Severe atopic dermatitis in early infancy: characteristics, challenges and new perspectives in clinical practice.

Atopic dermatitis (AD) is the most common skin disease in infants and children with a prevalence of 10% in the first two years of life. In this age group up to 15% are severely affected. "Children are not little adults" - this applies in particular to infants with severe atopic dermatitis. Age-specific clinical aspects (psychosocial, neurocognitive, morphological) of the disease require an adjusted disease management. Considering recent approval of systemic treatment options, early identification of infants and children with severe and early persistent disease is of particular importance also in view of possible prevention of atopic comorbidity. As several inborn errors of immunity (IEI) share features of the atopic phenotype, it is essential for clinicians to distinguish signs of immunodeficiency from severe AD. Here, we describe a practical approach on the basis of clinical history and key dermatological and laboratory findings. Furthermore, this paper is aimed at providing an update on general management of severe AD in early infancy, including recommendations for systemic treatment.

Efficacy and Safety of Dupilumab Treatment with Concomitant Topical Corticosteroids in Children Aged 6 Months to 5 Years with Severe Atopic Dermatitis.

INTRODUCTION: Treatment options for children younger than 6 years with severe atopic dermatitis (AD) are limited, as systemic immunosuppressants may present safety concerns in this young age group. Dupilumab is the first systemic treatment option approved for infants and young children with severe AD in the European Union. This study reports the efficacy and safety of dupilumab with concomitant low-potency corticosteroids in children aged 6 months to 5 years with severe AD. METHODS: This was a pre-specified subgroup analysis of data for patients aged 6 months to 5 years with severe AD at baseline (Investigator's Global Assessment [IGA] = 4) from a randomised, double-blind, placebo-controlled, phase III trial of dupilumab. Patients were randomised to either subcutaneously administered dupilumab (200/300 mg) or matched placebo every 4 weeks, plus low-potency topical corticosteroids for 16 weeks. Co-primary endpoints at week 16 were the proportion of patients with IGA ≤ 1 (clear or almost clear skin) and the proportion of patients with ≥ 75% improvement from baseline in Eczema Area and Severity Index (EASI-75). Secondary endpoints at week 16 included mean changes in EASI, pruritus, skin pain, sleep loss and quality of life. RESULTS: The analysis included 125 patients (63 receiving dupilumab vs. 62 placebo). At week 16, significantly more patients receiving dupilumab vs. placebo had achieved IGA ≤ 1 (14.3% vs. 1.6%; P = 0.0085) and EASI-75 (46.0% vs. 6.6%; P < 0.0001). Significant improvements with dupilumab were observed in all secondary endpoints, including a least squares mean 48.9% reduction in pruritus. The overall incidence of adverse events (AEs) was similar between the dupilumab and placebo groups (66.7% vs. 73.8%). No dupilumab-related AEs were serious or led to treatment discontinuation. CONCLUSION: Dupilumab significantly improved AD signs, symptoms and quality of life in children aged 6 months to 5 years with severe AD with acceptable safety. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov with ID number NCT03346434, part B.

Atopic dermatitis (AD) is a chronic skin disease that is relatively common in infants and young children worldwide. Severe AD causes skin rashes and intense itch that strongly interfere with sleep quality and normal daily activities, thereby affecting the quality of life of patients and their families. When therapies for AD that are applied to the skin do not work, limited options are available to treat severe AD in children younger than 6 years. In this study, we evaluated the efficacy and safety of dupilumab in children aged 6 months to 5 years with severe AD, recruited from various sites in Europe and North America. Patients received 200 or 300 mg of dupilumab (based on the child's weight) or placebo, together with mild steroids applied to the skin, every 4 weeks for 16 weeks. At the end of treatment, AD severity was greatly improved in patients receiving dupilumab, with 14% of patients achieving almost clear skin. Patients receiving dupilumab also experienced significant improvements in itch intensity, sleep quality, skin pain, and quality of life. Furthermore, dupilumab did not increase the risk of infections. This study demonstrates that dupilumab can be effective at treating severe AD in infants and young children, with important benefits for the quality of life of patients and their families.

Basic skin care in atopic dermatitis - new and established treatment options.

Basic skin care (basic therapy) is a mainstay in the treatment of atopic dermatitis, irrespective of disease severity and current disease activity. Consistent application of basic skin care plays a key role in restoring skin barrier function and reducing xerosis as well as pruritus. Moreover, it has been shown that concurrent basic therapy has steroid-sparing effects in acute disease flares. In long-term atopic dermatitis management, the use of basic skin care is associated with prolonged recurrence-free intervals. Recent studies have also demonstrated that early initiation of basic skin therapy has protective effects in infants at risk of developing atopic dermatitis. The present review addresses these topics with a focus on established treatments and new developments.

Effects of structured patient education in adults with atopic dermatitis: Multicenter randomized controlled trial.

BACKGROUND: Atopic dermatitis (AD) is a chronic relapsing skin disease prevalent in 1% to 3% of adults in Western industrialized countries. OBJECTIVE: We sought to investigate the effectiveness of educational training in an outpatient setting on coping with the disease, quality of life, symptoms, and severity in adults with AD. METHODS: In this German prospective, randomized controlled multicenter study, adult patients with moderate-to-severe AD were educated by referring to a comprehensive 12-hour training manual consented by a multiprofessional study group from different centers (Arbeitsgemeinschaft Neurodermitisschulung für Erwachsene [ARNE]). Patients were randomly allocated to the intervention or waiting control groups. Study visits were performed at baseline and after 1 year (1 year of follow-up). Primary outcomes were defined as a decrease in (1) "catastrophizing cognitions" with respect to itching (Juckreiz-Kognitions-Fragebogen questionnaire), (2) "social anxiety" (Marburger Hautfragebogen questionnaire), (3) subjective burden by symptoms of the disease (Skindex-29 questionnaire), and (4) improvement of disease signs and symptoms assessed by using the SCORAD index at 1 year of follow-up. Data were analyzed on an intention-to-treat basis. RESULTS: At 1 year of follow-up, patients from the intervention group (n = 168) showed a significantly better improvement compared with the waiting group (n = 147) in the following defined primary study outcomes: coping behavior with respect to itching (P < .001), quality of life assessed by using the Skindex-29 questionnaire (P < .001), and the SCORAD index (P < .001). CONCLUSIONS: This is the first randomized, controlled multicenter study on patient education in adult AD. The ARNE training program shows significant beneficial effects on a variety of psychosocial parameters, as well as AD severity.

Predictors of benefit from an atopic dermatitis education programme.

BACKGROUND: Multidisciplinary, age-related, structured, group educational programmes for children with atopic dermatitis (AD) and their parents have shown positive long-term outcomes with respect to quality of life and coping behaviour of the participants. We aimed to identify predictors of favourable long-term outcome of an education measure for parents of children with AD aged 3 months to 7 years in the framework of The German Atopic Dermatitis Intervention Study (GADIS). METHODS: In an exploratory approach, the data of 274 child-parent pairs were analysed with respect to the influence of various somatic and psychological variables as possible predictors of treatment success. Changes in parents' QoL, SCORAD (Scoring Atopic Dermatitis), topical corticosteroid use and parents' knowledge about AD between baseline and 12-months' follow-up were chosen as measures of long-term treatment success (outcome). RESULTS: Psychological rather than somatic parameters were identified as predictors of treatment success. Parents who had negative treatment experiences in the past and possessed only poor coping abilities with regard to scratch control benefitted the most from the training programme. The outcome of the education measure was independent of parents' schooling, vocational level and income. CONCLUSIONS: Parents of children with AD who lack adequate coping abilities should be particularly encouraged to take part in such an education programme.

Allergic contact dermatitis in psoriasis patients: typical, delayed, and non-interacting.

Psoriasis is characterized by an apoptosis-resistant and metabolic active epidermis, while a hallmark for allergic contact dermatitis (ACD) is T cell-induced keratinocyte apoptosis. Here, we induced ACD reactions in psoriasis patients sensitized to nickel (n = 14) to investigate underlying mechanisms of psoriasis and ACD simultaneously. All patients developed a clinically and histologically typical dermatitis upon nickel challenge even in close proximity to pre-existing psoriasis plaques. However, the ACD reaction was delayed as compared to non-psoriatic patients, with a maximum intensity after 7 days. Whole genome expression analysis revealed alterations in numerous pathways related to metabolism and proliferation in non-involved skin of psoriasis patients as compared to non-psoriatic individuals, indicating that even in clinically non-involved skin of psoriasis patients molecular events opposing contact dermatitis may occur. Immunohistochemical comparison of ACD reactions as well as in vitro secretion analysis of lesional T cells showed a higher Th17 and neutrophilic migration as well as epidermal proliferation in psoriasis, while ACD reactions were dominated by cytotoxic CD8+ T cells and a Th2 signature. Based on these findings, we hypothesized an ACD reaction directly on top of a pre-existing psoriasis plaque might influence the clinical course of psoriasis. We observed a strong clinical inflammation with a mixed psoriasis and eczema phenotype in histology. Surprisingly, the initial psoriasis plaque was unaltered after self-limitation of the ACD reaction. We conclude that sensitized psoriasis patients develop a typical, but delayed ACD reaction which might be relevant for patch test evaluation in clinical practice. Psoriasis and ACD are driven by distinct and independent immune mechanisms.

Pimecrolimus, a topical calcineurin inhibitor used in the treatment of atopic eczema.

INTRODUCTION: Pimecrolimus , a calcineurin inhibitor, is a non-steroidal treatment option in patients aged ≥ 2 years with mild-to-moderate atopic eczema (AE). It was approved as a viable therapeutic option by the FDA in 2001 and in the European Union a year later in 2002. Calcineurin inhibitors inhibit the synthesis of inflammatory cytokines released from T cells and mast cells. In contrast to corticosteroids, calcineurin inhibitors act specifically on proinflammatory cells. Pimecrolimus shows comparative efficacy to mild topical corticosteroids and a special antipruritic effect. Furthermore, examinations of the systemic absorption of pimecrolimus implicated no systemic immunosuppression. In 2006, the FDA set a black box warning in the packaging materials of pimecrolimus alluding to the risk of skin malignancy or lymphomas due to theoretical consideration. AREAS COVERED: The authors provide a review of pimecrolimus as a treatment for AE. Specifically, the authors present the pharmacokinetic and pharmacodynamic information on pimecrolimus and also review its efficacy. The authors also discuss pimecrolimus' safety and tolerability profile. EXPERT OPINION: Pimecrolimus represents a valuable part of active and proactive therapy in AE. That being said, the long-term safety of topical calcineurin inhibitors remains to be investigated. Given the results from experimental photocarcinogenicity studies, effective sun protection should be employed during the therapy, although an increased risk for skin malignancies and lymphomas was not found in recent studies. Pimecrolimus should be considered as an alternative therapeutic approach in AE treatment management going along with a corticoid-sparing effect.