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  1. Article ; Online: Immediate global support is needed for Myanmar.

    Lwin, S M / Griffiths, C E M

    The British journal of dermatology

    2021  Volume 185, Issue 2, Page(s) 466–467

    Language English
    Publishing date 2021-05-17
    Publishing country England
    Document type Letter
    ZDB-ID 80076-4
    ISSN 1365-2133 ; 0007-0963
    ISSN (online) 1365-2133
    ISSN 0007-0963
    DOI 10.1111/bjd.20385
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Ui VI Zs.23: Show issues Location:
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  2. Article ; Online: The promise and challenges of cell therapy for psoriasis.

    Lwin, S M / Snowden, J A / Griffiths, C E M

    The British journal of dermatology

    2021  Volume 185, Issue 5, Page(s) 887–898

    Abstract: The management of moderate-to-severe psoriasis has been transformed by the introduction of biological therapies. These medicines, particularly those targeting interleukin (IL)-17 and IL-23p19, can offer clear or nearly clear skin for the majority of ... ...

    Abstract The management of moderate-to-severe psoriasis has been transformed by the introduction of biological therapies. These medicines, particularly those targeting interleukin (IL)-17 and IL-23p19, can offer clear or nearly clear skin for the majority of patients with psoriasis, with good long-term drug survival. However, as currently used, none of these therapies is curative and disconcertingly there is a small but increasing number of patients with severe psoriasis who have failed all currently available therapeutic modalities. A similar scenario has occurred in other immune-mediated inflammatory diseases (IMIDs) where treatment options are limited in severely affected patients. In these cases, cell therapy, including haematopoietic stem cell transplantation (HSCT) and mesenchymal stromal cells (MSC), has been utilized. This review discusses the various forms of cell therapy currently available, their utility in the management of IMIDs and emerging evidence for efficacy in severe psoriasis that is unresponsive to biological therapy. Balancing the risks and benefits of treatment vs. the underlying disease is key; cell therapy carries significant risks, costs, regulation and other complexities, which must be justified by outcomes. Although HSCT has anecdotally been reported to benefit severe psoriasis, sometimes with apparent cure, this has mainly been in the setting of other coincidental 'routine' indications. In psoriasis, cell therapies, such as MSC and regulatory T cells, with a lower risk of complications are likely to be more appropriate. Well-designed controlled trials coupled with mechanistic studies are warranted if advanced cell therapies are to be developed and delivered as a realistic option for severe psoriasis.
    MeSH term(s) Biological Therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Psoriasis/therapy
    Language English
    Publishing date 2021-07-27
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 80076-4
    ISSN 1365-2133 ; 0007-0963
    ISSN (online) 1365-2133
    ISSN 0007-0963
    DOI 10.1111/bjd.20517
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The potential of gene therapy for recessive dystrophic epidermolysis bullosa.

    Subramaniam, K S / Antoniou, M N / McGrath, J A / Lwin, S M

    The British journal of dermatology

    2022  Volume 186, Issue 4, Page(s) 609–619

    Abstract: Epidermolysis bullosa (EB) encompasses a heterogeneous group of inherited skin fragility disorders, with mutations in genes encoding the basement membrane zone (BMZ) proteins that normally ensure dermal-epidermal integrity. Of the four main EB types, ... ...

    Abstract Epidermolysis bullosa (EB) encompasses a heterogeneous group of inherited skin fragility disorders, with mutations in genes encoding the basement membrane zone (BMZ) proteins that normally ensure dermal-epidermal integrity. Of the four main EB types, recessive dystrophic EB (RDEB), especially the severe variant, represents one of the most debilitating clinical entities, with recurrent mucocutaneous blistering and ulceration leading to chronic wounds, infections, inflammation, scarring and ultimately cutaneous squamous cell carcinoma, which leads to premature death. Improved understanding of the molecular genetics of EB over the past three decades and advances in biotechnology have led to rapid progress in developing gene and cell-based regenerative therapies for EB. In particular, RDEB is at the vanguard of advances in human clinical trials of advanced therapeutics. Furthermore, the past decade has witnessed the emergence of a real collective, global effort involving academia and industry, supported by international EB patient organizations such as the Dystrophic Epidermolysis Bullosa Research Association (DEBRA), among others, to develop clinically relevant and marketable targeted therapeutics for EB. Thus, there is an increasing need for the practising dermatologist to become familiar with the concept of gene therapy, fundamental differences between various approaches, and their human applications. This review explains the principles of different approaches of gene therapy, summarizes its journey, and discusses its current and future impact in RDEB.
    MeSH term(s) Carcinoma, Squamous Cell/therapy ; Epidermolysis Bullosa/genetics ; Epidermolysis Bullosa/pathology ; Epidermolysis Bullosa/therapy ; Epidermolysis Bullosa Dystrophica/genetics ; Epidermolysis Bullosa Dystrophica/pathology ; Epidermolysis Bullosa Dystrophica/therapy ; Genetic Therapy ; Humans ; Skin Neoplasms/therapy
    Language English
    Publishing date 2022-04-01
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 80076-4
    ISSN 1365-2133 ; 0007-0963
    ISSN (online) 1365-2133
    ISSN 0007-0963
    DOI 10.1111/bjd.20910
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Acne, quorum sensing and danger.

    Lwin, S M / Kimber, I / McFadden, J P

    Clinical and experimental dermatology

    2014  Volume 39, Issue 2, Page(s) 162–167

    Abstract: Propionibacterium acnes is a ubiquitous skin commensal bacterium, which is normally well tolerated by the immune system in healthy human skin. However, there is increasing evidence to suggest a pivotal role for P. acnes in the inflammatory process ... ...

    Abstract Propionibacterium acnes is a ubiquitous skin commensal bacterium, which is normally well tolerated by the immune system in healthy human skin. However, there is increasing evidence to suggest a pivotal role for P. acnes in the inflammatory process underlying the acne pathogenesis. With its features of inflammation and pustulation, acne vulgaris resembles the skin's normal reaction to bacterial pathogens. P. acnes flourishes when sebum production increases in the follicles. Bacteria may undergo behavioural changes based on the surrounding bacterial population, a process called quorum sensing (QS). Evidence from in vitro studies suggests that QS enables P. acnes to upregulate its hydrolysis of sebum triglycerides by its bacterial lipases, secreting free fatty acids (FFAs) such as oleic, palmitic and lauric acids. These FFAs act as danger-associated molecular patterns (DAMPs), and activate Toll-like receptor (TLR)2 and TLR4, leading to selective T-helper (Th)-driven immunity, with subsequent expression of Th1/Th17-associated inflammatory cytokines. To our knowledge, there is currently no explanation as to what determines the shift of recognition by the immune system of P. acnes from being symbiotic to pathogenic. We present a novel hypothesis based on the essence of QS and DAMPs. P. acnes sends no or only 'safety' signals when present in 'controlled' quantities under commensal conditions, but becomes pathogenic and sends 'danger' signals via QS in the form of excess FFA production, which stimulates TLR2 and TLR4 as the bacterial population flourishes.
    MeSH term(s) Acne Vulgaris/immunology ; Acne Vulgaris/microbiology ; Cytokines/metabolism ; Humans ; Propionibacterium acnes/immunology ; Propionibacterium acnes/physiology ; Quorum Sensing/physiology ; Signal Transduction/physiology ; Toll-Like Receptors/immunology
    Chemical Substances Cytokines ; Toll-Like Receptors
    Language English
    Publishing date 2014-03
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 195504-4
    ISSN 1365-2230 ; 0307-6938
    ISSN (online) 1365-2230
    ISSN 0307-6938
    DOI 10.1111/ced.12252
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Beneficial effect of ustekinumab in familial pityriasis rubra pilaris with a new missense mutation in CARD14.

    Lwin, S M / Hsu, C-K / Liu, L / Huang, H-Y / Levell, N J / McGrath, J A

    The British journal of dermatology

    2017  Volume 178, Issue 4, Page(s) 969–972

    Abstract: Pityriasis rubra pilaris (PRP) represents a group of rare chronic inflammatory skin disorders in which around one in 20 affected individuals show autosomal dominant inheritance. In such cases there may be gain-of-function mutations in CARD14, encoding ... ...

    Abstract Pityriasis rubra pilaris (PRP) represents a group of rare chronic inflammatory skin disorders in which around one in 20 affected individuals show autosomal dominant inheritance. In such cases there may be gain-of-function mutations in CARD14, encoding caspase recruitment domain-containing protein 14 (CARD14), which activates the noncanonical nuclear factor (NF)-κB pathway, thereby promoting cutaneous inflammation. Here we report a mother and son with PRP due to a new missense mutation in CARD14 and describe the beneficial clinical effects of ustekinumab, a monoclonal antibody against interleukins 12 and 23, in both patients. A 49-year-old woman and her 20-year-old son had lifelong, generalized, patchy erythematous scale with a few islands of sparing, as well as minor nail ridging and mild palmoplantar keratoderma, features consistent with generalized PRP. Topical steroids, phototherapy and oral retinoids proved ineffective. Following informed consent, Sanger sequencing of CARD14 in both individuals revealed a new heterozygous single-nucleotide transversion in exon 4, c.356T>G, resulting in the missense mutation p.Met119Arg. Ustekinumab, at a dose of 45 mg every 12 weeks, brought about a significant physical and emotional improvement in both the mother and son within a few days of the initial dose, which was sustained on maintenance dosing. This report highlights the therapeutic potential of biologics that downregulate NF-κB signalling in familial PRP with mutations in CARD14.
    MeSH term(s) CARD Signaling Adaptor Proteins/genetics ; Dermatologic Agents/therapeutic use ; Female ; Guanylate Cyclase/genetics ; Humans ; Incidental Findings ; Male ; Membrane Proteins/genetics ; Middle Aged ; Mutation, Missense/genetics ; Pedigree ; Pityriasis Rubra Pilaris/drug therapy ; Pityriasis Rubra Pilaris/genetics ; Ustekinumab/therapeutic use ; Young Adult
    Chemical Substances CARD Signaling Adaptor Proteins ; Dermatologic Agents ; Membrane Proteins ; CARD14 protein, human (EC 4.6.1.-) ; Guanylate Cyclase (EC 4.6.1.2) ; Ustekinumab (FU77B4U5Z0)
    Language English
    Publishing date 2017-10-01
    Publishing country England
    Document type Case Reports
    ZDB-ID 80076-4
    ISSN 1365-2133 ; 0007-0963
    ISSN (online) 1365-2133
    ISSN 0007-0963
    DOI 10.1111/bjd.15462
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    Ui VI Zs.23: Show issues Location:
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  6. Article ; Online: EBGene trial: patient preselection outcomes for the European GENEGRAFT ex vivo phase I/II gene therapy trial for recessive dystrophic epidermolysis bullosa.

    Gaucher, S / Lwin, S M / Titeux, M / Abdul-Wahab, A / Pironon, N / Izmiryan, A / Miskinyte, S / Ganier, C / Duchatelet, S / Mellerio, J E / Bourrat, E / McGrath, J A / Hovnanian, A

    The British journal of dermatology

    2019  Volume 182, Issue 3, Page(s) 794–797

    MeSH term(s) Collagen Type VII/genetics ; Epidermolysis Bullosa/genetics ; Epidermolysis Bullosa Dystrophica/genetics ; Epidermolysis Bullosa Dystrophica/therapy ; Genes, Recessive ; Genetic Therapy ; Humans
    Chemical Substances Collagen Type VII
    Language English
    Publishing date 2019-11-27
    Publishing country England
    Document type Clinical Trial, Phase I ; Clinical Trial, Phase II ; Letter
    ZDB-ID 80076-4
    ISSN 1365-2133 ; 0007-0963
    ISSN (online) 1365-2133
    ISSN 0007-0963
    DOI 10.1111/bjd.18559
    Database MEDical Literature Analysis and Retrieval System OnLINE

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