Background: In the SARS-CoV-2/COVID-19 pandemic, we need to understand the impact of immunomodulatory medications on COVID-19 symptom severity in patients with inflammatory diseases, including the Type 2/Th2 polarized skin disease, atopic dermatitis/AD. Since it is believed that Type 1/Th1immunity controls viral infections, and that there is a Th1/Th2 counter-regulation, we hypothesized that Th2 targeting with the IL-4Rα-antagonist, dupilumab, in patients with moderate-to-severe AD rebalances Th1/Th2 axis, potentially leading to attenuated COVID-19 symptoms. Methods: 1,237 moderate-to-severe AD patients in the Icahn School of Medicine at Mount Sinai Department of Dermatology were enrolled in a registry. Patients were screened for COVID-19-related symptoms and assigned a severity score (asymptomatic[0]-fatal[5]). Scores were compared among 3 treatment groups: dupilumab (n=632), other systemic treatments (n=107), and limited/no treatment (n=498). Demographic and comorbid covariates were adjusted by multivariate logistic regression models. Results: The dupilumab-treated group showed reduced incidence and severity of COVID-19 symptoms versus other treatment groups. Dupilumab-treated patients were less likely to experience moderate-to-severe symptoms versus patients on other systemics (p=0.01) and on limited/no treatment (p=0.04), and less likely to experience any symptoms versus patients on other systemics (p=0.01). This effect was seen in our entire cohort and in the subgroup of patients with verified COVID-19 or high-risk exposure. Conclusions: Patients on dupilumab experienced less severe COVID-19 manifestations and lesser symptoms compared to patients on other systemics and on limited/no treatment. These results suggest that Th2 modulation with dupilumab may have a protective effect on anti-viral immune response in AD patients.

CLA + memory T cells constitute a small subset of human memory T cells. Circulating skin-homing T cells participate in several aspects of atopic dermatitis, such as Staphylococcus aureus involvement in inflammation, the abnormal Th2 immune response, biomarkers, clinical aspects of the patients, pruritus, and the mechanism of action of targeted therapies. Superantigens, IL-13, IL-31, pruritus, CCL17 and early effects on dupilumab-treated patients have in common that they are related to CLA + T cell response in patients. The function of CLA + T cells is closely related to the role of T cells belonging to the skin-associated lymphoid tissue and could be a reason why they reflect different mechanisms of atopic dermatitis. The goal of this review is to gather all this translational information of atopic dermatitis pathology.

Journal: Allergy

Food Allergy (FA) is now one of the most common chronic diseases of childhood often lasting throughout life and leading to significant worldwide healthcare burden. The precise mechanisms responsible for the development of this inflammatory condition are largely unknown; however, a multifactorial aetiology involving both environmental and genetic contributions is well accepted. A precise understanding of the pathogenesis of FA is an essential first step to developing comprehensive prevention strategies that could mitigate this epidemic. As it is frequently preceded by atopic dermatitis and can be prevented by early antigen introduction, the development of FA is likely facilitated by the improper initial presentation of antigen to the developing immune system. Primary oral exposure of antigens allowing for presentation via a well-developed mucosal immune system, rather than through a disrupted skin epidermal barrier, is essential to prevent FA. In this review, we present the data supporting the necessity of 1) an intact epidermal barrier to prevent epicutaneous antigen presentation, 2) the presence of specific commensal bacteria to maintain an intact mucosal immune system and 3) maternal/infant diet diversity, including vitamins and minerals, and appropriately timed allergenic food introduction to prevent FA.

This systematic review evaluates the efficacy, safety and economic impact of dupilumabcompared 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 dupilumab16 to 52 weeks were evaluated. For adultsthere is high certainty that dupilumabdecreasesSCORAD (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), 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 adults, together with more efficacy data in the paediatric population.

This systematic review evaluates the efficacyand 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); 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), theISS7 (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); 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).