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Atopic dermatitis (AD) is a chronic, inflammatory skin disease with an eczematous rash and itching. Due to undesired adverse effects of traditional systemic treatment, there is still an unmet need for safe and effective long-term therapy for refractory AD. As our understanding of the pathogenesis underlying AD grows, novel treatments targeting specific molecules have been developed. Here, we discuss the efficacy and safety profiles of these drugs in recent clinical trials. Among their adverse effects, of particular note is AD acceleration. Although there is still debate about whether certain adverse reactions can be said to be paradoxical adverse events (PAEs), a wide range of PAEs have been reported during biological treatment for chronic immune-mediated diseases. Close surveillance of novel biologics is crucial to detect new undescribed paradoxical reactions and to shed light on the convoluted pathogenesis of AD. [ABSTRACT FROM AUTHOR]

Background: The US Food and Drug Administration (FDA) interchangeability guidelines state that the primary endpoint in a switching study should assess the impact of switching between the proposed interchangeable product and the reference product on clinical pharmacokinetics (PK) and pharmacodynamics (if available), as these assessments are generally sensitive to changes in immunogenicity and/or exposure that may arise due to switching. In addition, interchangeability designation requires no clinically meaningful difference in safety and efficacy of switching between the biosimilar and reference, compared with when using the reference product alone., Objectives:  The aim of this study was to investigate the PK, immunogenicity, efficacy, and safety in participants undergoing repeated switches between Humira ® and AVT02 as part of a global interchangeable development program., Methods: This multicenter, randomized, double-blind, parallel-group study in patients with moderate-to-severe plaque psoriasis comprises three parts: lead-in period (weeks 1-12), switching module (weeks 12-28), and the optional extension phase (weeks 28-52). Following the lead-in period during which all participants received the reference product (80 mg in week 1, followed by 40 mg every other week), participants with a clinical response of ≥ 75% improvement in the Psoriasis Area and Severity Index (PASI75) were randomized 1:1 to receive AVT02 alternating with the reference product (switching arm) or reference product only (non-switching arm). At week 28, participants who were PASI50 responders could opt to take part in an open-label extension phase receiving AVT02 up to week 50, with an end of study visit at week 52. PK, safety, immunogenicity, and efficacy were evaluated at various timepoints throughout the study for both switching and non-switching arms., Results: In total, 550 participants were randomized to switching (277) and non-switching arms (273). The switching versus non-switching arithmetic least square means ratio [90% confidence intervals (CIs)] was 101.7% (91.4-112.0%) for the area under the concentration-time curve over the dosing interval from weeks 26-28 (AUC tau, W26-28 ) and 108.1% (98.3-117.9%) for maximum concentration over the dosing interval from weeks 26-28 (C max, W26-28 ). The 90% CIs for the switching versus non-switching arithmetic means ratio for primary endpoints AUC tau, W26-28 and C max, W26-28 were within the prespecified limits of 80-125%, demonstrating comparable PK profiles between groups. In addition, the PASI, Dermatology Life Quality Index, and static Physician's Global Assessment efficacy scores were highly similar for both treatment groups. There were no clinically meaningful differences between the immunogenicity and safety assessments of repeated switching between AVT02 and the reference product, versus the reference product alone., Conclusions: This study demonstrated that the risk, in terms of safety or diminished efficacy of switching between the biosimilar and the reference product, is not greater than the risk of using the reference product alone, as required by the FDA for interchangeability designation. Beyond the scope of interchangeability, a consistent long-term safety and immunogenicity profile, with no impact on the trough levels up to 52 weeks, was established., Clinical Trial Registration: NCT04453137; date of registration: 1 July 2020., (© 2023. The Author(s).)

Classically, skin was considered a mere structural barrier protecting organisms from a diversity of environmental insults. In recent decades, the cutaneous immune system has become recognized as a complex immunologic barrier involved in both antimicrobial immunity and homeostatic processes like wound healing. To sense a variety of chemical, mechanical, and thermal stimuli, the skin harbors one of the most sophisticated sensory networks in the body. However, recent studies suggest that the cutaneous nervous system is highly integrated with the immune system to encode specific sensations into evolutionarily conserved protective behaviors. In addition to directly sensing pathogens, neurons employ novel neuroimmune mechanisms to provide host immunity. Therefore, given that sensation underlies various physiologies through increasingly complex reflex arcs, a much more dynamic picture is emerging of the skin as a truly systemic organ with highly coordinated physical, immunologic, and neural functions in barrier immunology. [ABSTRACT FROM AUTHOR]

A number of inherited conditions cause chronic itch as a part of the recognized phenotype. Advances in the understanding of the genetic factors that cause these diseases elucidate the molecular underpinning of itch as a symptom. Our knowledge of the causes of chronic itch has also advanced, providing an opportunity to integrate the genetic pathophysiology with the molecular landscape of chronic itch mediators. This article reviews select genodermatoses that have itch as a predominant feature with a focus on the pathophysiology of the disease, how it may lead to itch and potential therapeutic targets. [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]

Atopic dermatitis imposes a significant burden on patients, families and healthcare systems. Management is difficult, due to disease heterogeneity, co‐morbidities, complexity in care pathways and differences between national or regional healthcare systems. Better understanding of the mechanisms has enabled a stratified approach to the management of atopic dermatitis, supporting the use of targeted treatments with biologicals. However, there are still many issues that require further clarification. These include the definition of response, strategies to enhance the responder rate, the duration of treatment and its regimen (in the clinic or home‐based), its cost‐effectiveness and long‐term safety. The EAACI Guidelines on the use of dupilumab in atopic dermatitis follow the GRADE approach in formulating recommendations for each outcome and age group. In addition, future approaches and research priorities are discussed. [ABSTRACT FROM AUTHOR]

Allergic diseases are highly complex with respect to pathogenesis, inflammation, and response to treatment. Current efforts for allergic disease diagnosis have focused on clinical evidence as a binary outcome. Although outcome status based on clinical phenotypes (observable characteristics) is convenient and inexpensive to measure in large studies, it does not adequately provide insight into the complex molecular determinants of allergic disease. Individuals with similar clinical diagnoses do not necessarily have similar disease etiologies, natural histories, or responses to treatment. This heterogeneity contributes to the ineffective response to treatment leading to an annual estimated cost of $350 billion in the USA alone. There has been a recent focus to deconvolute the clinical heterogeneity of allergic diseases into specific endotypes using molecular and omics approaches. Endotypes are a means to classify patients based on the underlying pathophysiological mechanisms involving distinct functions or treatment response. The advent of high-throughput molecular omics, immunophenotyping, and bioinformatics methods including machine learning algorithms is facilitating the development of endotype-based diagnosis. As we move to the next decade, we should truly start treating clinical endotypes not clinical phenotype. This review highlights current efforts taking place to improve allergic disease endotyping via molecular omics profiling, immunophenotyping, and machine learning approaches in the context of precision diagnostics in allergic diseases. [ABSTRACT FROM AUTHOR]

Novel Insights Into the Pathogenesis of Skin Autoimmune Diseases A complex interaction of genetics and environmental factors is one of the key underlying pathogenic mechanisms in skin autoimmune diseases. Keywords: skin; autoimmunity; pemphigus; pemphigoid; psoriasis; alopecia aerata (AA) EN skin autoimmunity pemphigus pemphigoid psoriasis alopecia aerata (AA) N.PAG N.PAG 6 04/09/21 20210325 NES 210325 The Spectrum of Skin Autoimmune Diseases According to the revised Witebsky's criteria by Rose and Bona, a disease is considered of autoimmune origin if (i) it can be transferred by pathogenic T cells or autoantibodies, (ii) it can be induced in experimental animals, or if (iii) autoimmunity is suggested by circumstantial evidence from clinical clues ([1]). Comorbidity in Skin Autoimmune Diseases With the availability of (relatively) effective treatments for chronic skin inflammation ([15]-[17]), comorbid diseases, mostly metabolic and cardiovascular, now significantly contributes to the morbidity of patients with skin autoimmune diseases. To guide the reading, we have classified the articles into the following subheadings: "Emerging" autoimmune diseases Novel insights into the pathogenesis of skin autoimmune diseases New diagnostic approaches in skin autoimmune diseases Comorbidity in skin autoimmune diseases Epidemiology of skin autoimmune diseases Novel treatment targets and therapeutic approaches for skin autoimmune diseases Characterization of patient biomaterials and model systems of skin autoimmune diseases "Emerging" Autoimmune Diseases In contrast to these more "classical" autoimmune diseases, fulfilling the revised Witebsky's criteria, there is an increasing evidence for a role of autoreactive T- and/or B-cells in chronic inflammatory skin diseases that have not been considered autoimmune so far ([7]). [Extracted from the article]

Background: Wide fluctuations in placebo responses have been reported in phase 3 trials of systemic therapies for moderate-to-severe plaque psoriasis. Methods: In this systematic review and meta-analysis, we assessed placebo responses in phase 3 trials of systemic therapies for moderate-to-severe plaque psoriasis. The medical databases PubMed Medline, Embase, and Web of Science were searched for studies reporting on phase 3 psoriasis trials. A proportion meta-analysis determined the proportion of placebo-treated psoriasis patients obtaining a 75, 90, or 100% reduction in Psoriasis Area and Severity Index (PASI), that is, PASI75, PASI90, or PASI100, respectively, at week 12. In the assessment of PASI75 response, 44 trials with a total number of 7,972 patients were included. Conclusion: In pooled analyses, 5.2% (95% CI 4.7–5.7%) obtained PASI75, 2.1% (95% CI 1.7–2.4%) obtained PASI90, and 0.3% (95% CI 0.1–0.5%) obtained PASI100 among placebo receivers. No temporal changes were observed. The overall proportion of placebo responders in phase 3 psoriasis trials is low and does not appear to be increasing in recent years. [ABSTRACT FROM AUTHOR]

Interleukin-31 (IL-31) is involved in excessive development of cutaneous sensory nerves in atopic dermatitis (AD), leading to severe pruritus. We previously reported that PQA-18, a prenylated quinolinecarboxylic acid (PQA) derivative, is an immunosuppressant with inhibition of p21-activated kinase 2 (PAK2) and improves skin lesions in Nc/Nga mice as an AD model. In the present study, we investigate the effect of PQA-18 on sensory nerves in lesional skin. PQA-18 alleviates cutaneous nerve fiber density in the skin of Nc/Nga mice. PQA-18 also inhibits IL-31-induced sensory nerve fiber outgrowth in dorsal root ganglion cultures. Signaling analysis reveals that PQA-18 suppresses phosphorylation of PAK2, Janus kinase 2, and signal transducer and activator of transcription 3 (STAT3), activated by IL-31 receptor (IL-31R), resulting in inhibition of neurite outgrowth in Neuro2A cells. Gene silencing analysis for PAK2 confirms the requirement for STAT3 phosphorylation and neurite outgrowth elicited by IL-31R activation. LC/MS/MS analysis reveals that PQA-18 prevents the formation of PAK2 activation complexes induced by IL-31R activation. These results suggest that PQA-18 inhibits the IL-31 pathway through suppressing PAK2 activity, which suppresses sensory nerve outgrowth. PQA-18 may be a valuable lead for the development of a novel drug for pruritus of AD. [ABSTRACT FROM AUTHOR]

Mast cells are innate immune cells located at many barrier sites in the body and known to protect the host against environmental threats and to be involved in allergic diseases. More recently, new studies have investigated their roles in the regulation of skin inflammation and transmission of pain and itch sensations. Mast cell signalling through the Mas‐related G protein‐coupled receptor (MRGPR) X2 or its mouse orthologue MRGPRB2 has been reported to be one of the major mechanism by which mast cell can regulate such processes. MRGPRX2 and MRGPRB2 can induce mast cell degranulation upon binding to a broad panel of cationic molecules such as neuropeptides, bacteria‐derived quorum sensing molecules, venom peptides, host defense peptides and, unfortunately, various FDA‐approved drugs. Upon activation, mast cells release granule‐associated proteases, lipids and multiple cytokines that can modulate vascular permeability, immune cells recruitment and activation status of tissue‐projecting nociceptive sensory neurons (ie nociceptors). Here, we discuss the modality of MRGPRX2‐dependent mast cell activation and its different consequences on the patterns of skin inflammation and associated diseases. We notably emphasize how MRGPRX2‐dependent skin mast cell activation might trigger various pathological traits such as pruritus, pain and inflammation and therefore become a potential therapeutic target for inflammatory pain, itch, atopic dermatitis and drugs‐induced injection site reactions. [ABSTRACT FROM AUTHOR]

135 © 2021 Indian Journal of Dermatology, Venereology and Leprology- Published by Scientific Scholar What is new in dermatotherapy? It may improve pruritus by decreasing peripheral itch sensory neuron signaling through its direct effects on IL-4 and IL-13 and through its effects on eosinophils which results in decreased IL-31 secretion Atopic dermatitis, prurigonodularis, bullous pemphigoid FDA approved for atopic dermatitis in March 2017 Lebrikizumab 17 It is a humanized monoclonal antibody inhibiting IL-13. It is given subcutaneously at 150 mg week 0, 4 and every 12 weeks thereafter Plaque psoriasis FDA approved (April 2019) Bimekizumab 12 It is a human monoclonal IgG antibody against IL-17A and IL-17F. It is given subcutaneously at a loading dose of 320 mg and 160 mg every 4 weeks thereafter Plaque psoriasis, psoriatic arthritis It is in the Phase 3 trial Mirikizumab 13 It is a human monoclonal antibody IgG4 antibody against IL-23. [Extracted from the article]

Background: Following the first investigational study on the use of extracorporeal photopheresis for the treatment of cutaneous T‐cell lymphoma published in 1983, this technology has received continued use and further recognition for additional earlier as well as refractory forms. After the publication of the first guidelines for this technology in the JEADV in 2014, this technology has maintained additional promise in the treatment of other severe and refractory conditions in a multidisciplinary setting. It has confirmed recognition in well‐known documented conditions such as graft‐vs.‐host disease after allogeneic bone marrow transplantation, systemic sclerosis, solid organ transplant rejection including lung, heart and liver and to a lesser extent inflammatory bowel disease. Materials and methods: In order to further provide recognized expert practical guidelines for the use of this technology for all indications, the European Dermatology Forum (EDF) again proceeded to address these questions in the hands of the recognized experts within and outside the field of dermatology. This was done using the recognized and approved guidelines of EDF for this task. All authors had the opportunity to review each contribution as it was added. Results and conclusion: These updated 2020 guidelines provide at present the most comprehensive available expert recommendations for the use of extracorporeal photopheresis based on the available published literature and expert consensus opinion. The guidelines were divided into two parts: PART I covers Cutaneous T‐cell lymphoma, chronic graft‐vs.‐host disease and acute graft‐vs.‐host disease, while PART II will cover scleroderma, solid organ transplantation, Crohn's disease, use of ECP in paediatric patients, atopic dermatitis, type 1 diabetes, pemphigus, epidermolysis bullosa acquisita and erosive oral lichen planus. [ABSTRACT FROM AUTHOR]

The Saudi Initiative for Asthma 2021 (SINA-2021) is the fifth version of asthma guidelines for the diagnosis and management of asthma for adults and children, which is developed by the SINA group, a subsidiary of the Saudi Thoracic Society. The main objective of the SINA is to have guidelines that are up to date, simple to understand, and easy to use by healthcare workers dealing with asthma patients. To facilitate achieving the goals of asthma management, the SINA panel approach is mainly based on the assessment of symptom control and risk for both adults and children. The approach to asthma management is aligned for age groups: adults, adolescents, children aged 5–12 years, and children aged less than 5 years. SINA guidelines have focused more on personalized approaches reflecting better understanding of disease heterogeneity with the integration of recommendations related to biologic agents, evidence-based updates on treatment, and the role of immunotherapy in management. Medication appendix has also been updated with the addition of recent evidence, new indications for existing medication, and new medications. The guidelines are constructed based on the available evidence, local literature, and the current situation at national and regional levels. There is also an emphasis on patient–doctor partnership in the management that also includes a self-management plan. [ABSTRACT FROM AUTHOR]

Vitamin D supplementation with standard treatment yielded positive clinical outcomes in mild and moderate atopic dermatitis; however, the potential benefit of vitamin D in severe cases remains unclear. This study aimed to evaluate the impact of vitamin D supplementation on response to standard treatment in pediatrics with severe atopic dermatitis. The patients were randomized to receive either vitamin D 3 1600 IU/day or placebo, plus baseline therapy of topical 1% hydrocortisone cream twice daily for 12 weeks. The primary endpoints were the change in mean Eczema Area and Severity Index (EASI) score at the end of the study and the mean percent change in EASI score from baseline to week 12. Eighty-six subjects completed the study. The treated group achieved a significant higher level of 25 hydroxy vitamin D (P < .001) compared to control group at week 12. The mean EASI score was significantly lower in the treatment group compared to placebo group (P = .035). The percent change in EASI score from baseline differed significantly between the supplementation (56.44 ± 29.33) and placebo (42.09 ± 19.22) groups after intervention (P = .039). Vitamin D supplementation could be an effective adjuvant treatment that improves the clinical outcomes in severe atopic dermatitis. [ABSTRACT FROM AUTHOR]

Background: Asthma and bronchiectasis are 2 heterogeneous diseases that frequently coexist, particularly in severe asthma. Recognition of this co-diagnosis may importantly affect treatment decisions and outcome. Previous studies in asthma with bronchiectasis show inconsistent outcomes, probably due to the heterogeneity of the included asthma cohorts. Objectives: We hypothesized that bronchiectasis contributes to asthma severity and that patients with severe asthma and bronchiectasis present with distinct characteristics resulting in different treatable traits. In addition, we explored whether bronchiectasis in severe asthma is more common in a specific phenotype. Methods: This is a single-center study consecutively including patients with severe asthma from a tertiary referral center. Severe asthma was diagnosed according to the ATS/ERS guidelines. Asthma and infectious exacerbations were defined by the attending specialist as respiratory symptoms requiring treatment with systemic steroids or antibiotics, respectively. Two independent blinded radiologists evaluated each CT. Results: 19% of patients with severe asthma showed bronchiectasis on CT. Patients with bronchiectasis had a lower FEV1% predicted (p = 0.02) and FEV1/FVC (p = 0.004) and more infectious exacerbations (p = 0.003) compared to patients without bronchiectasis. Bronchiectasis is more common in patients with a longer duration of asthma, sensitization to A. fumigatus or a positive sputum culture. Sputum cultures of patients with severe asthma and bronchiectasis revealed more P. aeruginosa, S. maltophilia, H. parainfluenzae, and A. fumigates compared to the non-bronchiectasis group. The adult-onset, eosinophilic asthma phenotype showed the highest prevalence of bronchiectasis (29.4%). Conclusions: Patients with severe asthma and coexisting bronchiectasis were found to represent a distinct group, in terms of disease severity, microbiology, and asthma phenotype. Performing (HR)CT and sputum cultures can help to identify these patients. These results can possibly contribute to early recognition and targeted treatment of this patient group. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a highly pruritic, chronic inflammatory skin disease. The diagnosis is made using evaluated clinical criteria. Disease activity and burden are best measured with a composite score, assessing both objective and subjective symptoms, such as SCORing Atopic Dermatitis (SCORAD). AD management must take into account clinical and pathogenic variabilities, the patient's age and also target flare prevention. Basic therapy includes hydrating and barrier‐stabilizing topical treatment universally applied, as well as avoiding specific and unspecific provocation factors. Visible skin lesions are treated with anti‐inflammatory topical agents such as corticosteroids and calcineurin inhibitors (tacrolimus and pimecrolimus), which are preferred in sensitive locations. Topical tacrolimus and some mid‐potency corticosteroids are proven agents for proactive therapy, which is defined as the long‐term intermittent anti‐inflammatory therapy of frequently relapsing skin areas. Systemic anti‐inflammatory or immunosuppressive treatment is a rapidly changing field requiring monitoring. Oral corticosteroids have a largely unfavourable benefit–risk ratio. The IL‐4R‐blocker dupilumab is a safe, effective and licensed, but expensive, treatment option with potential ocular side‐effects. Other biologicals targeting key pathways in the atopic immune response, as well as different Janus kinase inhibitors, are among emerging treatment options. Dysbalanced microbial colonization and infection may induce disease exacerbation and can justify additional antimicrobial treatment. Systemic antihistamines (H1R‐blockers) only have limited effects on AD‐related itch and eczema lesions. Adjuvant therapy includes UV irradiation, preferably narrowband UVB or UVA1. Coal tar may be useful for atopic hand and foot eczema. Dietary recommendations should be patient‐specific, and elimination diets should only be advised in case of proven food allergy. Allergen‐specific immunotherapy to aeroallergens may be useful in selected cases. Psychosomatic counselling is recommended to address stress‐induced exacerbations. Efficacy‐proven 'Eczema school' educational programmes and therapeutic patient education are recommended for both children and adults. [ABSTRACT FROM AUTHOR]

Objective: The inflammatory mechanisms underpinning asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) have not been fully elucidated. Here, we examined the levels of cysteinyl leukotrienes (cys-LTs), prostaglandin D2 (PG-D2), prostaglandin E2 (PG-E2), interleukin 5 (IL-5), and a disintegrin and metalloprotease domain (ADAM 33) in ACOS patients to determine the relationship between levels of these inflammatory markers and pulmonary functions. Methods: Blood samples were obtained from asthma, COPD, and ACOS patients who received combined therapy and were stable for the last month to measure cys-LTs, PG-D2, PG-E2, IL-5, and ADAM33 levels. Differences between groups and their correlations with pulmonary function tests were evaluated. Results: In total, 24 ACOS, 27 asthma, and 35 COPD patients were included.. PG-D2 levels were higher in ACOS (120.9 ± 117.2 ng/L) and asthma (119.6 ± 111.7 ng/L) patients than in COPD (82.6 ± 46.7 ng/L) patients (p = 0.036 and p = 0.038, respectively). In ACOS patients, PG-D2, cys-LTs, and ADAM33 levels were negatively correlated with FEV1/FVC% values (p = 0.021, p = 0.008, and p = 0.028, respectively). In COPD patients, a negative correlation was detected between PG-E2 and FEV1/FVC% (p = 0.007), whereas positive correlations were detected between IL-5 and pulmonary function tests, including FVC, FVC%, FEV1, FEV1%, FEF25-75, and FEF25-75% (p = 0.047, p = 0.005, p = 0.002, p = 0.002, p = 0.010, and p = 0.005, respectively). In asthma patients, cys-LTs levels were negatively correlated with FEV1 and FEF25-75 values (p = 0.045 and p = 0.037, respectively). Conclusions: PG-D2 levels may be a valuable biomarker to differentiate COPD in asthma and ACOS patients. [ABSTRACT FROM AUTHOR]

Background: Asthma is a heterogeneous disease of a complex etiology in which genetic, environmental and personality variables are important factors determining the development of complicated strategies related to coping with stress and temperament traits. Our thesis is that coping styles in asthmatic patients are modified by the environment (chronic inflammation and stress) which affects individual temperament traits in the course of time. Thus, patient age is one of factors which determine the clinical image of asthma and its natural history. Aim: The aim of the study was to evaluate the variables describing stress coping styles and temperament in young (18 to 35 years old) and elderly asthmatics (aged ≥60 years). Material and methods: A total of 200 patients, 104 elderly and 96 young asthmatics were enrolled in the study. Apart from medical examination, the following tests were performed in all subjects: the Formal Characteristics of Behavior- Temperament Inventory (FCB-TI), Coping Inventory for Stressful Situations (CISS), Beck Depression Inventory, State-Trait Anxiety Inventory, and Borg Rating of Perceived Exertion (RPE) Scale. Results: Elderly patients with asthma exhibited higher intensity of anxiety as a trait, a higher level of depression and experienced dyspnea, as well as higher levels of stress coping strategies such as Avoidance-Oriented Coping (AOC), Distraction Seeking (DS) and Social Diversion (SD) compared to young asthmatics. In elderly patients, Perseverance and Sensory Sensitivity traits have been observed to decline with the duration and development of asthma at later life stages as opposed to young asthmatics, in whom these temperament characteristics are elevated. Conclusions: Asthma is a heterogeneous disease of a complex etiopathogenesis that has a complex interplay with mental health. The present study confirms a relationship between age and stress coping strategies as well as temperament traits. [ABSTRACT FROM AUTHOR]

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: Atopic dermatitis (AD) is a frequent, chronic remittent skin disease. The pathophysiology of AD has been increasingly understood within the last years, which may help to identify different endotypes suitable for defined therapies in the future. A patient‐oriented therapy considers phenotypical features in addition to genetic and biological markers. The most recent developments in biologics and small‐molecule drugs for AD treatment are presented in this article. These molecules, if approved, could change the perspectives for future therapies. Dupilumab is the first approved biologic for the treatment of moderate to severe atopic dermatitis in adolescence and adulthood and has led to a significant improvement in the treatment of this chronic disease. In the present article we present real‐life data on the efficacy of dupilumab in adult dermatitis patients. We also discuss other data relevant to the use of dupilumab, and address open questions important for the standard care of atopic dermatitis patients. [ABSTRACT FROM AUTHOR]

Copyright of Polish Journal of Allergology / Alergologia Polska is the property of Termedia Publishing House and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Atopic dermatitis is a common immunologic skin disease. Mild atopic dermatitis can be managed with emollients and topical therapies such as low potency topical steroids, which have a favorable safety profile. Severe atopic dermatitis, in contrast, is a challenging disease to treat. Topical therapies are typically inadequate for control of severe atopic dermatitis. When topical therapies fail, the mainstay of therapy for severe atopic dermatitis has traditionally been phototherapy or off-label use of systemic immunosuppressant treatment, yet systemic immunosuppressants all have significant potential toxicities, drug interactions, and contraindications, requiring close monitoring. Targeted biologics are therefore attractive treatment options for topical therapy-refractory cases of atopic dermatitis, with the potential to offer effective, safer treatment of uncontrolled atopic dermatitis. Dupilumab, as the only biologic therapy currently FDA-approved for atopic dermatitis, is effective for many patients, but there is need for continuing study of additional biologic therapies to address the needs of diverse patients with uncontrolled atopic dermatitis. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is secondary to genetic, immunological and microbiological disorders as well as epidermal barrier defects, which are the main targets of therapy. The disease proceeds with periodic exacerbations. Its development and course are influenced by numerous environmental and individual factors. In recent decades, in industrialized countries, there has been a threefold increase in the incidence of AD. There is also an increasing number of cases resistant to topical treatment. Effective treatment of AD should provide control of clinical symptoms, prevent exacerbations and improve the quality of life of patients. The multifactorial etiopathogenesis and various endotypes and phenotypes of AD justify the tendency to optimize and personalize the therapy. Currently, we recommend the use of dupilumab for the treatment of patients from 12 years of age with moderate and severe atopic dermatitis, who do not respond to topical treatment. [ABSTRACT FROM AUTHOR]

Copyright of Dermatology Review / Przeglad Dermatologiczny is the property of Termedia Publishing House and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose of Review: Atopic dermatitis (AD), chronic spontaneous urticaria (CSU), and allergic contact dermatitis (ACD) represent three important allergic dermatoses with many unmet therapeutic needs. The development of biologic agents has opened the door to both new treatment options and improved understanding of the underlying pathophysiology, both shared and unique for these entities. With several FDA-approved medications available and many more in development, the biologic revolution has begun for allergic dermatoses. Recent Findings: This is a narrative review on the current state of pathomechanisms and appropriately targeted biologic agents for these three common allergic skin conditions. The importance of Th2 inflammation and the effect of inflammatory cytokines on the skin barrier may help explain the impressive efficacy of biologic agents, while maintaining relative safety. While some of the biologic agents show efficacy across multiple allergic dermatoses, more often it seems these more targeted pathways show accordingly precise efficacy. However, in each disease, multiple agents hold promise, and may be differentiated by safety and adverse effect profile rather than simply by efficacy. Summary: New understanding of the pathogenesis of the allergic dermatoses has ushered in a new era of biologic therapies. Competing mechanisms and molecules will continue to be developed and vetted in trials with hopes of continuously refined precision therapies with optimized safety and efficacy profiles. [ABSTRACT FROM AUTHOR]

Pro-opiomelanocortin (POMC) is a large precursor protein of and β-endorphin. POMC expressed in keratinocytes regulates various pathophysiological responses, such as pruritus in atopic dermatitis. Interleukin (IL)-31 is a T helper 2 (Th2)-derived cytokine that functions as a pruritogen, stimulating the sensory neurons in the skin. However, the regulatory mechanism underlying IL-31-induced POMC expression in keratinocytes remains largely unknown. Herein, using a 5′-serial deletion and site-specific mutation constructs of the regulatory region of POMC, we demonstrated that a putative EGR1-binding sequence (EBS) motif in POMC is required for its upregulation by IL-31 in HaCaT keratinocytes. Notably, EGR-1 directly interacted with the EBS motif in POMC. The ectopic expression of EGR-1 stimulated the POMC promoter activity, whereas the knockdown of EGR-1 expression by RNA interference reduced IL-31-induced POMC expression. Furthermore, we observed that three major mitogen-activated protein kinases, ERK, JNK, and p38 kinase, mediated IL-31-induced EGR-1 expression. In summary, our results suggest that EGR-1 trans-activates POMC in response to IL-31 stimulation in HaCaT keratinocytes. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a prevalent inflammatory skin condition that, depending on its severity, can cause enormous morbidity. Corticosteroids and systemic immunosuppression, traditionally standard of care for difficult-to-treat disease, have many undesirable side effects. The desire for targeted treatments along with an improved understanding of the pathophysiology of AD has spurred the development of novel treatments. In this article, we review promising new treatments and discuss how their targets—IL-13, IL-31, OX40 (CD134), and the Janus kinase family of proteins—participate in the pathogenesis of AD. We review the published phase II and III data for dupilumab, tralokinumab, lebrikizumab, nemolizumab, anti-OX40 antibody, baricitinib, abrocitinib, and upadacitinib. The introduction of new agents may offer new options, but it remains to be seen how narrow-acting agents, like single interleukin inhibitors, will compare in safety and efficacy to broad-acting agents such as JAK inhibitors. [ABSTRACT FROM AUTHOR]

Introduction: Venom immunotherapy (VIT) can protect against severe anaphylactic reactions (SR) in 80-100% of subjects allergic to Hymenoptera venom. The mechanisms of induction of immunological tolerance produced by VIT are still little known. It has been shown that VIT modulates Treg activity, Th2 or Th1 cells or both, increases production of IL-10, decreases secretion of IL-13, and causes an IgG4/IgE ratio shift. Aim: To investigate the blood eosinophil count, CCL5/RANTES and IL-17E/IL-25 concentrations before and after the initial phases of the rush protocol of VIT. Material and methods: Forty individuals (14 males, 26 females) of mean age 41.03 ±12.43 years were included in the study. The peripheral eosinophils and the concentration of serum interleukin IL-17E/IL-25 and RANTES were determined before and after the initial phase of VIT. Results: Paired sample t-test revealed that all patients after VIT had significantly higher eosinophil levels compared to the baseline (mean: 0.42 vs. 0.64, p < 0.05). Moreover, in subjects treated with bee venom, RANTES levels proved to rise significantly (51 × 103 vs. 62 × 103, p < 0.05) while IL-17E/IL-25 dropped with near-marginal significance (916 vs. 650, p = 0.069). Conclusions: Our immunological study on the early phase of venom immunotherapy suggested that eosinophils, cytokines such as CCL5/RANTES and IL-17E/IL-25 contribute to the immunological response. [ABSTRACT FROM AUTHOR]

Dupilumab is a treatment option newly licensed for adolescents with moderate to severe atopic dermatitis (AD). It reduces type 2 inflammation by blocking the shared receptor subunit for IL-4/-13. Dupilumab affects three disease mechanisms in atopic dermatitis: the skin barrier, the Th2-cell differentiation and the class switch to IgE. This report is based on a systematic literature search of the PubMed Database. Dupilumab showed promising results in improving AD signs, symptoms and quality of life in adolescents with moderate to severe AD. The safety profile of dupilumab in adolescents with moderate to severe AD closely resembled the known safety profile of dupilumab in adults with moderate to severe AD. Injection-site reactions and conjunctivitis were the relevant side-effects. Skin infections were less frequently observed compared to placebo. Dupilumab was approved by the Food and Drug Administration in March 2019 and by the European Medicines Agency in August 2019 for the treatment of adolescents with moderate to severe atopic dermatitis whose disease is not adequately controlled with topical therapies or when those therapies are not advisable. Since it is the first licensed drug it will likely become the reference drug for adolescents with moderate to severe AD. [ABSTRACT FROM AUTHOR]

Itch is a topic to which everyone can relate. The physiological roles of itch are increasingly understood and appreciated. The pathophysiological consequences of itch impact quality of life as much as pain. These dynamics have led to increasingly deep dives into the mechanisms that underlie and contribute to the sensation of itch. When the prior review on the physiology of itching was published in this journal in 1941, itch was a black box of interest to a small number of neuroscientists and dermatologists. Itch is now appreciated as a complex and colorful Rubik's cube. Acute and chronic itch are being carefully scratched apart and reassembled by puzzle solvers across the biomedical spectrum. New mediators are being identified. Mechanisms blur boundaries of the circuitry that blend neuroscience and immunology. Measures involve psychophysics and behavioral psychology. The efforts associated with these approaches are positively impacting the care of itchy patients. There is now the potential to markedly alleviate chronic itch, a condition that does not end life, but often ruins it. We review the itch field and provide a current understanding of the pathophysiology of itch. Itch is a disease, not only a symptom of disease. [ABSTRACT FROM AUTHOR]

To evaluate cellular response to oncostatin M (OSM) in comparison to interleukin (IL)-31, we analyzed monocyte chemoattractant protein 1 (MCP-1) as a readout for OSM responses with and without IL-4, IL-13, anti-OSM receptor β monoclonal antibody KPL-716, and anti-IL-31 receptor a antibody in human epidermal keratinocytes and human dermal fibroblasts in vitro. In human epidermal keratinocytes, OSM significantly induced STAT3 or STAT1 phosphorylation and synergized with IL-13 or IL-4 in elevating MCP-1. In human dermal fibroblasts, OSM results were similar, and leukemia inhibitory factor or IL-31 minimally activated STAT3 but not MCP-1. OSM significantly stimulated mRNA for type II IL-4 receptor and type II OSM receptor. KPL-716, not anti-IL-31Ra, significantly attenuated MCP-1 response to OSM and OSM + IL-4 in human epidermal keratinocytes and human dermal fibroblasts. OSM, not leukemia inhibitory factor or IL-31, synergized with IL-4 and IL-13 in human epidermal keratinocytes and human dermal fibroblasts, suggesting therapeutic potential of KPL-716 in inflammatory dermatologic diseases distinct from IL-31 inhibition. [ABSTRACT FROM AUTHOR]

Purpose: We conducted a systematic review and meta-regression analysis to evaluate the impact of increasing immunoglobulin G (IgG) trough levels on the clinical outcomes in patients with PID receiving intravenous immunoglobulin G (IVIG) treatment. Methods: Systematic search was conducted in PubMed and Cochrane. Other relevant articles were searched by reviewing the references of the reviewed article. All clinical trials with documented IgG trough levels and clinical outcome of interest in patients receiving IVIG treatment were eligible to be included in this review. Meta-regression analysis was conducted using Comprehensive Meta-analysis Software. Additional sensitivity analyses were undertaken to evaluate the robustness of the overall results. Results: Twenty-eight clinical studies with 1218 patients reported from year 2001 to 2018 were included. The mean IVIG dose used ranges from 387 to 560 mg/kg every 3 to 4 weekly, and mean IgG trough obtained ranges from 660 to 1280 mg/dL. Random-effects meta-regression slope shows that IgG trough level increases significantly by 73 mg/dL with every increase of 100 mg/kg dose of IVIG (p < 0.05). Overall infection rates reduced significantly by 13% with every increment of 100 mg/dL of IgG trough up to 960 mg/dL (p < 0.05). Conclusion: This meta-analysis concludes that titrating the IgG trough levels up to 960 mg/dL progressively reduces the rate of infections, and there is less additional benefit beyond that. Further studies to validate this result are required before it can be used in clinical practice. [ABSTRACT FROM AUTHOR]

Atopic dermatitis is a prevalent inflammatory skin condition characterized by itch and dry skin, which affects 15-20% of children and 3-5% of adults. This article reviews epidemiological, clinical and experimental data to provide an overview of the most important disease mechanisms in atopic dermatitis. Genetic predisposition, environmental insults, atopic triggers, complex host immune response and skin barrier changes, and altered skin microbiota are discussed. Whilst our understanding of atopic dermatitis has improved dramatically in recent years, many basic aspects are still not understood. Further research is needed to fully understand this complex skin disease. [ABSTRACT FROM AUTHOR]

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This article presents examples of the use of image filtering for various types of diagnostic medical imaging in order to improve their interpretative value, and thus to improve the diagnostic reliability of that imaging. As research and visual tests have shown, in many cases, the use of digital image filtering makes it possible to significantly improve not only image quality, but also their readability or clarity, thus contributing to a more accurate and precise reading and interpretation of information contained in the images. The author proposed specific filters that largely meet the assumed conditions and constitute a supplement, and sometimes introduce a possible new application in addition to those already known in subject literature. A visual assessment was also made of the degree of diagnostic usefulness of images after filtration compared to the source images. The most commonly used filters are those that not only help to improve the overall appearance and quality of the image, but also, on the one hand, help to extract or highlight certain information, or to reduce noise, on the other hand. Thanks to these solutions, it is possible to smoothen or sharpen some structures within the images, which impacts their readability and quality. Thus, image filtering has become a very desirable and useful tool in many fields of science, technology, as well as art and medicine. The subject matter of image transformation is here applied to the latter discipline. [ABSTRACT FROM AUTHOR]

Psoriasis is a prevalent skin disease that impairs multiple domains of quality of life (QoL). Pruritus, a common symptom in patients with psoriasis, may directly affect sleep, but studies investigating this are limited. We investigated the relationships between pruritus and sleep in 104 in-patients with psoriasis, who underwent dermatological assessment and completed questionnaires to determine psoriasis severity, pruritus intensity, sleep quality, QoL (skin disease-specific and generic), depressive mood and anxiety. In total, 80% of patients reported pruritus, and 39% had sleep disturbances, most commonly awakenings during sleep (33%) and sleepiness during the daytime (30%). Sleep impairment was more frequent in patients with pruritus, who had more difficulty falling asleep (P = 0.031). Overall, 14% of all patients and 34% of the patients who reported sleep disturbances reported that their sleep problems were caused by pruritus. Patients who reported sleep disturbances had lower generic QoL. Pruritus in patients with psoriasis was frequent and relevant, as evidenced by the higher rate of sleep problems in this patient group, and it was linked to a lower QoL. [ABSTRACT FROM AUTHOR]

The gain and refractive index dynamics of dilute nitride antimonide semiconductor optical amplifiers are studied using heterodyne pump probe spectroscopy, both in forward and reverse bias regimes. In the forward biased absorption regime, both gain and refractive index relax on the same timescale indicating that both quantities are linked to the same relaxation process, interband recombination. Above transparency, in the forward biased gain regime, the gain and phase exhibit differing timescales resulting in a dynamical alpha factor that varies strongly with time. Reversed bias measurements suggest a recombination dominated absorption recovery where the recovery timescale increases with increasing reversed bias, possibly due to charge separation effects. [ABSTRACT FROM AUTHOR]

Background and Aims: Pruritus is associated with multiple liver diseases, particularly those with cholestasis, but the mechanism remains incompletely understood. Our aim was to evaluate serum IL-31 as a putative biomarker of pruritus in clinical trials of an farnesoid X receptor (FXR) agonist, cilofexor, in patients with NASH, primary sclerosing cholangitis (PSC), and primary biliary cholangitis (PBC)., Approach and Results: Serum IL-31 was measured in clinical studies of cilofexor in NASH, PSC, and PBC. In patients with PSC or PBC, baseline IL-31 was elevated compared to patients with NASH and healthy volunteers (HVs). IL-31 correlated with serum bile acids among patients with NASH, PBC, and PSC. Baseline IL-31 levels in PSC and PBC were positively correlated with Visual Analog Scale for pruritus and 5-D itch scores. In patients with NASH, cilofexor dose-dependently increased IL-31 from Week (W)1 to W24. In patients with NASH receiving cilofexor 100 mg, IL-31 was higher in those with Grade 2-3 pruritus adverse events (AEs) than those with Grade 0-1 pruritus AEs. IL-31 weakly correlated with C4 at baseline in patients with NASH, and among those receiving cilofexor 100 mg, changes in IL-31 and C4 from baseline to W24 were negatively correlated. IL-31 messenger RNA (mRNA) was elevated in hepatocytes from patients with PSC and NASH compared to HVs. In a humanized liver murine model, obeticholic acid increased IL-31 mRNA expression in human hepatocytes and serum levels of human IL-31., Conclusions: IL-31 levels correlate with pruritus in patients with cholestatic disease and NASH, with FXR agonist therapy resulting in higher serum levels in the latter group. IL-31 appears to derive in part from increased hepatocyte expression. These findings have therapeutic implications for patients with liver disease and pruritus., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Given the inadequate overall awareness of the main disease features and treatment modalities of pruritus in pediatric patients with atopic dermatitis, a multidisciplinary Italian expert group met with the major aim of increasing knowledge of the condition for improved diagnosis and better management among specialists involved in disease management. Herein, the overall features of the condition are reviewed, along with its etiopathogenesis and symptoms. Likewise, management options are summarized, emphasizing the need for a multidisciplinary approach, minimally composed of a management team that includes a pediatrician, dermatologist, psychologist, play assistant, and dedicated nurse. In addition to more traditional therapies such as emollients as highlighted by European guidelines, therapeutic patient education in a group or individually is highly encouraged as it helps patients and their parents to better understand the disease and provide practical guidance for dressing and bandaging. It can also aid in outlining coping strategies for itching and sleep disturbance. The utility of distraction techniques should also be stressed as such educational interventions involving the child and their parents can substantially improve the overall quality of life. All approaches should be tailored according to patient age and clinical features and requires individualized strategy to ensure good adherence by both children and their parents. Thus, a holistic approach embracing systemic, topical and psychological interventions is advocated in order to provide patients and their caregivers the best possible care. [ABSTRACT FROM AUTHOR]

For decades, antihistamines have been the mainstay of treatment for chronic pruritus, yet they often only work by making patients drowsy and forgetful of their itch. A new era of antipruritic drugs is quickly approaching, presenting more effective treatments for patients suffering from chronic itch. Several treatments have been developed targeting specific receptors in the nervous system, such as the transient receptor potential channels, sodium channels, neurokinin-1 receptors, opioid receptors, and many more. Additionally, antipruritic therapies developed to work on the immune system have become more targeted, leading to greater safety and efficacy measures. These include crisaborole, several interleukin antagonists, and janus kinase inhibitors. The promising results presented with these new antipruritic therapies allow physicians to be better equipped to treat their itchy patients. [ABSTRACT FROM AUTHOR]