Funding informationNo support was given by any medical company for development of this document. All meetings were virtual meetings, therefore there were no costs. All participants in the working group filled in a structured form to declare financial or non-financial interests. Disclosures are given in the Supporting information. The Guidelines were approved by the executive committee of the ESCD in

Dupilumab is the first biologic registered for the treatment of atopic dermatitis (AD). We report on seven patients with AD presenting with a paradoxical head and neck erythema that appeared 10-39 weeks after the start of dupilumab treatment. The patients presented with a relatively sharply demarcated, patchy erythema in the head and neck area that showed no or less scaling compared with their usual eczema. Only one patient experienced symptoms of itch and burning, although this was notably different from his pre-existent facial AD. Except for a notable 'red face', eczema on other body parts had greatly improved in six of the seven patients, with a mean numerical rating scale for treatment satisfaction of 9 out of 10 at the time of biopsy. Treatment of the erythema with topical and systemic drugs was unsuccessful. Despite the presence of this erythema, none of our patients discontinued dupilumab treatment. Lesional skin biopsies showed an increased number of ectatic capillaries, and a perivascular lymphohistiocytic infiltration in all patients. In addition, epidermal hyperplasia with elongation of the rete ridges was observed in four patients, resembling a psoriasiform dermatitis. Additional immunohistochemical stainings revealed increased numbers of plasma cells, histiocytes and T lymphocytes. Interestingly, spongiosis was largely absent in all biopsies. We report on patients with AD treated with dupilumab developing a paradoxical erythema in a head and neck distribution. Both clinically and histopathologically we found a heterogeneous response, which was most suggestive of a drug-induced skin reaction. What's already known about this topic? • Dupilumab has proven to be an efficacious and effective treatment for atopic dermatitis with an acceptable safety profile. • The most frequently observed side-effects in patients with atopic dermatitis treated with dupilumab are conjunctivitis, herpes infections and injection-site reactions. What does this study add? • For the first time, we report on patients with atopic dermatitis treated with dupilumab who developed a paradoxical, mainly asymptomatic erythema in a head and neck distribution. • Histological examination of skin biopsies revealed a psoriasiform reaction pattern suggestive of a drug-induced skin reaction.

Summary Background Dupilumab is the first biologic registered for the treatment of moderate‐to‐severe atopic dermatitis (AD), and efficacy was shown in phase III clinical trials (primary outcome at week 16 was reached in 38% of patients). Currently, there are limited daily practice data available for dupilumab, especially when it is combined with systemic immunosuppressants. Objectives To evaluate dupilumab treatment in daily practice in patients with AD. Methods In this observational cohort study, we prospectively included all adult patients with AD who had been treated with dupilumab in two university hospitals in the Netherlands. Concomitant systemic immunosuppressive treatment was monitored. Physician‐reported outcome measures and patient‐reported outcome measures (PROMs) after ≥ 12 weeks of follow‐up were analysed. We used a linear mixed‐effects model to determine changes in scores during follow‐up. Results Ninety‐five patients were included. Of these, 62 patients were using systemic immunosuppressants at baseline; the use of systemic immunosuppressants was continued during dupilumab treatment in 43 patients. From baseline to 16 weeks of treatment, the estimated mean Eczema Area and Severity Index score (0–72) decreased from 18·6 [95% confidence interval (CI) 16·0–21·4)] to 7·3 (95% CI 5·4–10·0), and the estimated mean PROMs showed a decrease of 41–66%. Investigator's Global Assessment 0 or 1 (clear/almost clear) was reached in 38% of the patients. Five patients discontinued dupilumab treatment due to side‐effects or ineffectiveness. Eye symptoms and orofacial (nonocular) herpes simplex virus (HSV) reactivation were reported in 62% and 8% of the patients, respectively. Conclusions Dupilumab treatment in daily practice shows a clinically relevant improvement of physician‐reported outcome measures and PROMs, which is in line with efficacy data from clinical trials. Besides frequently reported eye symptoms and orofacial (nonocular) HSV reactivation, there were no apparent safety concerns. What's already known about this topic? Dupilumab has been shown to be an efficacious treatment for atopic dermatitis in several clinical trials. However, it is known that there may be considerable differences in patient characteristics and treatment responses between clinical trials and daily practice. What does this study add? This study presents the first experience with dupilumab treatment in 95 patients with atopic dermatitis in daily practice in two Dutch university hospitals. Less stringent inclusion and exclusion criteria and follow‐up schedules, in contrast to those used in clinical trials, might better represent daily practice. Dupilumab treatment shows a clinically relevant improvement of physician‐ and patient‐reported outcome measures; besides patient‐reported eye symptoms (in 59 of 95 patients; 62%) and an apparent increase in orofacial (nonocular) herpes simplex virus reactivation (eight of 95 patients; 8%), there were no other safety concerns during follow‐up up to 16 weeks of dupilumab treatment.

The hypothesis that calcipotriol ointment might be at least as effective as dithranol cream in the day-care setting could not be proven in the present study. Whereas calcipotriol has become a mainstay in the routine outpatient treatment of psoriasis not requiring a day-care setting, dithranol treatment, being difficult as a routine outpatient therapy, has increased efficacy and improved tolerability if the treatment is carried out in a day-care setting.