Summary
In vivo examination of the skin by reflectance confocal microscopy (RCM) has been performed for about 20 years, leading to a broad spectrum of imaged infectious and inflammatory skin diseases ...(ISD) with many described RCM features. We systematically reviewed all available literature concerning ISD evaluated by RCM. Furthermore, we assessed the accuracy of the features and defined recommendations for future studies after indicating the limitations in the current published literature. PubMed, Embase, Cochrane Library and Web of Science databases were searched for literature. All studies on RCM and ISD were reviewed and quality assessment was determined by using the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist. The literature search revealed 77 eligible studies for inclusion. Different RCM features in a broad spectrum of ISD have been described. Further, RCM has been used for monitoring treatment and evolution of ISD, as well as for diagnostic purposes. This systematic review provides an overview of the broad spectrum of ISD imaged by RCM. Although RCM seems to be a promising monitoring and diagnostic tool for ISD, studies with appropriate methodological quality are necessary to create adequate guidelines and protocols for further implementation of RCM in clinical practice.
What's already known about this topic?
Many inflammatory and infectious skin diseases have been imaged by in vivo reflectance confocal microscopy (RCM).
What does this study add?
This systematic review provides an overview and accuracy assessment of RCM features and diagnoses.
This review facilitates further implementation of RCM in dermatological practice.
Interleukin 17-antagonist secukinumab demonstrated high efficacy for treatment of psoriasis in randomized controlled trials. However, performance in daily practice may differ from trials. Drug ...survival is a comprehensive outcome covering effectiveness and safety, suitable for analyses of daily practice. The aim of this study was to evaluate drug survival of secukinumab in a daily practice psoriasis cohort. Data were collected from 13 hospitals. Drug survival was analysed using Kaplan-Meier survival curves, split for reason of discontinuation. In total, 196 patients were included (83% biologic experienced). Overall, 12 and 18 months drug survival of secukinumab was 76% and 67%, respectively, and was mostly determined by ineffectiveness. There was a trend towards shorter drug survival in women and in biologic experienced patients. Thirteen percent of patients experienced at least one episode of fungal infection. This is one of the first studies of drug survival of secukinumab in patients with psoriasis treated in daily practice.
Summary
Background
The use of recently introduced biologics targeting specific immune mechanisms has identified crucial steps in the pathogenesis of psoriasis. Studying the dynamics of changes of ...these target mechanisms in sequential skin biopsies during treatment with biologics may reveal potential biomarkers. Correlation between clinical parameters and the expression of specific genes during treatments may identify markers indicative of treatment response.
Objectives
This observational open‐label study aimed to provide an overview of important cell biological changes in lesional skin during treatment with adalimumab, and their relationship to clinical improvement.
Methods
Ten patients with moderate‐to‐severe plaque psoriasis were included and treated with adalimumab for 16 weeks. At baseline, and after 10 days and 16 weeks of treatment clinical scores were assessed and biopsies were taken to examine gene expression at the mRNA and protein level.
Results
The expression of marker genes for innate immunity, and epidermal differentiation and proliferation was rapidly restored to normal levels, whereas genes of the adaptive immune system showed a delayed decrease. The static and dynamic course of CD1a+ Langerhans cells and Ki67+ nuclei showed a significant strong correlation to the Psoriasis Area and Severity Index score. No correlation between interleukin‐17 expression and clinical scores was found.
Conclusions
The innate immune system is affected during adalimumab treatment well before the changes in the adaptive immune system become apparent. We may speculate that the addition of a treatment with an early effect on adaptive immunity to adalimumab may result in superior effectiveness compared with monotherapies.
What's already known about this topic?
Recently introduced biologics targeting specific immune mechanisms have identified crucial steps in the pathogenesis of psoriasis.
What does this study add?
During adalimumab treatment markers of epidermal differentiation, proliferation and the innate immune system revert rapidly to normal, well before changes in the adaptive immune system become apparent.
Psoriasis may express as active severe disease or as mild stable disease. In particular, patients with active severe disease present systemic involvement, including comorbidities and increased values ...of parameters reflecting an active state of innate immunity. In contrast, patients with mild stable disease show a dominancy of acquired immunity. In this review article, we report the clinical aspects of disease manifestations of both active and quiescent psoriasis as well as the immunological aspects, as well as the impact on antimicrobial resistance. The activity of psoriasis is not captured in the present outcome measures for severity assessment. The present review suggests that incorporating disease activity may be important in the assessment of the efficacy of treatments.
Summary
Background
Psoriasis in children has a significant negative impact on the quality of life (QoL) and effective treatment can improve this. The two‐compound ointment calcipotriol 50 μg g−1 and ...betamethasone dipropionate 0·5 mg g−1 is an effective treatment option for moderate‐to‐severe psoriasis in adults.
Objectives
To study prospectively the effectiveness and safety of calcipotriol/betamethasone dipropionate ointment in paediatric patients with mild‐to‐moderate plaque psoriasis in daily clinical practice and to investigate the influence on QoL.
Methods
Data were obtained from a prospective, longitudinal paediatric psoriasis registry, called Child‐CAPTURE. Severity was assessed using the Psoriasis Area and Severity Index (PASI) and body surface area (BSA). The Children's Dermatology Life Quality Index (CDLQI) was used to assess QoL and visual analogue scores (VAS) for pain and itch were collected. For safety data the number of (serious) adverse events was recorded.
Results
Seventy‐three patients (mean age 10·8 years, range 3–18) were treated for a median time of 35·0 weeks (range 1·0–176·0). At week 12, mean PASI decreased 15·4% (from 5·2 to 4·4), BSA barely changed, and median CDLQI decreased significantly from 5·5 to 4·0. VAS scores for pain and itch declined. At week 24, mean PASI decreased to 4·3 (17·3%). No related serious adverse events were observed.
Conclusions
In this daily clinical practice study in paediatric psoriasis, calcipotriol/betamethasone dipropionate ointment initially improved mild‐to‐moderate psoriasis and then maintained its effect. In addition, it improved QoL, with few adverse events.
What's already known about this topic?
A two‐compound ointment containing calcipotriol 50 μg g−1 and betamethasone dipropionate 0·5 mg g−1 is an effective treatment for moderate‐to‐severe psoriasis in adults.
Studies on its effectiveness in paediatric psoriasis are not available.
What does this study add?
In this prospective observational study, we provide daily clinical practice evidence on the effectiveness and safety of calcipotriol/betamethasone dipropionate ointment in children with mild‐to‐moderate plaque psoriasis.
Background
Appropriate management and prevention of both under‐ and overtreatment in older skin cancer patients can be challenging. It could be helpful to incorporate frailty screening in ...dermato‐oncology care, since frailty is associated with adverse health outcomes.
Objectives
This study aimed to identify and prioritize the requirements a frailty screening tool (FST) should fulfil in dermato‐oncology practice and to select the best existing FST(s) for this purpose.
Methods
A modified two‐round Delphi procedure was performed among 50 Italian and Dutch specialists and patients to review and prioritize a list of potential FST requirements, using a 5‐point Likert scale. Consensus was defined as a mean score of ≥4.0. A systematic literature search was performed to identify existing multidomain FSTs, which were then assessed on the requirements resulting from the modified Delphi procedure.
Results
Consensus was achieved on evaluation of comorbidities (4.3 ± 0.7), polypharmacy (4.0 ± 0.9) and cognition (4.1 ± 0.8). The FST should have appropriate measurement properties (4.0 ± 1.0), be quickly executed (4.2 ± 0.7), clinically relevant (4.3 ± 0.7), and both easily understandable (4.1 ± 1.2) and interpretable (4.3 ± 0.7). Of the 26 identified FSTs, four evaluated the content‐related domains: the Geriatric‐8 (G8), the modified Geriatric‐8 (mG8), the Groningen Frailty Indicator (GFI) and the Senior Adult Oncology Program 2 (SAOP2) screening tool. Of these, the G8 was the most extensively studied FST, with the best psychometric properties and execution within 5 min.
Conclusions
The G8 appears the most suitable FST for assessing frailty in older adults with skin cancer, although clinical studies assessing its use in a dermato‐oncology population are needed to further assess whether or not frailty in this particular patient group is associated with relevant outcomes (e.g. complications and mortality), as seen in previous studies in other medical fields.
Summary
Background In previous studies, etanercept 25 mg twice weekly (BIW) or 50 mg BIW significantly reduced disease severity in patients with plaque psoriasis and demonstrated a favourable safety ...profile.
Objectives To assess the efficacy and safety of etanercept 50 mg administered once weekly (QW) compared with placebo in patients with moderate‐to‐severe plaque psoriasis over 24 weeks.
Methods This study was conducted in two parts: (i) a 12‐week, double‐blind, placebo‐controlled phase, in which patients received etanercept 50 mg QW or placebo QW; and (ii) a 12‐week, open‐label extension phase, in which all patients received etanercept 50 mg QW. Primary endpoint was a 75% or greater improvement from baseline in the Psoriasis Area and Severity Index (PASI 75) at week 12. Secondary endpoints included percentage PASI improvement and Physician’s Global Assessment (PGA).
Results One hundred and forty‐two patients were analysed in the double‐blind phase; 126 patients entered the open‐label phase. At week 12, significantly more patients receiving etanercept 50 mg QW (37·5%) achieved PASI 75 response than patients receiving placebo (2·2%; P < 0·0001). At week 24, 71·1% in the etanercept–etanercept group and 44·4% in the placebo–etanercept group achieved PASI 75. Mean percentage of PASI improvement from baseline was 55·4% with etanercept vs. 9·4% worsening with placebo at week 12 (P < 0·0001), with 77·4% and 57·7% improvement in the etanercept–etanercept and placebo–etanercept groups at week 24. A PGA score of 0–1 (clear–almost clear) was achieved by 64% and 42% in the etanercept–etanercept and placebo–etanercept groups at week 24, respectively. Etanercept 50 mg QW was well tolerated. No deaths, serious infections, opportunistic infections (including tuberculosis), demyelinating disorders, malignancies or new safety signals were reported.
Conclusions Nearly three‐quarters of patients with moderate‐to‐severe psoriasis receiving etanercept 50 mg QW achieved significant improvement in disease severity over 24 weeks. This study also showed a favourable tolerability and safety profile with etanercept 50 mg QW.
According to the guidelines for the treatment of psoriasis, phototherapy is given in courses of UVB exposure starting at 50–70% of the minimal erythema dose, MED, with subsequently incremental ...dosages, but keeping erythemal skin reactions to a minimum by restraining the dosages when necessary. In this review, this classical principle of short‐term near erythematogenic UVB therapy without further UVB maintenance therapy is challenged as it is evidently not optimal for psoriasis as a chronic condition. There is old experimental evidence supplemented with growing knowledge on the mode of action of phototherapy and more recent data on low‐level UVB regimens as maintenance therapy that should urge us to revisit our guidelines on phototherapy to address psoriasis for what it is: a chronic condition.
Clinical trials successfully using antibodies targeting IL-17 in psoriasis support the importance of IL-17 in the pathophysiology of this disease. However, there is a debate concerning the source and ...dynamics of IL-17 production in inflamed skin. Here we characterized IL-17-producing immune cells over time, using two established in vivo models of human skin inflammation that share many histological features with psoriasis, i.e., leukotriene B4 application and tape-stripping. Both treatments revealed a clear influx of neutrophils and T cells. Staining for IL-17 revealed that the majority of IL-17 was expressed by neutrophils and mast cells, in both models. Neutrophils, but not mast cells, coexpressed the IL-17-associated transcription factor RORγt and were able to form extracellular traps. While the presence of mast cells remained steady during the skin inflammatory process, the presence of neutrophils was clearly dynamic in time. Therefore, it is attractive to hypothesize that IL-17+/RORγt+ neutrophils contribute to human skin inflammation in vivo and possibly to the pathogenesis of skin diseases such as psoriasis. Surprisingly, T cells represented a minority of the IL-17-expressing cell population. These observations challenge the classical opinion that IL-17 is predominantly associated with T cells in skin inflammation.
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