Summary
Background
Cutaneous mosaicism is an area of dermatology in which there has been an explosion of knowledge within the current decade. This has led to fundamental changes in the understanding ...of the conditions in this field, and to an ongoing paradigm shift in the approach to management of mosaic skin disorders.
Objectives
To lay out the general principles of mosaicism as they are currently understood, summarize the known cutaneous mosaic abnormalities of the skin with associated phenotypic and genotypic information, review the latest trials on targeted therapies and propose guidelines for the general approach to a patient with suspected mosaicism.
Methods
This was a consensus expert review as part of the European Reference Network project (ERN‐Skin).
Conclusions
This study provides clinicians with a practical approach to the patient with suspected mosaicism, redefines mosaicism for the modern genetic era, and proposes a new classification system based on genetic mechanism.
What's already known about this topic?
Cutaneous mosaicism is a complex field of dermatology that encompasses most birthmarks, and many rare syndromes.
Some cutaneous patterns are known to be seen in mosaicism.
Very few treatment options are available for most mosaic abnormalities of the skin.
Recent high‐sensitivity genetic techniques have led to an explosion of knowledge about genotype and phenotype in the literature.
What does this study add?
Expert consensus from the European Reference Network project.
Review of knowledge of confirmed mosaic abnormalities of the skin, including cutaneous phenotype, extracutaneous associated features and genotype.
Proposed new classification of mosaic abnormalities of the skin by genetic mechanism and therefore inheritance potential.
Practical tips on correct sample collection and genetic investigation.
Review of trials of targeted therapies.
Guidelines for a practical clinical approach to the patient with suspected mosaicism.
Plain language summary available online
Background
Acral chilblain‐like lesions are being increasingly reported during COVID‐19 pandemic. However, only few patients proved positivity for SARS‐CoV‐2 infection. The relationship between this ...skin manifestation and COVID‐19 infection has not been clarified yet.
Objective
To thoroughly characterize a prospective group of patients with chilblain‐like lesions and to investigate the possible relationship with SARS‐CoV‐2 infection.
Methods
Following informed consent, patients underwent (i) clinical evaluation, (ii) RT‐PCR and serology testing for SARS‐CoV‐2, (iii) digital videocapillaroscopy of finger and toe nailfolds, (iv) blood testing to screen for autoimmune diseases and coagulation anomalies, and (v) skin biopsy for histopathology, direct immunofluorescence and, in selected cases, electron microscopy.
Results
Nineteen patients, all adolescents (mean age: 14 years), were recruited. 11/19 (58%) of them and/or their cohabitants reported flu‐like symptoms one to two months prior to skin manifestation onset. Lesions were localized to toes and also heels and soles. Videocapillaroscopy showed pericapillary oedema, dilated and abnormal capillaries, and microhaemorrhages both in finger and toe in the majority of patients. Major pathological findings included epidermal basal layer vacuolation, papillary dermis oedema and erythrocyte extravasation, perivascular and perieccrine dermal lymphocytic infiltrate, and mucin deposition in the dermis and hypodermis; dermal vessel thrombi were observed in two cases. Blood examinations were normal. Nasopharyngeal swab for SARS‐CoV‐2 and IgG serology for SARS‐CoV‐2 nucleocapsid protein were negative. Importantly, IgA serology for S1 domain of SARS‐CoV‐2 spike protein was positive in 6 patients and borderline in 3.
Conclusions
Chilblain‐like lesions during COVID‐19 pandemic have specific epidemiologic, clinical, capillaroscopic and histopathological characteristics, which distinguish them from idiopathic perniosis. Though we could not formally prove SARS‐CoV‐2 infection in our patients, history data and the detection of anti‐SARS‐COV‐2 IgA strongly suggest a relationship between skin lesions and COVID‐19. Further investigations on the mechanisms of SARS‐CoV‐2 infection in children and pathogenesis of chilblain‐like lesions are warranted.
Summary
These guidelines for the management of congenital ichthyoses have been developed by a multidisciplinary group of European experts following a systematic review of the current literature, an ...expert conference held in Toulouse in 2016, and a consensus on the discussions. These guidelines summarize evidence and expert‐based recommendations and intend to help clinicians with the management of these rare and often complex diseases. These guidelines comprise two sections. This is part two, covering the management of complications and the particularities of some forms of congenital ichthyosis.
What's already known about this topic?
Various symptomatic treatment options exist for congenital ichthyoses, but there are no European guidelines.
What does this study add?
These European guidelines for the management of congenital ichthyosis may help to improve outcomes and quality of life for patients.
Linked Comment: Akiyama. Br J Dermatol 2019; 180:449–450.
Plain language summary available online
Summary
These guidelines for the management of congenital ichthyoses have been developed by a multidisciplinary group of European experts following a systematic review of the current literature, an ...expert conference held in Toulouse in 2016 and a consensus on the discussions. They summarize evidence and expert‐based recommendations and are intended to help clinicians with the management of these rare and often complex diseases. These guidelines comprise two sections. This is part one, covering topical therapies, systemic therapies, psychosocial management, communicating the diagnosis and genetic counselling.
Linked Comment: Levy. Br J Dermatol 2019; 180:253.
Summary
The current COVID‐19 pandemic is caused by the SARS‐CoV‐2 coronavirus. The initial recognized symptoms were respiratory, sometimes culminating in severe respiratory distress requiring ...ventilation, and causing death in a percentage of those infected. As time has passed, other symptoms have been recognized. The initial reports of cutaneous manifestations were from Italian dermatologists, probably because Italy was the first European country to be heavily affected by the pandemic. The overall clinical presentation, course and outcome of SARS‐CoV‐2 infection in children differ from those in adults as do the cutaneous manifestations of childhood. In this review, we summarize the current knowledge on the cutaneous manifestations of COVID‐19 in children after thorough and critical review of articles published in the literature and from the personal experience of a large panel of paediatric dermatologists in Europe. In Part 1, we discuss one of the first and most widespread cutaneous manifestation of COVID‐19, chilblain‐like lesions. In Part 2, we review other manifestations, including erythema multiforme, urticaria and Kawasaki disease‐like inflammatory multisystemic syndrome, while in Part 3, we discuss the histological findings of COVID‐19 manifestations, and the testing and management of infected children, for both COVID‐19 and any other pre‐existing conditions.
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Summary
Background
Recessive dystrophic epidermolysis bullosa (RDEB) is a skin fragility disorder caused by mutations in the COL7A1 gene encoding type VII collagen, a cutaneous basement membrane ...component essential for epidermal–dermal adhesion. Hallmarks of the disease are unremitting blistering and chronic wounds with severe inflammation and fibrosis. MicroRNAs (miRNAs) are post‐transcriptional regulators of gene expression also implicated in fibrotic processes. However, the role of miRNAs in RDEB fibrosis is almost unexplored.
Objectives
Our study aimed to identify miRNAs deregulated in primary RDEB skin fibroblasts (RDEBFs) and to characterize their function in RDEB fibrosis.
Methods
Real‐time quantitative polymerase chain reaction (qRT‐PCR) was used to screen RDEBFs for expression levels of a group of miRNAs deregulated in hypertrophic scars and keloids, pathological conditions with abnormal wound healing and fibrosis. Contractility, proliferation and migration rate were evaluated by different in vitro assays in RDEBFs transfected with a miR‐145‐5p inhibitor. Expression levels of fibrotic markers and miR‐145‐5p targets were measured using qRT‐PCR and western blot.
Results
The miR‐143/145 cluster was upregulated in RDEBFs compared with fibroblasts from healthy subjects. RDEBFs transfected with a miR‐145‐5p inhibitor showed attenuated fibrotic traits of contraction, proliferation and migration, accompanied by reduced expression of the contractile proteins α‐smooth muscle actin and transgelin. These effects were associated with upregulation of Krüppel‐like factor 4 transcriptional repressor and downregulation of Jagged1, a known inducer of fibrosis.
Conclusions
Our results highlight the profibrotic role of miR‐145‐5p and its regulatory networks in RDEB, shedding light on novel disease pathomechanisms and targets for future therapeutic approaches.
What's already known about this topic?
Recessive dystrophic epidermolysis bullosa (RDEB) is a highly disabling genetic skin disease caused by mutations in the collagen VII gene and characterized by unremitting blistering and defective wound healing, leading to inflammation and fibrosis.
MicroRNAs (miRNAs) are post‐transcriptional regulators of gene expression in health and disease, and their deregulation has been implicated in fibrotic skin conditions. To date, only miR‐29 has been associated with injury‐driven fibrosis in RDEB.
What does this study add?
In patients with RDEB, miR‐145‐5p is overexpressed in RDEB skin fibroblasts (RDEBFs), where it plays a profibrotic role, as its inhibition reduces RDEBF fibrotic traits (contraction, proliferation and migration).
miR‐145‐5p inhibition in RDEBFs determines the reduction of contractile markers α‐smooth muscle actin and transgelin through upregulation of Krüppel‐like factor 4, a transcriptional repressor of contractile proteins, and downregulation of Jagged1 (JAG1), an inducer of fibrosis.
What is the translational message?
Our findings expand the knowledge on miRNA‐driven pathomechanisms implicated in RDEB fibrosis.
miR‐145‐5p and its targets (e.g. JAG1) could represent relevant molecules for the development of novel therapeutic strategies to counteract fibrosis progression in patients with RDEB.
Linked Comment: Wally and Bauer. Br J Dermatol 2019; 181:890–891.
Plain language summary available online
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