Effectiveness of antibacterial therapeutic clothing vs. nonantibacterial therapeutic clothing in patients with moderate-to-severe atopic dermatitis: a randomized controlled observer-blind pragmatic trial (ABC trial).

BACKGROUND: Increased Staphylococcus aureus (SA) colonization is considered an important factor in the pathogenesis of atopic dermatitis (AD). Antibacterial therapeutic clothing aims to reduce SA colonization and AD inflammation; however, its role in the management of AD remains poorly understood. OBJECTIVES: To investigate the effectiveness of antibacterial therapeutic clothing + standard topical treatment in patients with moderate-to-severe AD vs. standard therapeutic clothing + standard topical treatment; and, if effectiveness was demonstrated, to demonstrate its cost-effectiveness. METHODS: A pragmatic double-blinded multicentre randomized controlled trial (NCT04297215) was conducted in patients of all ages with moderate-to-severe AD. Patients were centrally randomized 1 : 1 : 1 to receive standard therapeutic clothing or antibacterial clothing based on chitosan or silver. The primary outcome was the between-group difference in Eczema Area and Severity Index (EASI) measured over 52 weeks. Secondary outcomes included patient-reported outcomes (PROs), topical corticosteroid (TCS) use, SA colonization, safety and cost-effectiveness. Outcomes were assessed by means of (generalized) linear mixed-model analyses. RESULTS: Between 16 March 2020 and 20 December 2021, 171 patients were enrolled. In total, 159 patients were included (54 in the standard therapeutic clothing group, 50 in the chitosan group and 55 in the silver group). Adherence was high [median 7 nights a week wear (interquartile range 3-7)]. Median EASI scores at baseline and at 4, 12, 26 and 52 weeks were 11.8, 4.3, 4.6, 4.2 and 3.6, respectively, in the standard therapeutic clothing group vs. 11.3, 5.0, 3.0, 3.0 and 4.4, respectively, in the chitosan group, and 11.6, 5.0, 5.4, 4.6 and 5.8, respectively, in the silver group. No differences in EASI over 52 weeks between the standard therapeutic clothing group, the chitosan group [-0.1, 95% confidence interval (CI) -0.3 to 0.2; P = 0.53] or the silver group (-0.1, 95% CI -0.3 to 0.2; P = 0.58) were found. However, a small significant group × time interaction effect between the standard and silver groups was found (P = 0.03), in which the silver group performed worse after 26 weeks. No differences between groups were found in PROs, TCS use, SA skin colonization and healthcare utilization. No severe adverse events or silver absorption were observed. CONCLUSIONS: The results of this study suggest no additional benefits of antibacterial agents in therapeutic clothing in patients with moderate-to-severe AD.

Treatment Experiences with Intravenous Immunoglobulins, Ixekizumab, Dupilumab, and Anakinra in Netherton Syndrome: A Case Series.

BACKGROUND: Netherton syndrome (NS) is a rare potential life-threatening disorder that causes severe defects to the skin barrier. No effective treatment options are available for patients with NS and current therapy is mostly supportive. The effects of intravenous immunoglobulins (IVIGs), ixekizumab, and dupilumab have scarcely been reported. Additionally, the role of anakinra in patients with NS has never been investigated. OBJECTIVES: The objective was to report our experiences of treatment with IVIG, ixekizumab, dupi-lumab, and anakinra in patients with NS. METHODS: A retrospective case series, including 5 patients with NS, was performed in a tertiary referral hospital between 2016 and 2021. Patients were treated with IVIG, ixekizumab, dupilumab, and/or anakinra. Long-term experiences with treatment regimens and adverse events requiring medical attention were reported. RESULTS: IVIG, ixekizumab, dupilumab, and anakinra were well tolerated with no severe adverse events. The 2 patients that received IVIG showed clinical response for 6 months and 2.5 years. Ixekizumab was effective in 1 of our patients for 3.5 years, while in another patient ixekizumab lost its effect after 1.5 years. Dupilumab treatment did not result in persistent improvement of NS-related skin symptoms in 1 patient. Anakinra showed physician-assessed clinical response during the first months of treatment in 4 patients with NS. During anakinra treatment, no changes in blood levels of IL-1ß, IL-6, and TNF-α levels were measured at routine blood examinations. CONCLUSIONS: This case series suggests that the use of IVIG, ixekizumab, dupilumab, and anakinra in NS is safe and moderately effective on the short term. On the long term, a decline in effect was observed. Our experiences may help clinicians and researchers to provide adequate care and develop treatment for these severely affected patients. More international research, especially on the long term, is needed to determine if and which patients benefit most from the emerging therapies for NS.

The Skin and Nose Microbiome and Its Association with Filaggrin Gene Mutations in Pediatric Atopic Dermatitis.

BACKGROUND: Interactions between the skin barrier, immune system, and microbiome underlie the development of atopic dermatitis (AD). OBJECTIVE: To investigate the skin and nasal microbiome in relation to filaggrin gene (FLG) mutations. METHODS: A cross-sectional study including 77 children with difficult-to-treat AD. The entire encoding region of FLG was screened for mutations using single molecule molecular inversion probes and next-generation sequencing. Bacterial swabs from the anterior nares, lesional and nonlesional skin were analyzed using 16S rRNA sequencing. For skin samples, additional qPCR was performed for Staphylococcus aureus and Staphylococcus epidermidis. RESULTS: The prevalence of patients with a mutation in FLG was 40%, including 10 different mutations. Analyzing bacterial swabs from all three niches showed a significant effect for both niche and FLG mutation status on the overall microbiome composition. Using a subset analysis to test the effect of FLG mutation status per niche separately did not show a significant association to the microbiome. Shannon diversity and S. aureus abundance were significantly affected by the niche, but not by the presence of an FLG mutation. CONCLUSIONS: Our results suggest only a minor role for FLG mutation status on the overall microbiome, which is rather caused by differences in the present genera than by microbe richness and evenness.

Increased Th22 cell numbers in a general pediatric population with filaggrin haploinsufficiency: The Generation R Study.

BACKGROUND: Mutations in the filaggrin gene (FLG) affect epidermal barrier function and increase the risk of atopic dermatitis (AD). We hypothesized that FLG mutations affect immune cell composition in a general pediatric population. Therefore, we investigated whether school-aged children with and without FLG mutations have differences in T- and B-cell subsets. METHODS: This study was embedded in a population-based prospective cohort study, the Generation R Study, and included 523 children of European genetic ancestry aged 10 years. The most common FLG mutations in the European population (R501X, S1085CfsX36, R2447X, and S3247X) were genotyped. Additionally, 11-color flow cytometry was performed on peripheral blood samples to determine helper T (Th), regulatory T (Treg), and CD27+ and CD27- memory B cells. Subset analysis was performed in 358 non-AD and 102 AD cases, assessed by parental questionnaires. RESULTS: FLG mutations were observed in 8.4% of the total population and in 15.7% of the AD cases. Children with any FLG mutation had higher Th22 cell numbers compared to FLG wild-type children in the general and non-AD population. Children with and without FLG mutations had no difference in Th1, Th2, Th17, Treg, or memory B-cell numbers. Furthermore, in children with AD, FLG mutation carriership was not associated with differences in T- and B-cell subsets. CONCLUSIONS: School-aged children of a general population with FLG mutations have higher Th22 cell numbers, which reflects the immunological response to the skin barrier dysfunction. FLG mutations did not otherwise affect the composition of the adaptive immunity in this general pediatric population.

Temporal Variation in Staphylococcus aureus Protein A Genotypes from Nose and Skin in Atopic Dermatitis Patients.

BACKGROUND: Staphylococcus aureus colonization is associated with disease severity in patients with atopic dermatitis (AD). OBJECTIVE: To investigate temporal variation in S. aureus protein A gene (spa)-types isolated from the nose and lesional skin and the correlation of spa-types with disease severity. RESULTS: This study included 96 adult AD patients who were assessed at baseline (T0) and after a strict 2-week follow-up period (T1) in which treatment was standardized with a topical corticosteroid. Fifty-five different spa-types were detected in the nose and skin cultures. Seventy-three patients were colonized with S. aureus in the nasal cavity at both time points (persistent carriership), 59 of whom (81%) had identical spa-types over time. For skin samples, 42 (75%) of the 56 persistent skin carriers had identical spa-types over time. The same spa-type was carried in the nose and skin in 79 and 77% of the patients at T0 and T1, respectively. More severe disease was not associated with specific spa-types or with temporal variation in spa-type. CONCLUSION: S. aureus strains in AD are highly heterogeneous between patients. The majority of patients carry the same spa-type in the nose and skin without temporal variation, suggesting clonal colonization within individual patients. No predominant spa-type or temporal variation is associated with increased disease severity.

The influence of treatment in alpine and moderate maritime climate on the composition of the skin microbiome in patients with difficult to treat atopic dermatitis.

BACKGROUND: The skin microbiome, characterized by an overgrowth of Staphylococcus aureus, plays an important role in the pathogenesis of atopic dermatitis (AD). Multidisciplinary treatment in alpine climate is known for its positive effect on disease severity in children with AD and can result in a different immune response compared with moderate maritime climate. However, the effect on the composition of the skin microbiome in AD is unknown. OBJECTIVE: To determine the effect of treatment in alpine climate and moderate maritime climate on the microbiome for lesional and non-lesional skin in children with difficult to treat AD. RESULTS: Alpine climate treatment led to a significant change in the microbiota on lesional skin, whereas no significant change was found after moderate maritime climate. On both lesional and non-lesional skin, we observed a significant increase in Shannon diversity and a significant decrease in both Staphylococcus abundance and S aureus load after alpine climate treatment. The decrease in S aureus was significantly larger on lesional skin following alpine climate treatment compared with moderate maritime climate treatment. Staphylococcus epidermidis load was stable over time. CONCLUSIONS AND CLINICAL RELEVANCE: Alpine climate treatment leads to significant changes in the composition of the skin microbiome in children with AD, mainly caused by a reduction in the Staphylococcus genus. This study shows new perspectives in the potential mode of action for therapies in AD.

The effectiveness of antibacterial therapeutic clothing based on silver or chitosan as compared with non-antibacterial therapeutic clothing in patients with moderate to severe atopic dermatitis (ABC trial): study protocol for a pragmatic randomized controlled trial.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects 10 to 20% of children and between 2 and 15% of the adults in Western Europe. Since 2000, therapeutic clothing or functional textiles based on silver or chitosan as antibacterial agents were introduced for AD. These agents aim to reduce skin colonization with Staphylococcus (S.) aureus. Increased colonization with S. aureus is correlated with increased AD severity. The antimicrobial effects of silver and chitosan have been demonstrated before. At this point, there is insufficient evidence for the effectiveness of antibacterial therapeutic clothing in patients with AD. METHODS: This is a pragmatic randomized controlled double-blind multi-center trial comparing the effectiveness of antibacterial therapeutic clothing based on silver or chitosan as compared with non-antibacterial therapeutic clothing in patients with moderate to severe AD. A total of 165 participants, aged 0 to 80, diagnosed with moderate to severe AD are included. The study is performed in the Erasmus MC University Medical Center, University Medical Center Groningen, University Medical Center Utrecht, Amsterdam University Medical Centers, and St. Antonius Hospital Nieuwegein. Patients will be randomized 1:1:1 into one of the three intervention groups: group A will receive therapeutic clothing without antimicrobial agents, group B will receive microbial growth reducing therapeutic clothing based on chitosan, and group C will receive antimicrobial clothing based on silver. All therapeutic clothing is to be worn at night during the 12-month intervention period. Usual care is continued. The primary objective is to assess the effectiveness of antibacterial clothing (silver and chitosan group) as compared to non-antibacterial clothing assessed with the Eczema Area and Severity Index at 12 months compared to baseline. Secondary outcomes include between-group differences in physician- and patient-reported outcome measures, topical therapy use, S. aureus skin colonization, and safety. Data will be collected at baseline and after 1 month, 3 months, 6 months, and 12 months. A cost-effectiveness analysis will be performed. DISCUSSION: This trial will provide data on the effectiveness, cost-effectiveness, and safety of antibacterial therapeutic clothing for patients with AD. TRIAL REGISTRATION: ClinicalTrials.gov NCT04297215. Registered on 5 March 2020.