as pruritus mediators and induce an inflammatory response. Interestingly, there has been accumulating evidence that peripheral nerves are also involved in the inflammation via neuropeptides. In this article, we summarize the findings on pruritus mediators secreted by immune cells and the roles of peripheral nerves in pruritus in terms of their interactions with immunity. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is one of the most prevalent chronic inflammatory skin diseases in the world. It is characterized by recurrent eczematous lesions and intense itch, and many cytokines are involved in the pathogenesis of AD. Among them, much attention has been paid to interleukin 31 (IL-31) as an AD-associated itch mediator. IL-31 is mainly produced by CD4+ helper T cells and transmits the signals via a heterodimeric receptor composed of IL-31 receptor A (IL-31RA) and oncostatin M receptor (OSMR), both of which are expressed in dorsal root ganglion (DRG) neurons. However, the molecular mechanisms of how IL-31 is produced in helper T cells upon stimulation and transmits the itch sensation to the brain were largely unknown. Recently, by using original mouse models of AD, we have identified endothelial PAS domain 1 (EPAS1) and neurokinin B (NKB) as key molecules critical for IL-31 production and IL-31-mediated itch transmission, respectively. These molecules could be novel drug targets for AD-associated itch. This review highlights our recent findings, which show the functional significance of these molecules in the IL-31-induced itch sensation, referring to their application to drug development. [ABSTRACT FROM AUTHOR]