Effectiveness of systemic treatments on pruritus associated with atopic dermatitis: A systematic review in pediatric patients.

BACKGROUND/OBJECTIVES: Itch is one of the hallmarks of atopic dermatitis (AD), which has a significant impact on the quality of life of pediatric patients with AD and their caregivers. We aimed to conduct a systematic review and meta-analysis to evaluate the antipruritic effects of systemic AD treatments in pediatric patients with AD. METHODS: PubMed, EMBASE, Cochrane, and Web of Science databases were searched, including studies providing original data on the effects of systemic treatment on pruritus in pediatric patients (<18 years) with AD. Placebo-controlled trials reporting a Peak Pruritus Numerical Rating Scale 4 (PP-NRS4) response were included in a meta-analysis. RESULTS: A total of 30 studies were included, with most evidence available for dupilumab. Overall, marked improvements of pruritus (50% or greater reduction in pruritus outcome measurements) were found for treatment with cyclosporin A (2-16 years), dupilumab (6 months-17 years), abrocitinib, and upadacitinib (both 12 and 17 years). Nemolizumab (12-17 years) may be promising in reducing pruritus in pediatric patients; however, data are limited. Only five randomized controlled trials could be included in our meta-analysis, in which dupilumab, abrocitinib, and upadacitinib showed a significantly higher probability of achieving a PP-NRS4 response compared with placebo. Our study was limited by a lack of homogeneity of included studies. CONCLUSIONS: Cyclosporin A, dupilumab, abrocitinib, and upadacitinib are all effective in decreasing pruritus and, therefore, in improving the quality of life in children with AD. As more systemic treatments for AD become available, it will be imperative to incorporate patient-oriented treatment goals such as reduction of pruritus into therapeutic decision-making.

Dupilumab shows long-term effectiveness in a large cohort of treatment-refractory atopic dermatitis patients in daily practice: 52-Week results from the Dutch BioDay registry.

BACKGROUND: Real-life data on long-term effectiveness and safety of dupilumab in atopic dermatitis patients are limited. OBJECTIVE: To study 52-week effectiveness and safety of dupilumab in a prospective multicenter cohort of adult patients with treatment-refractory atopic dermatitis. METHODS: Patients treated with dupilumab and participating in the Dutch BioDay registry were included. Clinical effectiveness and safety were evaluated. RESULTS: Two hundred ten atopic dermatitis patients were included. Mean percentage change in Eczema Area and Severity Index score after 16 weeks was -70.0% (standard deviation 33.2%) and further decreased to -76.6% (standard deviation 30.6%) by week 52. A greater than or equal to 75% improvement in the score was achieved by 59.9% of individuals by week 16 and by 70.3% by week 52. The most reported adverse effect was conjunctivitis (34%). Limited patients (17; 8.1%) discontinued dupilumab treatment. LIMITATIONS: Because of the lack of a control group and observational design, factors of bias may have been induced. CONCLUSION: Treatment with dupilumab resulted in a rapid improvement in clinical outcome measures, and effectiveness further improved during the 52-week follow-up period.

Treatment goals in psoriasis from a patient perspective: a qualitative study.

Background: Psoriasis is a chronic inflammatory skin disorder with marked impact on quality of life. In view of the well-recognized need to integrate the patient perspective in psoriasis care, treatment goals which originate entirely from the experiences of the patients are of utmost importance.Objective: To explore treatment goals in patients with psoriasis that originate entirely from the patient perspective.Methods: Data was generated using face-to-face in-depth interviews with 15 Dutch psoriasis patients, which were analyzed using template analysis resulting in 2 first-level, 10 second-level, and 14 third-level themes.Results: A wide variety of treatment goals was reported. Almost all patients reported their 'ultimate' treatment goal would be achieving total skin clearance. Barriers in achieving treatment goals included the fact that psoriasis is a chronic disease with no cure available, lack of effectiveness of current treatment options and side effects of treatments of which the treatment effect does not compensate.Conclusion: There is a great variety and inter-individual difference in treatment goals. Therefore, we recommend to define individualized patient-defined treatment goals, as every patient with psoriasis requires a tailor-made treatment program.

A generic workflow for Single Locus Sequence Typing (SLST) design and subspecies characterization of microbiota.

We present TaxPhlAn, a new method and bioinformatics pipeline for design and analysis of single-locus sequence typing (SLST) markers to type and profile bacteria beyond the species-level in a complex microbial community background. TaxPhlAn can be applied to any group of phylogenetically-related bacteria, provided reference genomes are available. As TaxPhlAn requires the SLST targets identified to fit the phylogenetic pattern as determined through comprehensive evolutionary reconstruction of input genomes, TaxPhlAn allows for the identification and phylogenetic inference of new biodiversity. Here, we present a clinically relevant case study of high-resolution Staphylococcus profiling on skin of atopic dermatitis (AD) patients. We demonstrate that SLST enables profiling of cutaneous Staphylococcus members at (sub)species level and provides higher resolution than current 16S-based techniques. With the higher discriminative ability provided by our approach, we further show that the presence of Staphylococcus capitis on the skin together with Staphylococcus aureus associates with AD disease.

Use of Systemic Treatment in Patients with Chronic Pruritus: A Survey of Dermatologists in the Netherlands.

Treatment of chronic pruritus can be a challenge for clinicians. Several systemic treatments have been suggested to reduce itch, such as gabapentinoids and antidepressants. The aim of this study was to assess the current practice of dermatologists regarding systemic treatment in patients with chronic pruritus, and to identify possible barriers in the prescription of these treatments. An online survey was sent to all dermatologists and dermatology residents in the Netherlands between July 2017 and April 2018. A total of 193 physicians completed the questionnaire (response rate 27.0%). Overall, 61.7% prescribed gabapentinoids or antidepressants in patients with chronic pruritus. Amitriptyline was prescribed most frequently, followed by gabapentin, doxepin and mirtazapine. Reasons not to prescribe systemic treatment included lack of knowledge or experience, risk of side-effects, and lack of available evidence. As only a minority of respondents felt comfortable prescribing these drugs, more education on effective and safe dosing is needed.

Use of oral antidepressants in patients with chronic pruritus: A systematic review.

BACKGROUND: Chronic pruritus is a common skin symptom with marked impact on quality of life. Adequate treatment can be challenging for clinicians, demanding the exploration of new treatment options such as oral antidepressants. OBJECTIVE: To evaluate the use of oral antidepressants in chronic pruritus by a systematic overview of the available relevant literature. METHODS: The PubMed, EMBASE, Cochrane, and Web of Science databases were searched. Studies providing original data on the efficacy of oral antidepressants in patients with chronic pruritus were included. We assessed the risk for bias by using the Cochrane Risk of Bias tool for randomized controlled trials and the Newcastle-Ottawa Scale for observational studies. RESULTS: A total of 35 studies evaluating the oral use of fluoxetine, fluvoxamine, paroxetine, sertraline, amitriptyline, nortriptyline, doxepin, and mirtazapine were included. The majority of included articles showed a marked improvement of pruritus during treatment with oral antidepressants. LIMITATIONS: Recommendations are mainly based on open-label trials, case series, and case reports. CONCLUSION: Oral antidepressants should be considered in patients with chronic pruritus that is unresponsive to topical treatment and oral antihistamines, particularly in patients with uremic pruritus, cholestatic pruritus, or paraneoplastic pruritus. More evidence based on randomized-controlled trials is required.