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Atopic dermatitis (AD) is a chronic, heterogenous, inflammatory skin disorder associated with a high skin‐related health burden, typically starting in childhood and often persisting into adulthood. AD is characterized by a wide range of clinical phenotypes, reflecting multiple underlying pathophysiological mechanisms and interactions between genetics, immune system dysregulation and environmental factors. In this review, we describe the diverse cellular and molecular mechanisms involved in AD, including the critical role of T‐cell‐driven inflammation, primarily via T helper (Th) 2‐ and Th17‐derived cytokines, many of which are mediated by the Janus kinase (JAK) signaling pathway. These local inflammatory processes interact with sensory neuronal pathways, contributing to the clinical manifestations of AD, including itch, pain and sleep disturbance. The recent elucidation of the molecular pathways involved in AD has allowed treatment strategies to evolve from broad‐acting systemic immunosuppressive therapies to more targeted agents, including JAK inhibitors and cytokine‐specific biologic agents. Evidence from the clinical development of these targeted therapies has reinforced and expanded our understanding of the pathophysiological mechanisms underlying AD and holds promise for individualized treatment strategies tailored to specific AD subtypes. [ABSTRACT FROM AUTHOR]

Background: The oral Janus kinase 1 (JAK1) inhibitor abrocitinib, which reduces interleukin-4 and interleukin-13 signaling, is being investigated for the treatment of atopic dermatitis. Data from trials comparing JAK1 inhibitors with monoclonal antibodies, such as dupilumab, that block interleukin-4 receptors are limited.Methods: In a phase 3, double-blind trial, we randomly assigned patients with atopic dermatitis that was unresponsive to topical agents or that warranted systemic therapy (in a 2:2:2:1 ratio) to receive 200 mg or 100 mg of abrocitinib orally once daily, 300 mg of dupilumab subcutaneously every other week (after a loading dose of 600 mg), or placebo; all the patients received topical therapy. The primary end points were an Investigator's Global Assessment (IGA) response (defined as a score of 0 [clear] or 1 [almost clear] on the IGA [scores range from 0 to 4], with an improvement of ≥2 points from baseline) and an Eczema Area and Severity Index-75 (EASI-75) response (defined as ≥75% improvement from baseline in the score on the EASI [scores range from 0 to 72]) at week 12. The key secondary end points were itch response (defined as an improvement of ≥4 points in the score on the Peak Pruritus Numerical Rating Scale [scores range from 0 to 10]) at week 2 and IGA and EASI-75 responses at week 16.Results: A total of 838 patients underwent randomization; 226 patients were assigned to the 200-mg abrocitinib group, 238 to the 100-mg abrocitinib group, 243 to the dupilumab group, and 131 to the placebo group. An IGA response at week 12 was observed in 48.4% of patients in the 200-mg abrocitinib group, 36.6% in the 100-mg abrocitinib group, 36.5% in the dupilumab group, and 14.0% in the placebo group (P<0.001 for both abrocitinib doses vs. placebo); an EASI-75 response at week 12 was observed in 70.3%, 58.7%, 58.1%, and 27.1%, respectively (P<0.001 for both abrocitinib doses vs. placebo). The 200-mg dose, but not the 100-mg dose, of abrocitinib was superior to dupilumab with respect to itch response at week 2. Neither abrocitinib dose differed significantly from dupilumab with respect to most other key secondary end-point comparisons at week 16. Nausea occurred in 11.1% of the patients in the 200-mg abrocitinib group and 4.2% of those in the 100-mg abrocitinib group, and acne occurred in 6.6% and 2.9%, respectively.Conclusions: In this trial, abrocitinib at a dose of either 200 mg or 100 mg once daily resulted in significantly greater reductions in signs and symptoms of moderate-to-severe atopic dermatitis than placebo at weeks 12 and 16. The 200-mg dose, but not the 100-mg dose, of abrocitinib was superior to dupilumab with respect to itch response at week 2. Neither abrocitinib dose differed significantly from dupilumab with respect to most other key secondary end-point comparisons at week 16. (Funded by Pfizer; JADE COMPARE ClinicalTrials.gov number, NCT03720470.). [ABSTRACT FROM AUTHOR]

Background: Janus kinase (JAK) inhibition is a new mode of action in atopic dermatitis (AD); clarity about drug class safety considerations in the context of AD is important. Baricitinib, an oral, reversible, selective inhibitor of JAK1/JAK2, is in late‐stage development for adult patients with moderate‐to‐severe AD. Objective: To report pooled safety data for baricitinib in patients with moderate‐to‐severe AD in the clinical development program including long‐term extension (LTE) studies. Methods: This analysis included patient‐level safety data from six double‐blinded, randomized, placebo‐controlled studies (one phase 2 and five phase 3), one double‐blinded, randomized, LTE study and one open‐label LTE study, reported in three data sets: placebo‐controlled, 2‐mg – 4‐mg extended and All‐bari AD. Safety outcomes include treatment‐emergent adverse events, adverse events of special interest and abnormal laboratory changes. Proportions of patients with events and incidence rates were calculated. Results: Data were collected for 2531 patients who were given baricitinib for 2247 patient‐years (median duration 310 days). The frequency of serious infections, opportunistic infections and conjunctival disorders was low and similar between treatment groups in the placebo‐controlled period. The most common serious infections were eczema herpeticum [n = 11, incidence rates (IR) = 0.5], cellulitis (n = 6, IR = 0.3) and pneumonia (n = 3, IR = 0.1). There were four opportunistic infections (IR = 0.2). No malignancies, gastrointestinal perforations, positively adjudicated cardiovascular events or tuberculosis were reported in the placebo‐controlled period in baricitinib‐treated patients. Frequency of herpes simplex was higher in the 4‐mg group (6.1%) vs. the 2‐mg (3.6%) and placebo group (2.7%); IRs in the extended data set (2‐mg IR = 9.6; 4‐mg IR = 14.5) were lower vs. the placebo‐controlled data set (2‐mg IR = 12.4; 4‐mg IR = 21.3). In the All‐bari AD data set, there were two positively adjudicated major adverse cardiovascular events (2‐mg group): two venous thrombosis events (4‐mg group) and one death. Conclusion: This integrated safety analysis in patients with moderate‐to‐severe AD confirms the established safety profile of baricitinib. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is a heterogeneous inflammatory skin disease with different clinical phenotypes based on factors such as age, race, comorbidities, and clinical signs and symptoms. The effect of these factors on therapeutic responses in AD has only been scarcely studied and not for upadacitinib. Currently, there is no biomarker predicting response to upadacitinib. Objectives: Evaluate the efficacy of the oral Janus kinase inhibitor upadacitinib across patient subgroups (baseline demographics, disease characteristics and prior treatment) in patients with moderate‐to‐severe AD. Methods: Data from phase 3 studies (Measure Up 1, Measure Up 2 and AD Up) were utilized for this post hoc analysis. Adults and adolescents with moderate‐to‐severe AD were randomized to receive once daily oral upadacitinib 15 mg, upadacitinib 30 mg or placebo; patients enrolled in the AD Up study received concomitant topical corticosteroids. Data from the Measure Up 1 and Measure Up 2 studies were integrated. Results: A total of 2584 patients were randomized. A consistently greater proportion of patients achieved at least 75% improvement in the Eczema Area and Severity Index, a 0 or 1 on the validated Investigator Global Assessment for Atopic Dermatitis, and improvement in itch (including an achievement of a reduction of ≥4; and score of 0/1 in Worst Pruritus Numerical Rating Scale) with upadacitinib compared with placebo at Week 16, regardless of age, sex, race, body mass index, AD severity, body surface area involvement, history of atopic comorbidities or asthma, or previous exposure to systemic therapy or cyclosporin. Conclusions: Upadacitinib had consistently high skin clearance rates and itch efficacy across subgroups of patients with moderate‐to‐severe AD through Week 16. These results support upadacitinib as a suitable treatment option in a variety of patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT03569293 (Measure Up 1), NCT03607422 (Measure Up 2) and NCT03568318 (AD Up). [ABSTRACT FROM AUTHOR]

Background: Dupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, inhibits signaling of interleukin-4 and interleukin-13, type 2 cytokines that may be important drivers of atopic or allergic diseases such as atopic dermatitis.Methods: In two randomized, placebo-controlled, phase 3 trials of identical design (SOLO 1 and SOLO 2), we enrolled adults with moderate-to-severe atopic dermatitis whose disease was inadequately controlled by topical treatment. Patients were randomly assigned in a 1:1:1 ratio to receive, for 16 weeks, subcutaneous dupilumab (300 mg) or placebo weekly or the same dose of dupilumab every other week alternating with placebo. The primary outcome was the proportion of patients who had both a score of 0 or 1 (clear or almost clear) on the Investigator's Global Assessment and a reduction of 2 points or more in that score from baseline at week 16.Results: We enrolled 671 patients in SOLO 1 and 708 in SOLO 2. In SOLO 1, the primary outcome occurred in 85 patients (38%) who received dupilumab every other week and in 83 (37%) who received dupilumab weekly, as compared with 23 (10%) who received placebo (P<0.001 for both comparisons with placebo). The results were similar in SOLO 2, with the primary outcome occurring in 84 patients (36%) who received dupilumab every other week and in 87 (36%) who received dupilumab weekly, as compared with 20 (8%) who received placebo (P<0.001 for both comparisons). In addition, in the two trials, an improvement from baseline to week 16 of at least 75% on the Eczema Area and Severity Index was reported in significantly more patients who received each regimen of dupilumab than in patients who received placebo (P<0.001 for all comparisons). Dupilumab was also associated with improvement in other clinical end points, including reduction in pruritus and symptoms of anxiety or depression and improvement in quality of life. Injection-site reactions and conjunctivitis were more frequent in the dupilumab groups than in the placebo groups.Conclusions: In two phase 3 trials of identical design involving patients with atopic dermatitis, dupilumab improved the signs and symptoms of atopic dermatitis, including pruritus, symptoms of anxiety and depression, and quality of life, as compared with placebo. Trials of longer duration are needed to assess the long-term effectiveness and safety of dupilumab. (Funded by Sanofi and Regeneron Pharmaceuticals; SOLO 1 ClinicalTrials.gov number, NCT02277743 ; SOLO 2 ClinicalTrials.gov number, NCT02277769 .). [ABSTRACT FROM AUTHOR]

Atopic conditions (atopic dermatitis, rhinitis, and asthma) belong to the most common noncommunicable diseases and are driven by chronic inflammatory reactions. They have a strong impact on the quality of life and represent a substantial and growing socio-economic burden. Interestingly, there is an increasing interest in the development of new therapeutic options with a number of biologics and small molecules targeting potential key mechanisms in atopic conditions. However, besides the safety issue, most of the new active substances are still evaluated according to the traditional efficacy paradigm focusing on the success in treating exacerbations and flares. Instead, the future approaches in drug development and assessment should rather concentrate on the long-term control of these diseases and consider their potential as disease-modifying strategies in the era of precision medicine. To reach this goal, a number of unsolved issues have to be addressed and consensually accepted by the stakeholders in this field. Thus, a successful and rapid development of new treatments requests a paradigm shift and a new way of thinking in the mind of physicians, pharmaceutical industry, regulators, and HTAs. This seems mandatory in order to optimize drug development and to facilitate the accessibility of new therapies to the growing population of patients suffering from atopic conditions on a global level. [ABSTRACT FROM AUTHOR]

The author discusses the results of the 3rd Global Allergy Forum held in Davos, Switzerland and was sponsored by the Center for Allergy Research and Education (CK-CARE). The author mentions the standardization of the epidemiology of the atopic dermatitis (AD) and its etiology and treatment. The author cites the discussion of other issues related on AD including the establishment of global registries.

Moderate-to-severe forms of atopic dermatitis ( AD) have a substantial impact on the quality of life of patients and their relatives, carrying a significant socioeconomic burden. They often require a systemic therapy, and ciclosporine A (CsA) is the only medicinal product approved for this indication in a limited number of European countries. However, due to the safety profile of CsA and its approval conditions, this treatment can only be prescribed for a limited period of time. Thus, moderate-to-severe forms of AD represent a significant unmet medical need and are subject to off-label prescriptions. Besides giving some insights into the approval procedures for medicinal products in the European Union, this short review is aimed to provide some relevant background information for off-label prescription in AD. It also provides a clinical algorithm for the off-label prescription of systemic immunosuppressants in AD, discusses the apparent dilemma between approval and guidelines, and finally suggests practical rules to be considered in the context of off-label prescription. [ABSTRACT FROM AUTHOR]

Systemic therapy for atopic dermatitis ( AD) is indicated in patients with severe disease refractory to adequate topical treatment. Currently available drugs aim to decrease inflammation by suppressing and/or modulating immune responses and thus may indirectly improve skin barrier function, resulting in a decrease in clinical signs and symptoms in particular pruritus. Before considering systemic treatment, patient adherence to topical treatment including skin care has to be ensured. The selection of the drug depends on the disease severity, localization, complications, concomitant diseases, and age of the patient, but also on their availability and costs as well as the doctor's experience. Bearing in mind the potential risk of resistance, systemic therapy with antibiotics should be exclusively considered in clinically manifest infections such as in children. Here, we review recently published clinical trials and case reports on systemic therapy of pediatric and adult patients with AD to draw conclusions for clinical practice. Although AD is a common disease, controlled clinical studies investigating the efficacy of systemic drugs are scarce, except for cyclosporine, which has been approved for the therapy of severe AD. [ABSTRACT FROM AUTHOR]

The concept of disease modification has been introduced to define the therapeutic strategies aimed to break, stop, or reverse the natural course of a chronic invalidating disease. This strategy is tightly related to the biomarker-based stratification of affected patients using genetic and other biological markers. With regard to the progress in understanding the genetic background of atopic dermatitis ( AD), its natural history and its pivotal role in the emergence of allergic asthma, the time is mature to foster the research field of biomarkers in AD and to consider the elaboration of disease-modifying strategies in the management of AD with the goal to stop or even reverse the atopic march. [ABSTRACT FROM AUTHOR]

A series of recent studies have demonstrated that the immunoregulatory pathway of tryptophan catabolism, initiated by the enzyme indoleamine 2,3-dioxygenase ( IDO), is a critical participant in allergic inflammation. Originally known for its regulatory function during pregnancy and during chronic inflammation in tumorigenesis and infection, the activity of IDO seems to positively modify the inflammatory state of atopy or allergy. The tryptophan degradation pathway is important for tolerance induction during systemic allergen immunotherapy. Here, we focus on recent findings that establish the IDO pathway as central to allergic inflammation. [ABSTRACT FROM AUTHOR]

Within the last 100 years of allergen-specific immunotherapy, many clinical and scientific efforts have been made to establish alternative noninvasive allergen application strategies. Thus, intra-oral allergen delivery to the sublingual mucosa has been proven to be safe and effective. As a consequence, to date, sublingual immunotherapy (SLIT) is widely accepted by most allergists as an alternative to conventional subcutaneous immunotherapy. Although immunological mechanisms remain to be elucidated in detail, several studies in mice and humans within recent years provided deeper insights into local as well as systemic immunological features in response to SLIT. First of all, it was shown that the target organ, the oral mucosa, harbours a sophisticated immunological network as an important prerequisite for SLIT, which contains among other cells, local antigen-presenting cells (APC), such as dendritic cells (DCs), with a constitutive disposition to enforce tolerogenic mechanisms. Further on, basic research on local DCs within the oral mucosa gave rise to possible alternative strategies to deliver the allergens to other mucosal regions than sublingual tissue, such as the vestibulum oris. Moreover, characterization of oral DCs led to the identification of target structures for both allergens as well as adjuvants, which could be applied during SLIT. Altogether, SLIT came a long way since its very beginning in the last century and some, but not all questions about SLIT could be answered so far. However, recent research efforts as well as clinical approaches paved the way for another exciting 100 years of SLIT. [ABSTRACT FROM AUTHOR]

The author reflects on the current and future concepts of immunological mechanisms of allergen-specific immunotherapy, an effective treatment for immunoglobulin E (IgE) mediated allergic diseases. According to the author, allergen-specific immunotherapy strategy aims to improve efficacy and safety of the causative therapy to benefit allergic patients. The author suggests that there is growing evidence that the development on the use of allergen-specific immunotherapy is expected to move on.

The article introduces the topics discussed in the issue, including the global distribution of rhinoconjunctivitis, the relationship between topical corticosteroids and COX-1 positive cells in nasal polyps, and the pharmacoeconomics of allergic rhinitis.

The authors reflect on the significance of allergy research in promoting health care programs in Europe. They define allergy as a multifactorial disease that needs to be treated. They cite the influential role played by the European Union in all allergies research projects. They recognize the European Community Respiratory Health Survey as the first and most successful allergy research project. They further discuss other allergy issues like drug allergy, allergic rhinitis and atopic dermatitis.

The article discusses the relations between consensus statements (CS), evidence-based medicine (EBM) and guidelines in allergic diseases. According to the authors, CS is a document that corresponds the collective opinion of a convened expert panel, while EBM is an essential component in the preparation of guidelines. They note that EBM attempts to provide a logical framework from which the quality and relevance of clinical studies may be assessed in an unbiased manner.

Background: Topical glucocorticosteroids are the gold standard in treatment of atopic dermatitis (AD). Recently, topical calcineurin inhibitors have been developed for treatment of this condition. This study compared efficacy and safety of 0.1% methylprednisolone aceponate (MPA) ointment with 0.03% tacrolimus ointment for 3 weeks, in children and adolescents with severe to very severe flare of AD. Methods: The primary end point was treatment success, defined as a score of ‘clear’ or ‘almost clear’ in the static Investigator's Global Assessment (IGA) score. Secondary end points were the percentage change in the Eczema Area and Severity Index (EASI) and patients’ assessment of itch and sleep, Children's Dermatology Life Quality Index, patient's assessment of global response, affected Body Surface Area and medication costs. Results: 265 patients were randomized to either MPA ( n = 129) or tacrolimus ( n = 136) treatment, 257 patients completed the study. Methylprednisolone aceponate 0.1% ointment once daily provided rapid and relevant clinical benefit. Tacrolimus 0.03% ointment twice daily was equally effective with regard to success rate. Methylprednisolone aceponate was superior to tacrolimus for EASI, itch and sleep. Both treatments were well tolerated. Drug-related adverse events were only observed in the tacrolimus group. Medication costs were significantly lower for MPA. Conclusions: While both treatment groups showed similar efficacy results regarding treatment success (IGA), significant advantages were observed for EASI, itch and sleep with MPA 0.1%. These advantages and the significantly lower treatment costs highlight the benefits of MPA treatment, underlining its first-line role in treatment of children and adolescents with severe AD. [ABSTRACT FROM AUTHOR]

Linked article: R. Cheng et al. J Eur Acad Dermatol Venereol 2020; 34: 542–548. https://doi.org/10.1111/jdv.15979. [ABSTRACT FROM AUTHOR]

Background: Pimecrolimus cream 1% (Elidel, Novartis Pharmaceuticals AG) effectively improves/relieves pruritus associated with atopic dermatitis (AD), but few data are available regarding the timing of relief. The purpose of this study was to investigate the timing of pruritus relief produced with pimecrolimus in adults with mild/moderate AD and moderate/severe pruritus. Methods: Patients were randomized to 7 days of treatment with pimecrolimus ( n = 100) or vehicle ( n = 98). Pruritus severity was assessed daily on a 4-point scale (0 = absent, 3 = severe), reflecting the previous 24 h experience. Patients who completed this core study were eligible to enter a voluntary 5-week, open-label extension study. Results: A significant effect was noted within 48 h of treatment, with pruritus improving in 56% of pimecrolimus-treated patients and 34% of vehicle-treated patients ( P = 0.003). Pruritus relief was maintained during the remainder of the core and extension phases, and was accompanied by an improvement in the Investigator's Global Assessment score. Conclusion: Pimecrolimus cream 1% significantly reduced pruritus within 48 h. [ABSTRACT FROM AUTHOR]

Atopic eczema (AE) belongs to the group of atopic diseases that have become increasingly prevalent over the last decades. The pathophysiology of AE has long remained enigmatic, but much scientific effort has been invested in elucidating the genetic background and the immunological mechanisms underlying AE, leading to a better understanding of this complex disease and to new therapeutic strategies. This review provides an update on the scientific progress that has been achieved in clarifying the pathophysiological mechanisms of AE. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Atopic dermatitis(AD) is a biphasic inflammatory skin disease characterized by an initial phase predominated by Th2 cytokines which switches into a second and more chronic Th1 dominated eczematous phase. Two different, the high affinity receptor for IgE(FcεRI) bearing dendritic cell subtypes have been identified in the skin of AD patients: FcεRIhigh Langerhans cells(LC) and FcεRIhigh inflammatory dendritic epidermal cells(IDEC). These two dendritic cell subtypes are supposed to contribute distinctly to the biphasic nature and the outcome of T-cell responses in AD. In the light of recent developments a picture emerges that different IgE-receptor bearing DC subtypes in the blood and the skin of AD patients play a pivotal role in the complex pathophysiological network of AD. [ABSTRACT FROM AUTHOR]

Focuses on atopic dermatitis (AD). Discovery of the disease; Basic clinical aspects; Incidence; Definition and diagnostic criteria of AD; Epidemiologic studies on AD; Immunohistology of AD lesions.

Editorial. Discusses the skin as a target of various types of allergic reactions. Categories of the mechanisms of skin immune defense; Functional architecture of the skin immune system; Clinical expressions of various immunoallergic reactions in the skin.

This issue contains summaries of the best articles relevant to pediatric allergy and immunology, elected by members of the Section on Allergy and Immunology of the American Academy of Pediatrics. This information is from articles that appeared in the medical literature between December 1, 1996 and November 30, 1997. Among the articles are studies related to atopic dermatitis, food allergy, immunotherapy, pathophysiology, urticaria and angioedema and many more. Titles include: 'A Short-Term Trial of Tacrolimus Ointment for Atopic Dermatitis,' Allergenicity of Gourmet Nut Oils Processed by Different Methods, ' Treatment of Anaphylactic Sensitivity to Peanuts by Immunotherapy with Injections of Aqueous Peanut Extract,' 'Life-Threatening Fish Allerge Successfully Treated with Immunotherapy,' and many more.

The article provides information on atopic dermatitis (AD), a skin disease with a spectra of clinical manifestations. It notes the common long-term treatment for AD such as the reactive treatment approach and proactive approach. It also discusses defects of epidermal barrier function in AD lesions. The result of the profilometric examination conducted on AD is presented. Moreover, it highlights the need for patients and physicians' understanding of proactive therapy

The author reflects on the prevalence of allergic disease. The author relates that allergic disease has grown in all countries of the world resulting in a global health problem. The author added that the increase in allergic disease is not restricted to developed countries although in countries with endemic parasitosis, mechanisms associated with the increased allergy prevalence may differ.

The author reflects on the need for a harmonized nomenclature for the condition atopic dermatitis, atopic eczema, or eczema to determine the different levels of the most common skin disease. He cites the study by Kantor et al. which established the widespread acceptance of the term atopic dermatitis which is ripe for international agreement. The author believes that the term can impact the data mining of the scientific community in terms of search strategies in databases.

Summary: Background: Tralokinumab is a fully human monoclonal antibody that specifically neutralizes interleukin‐13, a key driver of atopic dermatitis (AD). Objectives: To evaluate the efficacy and safety of tralokinumab in combination with topical corticosteroids (TCS) in patients with moderate‐to‐severe AD who were candidates for systemic therapy. Methods: This was a double‐blind, placebo plus TCS controlled phase III trial. Patients were randomized 2 : 1 to subcutaneous tralokinumab 300 mg or placebo every 2 weeks (Q2W) with TCS as needed over 16 weeks. Patients who achieved an Investigator's Global Assessment (IGA) score of 0/1 and/or 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16 with tralokinumab were rerandomized 1 : 1 to tralokinumab Q2W or every 4 weeks (Q4W), with TCS as needed, for another 16 weeks. Results: At week 16, more patients treated with tralokinumab than with placebo achieved IGA 0/1: 38·9% vs. 26·2% [difference (95% confidence interval): 12·4% (2·9–21·9); P = 0·015] and EASI 75: 56·0% vs. 35·7% [20·2% (9·8–30·6); P < 0·001]. Of the patients who were tralokinumab responders at week 16, 89·6% and 92·5% of those treated with tralokinumab Q2W and 77·6% and 90·8% treated with tralokinumab Q4W maintained an IGA 0/1 and EASI 75 response at week 32, respectively. Among patients who did not achieve IGA 0/1 and EASI 75 with tralokinumab Q2W at 16 weeks, 30·5% and 55·8% achieved these endpoints, respectively, at week 32. The overall incidence of adverse events was similar across treatment groups. Conclusions: Tralokinumab 300 mg in combination with TCS as needed was effective and well tolerated in patients with moderate‐to‐severe AD. What is already known about this topic?Atopic dermatitis (AD) is a chronic interleukin (IL)‐13‐mediated disease.In clinical practice, biologics are commonly initiated as add‐on therapy to topical corticosteroids (TCS).Tralokinumab is a fully human monoclonal antibody that binds specifically to the IL‐13 cytokine with high affinity, thereby preventing receptor interaction and subsequent downstream signalling.Tralokinumab combined with TCS showed early and sustained efficacy and safety in a 12‐week, phase IIb trial in moderate‐to‐severe AD. What does this study add?This is the first phase III trial evaluating a targeted anti‐IL‐13 biologic in combination with TCS.These data demonstrate that tralokinumab plus TCS can achieve significant improvements in AD signs and symptoms and quality of life, as well as exert a steroid‐sparing effect.Response with tralokinumab in combination with TCS was maintained over 32 weeks.Tralokinumab may be considered a targeted biological treatment option for patients with moderate‐to‐severe AD. Linked Comment: Morra and Drucker. Br J Dermatol 2021; 184:386–387. Plain language summary available online [ABSTRACT FROM AUTHOR]

The article offers information on the journal's continued commitment and development which include its collaboration between the scientific and production teams of the journal.

The article discusses the changes in the pathogenesis and biomarkers in atopic dermatitis (AD) since the 1994 publication of the Diagnostic Criteria for Atopic Dermatitis (AD). Topics discussed include the serum immunoglobulin E (IgE) as the earliest molecules tested as a biomarker in AD and increased risk of AD development associated with a genetically mediated keratinocyte deficiency of filaggrin.

Mineral oils and waxes are mixtures of predominantly saturated hydrocarbons consisting of straight‐chain, branched and ring structures with carbon chain lengths greater than C14. They have been used for many decades in skin and lip care cosmetic products due to their excellent skin tolerance as well as their high protecting and cleansing performance and broad viscosity options. In contrast to vegetable oils, mineral oils are non‐allergenic since they are highly stable and not susceptible to oxidation or rancidity. They have a long history of safe use which is confirmed by clinical and epidemiological data. In Europe, mineral oils are only permitted in cosmetics if compliant with purity specifications on polycyclic aromatic hydrocarbons and safety requirements laid down in the European pharmacopoeia and the EU cosmetics regulation EC/1223/2009. The high quality of these mineral oils is assured by robust quality assurance and a refining/purification process designed to exclude substances with carcinogenic potential and to minimize the presence of mineral oil aromatic hydrocarbons. Given their highly lipophilic properties, mineral oils do not penetrate human skin and, thus, are not systemically bioavailable in the body. Moreover, no significant changes in the skin and no effects on any internal organ system have been reported and attributed to the topical application of refined mineral oils. Regarding potential oral exposure from cosmetic lip care products, Cosmetics Europe, the European trade association for the cosmetics and personal care industry, has advised cosmetic manufacturers to only use mineral oil fractions for which recognized food acceptable daily intake (ADI) values apply. The estimated dose of mineral oils ingested via lip care products contributes to <10% of the ADI value and should therefore be considered of no toxicological concern. [ABSTRACT FROM AUTHOR]

Indoor and outdoor airborne pollutants modify our environment and represent a growing threat to human health worldwide. Airborne pollution effects on respiratory and cardiac health and diseases have been well established, but its impact on skin remains poorly described. Nonetheless, the skin is one of the main targets of pollutants, which reach the superficial and deeper skin layers by transcutaneous and systemic routes. In this review, we report the outcomes of basic and clinical research studies monitoring pollutant levels in human tissues including the skin and hair. We present a current understanding of the biochemical and biophysical effects of pollutants on skin metabolism, inflammatory processes and oxidative stress, with a focus on polyaromatic hydrocarbons and ground‐level ozone that are widespread outdoor pollutants whose effects are mostly studied. We reviewed the literature to report the clinical effects of pollutants on skin health and skin ageing and their impact on some chronic inflammatory skin diseases. We also discuss the potential interactions of airborne pollutants with either ultraviolet radiation or human skin microbiota and their specific impact on skin health. [ABSTRACT FROM AUTHOR]

In this article, the author focuses on the multiple immunological pathways underlying atopic dermatitis (AD). He states that AD represents a genetic complex disease where gene-gene interactions and gene-environment interactions form a highly complex mosaic. He mentions that AD has a deep impact on the gene expression of filaggrin (FLG) and proteins of epidermal barrier. He discusses the lack of appropriate secretion of antimicrobial peptides (AMP) in inflamed skin of AD.

The article presents a case of leucopenia developed after treatment with adalimumab for severe plaque psoriasis and psoriatic arthritis. It states that a 34-year-old man had developed leucopenia after he was injected with two 40 milligrams adalimumab given with an interval of one week. The treatment was discontinued and re-introduced with 14-16 days interval and the leucocytes remained stable. It adds that the risk of leucopenia which might link to the number of previous systemic medications.

A letter to the editor is presented regarding the use of adalimumab in treating severe pustular psoriasis.

The article focuses on the subject matter of the journal's publication. According to the author, the format of the journal took up the diversity of allergic diseases into account by introducing a specific theme into some of its issues. These special themes would include one or two review papers as well as three to five original papers already accepted for publication. This year, two themes were proposed, for food allergy and for atopic dermatitis.

The article provides information on specific sublingual immunotherapy (SLIT). Clinical studies have shown that SLIT can be considered as a meaningful alternative to subcutaneous immunotherapy. These studies has clearly revealed that SLIT is an efficient and safe approach to treat allergic rhinoconjunctivitis and asthma. The development of allergen tables is the most recent progress in SLIT.

The article focuses on the grouping and publication of papers concerning the mechanisms, epidemiology, risk factors, prevention, diagnosis, control or pharmacoeconomics of allergic diseases. The format of "Allergy," the Official Organ of the European Academy of Allergy and Clinical Immunology, will take into account the diversity of allergic diseases by introducing in some issues a specific theme. The fist theme is devoted to the immune mechanisms of the Immoglobulin E mediated allergic reaction. Themes showing the widespread coverage of our journal, and it is of importance to mention that authors from Central European countries increasingly contribute to the field.

Discusses various aspects of atopic dermatitis (AD). Identification of the yeast Malassezia sympodialis as factor triggering AD; Level of circulating antibodies to staphylococcal enterotoxin B; Effective topical treatment regimen; Benefit of probiotics; Predominance of a Th2 cytokine profile.

Describes a case of subacute cutaneous lupus erythematosus (EL) showing kobnerization after a wasp sting. Isomorphic reaction; Skin biopsy; Edematous swelling; Induction of the LE by contact sensitization to one or more allergens of applied creams.

Abstract: This guideline was developed as a joint interdisciplinary European project, including physicians from all relevant disciplines as well as patients. It is a consensus‐based guideline, taking available evidence from other guidelines, systematic reviews and published studies into account. This second part of the guideline covers antimicrobial therapy, systemic treatment, allergen‐specific immunotherapy, complementary medicine, psychosomatic counselling and educational interventions, whereas the first part covers methods, patient perspective, general measures and avoidance strategies, basic emollient treatment and bathing, dietary intervention, topical anti‐inflammatory therapy, phototherapy and antipruritic therapy. Management of AE must consider the individual clinical variability of the disease. Systemic immunosuppressive treatment with cyclosporine, methotrexate, azathioprine and mycophenolic acid is established option for severe refractory cases, and widely available. Biologicals targeting the T helper 2 pathway such as dupilumab may be a safe and effective, disease‐modifying alternative when available. Oral drugs such as JAK inhibitors and histamine 4 receptor antagonists are in development. Microbial colonization and superinfection may cause disease exacerbation and can require additional antimicrobial treatment. Allergen‐specific immunotherapy with aeroallergens may be considered in selected cases. Psychosomatic counselling is recommended especially in stress‐induced exacerbations. Therapeutic patient education (‘Eczema school’) is recommended for children and adult patients. General measures, basic emollient treatment, bathing, dietary intervention, topical anti‐inflammatory therapy, phototherapy and antipruritic therapy have been addressed in the first part of the guideline. [ABSTRACT FROM AUTHOR]

Abstract: This guideline was developed as a joint interdisciplinary European project, including physicians from all relevant disciplines as well as patients. It is a consensus‐based guideline, taking available evidence from other guidelines, systematic reviews and published studies into account. This first part of the guideline covers methods, patient perspective, general measures and avoidance strategies, basic emollient treatment and bathing, dietary intervention, topical anti‐inflammatory therapy, phototherapy and antipruritic therapy, whereas the second part covers antimicrobial therapy, systemic treatment, allergen‐specific immunotherapy, complementary medicine, psychosomatic counselling and educational interventions. Management of AE must consider the individual clinical variability of the disease; highly standardized treatment rules are not recommended. Basic therapy is focused on treatment of disturbed barrier function by hydrating and lubricating topical treatment, besides further avoidance of specific and unspecific provocation factors. Topical anti‐inflammatory treatment based on glucocorticosteroids and calcineurin inhibitors is used for flare management and for proactive therapy for long‐term control. Topical corticosteroids remain the mainstay of therapy, whereas tacrolimus and pimecrolimus are preferred in sensitive skin areas and for long‐term use. Topical phosphodiesterase inhibitors may be a treatment alternative when available. Adjuvant therapy includes UV irradiation, preferably with UVB 311 nm or UVA1. Pruritus is targeted with the majority of the recommended therapies, but some patients may need additional antipruritic therapy. Antimicrobial therapy, systemic anti‐inflammatory treatment, immunotherapy, complementary medicine and educational intervention will be addressed in part II of the guideline. [ABSTRACT FROM AUTHOR]

The evidence‐ and consensus‐based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty‐nine experts (including clinicians and patient representatives) from 12 European countries participated. This second part of the guideline includes recommendations and detailed information on basic therapy with emollients and moisturizers, topical anti‐inflammatory treatment, antimicrobial and antipruritic treatment and UV phototherapy. Furthermore, this part of the guideline covers techniques for avoiding provocation factors, as well as dietary interventions, immunotherapy, complementary medicine and educational interventions for patients with atopic eczema and deals with occupational and psychodermatological aspects of the disease. It also contains guidance on treatment for paediatric and adolescent patients and pregnant or breastfeeding women, as well as considerations for patients who want to have a child. A chapter on the patient perspective is also provided. The first part of the guideline, published separately, contains recommendations and guidance on systemic treatment with conventional immunosuppressive drugs, biologics and janus kinase (JAK) inhibitors, as well as information on the scope and purpose of the guideline, and a section on guideline methodology. [ABSTRACT FROM AUTHOR]

Abstract: This paper deals with the characterization of an atomic hydrogen source created in a radio-frequency reactor with a helicon configuration. To achieve this purpose, optical (laser induced fluorescence) and electrical (Langmuir probe) diagnostics are used to monitor the behavior of the species composing the plasma. The influence of pressure, gas composition, and impact of the magnetic fields (in the source and diffusion chambers) are investigated. [Copyright &y& Elsevier]

The article reflects on the future of the journal "Allergy." It is said that to further improve the quality of the journal, the journal will be given a more global character and increase the expertise of the Associate Editors and the members of the Editorial board. Also, the journal will invite scientific leaders in the field to write reviews and opinion articles for the journal.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that develops on a complex genetic background, the so-called atopic diathesis. Genetic epidemiological studies based on linkage analysis with full genome scan strategies, as well as association and case-controlled studies, have unravelled several chromosomal loci with putative candidate genes. These loci were revealed to be distinct from those newly identified for allergic asthma. Some of these genes localized on chromosomes 3, 17 and 20 are shared with psoriasis, another chronic inflammatory skin disease. These observations suggest, at least, the role of putative genes involved in the down-regulation of inflammation in the skin. Single nucleotide polymorphisms have been identified in several genes for which the functional significance remains to be determined. In most (70–80%), but not all patients, AD is characterized by the presence of elevated total serum IgE levels. However, a subgroup of atopic patients (20–30%) exhibit normal IgE levels. Mechanisms contributing to the extrinsic/IgE-mediated and the intrinsic/non-IgE-mediated forms have been the focus of intensive research in recent years. These forms have been particularly studied in the context of AD, which has lead to new nomenclature recently approved by the World Allergy Organization. Moreover, we now have increasing evidence for the putative role of an autoimmune phenomenon in the complex pathophysiology of atopic dermatitis. Mainly adult patients exhibit specific IgE directed against self-proteins of epidermal origin. A new picture emerges in which the natural history of AD seems to be divided into three phases. First, an initial intrinsic phase, eczema, occurs in early infancy. This is then followed in 60–80% of cases by a sensitization to food and/or environmental allergens with the development of the extrinsic phase, true AD. In this form, it is speculated that antigen-presenting cells expressing the high-affinity receptor for IgE (FcεRI) play a major role in the control of inflammation. Consequently, these AD patients will have benefit from prevention measures. Finally, most probably due to molecular mimicry, an IgE sensitization to self-proteins is observed in 60–80% of AD patients. Whether these specific IgE antibodies have a pathophysiological role or are only to be considered as an epiphenomenon remains to be clarified. In summary, due to rapid advancements in the research field of atopic diseases, it now becomes possible for the first time to delineate a new disease classification of allergic and nonallergic subtypes of atopic diseases, thereby bringing hope to the clinician for a more specific treatment approach for each subgroup of these patients. [ABSTRACT FROM AUTHOR]

The evidence‐ and consensus‐based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty‐nine experts (including clinicians and patient representatives) from 12 European countries participated. This first part of the guideline includes general information on its scope and purpose, the health questions covered, target users and a methods section. It also provides guidance on which patients should be treated with systemic therapies, as well as recommendations and detailed information on each systemic drug. The systemic treatment options discussed in the guideline comprise conventional immunosuppressive drugs (azathioprine, ciclosporin, glucocorticosteroids, methotrexate and mycophenolate mofetil), biologics (dupilumab, lebrikizumab, nemolizumab, omalizumab and tralokinumab) and janus kinase inhibitors (abrocitinib, baricitinib and upadacitinib). Part two of the guideline will address avoidance of provocation factors, dietary interventions, immunotherapy, complementary medicine, educational interventions, occupational and psychodermatological aspects, patient perspective and considerations for paediatric, adolescent, pregnant and breastfeeding patients. [ABSTRACT FROM AUTHOR]