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INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin disease for which signs and symptoms have a negative impact on a patients quality of life (QoL) and mental health. Here, we assess the impact of lebrikizumab on QoL and mental health after 16 weeks of treatment in patients with moderate-to-severe AD. METHODS: Data were analyzed over 16 weeks from two separate phase 3, randomized, placebo-controlled, monotherapy trials (ADvocate1 and ADvocate2). Patient-reported outcomes were assessed using the following measures: Dermatology Life Quality Index (DLQI), EQ-5D-5L visual analogue scale (VAS), EQ-5D-5L index scores (UK and US), Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety, and PROMIS Depression. RESULTS: Treatment with lebrikizumab 250 mg every 2 weeks in two studies led to statistically significant improvements (based on nominal p values) versus placebo in DLQI since week 4 (the first timepoint assessed) for the following measures: change from baseline in DLQI total score (ADvocate1 - 7.8 vs - 2.8; ADvocate2 - 7.3 vs - 3.9), proportion of patients with DLQI ≥ 4-point improvement (ADvocate1 69.5% vs 36.2%; ADvocate2 60.5% vs 42.6%), DLQI total score ≤ 5 (ADvocate1 36.7% vs 8.8%; ADvocate2 29.6% vs 10.8%), and DLQI (0, 1) (ADvocate1 12.3% vs 1.7%; ADvocate2 9.2% vs 1.7%). Improvements in DLQI measures, EQ-5D-5L index scores (UK and US), and EQ-5D-5L VAS were sustained through week 16. Additionally, lebrikizumab improved PROMIS Anxiety and PROMIS Depression scores, and improvements were higher in patients with at least a mild score (≥ 55) versus placebo for PROMIS Anxiety (ADvocate1 - 7.43 vs - 1.51; ADvocate2 - 4.95 vs - 0.82) and PROMIS Depression (ADvocate1 - 7.42 vs - 2.46; ADvocate2 - 4.28 vs - 2.00). CONCLUSIONS: Treatment with monotherapy 250 mg lebrikizumab for 16 weeks provided clinically meaningful improvements in outcomes related to QoL and mental health for patients with moderate-to-severe AD. Lebrikizumab-treated patients reported improvements in DLQI as early as week 4, the first measure since baseline. TRIAL REGISTRATION: ClinicalTrials.gov Registration NCT04146363 (ADvocate1) and NCT04178967 (ADvocate2).

Background: Lebrikizumab improved itch, interference of itch on sleep, and quality of life (QoL) in patients with moderate-to-severe atopic dermatitis (AD), in two Phase 3 trials at 16weeks compared to placebo. Objectives: We assess improvements in itch and sleep interference due to itch and their impact on QoL measurements after treatment. Methods: Data were analyzed from ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967) in patients with moderate-to-severe AD. QoL was evaluated using Dermatology Life Quality Index (DLQI) at Week 16 in patients (>16years of age) who were itch responders/non-responders (defined as ≥4-point improvement in Pruritus Numeric Rating Scale) or Sleep-Loss Scale responders/non-responders (defined as ≥2-point improvement in itch interference on sleep). Results: In ADvocate1 and ADvocate2, significantly greater proportions of itch responders had a clinically meaningful improvement in measures related to QoL (DLQI scores (0/1), ≤5 DLQI total score and ≥4-point DLQI improvement) compared to itch non-responders. In both studies, a significantly greater proportion of Sleep-Loss Scale responders, reported a DLQI score of (0/1), DLQI total score of ≤5 and DLQI improvement of ≥4 points compared to Sleep-Loss Scale non-responders. Conclusions: Improvement in itch and sleep interference due to itch is associated with improvement in the QoL of patients after treatment with lebrikizumab for moderate-to-severe AD. ClinicalTrials.gov registration NCT04146363 (ADvocate1) and NCT04178967 (ADvocate2). [ABSTRACT FROM AUTHOR]

Background: Current treat‐to‐target recommendations for atopic dermatitis (AD) may not include high enough treatment targets and do not fully consider patient needs. Objective: To develop recommendations for optimized AD management, including disease severity assessments, treatment goals and targets, and guidance for treatment escalation/modification. Methods: An international group of expert dermatologists drafted a series of recommendations for AD management using insights from a global patient study and 87 expert dermatologists from 44 countries. Experts voted on recommendations using a modified eDelphi voting process. Results: The Aiming High in Eczema/Atopic Dermatitis (AHEAD) recommendations establish a novel approach to AD management, incorporating shared decision‐making and a concept for minimal disease activity (MDA). Consensus (≥70% agreement) was reached for all recommendations in 1 round of voting; strong consensus (≥90% agreement) was reached for 30/34 recommendations. In the AHEAD approach, patients select their most troublesome AD feature(s); the clinician chooses a corresponding patient‐reported severity measure and objective severity measure. Treatment targets are chosen from a list of 'moderate' and 'optimal' targets, with achievement of 'optimal' targets defined as MDA. Conclusions: Patient and expert insights led to the development of AHEAD recommendations, which establish a novel approach to AD management. Patients were not involved in the eDelphi voting process used to generate consensus on each recommendation. However, patient perspectives were captured in a global, qualitative patient research study that was considered by the experts in their initial drafting of the recommendations. [ABSTRACT FROM AUTHOR]

There are only a few clinical trials which address the treatment of acute urticaria (AU). Especially, the added value of systemic corticosteroids to antihistamines is unclear in treatment of severe AU. To review the existing evidence‐based approaches for AU treatment. A systematic electronic search was done in PubMed and Web of Science to retrieve all studies on the treatment of patients with AU. A descriptive synthesis was conducted based on the PRISMA statement. Quality assessment was independently performed by both reviewers ('Cochrane risk‐of‐bias tool' for RCTs). Ten randomized controlled trials (RCTs) (n = 857 participants) were included. Four studies assessed corticosteroid effectiveness added to antihistamines and six studies compared the efficacy of H1 and/ or H2‐antihistamines. The addition of corticosteroid (prednisone) to an antihistamine (levo)cetirizine did not improve symptoms of AU compared to antihistamine alone in two out of three RCTs. The combination of diphenhydramine (50 mg, IV) and ranitidine (50 mg, IV) or cimetidine (300 mg, IV) was most efficient for relief of urticaria in two out of five studies. Most frequent adverse effects were sedation and drowsiness. Recent guidelines on urticaria treatment mainly focus on chronic urticaria rather than on AU. Moreover, only few, small RCTs provide evidence for the management of AU. Thus, the state‐of‐the‐art management of this frequent condition remains unclear. The addition of corticosteroids to an antihistamine as treatment for AU needs to be further investigated. Well‐designed, high‐quality interventional trials are needed to establish evidence‐based treatment guidelines for AU. [ABSTRACT FROM AUTHOR]

Autoimmunity is the break of tolerance to self‐antigens that leads to organ‐specific or systemic diseases often characterized by the presence of pathogenic autoreactive antibodies (AAb) produced by plasmablast and/or plasma cells. AAb are prevalent in the general population and not systematically associated with clinical symptoms. In contrast, in some individuals, these AAb are pathogenic and drive the development of signs and symptoms of antibody‐mediated autoimmune diseases (AbAID). AAb production, isotype profiles, and glycosylations are promoted by pro‐inflammatory triggers linked to genetic, environmental, and hormonal parameters. Recent evidence supports a role for pathogenic AAb of the IgE isotype in a number of AbAID. Autoreactive IgE can drive the activation of mast cells, basophils, and other types of FcεRI‐bearing cells and may play a role in promoting autoantibody production and other pro‐inflammatory pathways. In this review, we discuss the current knowledge on the pathogenicity of autoreactive IgE in AbAID and their status as therapeutic targets. We also highlight unresolved issues including the need for assays that reproducibly quantify IgE AAbs, to validate their diagnostic and prognostic value, and to further study their pathophysiological contributions to AbAID. [ABSTRACT FROM AUTHOR]

Background: Autoreactive immunoglobulin E (IgE) antibodies to self‐peptides within the epidermis have been identified in patients with atopic dermatitis (AD). Prevalence, concomitant diseases, patient characteristics, and risk factors of IgE autoantibody development remain elusive. We aimed to determine IgE autoantibodies in serum samples (n = 672) from well‐characterized patients with AD and controls (1.2–88.9 years). Methods: Atopic dermatitis patients were sub‐grouped in AD with comorbid Type‐2 diseases ("AD + Type 2"; asthma, allergic rhinitis, food allergy, n = 431) or "solely AD" (n = 115). Also, subjects without AD but with Type‐2 diseases ("atopic controls," n = 52) and non‐atopic "healthy controls" (n = 74) were included. Total proteins from primary human keratinocytes were used for the immunoassay to detect IgE autoantibodies. Values were compared to already known positive and negative serum samples. Results: Immunoglobulin E autoantibodies were found in 15.0% (82/546) of all analyzed AD‐patients. "AD + Type 2" showed a higher prevalence (16.4%) than "solely AD" (9.6%). "Atopic controls" (9.6%) were comparable with "solely AD" patients, while 2.7% of healthy controls showed IgE autoantibodies. Of those with high levels of IgE autoantibodies, 15 out of 16 were patients with "AD + Type 2". AD patients with IgE autoantibodies were younger than those without. Patients with IgE autoreactivity also displayed higher total serum IgE levels. Factors that affected IgE autoantibody development were as follows: birth between January and June, cesarean‐section and diversity of domestic pets. Conclusions: Immunoglobulin E autoantibodies in AD seem to associate with the presence of atopic comorbidities and environmental factors. The potential value of IgE autoantibodies as a predictive biomarker for the course of AD, including the atopic march, needs further exploration. [ABSTRACT FROM AUTHOR]

Background: With the current trend in healthcare moving towards a more value‐based approach, it is essential to understand what value encompasses. Objectives: To develop an actionable value‐based outcome set (VOS) for daily practice. Methods: A mixed method approach was used consisting of four phases. Formerly, a systematic review was conducted, providing an overview of all patient‐relevant outcomes defined in current literature. These 23 outcomes were then presented to a group of patients, using a modified nominal group technique (NGT), to establish whether these results represented all of their relevant outcomes. Subsequently, these outcomes were ranked according to importance by patients attending our academic specialized psoriasis clinic. A review of the literature was performed to assess which instruments were available and suitable to evaluate the outcomes in this VOS. Finally, a pilot feasibility test was performed amongst patients. Results: Of the 23 outcomes, two were omitted from the ranking exercise after the NGT. In the ranking exercise, 120 patients participated. The median age was 50.0 (IQR 25.0) years and 36.7% were female. Median PASI score was 2.4 (IQR 5.2), and treatments varied from topicals to biologicals. The outcomes scored as most important were symptom control, treatment efficacy, confidence in care and control of disease. The least important outcomes were comorbidity control, productivity and cost of care. A significant difference was shown between the ranking of the outcomes (p < 0.001). In total, 12 instruments were selected, which are reported by both patient and provider, to measure the outcomes in this VOS. Median completion time for the patient part was 30 min (IQR 2.8). Conclusions: This VOS is a first proposal to evaluate psoriasis care in a value‐based manner. Measuring these outcomes can enable us to critically appraise and improve current care processes, within the reality of available resources, thereby increasing value for patients. [ABSTRACT FROM AUTHOR]

Dupilumab is a treatment option for moderate-to-severe atopic dermatitis (AD). Not all patients treated with dupilumab achieve and maintain clinically meaningful responses; some experience adverse events and some discontinue dupilumab for other reasons. For these patients, prospective data are needed to better understand the efficacy of systemic medications administered after discontinuation of dupilumab. Lebrikizumab (LEB) is a monoclonal antibody that binds with high affinity and slow off-rate to interleukin (IL)-13, thereby blocking the downstream effects of IL-13 with high potency. ADhere (NCT04250337) is a randomized, double-blind phase 3 trial evaluating the efficacy of lebrikizumab in combination with topical corticosteroids (TCS) over 16 weeks in adults and adolescents with moderate-to-severe AD. The results of this study, previously reported, showed statistically and clinically meaningful improvements in the signs and symptoms of AD in patients treated with LEB plus TCS vs. placebo (PBO) plus TCS. Of the patients randomized to LEB plus TCS, 20 reported prior dupilumab exposure. This study aims to evaluate the efficacy of LEB plus low to mid-potency TCS for the treatment of moderate-to-severe AD in the subpopulation of ADhere patients with prior exposure to dupilumab. At baseline, eligible patients in ADhere were randomized 2 : 1 to LEB 250 mg plus TCS or PBO plus TCS. Patients with prior exposure to dupilumab were permitted, with at least 8 weeks of washout prior to entering the study. Reported medical history was used to identify patients with prior exposure to dupilumab. Efficacy was measured through Investigator's Global Assessment (IGA), Eczema Area and Severity Index (EASI) and Pruritus Numeric Rating Scale (NRS). ADhere analyses were performed on a modified population, excluding 17 patients (from a single study site) whose eligibility could not be confirmed. All analyses are descriptive summaries using post hoc, as-observed analyses. The Pruritus NRS analysis only includes patients with baseline values ≥4. Observed results exclude data collected after use of rescue medication or treatment discontinuation. In ADhere, 211 patients were randomized 2 : 1 to LEB plus TCS (n = 145) or PBO plus TCS (n = 66). Of the patients randomized to LEB plus TCS, 20 reported prior dupilumab exposure. Of these 20 patients, the reason for dupilumab discontinuation was loss of response or inadequate response (10 patients), subject decision (four patients) or intolerance to medication (one patient). The final five patients discontinued due to affordability, treatment availability or unspecified reasons. In patients treated with LEB plus TCS, baseline disease characteristics were comparable between the overall LEB-treated population (n = 145) and the subpopulation with prior dupilumab exposure (n = 20). Of the 20 patients with prior dupilumab exposure, 13 patients presented with an IGA of three and seven patients presented with an IGA of 4. The mean [standard deviation (SD)] body surface area reported at baseline was 37.3 (15.7). The mean (SD) baseline scores for EASI and Pruritus NRS were 25.9 (8.1) and 7.8 (1.9), respectively. The mean (SD) duration since AD onset was longer in patients with prior dupilumab experience vs. the overall LEB-treated population 27.0 (22.5) vs. 21.0 (17.4) years, respectively]. In patients treated with LEB plus TCS, two of the 20 with prior dupilumab exposure were excluded due to use of rescue medication or treatment discontinuation. The IGA 0/1 with 2-point improvement was achieved by 6/18 patients, EASI 75 was achieved by 13/18 patients and Pruritus NRS 4-point improvement was achieved by 8/15 patients at Week 16. One patient reported rescue medication use. The results of this subpopulation analysis suggest that patients with prior dupilumab exposure can benefit from lebrikizumab treatment in combination with TCS. Additional data are needed to confirm this finding due to the small number of patients in the subpopulation. [ABSTRACT FROM AUTHOR]

T lymphocytes (T cells) are major players of the adaptive immune response. Naive T cells are primed in the presence of cytokines, leading to polarization into distinct T‐cell subsets with specific functions. These subsets are classified based on their T‐cell receptor profile, expression of transcription factors, surface cytokine and chemokine receptors, and their cytokine production, which together determine their specific function. This review provides an overview of the various T‐cell subsets and their function in several inflammatory skin disorders ranging from allergic inflammation to skin tumors. Moreover, we highlight similarities of T‐cell responses across different skin disorders, demonstrating the presence of similar and opposing functions for the different T‐cell subsets. Finally, we discuss the effects of currently available and promising therapeutic approaches to harness T cells in inflammatory skin diseases for which efficacy next to unwanted side effects provide new insights into the pathophysiology of skin disorders. [ABSTRACT FROM AUTHOR]

Chronic spontaneous urticaria (CSU) imposes a significant burden on patients, families and healthcare systems. Management is difficult, due to disease heterogeneity and insufficient efficacy of classical drugs such as H1R‐antihistamines. Better understanding of the mechanisms has enabled a stratified approach to the management of CSU, supporting the use of targeted treatment with omalizumab. However, many practical issues including selection of responders, the definition of response, strategies to enhance the responder rate, the duration of treatment and its regimen (in the clinic or home‐based) and its cost‐effectiveness still require further clarification. The EAACI Guidelines on the use of omalizumab in CSU follow the GRADE approach in formulating recommendations for each outcome. In addition, future therapeutic approaches and perspectives as well as research priorities are discussed. [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]

Keywords: algorithm; allergy; atopic; atopic dermatitis; childhood; children; diagnosis; eczema; immune system; medical algorithm; pediatric EN algorithm allergy atopic atopic dermatitis childhood children diagnosis eczema immune system medical algorithm pediatric 403 406 4 01/09/21 20210101 NES 210101 Atopic dermatitis (AD, atopic eczema) is a chronic, relapsing, pruritic, noncommunicable inflammatory skin disease that affects children and adults.1 It almost always has its debut in early life;2,3 therefore, this medical algorithm focuses on diagnosis (part I) and therapy (part II4) of AD in early childhood, which is defined by UNESCO as "the period from birth to eight years old." ETFAD/EADV Eczema task force 2015 position paper on diagnosis and treatment of atopic dermatitis in adult and paediatric patients. Algorithm, allergy, atopic, atopic dermatitis, childhood, children, diagnosis, eczema, immune system, medical algorithm, pediatric. [Extracted from the article]

This systematic review evaluates the efficacy and safety of omalizumab for chronic spontaneous urticaria (CSU). PubMed, Embase, and Cochrane Library were searched for RCTs. Critical and important CSU‐related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. Ten RCTs including 1620 subjects aged 12 to 75 years old treated with omalizumab for 16 to 40 weeks were evaluated. Omalizumab 150 mg does not result in clinically meaningful improvement (high certainty) of the urticaria activity score (UAS)7 (mean difference (MD) −5; 95%CI −7.75 to −2.25), and the itch severity score (ISS)7 (MD −2.15; 95% CI −3.2 to −1.1) does not increase (moderate certainty) quality of life (QoL) (Dermatology Life Quality Index (DLQI); MD −2.01; 95%CI −3.22 to −0.81) and decreases (moderate certainty) rescue medication use (MD −1.68; 95%CI −2.95 to −0.4). Omalizumab 300 mg results in clinically meaningful improvements (moderate certainty) of the UAS7 (MD −11.05; 95%CI −12.87 to −9.24), the ISS7 (MD −4.45; 95%CI −5.39 to −3.51), and QoL (high certainty) (DLQI; MD −4.03; 95% CI −5.56 to −2.5) and decreases (moderate certainty) rescue medication use (MD −2.04; 95%CI −3.19 to −0.88) and drug‐related serious AEs (RR 0.77; 95%CI 0.20 to 2.91). [ABSTRACT FROM AUTHOR]

This systematic review evaluates the efficacy, safety and economic impact of dupilumab compared to standard of care for uncontrolled moderate‐to‐severe atopic dermatitis (AD). Pubmed, EMBASE and Cochrane Library were searched for RCTs and health economic evaluations. Critical and important AD‐related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. Seven RCTs including 1845 subjects >12 years treated with dupilumab 16 to 52 weeks were evaluated. For adults, there is high certainty that dupilumab decreases SCORAD (MD −30,72; 95% CI −34,65% to −26,79%) and EASI‐75 (RR 3.09; 95% CI 2.45 to 3.89), pruritus (RR 2.96; 95% CI 2.37 to 3.70), rescue medication (RR 3.46; 95% CI 2.79 to 4.30), sleep disturbance (MD −7.29; 95% CI −8.23 to −6.35) and anxiety/depression (MD −3.08; 95% CI −4.41 to −1.75) and improves quality of life (MD −4.80; 95% CI −5.55 to −4.06). The efficacy for adolescents is similar. Dupilumab‐related adverse events (AEs) slightly increase (low certainty). The evidence for dupilumab‐related serious AE is uncertain. The incremental cost‐effectiveness ratio ranged from 28 500 £ (low certainty) to 124 541 US$ (moderate certainty). More data on long‐term safety are needed both for children and for adults, together with more efficacy data in the paediatric population. Registration: PROSPERO (CRD42020153645). [ABSTRACT FROM AUTHOR]

Keywords: algorithm; atopic dermatitis; children; eczema; therapy EN algorithm atopic dermatitis children eczema therapy 407 410 4 01/09/21 20210101 NES 210101 The diagnostic work-up of atopic dermatitis (AD, atopic eczema) was discussed in part I.1 This part of the medical algorithm focuses on the therapy of AD in early childhood and is based on recent literature and international guidelines.2-4 The management of AD is mainly based on disease severity, which has already been discussed in part I. Basic therapy of the disturbed skin barrier is always necessary, that is, also for children that do not suffer from active lesions. Climate therapy at high altitude is beneficial for atopic dermatitis, probably due to UV exposure, avoidance of allergen exposure, and decreased stress.7 For severe AD, or for cases that do not respond well to topical therapy, wet wrap therapy can be initiated in inpatient or outpatient settings.8 Ultraviolet (UV) therapy is used reluctantly in early childhood due to the cumulative UV dosage, time necessary, and anxiety in the UV cabin. Given the special pace of innovation in AD treatment, the future is bright for young children with severe atopic dermatitis!. [Extracted from the article]

Objective SSc and localized sclerosis (LoS) are considered clinically distinct entities. We describe herein the coexistence of SSc and LoS by both a systematic literature review and an observational cohort study of unselected SSc patients. Methods Original studies documenting the coexistence of SSc and LoS were identified in three electronic databases by means of a systematic literature search according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Additionally, the coexistence of SSc and LoS was studied in a prospective cohort of SSc patients visiting the Ghent University Scleroderma Unit for their yearly follow-up visit between January 2018 and January 2019. Results Five studies were finally included for quality appraisal and data extraction. The coexistence of SSc and LoS ranged between 2.4 and 7.4%. RP, scleroderma pattern on nailfold videocapillaroscopy (NVC) and the presence of SSc-specific antibodies were commonly observed in coexistent cases. Additionally, coexistence of SSc and LoS was found in 8/296 (2.7%) consecutive SSc patients of the Ghent University Scleroderma Unit. RP was present in 6/8 coexistent cases; a scleroderma pattern on NVC was observed in all coexistent cases, and SSc-specific antibodies (i.e. cenp-B) were found in 4/8 coexistent cases. Conclusion This is the first systematic literature review with additional cohort evaluation investigating the coexistence of SSc and LoS. A relatively high overlap of SSc and LoS was revealed, which is peculiar because both are rare diseases. [ABSTRACT FROM AUTHOR]

This update on chronic urticaria (CU) focuses on the prevalence and pathogenesis of chronic spontaneous urticaria (CSU), the expanding spectrum of patient-reported outcome measures (PROMs) for assessing CU disease activity, impact, and control, as well as future treatment options for CU. This update is needed, as several recently reported findings have led to significant advances in these areas. Some of these key discoveries were first presented at past meetings of the Collegium Internationale Allergologicum (CIA). New evidence shows that the prevalence of CSU is geographically heterogeneous, high in all age groups, and increasing. Several recent reports have helped to better characterize two endotypes of CSU: type I autoimmune (or autoallergic) CSU, driven by IgE to autoallergens, and type IIb autoimmune CSU, which is due to mast cell (MC)-targeted autoantibodies. The aim of treatment in CU is complete disease control with absence of signs and symptoms as well as normalization of quality of life (QoL). This is best monitored by the use of an expanding set of PROMs, to which the Angioedema Control Test, the Cholinergic Urticaria Quality of Life Questionnaire, and the Cholinergic Urticaria Activity Score have recently been added. Current treatment approaches for CU under development include drugs that inhibit the effects of signals that drive MC activation and accumulation, drugs that inhibit intracellular pathways of MC activation and degranulation, and drugs that silence MCs by binding to inhibitory receptors. The understanding, knowledge, and management of CU are rapidly increasing. The aim of this review is to provide physicians who treat CU patients with an update on where we stand and where we will go. Many questions and unmet needs remain to be addressed, such as the development of routine diagnostic tests for type I and type IIb autoimmune CSU, the global dissemination and consistent use of PROMs to assess disease activity, impact, and control, and the development of more effective and well-tolerated long-term treatments for all forms of CU. [ABSTRACT FROM AUTHOR]

Biologicals have transformed the way of treatment of many immune-mediated disorders including cancer, autoimmune, and allergic diseases.[[1]] Biologicals and the understanding of their impact on diseases is a rapidly evolving field in which emerging important questions arise. Therefore, current EAACI AIT guidelines for HDM-driven allergic asthma do not recommend co-administration of biologicals with HDM AIT.[5] Large clinical trials with other biologicals are currently under development. EAACI Guidelines on biologicals will be of great relevance to move forward and consolidate the concept of personalized medicine and precision health for allergic diseases and asthma. [Extracted from the article]

Background: Allergen-specific immunotherapy (AIT) is the only curative treatment for type-1 allergies, but sometimes shows limited therapeutic response as well as local and systemic side effects. Limited control of local inflammation and patient symptoms hampers its widespread use in severe allergic asthma. Objective: Our aim was to evaluate whether AIT is more effective in suppression of local inflammation if performed under the umbrella of short-term non-specific immunomodulation using a small molecule inhibitor of JAK pathways. Methods: In C57BL/6J mice, a model of ovalbumin (OVA)-induced allergic airway inflammation and allergen-specific immunotherapy was combined with the administration of Tofacitinib (TOFA, a FDA-approved JAK inhibitor) from 48 hours prior to 48 hours after therapeutic OVA-injection. The effect of TOFA on human FOXP3+CD4+ T cells was studied in vitro. Results: AIT combined with short-term TOFA administration was significantly more effective in suppressing total cell and eosinophil infiltration into the lung, local cytokine production including IL-1β and CXCL1 and showed a trend for the reduction of IL-4, IL-13, TNF-α and IL-6 compared to AIT alone. Furthermore, TOFA co-administration significantly reduced systemic IL-6, IL-1β and OVA-specific IgE levels and induced IgG1 to the same extent as AIT alone. Additionally, TOFA enhanced the induction of human FOXP3+CD4+ T cells. Conclusions: This proof of concept study shows that JAK inhibition did not inhibit tolerance induction, but improved experimental AIT at the level of local inflammation. The improved control of local inflammation might extend the use of AIT in more severe conditions such as polyallergy, asthma and high-risk patients suffering from mastocytosis or anaphylaxis. [ABSTRACT FROM AUTHOR]

Supporting allergen-specific immunotherapy by inhibition of Janus kinases Allergen-specific immunotherapy (AIT) is the only disease-modifying and curative treatment for allergic diseases. The invention described here shows that inhibition of the JAK/STAT pathway for short periods of a few days during AIT is able to shift the balance of newly induced T-cell reactivity by restricting local inflammation. [Extracted from the article]

The article offers information on Body dysmorphic disorder (BDD), a mental health condition characterized by disproportional occupation with imagined or minimal defects in appearance. Topics discussed include association of obsession with shame, anxiety, depression, and poor quality of life; associations between BDD and anxiety and depression; and prevalence of BDD in dermatology patients.

Increased transepidermal water loss (TEWL) and decreased skin capacitance are characteristic features of the disturbed epidermal barrier in atopic eczema (AE). The "acid mantle", which is a slightly acidic film on the surface of the skin has led to the development of acidic emollients for skin care. In this context, the effect of citric acid-coated textiles on atopic skin has not been examined to date. A textile carrier composed of cellulose fibres was coated with a citric acid surface layer by esterification, ensuring a constant pH of 5.5-6.5. Twenty patients with AE or atopic diathesis were enrolled in the study. In a double-blind, half-side experiment, patients had to wear these textiles for 12 h a day for 14 days. On day 0 (baseline), 7 and 14, tolerability (erythema, pruritus, eczema, wearing comfort) and efficacy on skin barrier were assessed by TEWL skin hydration (corneometry/capacitance), pH and clinical scoring of eczema (SCORAD). Citric acid-coated textiles were well tolerated and improved eczema and objective parameters of skin physiology, including barrier function and a reduced skin surface pH, with potential lower pathogenic microbial colonisation. [ABSTRACT FROM AUTHOR]

We describe a 3‐month‐old child with an infantile hemangioma on the forehead with a blanched macule provoked by topical treatment with propranolol. This observation demonstrates that topically applied (non‐selective) beta‐blockers may induce blanched macules at the site of application, a side effect due to peripheral vasoconstriction of blood vessels by non‐selective beta‐2 blockade. This side effect was linked due to overuse and was reversible. This case illustrates the importance of providing thorough instructions regarding topical propranolol application. [ABSTRACT FROM AUTHOR]

Mast cells are pivotal effector cells in IgE-mediated allergic inflammatory diseases. Central for mast cell activation are signals from the IgE receptor FCεRI, which induce cell degranulation with the release of preformed mediators and de novo synthesis of proinflammatory leukotrienes and cytokines. How these individual mast cell responses are differentially controlled is still unresolved. We identify B cell lymphoma 10 (Bcl10) and mucosa-associated lymphoid tissue 1 (Malt1) as novel key regulators of mast cell signaling. Mice deficient for either protein display severely impaired IgE-dependent late phase anaphylactic reactions. Mast cells from these animals neither activate nuclear factor κB (NF-κB) nor produce tumor necrosis factor α or interleukin 6 upon FcεRI ligation even though proximal signaling, degranulation, and leukotriene secretion are normal. Thus, Bcl10 and Malt1 are essential positive mediators of FcεRI-dependent mast cell activation that selectively uncouple NF-κB-induced proinflammatory cytokine production from degranulation and leukotriene synthesis. [ABSTRACT FROM AUTHOR]

Atopic eczema (AE) is a chronic relapsing inflammatory skin disorder with increasing prevalence in Western societies. Even though we have made considerable progress in understanding the cellular and molecular nature of cutaneous inflammation, the precise pathomechanisms of AE still remain elusive. Experimental animal models are indispensable tools to study the pathogenic mechanisms and to test novel therapeutic approaches in vivo. For AE a considerable number of mouse models have been proposed and have been used to study specific aspects of the disease, such as genetics, skin barrier defects, immune deviations, bacteria–host interactions or the role of cytokines or chemokines in the inflammatory process. While some models closely resemble human AE, others appear to reflect only specific aspects of the disease. Here we review the currently available mouse models of AE in light of the novel World Allergy Organization classification of eczematous skin diseases and evaluate them according to their clinical, histopathological and immunological findings. The pathogenetic analogies between mice and men will be discussed. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]