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Dr. Seneschal has been an investigator, speaker, or consultant for Novartis, Abbvie, Sanofi, LeoPharma and Eli Lilly. Dr. De Raeve is a consultant, member of scientific advisory boards and/ or received personal fees and non-financial support from LEO Pharma, Pierre Fabre, Sanofi-Genzyme and Bioderma. Dr. Vestergaard has been investigator, speaker, or consultant for Novartis, Abbvie, Sanofi, LeoPharma and Eli Lilly. [Extracted from the article]

Dr. Chernyshov, Dr. Stalder, Dr. Svensson, Dr. Kunz reports no conflict of interest. At least 3 weeks are recommended between the two COVID-19 vaccine doses, which increases the risk of AD flares and loss of AD control if the systemic AD medication is paused or reduced in dose for longer periods. European Task Force on Atopic Dermatitis: position on vaccination of adult patients with atopic dermatitis against COVID-19 (SARS-CoV-2) being treated with systemic medication and biologics. [Extracted from the article]

(context of the research) Previous analyses based on short-term, phase 2 studies reported that baseline biomarkers do not correlate with clinical outcomes following dupilumab treatment in patients with atopic dermatitis (AD). To report whether pre-treatment levels of common serum biomarkers can predict treatment response to dupilumab in adults with moderate-to-severe AD using data from a new analysis based on 16-week, phase 3 studies. LIBERTY AD SOLO 1 and 2 (NCT02277743 , NCT02277769), two randomized, double-blind studies, included patients ≥ 18 years-old with moderate-to-severe AD treated with dupilumab 300 mg every 2 weeks or placebo for 16 weeks. Correlation between change in Eczema Area and Severity Index (EASI) and log of baseline IgE, CC chemokine ligand 17 (CCL17; previously referred to as thymus and activation-regulated chemokine [TARC]) and lactate dehydrogenase (LDH) at baseline was assessed using Spearman's correlation coefficient (ρ). At Week 16, change in EASI showed little correlation with baseline total IgE (Spearman's correlation coefficient [ρ] = –0.14, n = 370 for dupilumab; ρ = –0.03, n = 202 for placebo), baseline CCL17 (ρ = –0.28, n = 369 for dupilumab; ρ = –0.05, n = 201 for placebo), or baseline LDH (ρ = –0.30, n = 370 for dupilumab; ρ = –0.08, n = 202 for placebo). Overall safety was consistent with the known dupilumab safety profile. Baseline levels of total IgE, CCL17 and LDH do not predict treatment response to dupilumab, as measured by EASI, in adults with moderate-to-severe AD. [ABSTRACT FROM AUTHOR]

Editor Atopic dermatitis (AD), a common inflammatory skin condition characterized by chronic or relapsing episodes of eczema, itch and sleep disturbance,1 is associated with psychiatric, infectious and allergic comorbidities. Dr. Hijnen has been investigator, speaker or consultant for Abbvie, Eli Lilly, Incyte, LeoPharma, MedImmune/Astrazeneca, Pfizer, Sanofi and ThermoFisher. Dr. Ring has been an advisor or speaker for AbbVie, Allergika, Sanofi-Genzyme, Pfizer, Bencard, LEO Pharma and Mylan. [Extracted from the article]

Background: Conjunctivitis is common in patients with atopic dermatitis (AD) in general and a commonly reported adverse event in AD clinical trials with dupilumab. Objective: To survey opinions and experience about conjunctivitis occurring in AD, including those during dupilumab treatment in a group of AD experts from the International Eczema Council (IEC). Methods: Electronic survey and in‐person discussion of management strategies. Results: Forty‐six (53.5%) IEC members from 19 countries responded to the survey. Consensus was reached for several statements regarding diagnostic workup, referral and treatment. IEC members suggest that patients with AD should (i) routinely be asked about ocular complaints or symptoms, (ii) obtain information about the potential for conjunctivitis before starting dupilumab therapy and (iii) if indicated, be treated with dupilumab despite previous or current conjunctivitis. In cases of new‐onset conjunctivitis, there was consensus that dupilumab treatment should be continued when possible, with appropriate referral to an ophthalmologist. Limitations: The study relies on expert opinion from dermatologists. Responses from few dermatologists without dupilumab access were not excluded from the survey. Conclusion: The IEC recommends that dermatologists address conjunctivitis in patients with AD, especially during treatment with dupilumab. [ABSTRACT FROM AUTHOR]

A large proportion (8.6-22.1%) of patients receiving dupilumab for atopic dermatitis (AD) in clinical trials develops conjunctivitis.[1] We describe the histopathological characteristics of a patient with a severe, new-onset conjunctivitis during dupilumab treatment and four months after discontinuation of dupilumab. However, the treatment with prednisolone and azathioprine might have stimulated the recurrence of GCs, since several immunosuppressive drugs, such as cyclosporine and prednisolone, have been found to increase GC density.[4] Unfortunately, no biopsy was performed before dupilumab treatment to assess whether GC scarcity was already present in the patient. [Extracted from the article]

The article assesses various studies which examine the adverse pregnancy and fetal outcomes after paternal exposure to oral immunosuppressive drugs azathioprine, methotrexate or mycophenolic acid. Topics discussed include the use of immunosuppressive drugs in dermatology, the considerations when assessing human pregnancy drug exposure data such as human embryology, tetralogy and pharmacology, and the limitations of the studies.

A letter to the editor is presented that discusses drug survival for azathioprine and enteric-coated mycophenolate sodium in a long-term daily practice cohort of adult patients with atopic dermatitis.

Background: Hand eczema is a common condition; it is often chronic and can be difficult to treat. Cyclosporine is used off-label to treat severe hand eczema; however, the evidence for this treatment is scarce. Objective: To examine the drug survival of cyclosporine in a daily practice cohort of patients with chronic hand eczema. Methods: This retrospective daily use study included hand eczema patients who were treated with cyclosporine between 01-06-1999 and 01-06-2014 in two Dutch university hospitals. Patient and treatment characteristics were retrospectively collected from medical charts. First treatment episodes were analysed by means of Kaplan-Meier drug survival curves. Possible determinants of drug survival were analysed by Cox regression models. Treatment effectiveness was analysed with a retrospective physician's global assessment. Results: A total of 102 patients were treated with cyclosporine. The median drug survival rate was 0.86 years (10.3 months). The overall drug survival rate after 6 months, 1, 2 and 3 years were 61.7%, 45.2%, 18.6% and 13.9% respectively. Main reasons for discontinuation were adverse events, especially early in treatment, and ineffectiveness. After 3 months, a good response to treatment was recorded in 62.9% of the patients. Conclusion: Cyclosporine had a median drug survival of 10.3 months. Especially patients with recurrent vesicular hand eczema showed a good treatment response. [ABSTRACT FROM AUTHOR]

Background There is a lack of information on the use oral immunosuppressive drugs in atopic dermatitis ( AD) daily practice. Objective A 10-years overview of the use of oral immunosuppressive drugs in patients with severe AD. Methods Medical charts of patients with AD, who received oral immunosuppressive drugs at the Academic Medical Center Amsterdam and in the University Medical Center Utrecht between January 2001 and January 2011, were analysed. Particular attention was paid to patient characteristics, prior treatment, prescribed oral immunosuppressive drugs, the order of use, doses and treatment durations and reasons for discontinuation of treatment. Results Of 334 patients [53% male, mean age at start of an oral immunosuppressive drug 36.9 years ( SD 13.6)] with AD received oral immunosuppressive treatment of which 102 (31%) participated in clinical trials. Cyclosporine A (CyA) was given in 80% of the patients, mycophenolate mofetil or enteric-coated mycophenolate ( MMF/ EC- MPS) in 31%, azathioprine ( AZA) in 14%, methotrexate ( MTX) in 11%, systemic glucocorticosteroids in 7% and systemic tacrolimus in 5%. In these academic centra, CyA was the first choice oral immunosuppressive in 252 patients. Reasons for discontinuation of oral immunosuppressive drugs were controlled AD disease, ineffectiveness and adverse events. Conclusion Various types of oral immunosuppressive drugs have been used over the past 10 years for the treatment of severe AD with a prominent first choice for CyA. Adverse events and ineffectiveness were frequent reasons for discontinuation. A prospective database of patients using oral immunosuppressive treatments in daily practice will give more insight in the effectiveness and safety and may help to formulate future recommendations. [ABSTRACT FROM AUTHOR]

Background Long-term data of ciclosporin A (CsA) treatment in daily practice in patients with severe atopic dermatitis ( AD) are lacking. Objectives To perform a detailed analysis of drug survival, which is the length of time a patient continues to take a drug, for CsA in a long-term daily practice cohort of patients with AD. The secondary objective was to identify determinants of drug survival. Methods Data were extracted from a retrospective cohort of patients treated with CsA for AD. Drug survival was analysed using Kaplan-Meier survival curves. Determinants of drug survival were analysed using uni- and multivariate Cox regression analyses with backward selection. Results In total, 356 adult patients were analysed (386 patient-years). The overall drug survival rates were 34%, 18%, 12% and 4% after 1, 2, 3 and 6 years, respectively. Reasons for discontinuation were controlled AD (26·4%), side-effects (22·2%), ineffectiveness (16·3%), side-effects plus ineffectiveness (6·2%) or other reasons (11·0%). Older age was associated with a decreased drug survival related to controlled AD [hazard ratio ( HR) 0·91]. Older age was also associated with a decreased drug survival related to side-effects ( HR 1·14). An intermediate-to-high starting dose (> 3·5-5·0 mg kg−1 daily) was associated with an increased drug survival related to ineffectiveness ( HR 0·63). Conclusions This is the first study on drug survival for CsA treatment in AD. Older age was associated with decreased drug survival related to controlled AD and side-effects. An intermediate-to-high starting dose was associated with an increased drug survival related to ineffectiveness. [ABSTRACT FROM AUTHOR]

Background The Dermatology Department of the University Medical Centre Utrecht, the Netherlands, developed an e-health portal for patients with atopic dermatitis (AD), consisting of e-consultation, a patient-tailored website, monitoring and self-management training. Objectives To determine the cost-effectiveness of individualized e-health compared with usual face-to-face care for children and adults with AD. Methods A randomized controlled cost-effectiveness study from a societal perspective in adults and parents of children with moderate AD. Outcomes were quality of life, severity of AD, itching and direct and indirect costs. Data were collected at baseline and at 3 and 12 months after randomization. Linear mixed models were used to analyse clinical outcomes. After multiple imputation of missing data, costs and differences in costs were calculated over a period of 1 year. Results In total, 199 patients were included. There were no significant differences in disease-specific quality of life, severity of AD and intensity of itching between both groups at the three time points. The difference in direct costs between the intervention and control groups was €24 [95% confidence interval (CI) −360 to 383], whereas this difference was −€618 (95% CI −2502 to 1143) for indirect costs. Overall, individual e-health was expected to save €594 (95% CI −2545 to 1227) per patient in the first year of treatment, mainly through a reduction in work absenteeism. Uncertainty analyses revealed that the probability of e-health reducing costs was estimated to be ≥ 73%. Conclusions E-health during follow-up of patients with AD is, after initial diagnosis and treatment during face-to-face contact, just as effective as usual face-to-face care with regard to quality of life and severity of disease. However, when costs are considered, e-health is likely to result in substantial cost savings. Therefore, e-health is a valuable service for patients with AD. [ABSTRACT FROM AUTHOR]

Background Studies assessing the relationship between disease activity and quality of life (QoL) in adults with atopic dermatitis (AD), before and after therapy are lacking. The relation between disease activity and QoL in AD patients was evaluated before ( t = 0) and after 6 weeks ( t = 6) of treatment with cyclosporin 5 mg/kg. Methods In 54 patients with severe AD, disease activity was assessed using objective Scoring Atopic Dermatitis index (SCORAD), Six Area Six Sign Atopic Dermatitis (SASSAD), 'rule of nines' extent score and serum levels of thymus and activation-regulated chemokine (TARC). Patients filled out the Dermatology Life Quality Index (DLQI). To study the relation between disease activity and QoL, correlations were calculated and regression analysis was performed. Results At t = 0 there was a small, non-significant correlation between the DLQI and the objective SCORAD, 'rule of nines' or serum TARC levels. At t = 6 the objective SCORAD, serum TARC and the 'rule of nines' score showed moderate and significant correlations with the DLQI ( r = 0.34, P = 0.02; r = 0.31, P = 0.03; r = 0.49, P < 0.001). An individual's improvement in disease activity (objective SCORAD, SASSAD and 'rule of nines') with 10 points was associated with an improvement of 1.3, 1.5 and 1.1 points respectively in DLQI. Conclusions Disease activity correlated better with QoL when disease activity was less severe and disease extent ('rule of nines') correlated better with QoL than disease severity. An individual's improvement of 10 points in disease activity was accompanied by only a small improvement in QoL. Other factors than disease activity may influence QoL in patients with AD. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented on treatment of chronic hand eczema patients using methotrexate.

The article discusses a study which investigated drug survival for methotrexate in severe atopic dermatitis patients. Topics discussed include the off-label use of methotrexate for atopic dermatitis, side-effects reported by the patients which include fatigue, gastrointestinal problems and dizziness, and the effectiveness of the drug.

European Task Force on Atopic Dermatitis statement on severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection and atopic dermatitis Atopic dermatitis (AD) is a complex disease with elevated risk of respiratory comorbidities.[[1]] Severely affected patients are often treated with immune-modulating systemic drugs.[[3]] On 11 March 2020, the World Health Organization declared the 2019 novel coronavirus severe acute respiratory syndrome (SARS-Cov-2) epidemic to be a pandemic. If systemic treatment of AD needs to be paused, patients should be supplied with ample topical therapy and guidance on the amount needed to prevent flares until systemic therapy can be reinstated. [Extracted from the article]

Background: The use of anti-allergic mattress covers in patients with asthma can result in a large reduction in the level of house dust mite allergen in dust samples. Apart from a reduction in histamine induced bronchial hyperresponsiveness, there are few data on the effect of mattress covers on clinical efficacy and quality of life in patients with moderate to severe asthma.Methods: Thirty patients with asthma and house dust mite allergy were studied in a randomised, double blind, placebo controlled study. Before and after using anti-allergic covers for 1 year, dust was collected from the mattresses to determine concentrations of Dermatophagoides pteronyssinus (Der p 1), and bronchial hyperresponsiveness and quality of life were measured. The patients scored their symptoms (lungs and nose), morning and evening peak flow values, and rescue medication for 14 days before and after the intervention period.Results: There was a significant reduction in the concentration of Der p 1 in the dust collected from the mattresses in the actively treated group after 1 year compared with before treatment; no change was found in the placebo group. In both the actively treated and placebo groups there was no significant improvement in PC(20) histamine. Quality of life improved similarly in both groups. The symptom score of the lower airways did not significantly change in either group. A significant decrease in nasal symptom score was seen in the actively treated group compared with before treatment, but there was no significant difference between the groups. No changes in morning and evening peak flow values, peak flow variability, nor in the use of rescue medication were found in either group.Conclusion: The use of anti-allergic mattress covers results in significant reductions in Der p 1 concentrations in carpet-free bedrooms. However, in patients with moderate to severe asthma, airways hyperresponsiveness and clinical parameters are not affected by this effective allergen avoidance. [ABSTRACT FROM AUTHOR]

The article offers information on the goblet cell (GCs )scarcity and conjunctival inflammation during treatment with dupilumab in patients with atopic dermatitis. It mentions higher rates of conjunctivitis have been reported in patients with atopic dermatitis (AD) treated with dupilumab; and also mentions conjunctival GCs are specialized mucus-secreting cells, vital for ocular surface function.

The article discusses research which examined the increased in liver enzyme levels during treatment of azathioprine (AZA), a purine antagonist used in chronic inflammatory skin diseases. Topics discussed include the influence of genetic polymorphisms in thiopurine-S-methyltransferase (TPMT) on the AZA metabolism and association of high TPMT activity with increased 6-methylmercaptopurine levels.

A letter to the editor is presented regarding ocular application of tacrolimus as a treatment option for atopic keratoconjunctivitis in atopic dermatitis patients.