Recent Advances in the Inhibition of the IL-4 Cytokine Pathway for the Treatment of Allergen-Induced Asthma.

The IL-4 and IL-13 cytokine pathways play integral roles in stimulating IgE inflammation, with the IL-4 cytokine being a major cytokine in the etiology of thunderstorm asthma, atopic dermatitis, and allergic rhinitis. The increasing prevalence of thunderstorm asthma in the younger population and the lessening efficacy of corticosteroids and other anti-inflammatories has created a need for more effective pharmaceuticals. This review summarizes the IL-4 and IL-13 pathways while highlighting and discussing the current pathway inhibitors aimed at treating thunderstorm asthma and atopic dermatitis, as well as the potential efficacy of peptide therapeutics in this field.

Does aeroallergen sensitivity and allergic rhinitis in children cause milder COVID-19 infection?

Background: There are conflicting data with regard to the impact of respiratory and allergic comorbidities on the course of novel coronavirus disease 2019 (COVID-19) in children. Objective: This study aimed to investigate the relationship between allergic diseases and COVID-19 severity in pediatric patients. Methods: Seventy-five pediatric patients with COVID-19 were classified according to clinical severity and evaluated in the allergy/immunology and pulmonology departments 1 to 3 months after the infection resolved. Blood was collected from the patients for a complete blood cell count and assessment of immunoglobulin and total immunoglobulin E (IgE) levels, and skin-prick tests and spirometry tests were performed. Results: A total of 75 patients ages 5-18 years were evaluated. COVID-19 was asymptomatic/mild in 44 patients and moderate/severe/critical in 31 patients. Based on allergy evaluation, allergic rhinitis was diagnosed in 19 patients (25.3%), asthma in 10 patients (13%), and atopic dermatitis in 3 patients (4%). Aeroallergen sensitivity was detected in 26 patients (34.7%). COVID-19 infection was asymptomatic/mild in 15 patients with allergic rhinitis (78.9%) and in 21 with aeroallergen sensitivity (80.8%) (p = 0.038 and p = 0.005, respectively). There was no difference in severity between the patients with and without asthma (p = 0.550). The median (interquartile range) total IgE level was significantly higher in the asymptomatic/mild group (71.8 [30.7-211.2]) (p = 0.015). There were no differences in terms of spirometry parameters. Conclusion: Aeroallergen sensitization and allergic rhinitis in children may be associated with a milder course of COVID-19. The knowledge that atopy is associated with less-severe COVID-19 outcomes in children may guide clinical risk classification.

Impact of the COVID-19 pandemic on the course and management of chronic inflammatory immune-mediated skin diseases: What's the evidence?

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, medical professionals have been overwhelmed by questions beyond the infection itself. In dermatology practice, clinicians have been facing difficulties about the management of chronic immune-mediated skin diseases. Issues arose, such as the grade of immunosuppression or immunomodulation, discontinuation or modification of treatment, and initiation of new treatments. In this comprehensive review, we present the current evidence about the course and management of chronic inflammatory dermatoses during the COVID-19 pandemic, focusing on psoriasis, atopic dermatitis, and hidradenitis suppurativa.

Regulation of Tissue Immune Responses by Local Glucocorticoids at Epithelial Barriers and Their Impact on Interorgan Crosstalk.

The anti-inflammatory role of extra-adrenal glucocorticoid (GC) synthesis at epithelial barriers is of increasing interest with regard to the search for alternatives to synthetic corticosteroids in the therapy of inflammatory disorders. Despite being very effective in many situations the use of synthetic corticosteroids is often controversial, as exemplified in the treatment of influenza patients and only recently in the current COVID-19 pandemic. Exploring the regulatory capacity of locally produced GCs in balancing immune responses in barrier tissues and in pathogenic disorders that lead to symptoms in multiple organs, could provide new perspectives for drug development. Intestine, skin and lung represent the first contact zones between potentially harmful pathogens or substances and the body, and are therefore important sites of immunoregulatory mechanisms. Here, we review the role of locally produced GCs in the regulation of type 2 immune responses, like asthma, atopic dermatitis and ulcerative colitis, as well as type 1 and type 3 infectious, inflammatory and autoimmune diseases, like influenza infection, psoriasis and Crohn's disease. In particular, we focus on the role of locally produced GCs in the interorgan communication, referred to as gut-skin axis, gut-lung axis or lung-skin axis, all of which are interconnected in the pathogenic crosstalk atopic march.

Can we safely use systemic treatment in atopic dermatitis during the COVID-19 pandemic? Overview of selected conventional and biologic systemic therapies.

Introduction: Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, the medical community has faced major challenges that affect disease management in all areas. Dermatologists and immunologists have to choose appropriate treatment strategy taking into consideration the risk of infection and possible exacerbation of the course of the disease in patients with confirmed infection. Management of atopic dermatitis (AD) in moderate to severe cases is based on systemic therapy such as cyclosporine, azathioprine, methotrexate and dupilumab.Areas covered: A literature search in PubMed database was performed until 6 March 2021. In this review, the authors discuss non-biologic and biologic systemic medications for AD and provide an overview of therapeutic recommendations during COVID-19 pandemic.Expert opinion: In case of an active COVID-19 infection, conventional systemic treatment and biological treatment needs to be stopped until clinical recovery. Noninfected patients with systemic treatment of AD should continue their therapy via self-application. The authors can conclude that understanding of dupilumab therapy is better recognized in context AD treatment during COVID-19 pandemic in comparison to cyclosporine, azathioprine and methotrexate. However, this systemic immunosuppressants still require further investigation and literature complementation.

Management of Allergic Diseases During COVID-19 Outbreak.

PURPOSE OF REVIEW: The coronavirus disease 2019 (COVID-19) has challenged healthcare system capacities and safety for health care workers, reshaping doctor-patient interaction favoring e-Health or telemedicine. The pandemic situation may make difficult to prioritize patients with allergies diseases (AD), face-to-face evaluation, and moreover concern about the possible COVID-19 diagnosis, since COVID-19 shared many symptoms in common with AD. Being COVID-19 a novel disease, everyone is susceptible; there are some advances on vaccine and specific treatment. We evaluate existing literature on allergic diseases (AD): allergic rhinitis, asthma, food allergy, drug allergy, and skin allergy, and potential underlying mechanisms for any interrelationship between AD and COVID-19. RECENT FINDINGS: There is inconclusive and controversial evidence of the association between AD and the risk of adverse clinical outcomes of COVID-19. AD patients should minimize hospital and face-to-face visits, and those who have used biologics and allergen immunotherapy should continue the treatment. It is essential to wear personal protective equipment for the protection of health care workers. Social distancing, rational use of facemasks, eye protection, and hand disinfection for health care workers and patients deserve further attention and promotion. Teleconsultation during COVID-19 times for AD patients is very encouraging and telemedicine platform can provide a reliable service in patient care.

Efficacy and Safety of Baricitinib Combined With Topical Corticosteroids for Treatment of Moderate to Severe Atopic Dermatitis: A Randomized Clinical Trial.

Importance: Baricitinib, an oral selective Janus kinase 1 and 2 inhibitor, effectively reduced disease severity in moderate to severe atopic dermatitis (AD) in 2 phase 3 monotherapy studies. Objective: To assess the efficacy and safety of 4 mg and 2 mg of baricitinib in combination with background topical corticosteroid (TCS) therapy in adults with moderate to severe AD who previously had an inadequate response to TCS therapy. Design, Setting, and Participants: This double-blind, placebo-controlled, phase 3 randomized clinical trial, BREEZE-AD7 (Study of Baricitinib [LY3009104] in Combination With Topical Corticosteroids in Adults With Moderate to Severe Atopic Dermatitis) was conducted from November 16, 2018, to August 22, 2019, at 68 centers across 10 countries in Asia, Australia, Europe, and South America. Patients 18 years or older with moderate to severe AD and an inadequate response to TCSs were included. After completing the study, patients were followed up for up to 4 weeks or enrolled in a long-term extension study. Interventions: Patients were randomly assigned (1:1:1) to receive 2 mg of baricitinib once daily (n = 109), 4 mg of baricitinib once daily (n = 111), or placebo (n = 109) for 16 weeks. The use of low-to-moderate potency TCSs was allowed. Main Outcomes and Measures: The primary end point was the proportion of patients achieving a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0 (clear) or 1 (almost clear), with a 2-point or greater improvement from baseline at week 16. Results: Among 329 patients (mean [SD] age, 33.8 [12.4] years; 216 [66%] male), at week 16, a vIGA-AD score of 0 (clear) or 1 (almost clear) was achieved by 34 patients (31%) receiving 4 mg of baricitinib and 26 (24%) receiving 2 mg of baricitinib compared with 16 (15%) receiving placebo (odds ratio vs placebo, 2.8 [95% CI, 1.4-5.6]; P = .004 for the 4-mg group; 1.9 [95% CI, 0.9-3.9]; P = .08 for the 2-mg group). Treatment-emergent adverse events were reported in 64 of 111 patients (58%) in the 4-mg group, 61 of 109 patients (56%) in the 2-mg group, and 41 of 108 patients (38%) in the placebo group. Serious adverse events were reported in 4 patients (4%) in the 4-mg group, 2 (2%) in the 2-mg group, and 4 (4%) in the placebo group. The most common adverse events were nasopharyngitis, upper respiratory tract infections, and folliculitis. Conclusions and Relevance: A dose of 4 mg of baricitinib in combination with background TCS therapy significantly improved the signs and symptoms of moderate to severe AD, with a safety profile consistent with previous studies of baricitinib in AD. Trial Registration: ClinicalTrials.gov Identifier: NCT03733301.

Allergic disorders and susceptibility to and severity of COVID-19: A nationwide cohort study.

BACKGROUND: There is inconclusive and controversial evidence of the association between allergic diseases and the risk of adverse clinical outcomes of coronavirus disease 2019 (COVID-19). OBJECTIVE: We sought to determine the association of allergic disorders with the likelihood of a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test result and with clinical outcomes of COVID-19 (admission to intensive care unit, administration of invasive ventilation, and death). METHODS: A propensity-score-matched nationwide cohort study was performed in South Korea. Data obtained from the Health Insurance Review & Assessment Service of Korea from all adult patients (age, >20 years) who were tested for SARS-CoV-2 in South Korea between January 1, 2020, and May 15, 2020, were analyzed. The association of SARS-CoV-2 test positivity and allergic diseases in the entire cohort (n = 219,959) and the difference in clinical outcomes of COVID-19 were evaluated in patients with allergic diseases and SARS-CoV-2 positivity (n = 7,340). RESULTS: In the entire cohort, patients who underwent SARS-CoV-2 testing were evaluated to ascertain whether asthma and allergic rhinitis were associated with an increased likelihood of SARS-CoV-2 test positivity. After propensity score matching, we found that asthma and allergic rhinitis were associated with worse clinical outcomes of COVID-19 in patients with SARS-CoV-2 test positivity. Patients with nonallergic asthma had a greater risk of SARS-CoV-2 test positivity and worse clinical outcomes of COVID-19 than patients with allergic asthma. CONCLUSIONS: In a Korean nationwide cohort, allergic rhinitis and asthma, especially nonallergic asthma, confers a greater risk of susceptibility to SARS-CoV-2 infection and severe clinical outcomes of COVID-19.