Fernblock, a Nutriceutical with Photoprotective Properties and Potential Preventive Agent for Skin Photoaging and Photoinduced Skin Cancers

Many phytochemicals are endowed with photoprotective properties, i.e., the capability to prevent the harmful effects of excessive exposure to ultraviolet (UV) light. These effects include photoaging and skin cancer, and immunosuppression. Photoprotection is endowed through two major modes of action: UV absorption or reflection/scattering; and tissue repair post-exposure. We and others have uncovered the photoprotective properties of an extract of the fern Polypodium leucotomos (commercial name Fernblock). Fernblock is an all-natural antioxidant extract, administered both topically (on the skin) or orally. It inhibits generation of reactive oxygen species (ROS) production induced by UV including superoxide anion. It also prevents damage to the DNA, inhibits UV-induced AP1 and NF-κB, and protects endogenous skin natural antioxidant systems, i.e., CAT, GSH, and GSSR. Its photoprotective effects at a cellular level include a marked decrease of UV-mediated cellular apoptosis and necrosis and a profound inhibition of extracellular matrix remodeling. These molecular and cellular effects translate into long-term inhibition of photoaging and carcinogenesis that, together with its lack of toxicity, postulate its use as a novel-generation photoprotective nutriceutical of phytochemical origin

TREatment of ATopic eczema (TREAT) Registry Taskforce: consensus on how and when to measure the core dataset for atopic eczema treatment research registries.

BackgroundComparative, real-life and long-term evidence on the effectiveness and safety of phototherapy and systemic therapy in moderate-to-severe atopic eczema (AE) is limited. Such data must come from well-designed prospective patient registries. Standardization of data collection is needed for direct comparisons and data pooling.ObjectivesTo reach a consensus on how and when to measure the previously defined domain items of the TREatment of ATopic eczema (TREAT) Registry Taskforce core dataset for research registries for paediatric and adult patients with AE.MethodsProposals for the measurement instruments were based on recommendations of the Harmonising Outcome Measures for Eczema (HOME) initiative, the existing AE database of TREATgermany, systematic reviews of the literature and expert opinions. The proposals were discussed at three face-to-face consensus meetings, one teleconference and via e-mail. The frequency of follow-up visits was determined by an expert survey.ResultsA total of 16 experts from seven countries participated in the 'how to measure' consensus process and 12 external experts were consulted. A consensus was reached for all domain items on how they should be measured by assigning measurement instruments. A minimum follow-up frequency of initially 4 weeks after commencing treatment, then every 3 months while on treatment and every 6 months while off treatment was defined.ConclusionsThis core dataset for national AE research registries will aid in the comparability and pooling of data across centres and country borders, and enables international collaboration to assess the long-term effectiveness and safety of phototherapy and systemic therapy used in patients with AE. What's already known about this topic? Comparable, real-life and long-term data on the effectiveness and safety of phototherapy and systemic therapy in patients with atopic eczema (AE) are needed. There is a high diversity of outcomes and instruments used in AE research, which require harmonization to enhance comparability and allow data pooling. What does this study add? Our taskforce has reached international consensus on how and when to measure core domain items for national AE research registries. This core dataset is now available for use by researchers worldwide and will aid in the collection of unified data. What are the clinical implications of this work? The data collected through this core dataset will help to gain better insights into the long-term effectiveness and safety of phototherapy and systemic therapy in AE and will provide important information for clinical practice. Standardization of such data collection at the national level will also allow direct data comparisons and pooling across country borders (e.g. in the analysis of treatment-related adverse events that require large patient numbers)

Patients with atopic dermatitis with filaggrin loss-of-function mutations show good but lower responses to immunosuppressive treatment

Filaggrin (FLG) mutations are a strong risk factor to develop atopic dermatitis (AD). However, the relationship between FLG mutations and treatment outcome in AD has not been thoroughly studied. To investigate whether FLG mutations influence immunosuppressive treatment outcome in AD, we studied the effect of FLG mutations in patients with severe AD participating in a single blinded randomized controlled trial (RCT) with methotrexate (MTX) or azathioprine (AZA) during a 24 weeks treatment regimen.((1)) Two years after randomization buccal mucosa swabs were collected from 36 of the 42 RCT patients (86%) to determine the FLG genotype status (R501X, 2282del4, R2447X, S3247X and 3321delA mutations). This article is protected by copyright. All rights reserve

A minimally invasive tool to study immune response and skin barrier in children with atopic dermatitis

Background: Atopic dermatitis (AD) affects children of all skin types. Most research has focused on light skin types. Studies investigating biomarkers in people with AD with dark skin types are lacking. Objectives: To explore skin barrier and immune response biomarkers in stratum corneum (SC) tape strips from children with AD with different skin types. Methods: Tape strips were collected from lesional and nonlesional forearm skin of 53 children with AD and 50 controls. We analysed 28 immunomodulatory mediators, and natural moisturizing factors (NMF) and corneocyte morphology. Results: Interleukin (IL)-1β, IL-18, C-X-C motif chemokine (CXCL) 8 (CXCL8), C-C motif chemokine ligand (CCL) 22 (CCL22), CCL17, CXCL10 and CCL2 were significantly higher (P < 0·05) in lesional AD skin compared with nonlesional AD skin; the opposite trend was seen for IL-1α. CXCL8, CCL2 and CCL17 showed an association with objective SCORing Atopic Dermatitis score. NMF levels showed a gradual decrease from healthy skin to nonlesional and lesional AD skin. This gradual decreasing pattern was observed in skin type II but not in skin type VI. Skin type VI showed higher NMF levels in both nonlesional and lesional AD skin than skin type II. Corneocyte morphology was significantly different in lesional AD skin compared with nonlesional AD and healthy skin. Conclusions: Minimally invasive tape-stripping is suitable for the determination of many inflammatory mediators and skin barrier biomarkers in children with AD. This study shows differences between children with AD with skin type II and skin type VI in NMF levels, suggesting that some aspects of pathophysiological mechanisms may differ in AD children with light versus dark skin types

Classifying atopic dermatitis: a systematic review of phenotypes and associated characteristics.

Atopic dermatitis is a heterogeneous disease, accompanied by a wide variation in disease presentation and the potential to identify many phenotypes that may be relevant for prognosis and treatment. We aimed to systematically review previously reported phenotypes of atopic dermatitis and any characteristics associated with them. Ovid EMBASE, Ovid MEDLINE and Web of Science were searched from inception till 12 February 2021 for studies attempting to classify atopic dermatitis. Primary outcomes are atopic dermatitis phenotypes and characteristics associated with them in subsequent analyses. A secondary outcome is the methodological approach used to derive them. In total, 8511 records were found. By focussing only on certain clinical phenotypes, 186 studies were eligible for inclusion. The majority of studies were hospital-based (59%, 109/186) and cross-sectional (76%, 141/186). The number of included patients ranged from seven to 526 808. Data-driven approaches to identify phenotypes were only used in a minority of studies (7%, 13/186). Ninety-one studies (49%) investigated a phenotype based on disease severity. A phenotype based on disease trajectory, morphology and eczema herpeticum was investigated in 56 (30%), 22 (12%) and 11 (6%) studies respectively. Thirty-six studies (19%) investigated morphological characteristics in other phenotypes. Investigated associated characteristics differed between studies. In conclusion, we present an overview of phenotype definitions used in literature for severity, trajectory, morphology and eczema herpeticum, including associated characteristics. There is a lack of uniform and consistent use of atopic dermatitis phenotypes across studies

Nailfold capillary scleroderma pattern may be associated with disease damage in childhood-onset systemic lupus erythematosus:important lessons from longitudinal follow-up

OBJECTIVES: To observe if capillary patterns in childhood-onset SLE (cSLE) change over time and find associations between a capillary scleroderma pattern with disease activity, damage or scleroderma-like features. METHODS: Clinical and (yearly) capillaroscopy data from a longitudinal cohort of patients with cSLE (minimum of four Systemic Lupus International Collaborating Clinics (SLICC) criteria, onset <18 years) were analysed. Disease activity was measured by Systemic Lupus Erythematosus Activity Index (SLEDAI) and disease damage by SLICC Damage Index. A scleroderma pattern was defined according to the ‘fast track algorithm’ from the European League Against Rheumatism Study Group on Microcirculation in Rheumatic Diseases. An abnormal capillary pattern, not matching a scleroderma pattern, was defined as ‘microangiopathy’. RESULTS: Our cohort consisted of 53 patients with cSLE with a median disease onset of 14 years (IQR 12.5–15.5 years), median SLEDAI score at diagnosis was 11 (IQR 8–16), median SLEDAI at follow-up was 2 (IQR 1–6). A scleroderma pattern (ever) was seen in 18.9%, while only 13.2% of patients had a normal capillary pattern. Thirty-three patients had follow-up capillaroscopy of which 21.2% showed changes in type of capillary pattern over time. Type of capillary pattern was not associated with disease activity. Raynaud’s phenomenon (ever) was equally distributed among patients with different capillaroscopy patterns (p=0.26). Anti-ribonucleoprotein antibodies (ever) were significantly more detected (Χ(2), p=0.016) in the scleroderma pattern subgroup (n=7 of 10, 70%). Already 5 years after disease onset, more than 50% of patients with a scleroderma pattern had SLE-related disease damage (HR 4.5, 95% CI 1.1 to 18.8, p=0.034), but they did not develop clinical features of systemic sclerosis at follow-up. Number of detected fingers with a scleroderma pattern was similar between cSLE, juvenile systemic sclerosis and juvenile undifferentiated connective tissue disease. CONCLUSION: This longitudinal study shows that the majority of capillary patterns in cSLE are abnormal and they can change over time. Irrespective of disease activity, a capillary scleroderma pattern in cSLE may be associated with higher risk of SLE-related disease damage

Comparison of real-world treatment outcomes of systemic immunomodulating therapy in atopic dermatitis patients with dark and light skin types

Background Few data exist on differences in treatment effectiveness and safety in atopic dermatitis patients of different skin types. Objective To investigate treatment outcomes of dupilumab, methotrexate, and ciclosporin, and morphological phenotypes in atopic dermatitis patients, stratified by Fitzpatrick skin type. Methods In an observational prospective cohort study, pooling data from the Dutch TREAT (TREatment of ATopic eczema) NL (treatregister.nl) and UK-Irish A-STAR (Atopic eczema Systemic TherApy Register; astar-register.org) registries, data on morphological phenotypes and treatment outcomes were investigated. Results A total of 235 patients were included (light skin types [LST]: Fitzpatrick skin type 1-3, n = 156 [Ethnicity, White: 94.2%]; dark skin types [DST]: skin type 4-6, n = 68 [Black African/Afro-Caribbean: 25%, South-Asian: 26.5%, and Hispanics: 0%]). DST were younger (19.5 vs 29.0 years; P .05). Limitations Unblinded, non-randomized. Conclusion Atopic dermatitis differs in several characteristics between LST and DST. Skin type may influence treatment effectiveness of dupilumab

Effectiveness of dupilumab treatment in 95 patients with atopic dermatitis: daily practice data

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 we