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.

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.

Molecular clustering of genes related to the atopic syndrome: Towards a more tailored approach and personalized medicine?

BACKGROUND: The atopic syndrome consists of heterogeneous manifestations, in which multiple associated genetic loci have recently been identified. It is hypothesized that immune dysregulation plays a role in the pathogenesis. In primary immunodeficiency diseases (PIDs), which are often monogenic immunodysregulation disorders, the atopic syndrome is a frequently occurring comorbidity. Based on the genetic defects in PIDs, novel gene/pathway-targeted therapies have been evaluated, which could be relevant in the atopic syndrome as well. Therefore, we aimed to define subclasses within the atopic syndrome based on the expression profiles of immune cell lineages of healthy mice. METHODS: Overlap between known atopy-related genes as described in the Human Gene Mutation Database and disease-causing genes of monogenic PIDs was evaluated. Clusters of atopy-related genes were based on the overlap in their co-expressed genes using the gene expression profiles of immune cell lineages of healthy mice from the Immunological Genome Project. We analyzed pathways involved in the atopic syndrome using Ingenuity Pathway Analysis. RESULTS: Twenty-two (5.3%) genes were overlapping between the atopy-related genes (n = 160) and PID-related genes (n = 278). We identified seven distinct clusters of atopy-related genes. Functional pathway analysis of all atopy-related genes showed relevance of T helper cell-mediated pathways. CONCLUSIONS: This study shows a model to define clusters within the atopic syndrome based on gene expression profiles of immune cell lineages. Our results support the hypothesis that both genetic mechanisms and immune dysregulation play a role in the pathogenesis. It also opens up the possibility for novel therapeutic targets and a more tailored approach towards personalized medicine.

Skin disorders are prominent features in primary immunodeficiency diseases: A systematic overview of current data.

Primary immunodeficiency diseases (PIDs) are characterized by an increased risk of infections, autoimmunity, autoinflammation, malignancy, and allergic disorders. Skin disorders are also common clinical features in PIDs and may be among the presenting manifestations. Recognition of specific PID-associated skin conditions in combination with other clinical features as described in the currently used warning signs could raise suspicion of an underlying PID. We aimed to provide a systematically obtained overview of skin disorders and their prevalence in PIDs. Secondary, the prevalence of Staphylococcus (S.) aureus-associated skin disorders and atopy was reviewed, as these are the most prominent skin features in PIDs. A systematic search was performed in EMBASE, MEDLINE, Web of Science, Cochrane, and Google Scholar (up to May 9, 2018). All original observational and experimental human studies that address the presence of skin disorders in PIDs were selected. We rated study quality using the Institute of Health Economics Quality Appraisal Checklist for Case Series Studies. Sixty-seven articles (5030 patients) were included. Study quality ranged from 18.2% to 88.5%. A broad spectrum of skin disorders was reported in 30 PIDs, mostly in single studies with a low number of included patients. An overview of associated PIDs per skin disorder was generated. Data on S. aureus-associated skin disorders and atopy in PIDs were limited. In conclusion, skin disorders are prominent features in PIDs. Through clustering of PIDs per skin disorder, we provide a support tool to use in clinical practice that should raise awareness of PIDs based on presenting skin manifestations.

Targeted anti-staphylococcal therapy with endolysins in atopic dermatitis and the effect on steroid use, disease severity and the microbiome: study protocol for a randomized controlled trial (MAAS trial).

BACKGROUND: Atopic dermatitis (AD) is associated with reduced skin microbial diversity and overgrowth of Staphylococcus (S.) aureus. However, the importance of S. aureus colonisation in the complex pathogenesis remains unclear and studies on the effect of anti-staphylococcal therapy in non-infected AD show contradictory results. Long-term interventions against S. aureus might be needed to restore the microbial balance, but carry the risk of bacterial resistance induction. Staphefekt, an engineered bacteriophage endolysin, specifically kills S. aureus leaving other skin commensals unharmed. Bacterial resistance towards endolysins has not been reported, nor is it expected, which allows us to study its effect as long-term anti-staphylococcal treatment in non-infected AD. METHODS: This is a multi-centre, placebo-controlled, double-blinded and randomized superiority trial with a parallel group design. A total of 100 participants, aged 18 years or older, diagnosed with moderate to severe AD and using a topical corticosteroid in the weeks before enrolment are included in the study. The study is executed in the Erasmus MC University Medical Centre Rotterdam in collaboration with the Havenziekenhuis Rotterdam. After a 2-week run-in period to standardize the corticosteroid use with triamcinolone acetonide 0.1% cream, participants will be randomized to either treatment with Staphefekt in a cetomacrogol-based cream or a placebo for 12 weeks, followed by an 8-week follow-up period. The primary objective is to assess the difference in the need for corticosteroid co-therapy between the Staphefekt and the placebo group, measuring the number of days per week of corticosteroid cream (triamcinolone) use. Secondary outcomes include the difference in use of corticosteroid cream measured in grams, differences in clinical efficacy, quality of life (QoL), microbial composition (includi23ng S. aureus) between the Staphefekt and the placebo group, and the safety and tolerability. DISCUSSION: The results of this trial will provide data about the effect of long-term anti-staphylococcal therapy with Staphefekt on corticosteroid use, clinical symptoms and QoL in patients with moderate to severe AD. Additional data about growth characteristics of the skin microbiome, including S. aureus, will give insight into the role of the microbiome as a factor in the pathophysiology of AD. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02840955 . Registered on 11 July 2016.

A prospective assessment of the natural course of the exocrine pancreatic function in patients with a pancreatic head tumor.

INTRODUCTION: In cancer of the pancreatic head region, exocrine insufficiency is a well-known complication, leading to steatorrhea, weight loss, and malnutrition. Its presence is frequently overlooked, however, because the primary attention is focused on cancer treatment. To date, the risk of developing exocrine insufficiency is unspecified. Therefore, we assessed this function in patients with tumors of the pancreatic head, distal common bile duct, or ampulla of Vater. METHODS: Between March 2010 and August 2012, we prospectively included patients diagnosed with cancer of the pancreatic head region at our tertiary center. To preclude the effect of a resection, we excluded operated patients. Each month, the exocrine function was determined with a fecal elastase test. Furthermore, endocrine function, steatorrhea-related symptoms, and body weight were evaluated. Patients were followed for 6 months, or until death. RESULTS: Thirty-two patients were included. The tumor was located in the pancreas in 75%, in the bile duct in 16%, and in the ampullary region in 9%, with a median size of 2.5 cm. At diagnosis, the prevalence of exocrine insufficiency was 66%, which increased to 92% after a median follow-up of 2 months (interquartile range, 1 to 4 mo). DISCUSSION: Most patients with cancer of the pancreatic head region were already exocrine insufficient at diagnosis, and within several months, this function was impaired in almost all cases. Given this high prevalence, physicians should be focused on diagnosing and treating exocrine insufficiency, to optimize the nutritional status and physical condition, especially for those patients undergoing palliative chemotherapy and/or radiotherapy.