ORCID Profile
0000-0001-6372-8048
Current Organisations
Alfred Health
,
Monash University
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Publisher: BMJ
Date: 28-02-2011
Abstract: Junctional epidermolysis bullosa (JEB), a group of hereditary skin fragility disorders, is associated with a wide variety of phenotypes, although all forms are characterised by trauma induced skin blistering and tissue separation at the dermal-epidermal junction zone. A subgroup, coined JEB-other, is associated with mutations in the COL17A1 gene encoding collagen XVII or, more rarely, with mutations in the laminin 332 genes LAMA3, LAMB3, or LAMC2. The objective of this study is comprehensive genotype-phenotype analysis in JEB-other patients with COL17A1 mutations and elucidation of disease mechanisms underlying different skin phenotypes. COL17A1 mutations and their clinical and cellular consequences were systematically analysed in 43 patients with JEB-other. Cell culture, RT-PCR, and protein biochemistry were applied to assess the effects of splice site mutations-that is, the nature and amounts of transcripts and polypeptides synthesised and their association with the phenotypic outcome. 34 distinct COL17A1 mutations were disclosed, 12 of them novel. mRNA and protein analyses demonstrated that patients with only about 12-14% of the physiological collagen XVII levels had mild cutaneous involvement and a long life span. In contrast to complete null phenotypes, presence of minor amounts of collagen XVII protein in JEB skin is associated with mild phenotypic manifestations. The data have significant implications for design of molecular therapies for JEB, since they suggest that already a low extent of collagen XVII restoration will improve skin stability and alleviate symptoms.
Publisher: Wiley
Date: 11-06-2021
DOI: 10.1111/AJD.13642
Abstract: Nail psoriasis significantly impacts quality of life and is notoriously difficult to treat. Tildrakizumab, an IL‐23 inhibitor, has shown significant clinical improvement in the treatment of moderate‐to‐severe chronic plaque psoriasis. We report 2 cases of treatment resistant nail psoriasis which showed marked improvement with the use of off‐label tildrakizumab. The dosing regimen utilised was consistent with that used to treat chronic plaque psoriasis, with 100 mg subcutaneously at Day 0 and Week 4, and maintenance dosing of 100 mg every 12 weeks thereafter. Significant improvement at 6 and 12 months, as per the modified Nail Psoriasis Severity Index (mNAPSI) and Dermatology Life Quality Index (DLQI), was seen. There have been no tildrakizumab related side effects observed to date. Tildrakizumab appears to be an effective option in managing treatment resistant nail psoriasis.
Publisher: S. Karger AG
Date: 2010
DOI: 10.1159/000314155
Abstract: Pemphigus vulgaris (PV) is an auto-immune blistering skin disease characterized by flaccid blisters and painful erosions of mucous membranes and skin. Suprabasal blister formation results from a loss of epidermal cohesion induced by auto-antibodies against the desmosomal protein desmoglein 3. Treatment of PV currently consists of systemic glucocorticosteroids and adjuvant immunosuppressive drugs such as azathioprine, mycophenolate mofetil, cyclophosphamide or dapsone. Due to the low incidence of PV, there are insufficient data to conclude which treatment is the most effective and safest. Thus far, systemic tacrolimus (FK506, Prograf®) has not yet been reported as adjuvant medication for PV. Here, we describe the successful use of systemic tacrolimus in 2 patients with recalcitrant PV of the oral mucosa. Tacrolimus was well tolerated, and clinical improvement allowed tapering of corticosteroids. Thus, oral tacrolimus may be a therapeutic alternative for patients with recalcitrant PV.
Publisher: American Society for Clinical Investigation
Date: 05-2008
DOI: 10.1172/JCI34292
Publisher: Wiley
Date: 16-08-2021
DOI: 10.1111/AJD.13681
Publisher: Wiley
Date: 17-05-2023
DOI: 10.1111/AJD.14077
Publisher: The Company of Biologists
Date: 06-2021
DOI: 10.1242/DMM.048082
Abstract: Heterozygous missense mutations in the human COL7A1 gene – coding for collagen VII – lead to the rare, dominantly inherited skin disorder dominant dystrophic epidermolysis bullosa (DDEB), which is characterised by skin fragility, blistering, scarring and nail dystrophy. To better understand the pathophysiology of DDEB and develop more effective treatments, suitable mouse models for DDEB are required but to date none have existed. We identified the two most common COL7A1 mutations in DDEB patients (p.G2034R and p.G2043R) and used CRISPR-Cas9 to introduce the corresponding mutations into mouse Col7a1 (p.G2028R and p.G2037R). Dominant inheritance of either of these two alleles results in a phenotype that closely resembles that seen in DDEB patients. Specifically, mice carrying these alleles show recurrent blistering that is first observed transiently around the mouth and paws in the early neonatal period and then again around the digits from 5-10 weeks of age. Histologically, the mice show micro-blistering and reduced collagen VII immunostaining. Biochemically, collagen VII from these mice displays reduced thermal stability, which we also observed to be the case for DDEB patients carrying the analogous mutations. Unlike previous rodent models of epidermolysis bullosa, which frequently show early lethality and severe disease, these mouse models, which to our knowledge are the first for DDEB, show no reduction in growth and survival, and – together with a relatively mild phenotype – represent a practically and ethically tractable tool for better understanding and treating epidermolysis bullosa. This article has an associated First Person interview with the first author of the paper.
Publisher: No publisher found
Date: 2013
Publisher: Elsevier BV
Date: 05-2006
Abstract: Dystrophic epidermolysis bullosa (DEB), a heterogeneous hereditary skin disorder characterized by trauma-induced blistering and scarring, affects thousands of families worldwide. The clinical manifestations extend from minor nail dystrophy to severe life-threatening blistering, making early molecular diagnosis and prognostication of utmost importance for the affected families. DEB is caused by mutations in the COL7A1 gene encoding collagen VII in the skin. Molecular diagnostics and genotype-phenotype correlations in DEB remain complex owing to the gene structure, large variety of mutations, high rate of novel mutations, complex protein structure and assembly, and the heterogeneity of phenotypes. Here, we report an efficient strategy for COL7A1 mutation detection using direct automated DNA sequencing and implementation of software tools. With this approach, COL7A1 mutations of 41 DEB families were disclosed. Twenty-four mutations were novel and two recurrent. Elucidation of biological consequences of the mutations helped define disease mechanisms, but also revealed several unusual genotypic and/or phenotypic constellations, which impeded the diagnostics and prognostication. In addition, the studies disclosed a de novo mutation in recessive DEB and two new polymorphisms in the COL7A1 gene.
Publisher: Elsevier BV
Date: 11-2008
DOI: 10.1038/JID.2008.132
Publisher: Wiley
Date: 03-2013
DOI: 10.1111/EXD.12084
Abstract: Epidermolysis bullosa (EB) is a heterogeneous group of inherited diseases characterized by the formation of blisters in the skin and mucosa. There is no cure or effective treatment for these potentially severe and fatal diseases. Over the past few years, several reports have proposed different molecular strategies as new therapeutic options for the management of EB. From classical vector-based gene therapy to cell-based strategies such as systemic application of bone marrow stem cells or local application of fibroblasts, a broad range of molecular approaches have been explored. This array also includes novel methods, such as protein replacement therapy, gene silencing and the use of induced pluripotent stem cells (iPCs). In this review, we summarize current concepts of how inherited blistering diseases might be treated in the future and discuss the opportunities, promises, concerns and risks of these innovative approaches.
Publisher: Elsevier BV
Date: 04-2022
DOI: 10.1016/J.JID.2021.09.008
Abstract: Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic skin blistering disease associated with progressive multiorgan fibrosis. RDEB is caused by biallelic mutations in COL7A1 encoding the extracellular matrix protein collagen VII (C7), which is necessary for epidermal‒dermal adherence. C7 is not simply a structural protein but also has multiple functions, including the regulation of TGFβ bioavailability and the inhibition of skin scarring. Intravenous (IV) administration of recombinant C7 (rC7) rescues C7-deficient mice from neonatal lethality. However, the effect on established RDEB has not been determined. In this study, we used small and large adult RDEB animal models to investigate the disease-modulating abilities of IV rC7 on established RDEB. In adult RDEB mice, rC7 accumulated at the basement membrane zone in multiple organs after a single infusion. Fortnightly IV injections of rC7 for 7 weeks in adult RDEB mice reduced fibrosis of skin and eye. The fibrosis-delaying effect was associated with a reduction of TGFβ signaling. IV rC7 in adult RDEB dogs incorporated in the dermal‒epidermal junction of skin and improved disease by promoting wound healing and reducing dermal‒epidermal separation. In both species, IV C7 was well-tolerated. These preclinical studies suggest that repeated IV administration of rC7 is an option for systemic treatment of established adult RDEB.
Publisher: Wiley
Date: 22-10-2007
DOI: 10.1002/PATH.2253
Abstract: Kindlin-1 is an epithelium-specific phosphoprotein and focal adhesion adaptor component. Mutations in the corresponding gene (KIND1) cause Kindler syndrome (KS), which is manifested by skin blistering, poikiloderma, photosensitivity and carcinogenesis. Some patients also exhibit gastrointestinal symptoms, but it has remained unclear whether these represent a feature of Kindler syndrome or a coincidence. We examined kindlin-1 in human gastrointestinal epithelia and showed that it is involved in the aetiopathology of Kindler syndrome-associated colitis. Kindlin-1 expression was assessed by indirect immunofluorescence, western blot and RT-PCR. Kindlin-1 is expressed in oral mucosa, colon and rectum. Both the full-length 74 kDa kindlin-1 protein and a 43 kDa isoform were detected in CaCo2 cells, the latter resulting from alternative splicing. In the first months of life, patients (homozygous for null mutations) had severe intestinal involvement with haemorrhagic diarrhoea and showed morphological features of severe ulcerative colitis. Later in childhood, histopathology demonstrated focal detachment of the epithelium in all segments of the colon, chronic inflammation and mucosal atrophy. These findings define an intestinal phenotype for Kindler syndrome as a consequence of a primary epithelial barrier defect. The different clinical intestinal manifestations in Kindler syndrome patients may be explained by partial functional compensation of kindlin-1 deficiency by the intestinal isoform or by the presence of truncated mutant kindlin-1.
Publisher: Wiley
Date: 26-09-2011
DOI: 10.1002/PATH.2973
Abstract: Epidermolysis bullosa (EB) is a severe genetic skin fragility syndrome characterized by blister formation. The molecular basis of EB is still largely unknown and wound healing in patients suffering from EB remains a major challenge to their survival. Our previous studies have identified the actin remodelling protein Flightless I (Flii) as an important mediator of wound repair. Here we identify Flii as a novel target involved in skin blistering. Flii expression was significantly elevated in 30 patients with EB, most prominently in patients with recessive dystrophic EB (RDEB) who have defects in production of type VII collagen (ColVII). Using an autoimmune ColVII murine model of EB acquisita (EBA) and an immunocompetent-ColVII-hypomorphic genetic mouse model of RDEB together with murine Flii alleles, we investigated the contribution of Flii to EB. Overexpression of Flii produced severe blistering post-induction of EBA, while decreased Flii reduced blister severity, elevated integrin expression, and improved ColVII production. Flii(+/-) blistered skin showed reduced α-SMA, TGF-β1, and Smad 2/3 expression, suggesting that decreasing Flii may affect fibrosis. In support of this, Flii-deficient fibroblasts from EBA mice were less able to contract collagen gels in vitro however, addition of TGF-β1 restored collagen contraction, suggesting an interplay between Flii and TGF-β1. Elevated Flii gene and protein expression was further observed in the blisters of ColVII hypomorphic mice, a murine model of RDEB, suggesting that reducing Flii in blistered skin could be a potential new approach for treating patients with EB.
Publisher: No publisher found
Date: 2013
Publisher: Humana Press
Date: 20-10-2012
DOI: 10.1007/978-1-62703-227-8_29
Abstract: Dystrophic epidermolysis bullosa (DEB) is a clinically heterogeneous heritable skin fragility disorder characterized by mechanically induced mucocutaneous blistering. On the molecular level DEB is caused by mutations leading to deficiency in collagen VII (CVII), a large extracellular protein building anchoring fibrils that attach the epidermis to the dermis. Severely affected patients suffer from wounds, which heal with excessive scarring causing mutilating deformities of hands and feet. The patients are also predisposed to development of aggressive squamous cell carcinomas at sites of chronic wounds. Currently no available therapies exist for this extremely disabling and stigmatizing disorder. We are developing and evaluating cell- and protein-based therapies for the management of DEB. Dermal fibroblasts are easy to propagate in vitro, they produce CVII, and they have immunomodulating capacities, which makes it possible to use allogeneic fibroblasts for therapy without risking major adverse effects from the host's immune system. Hence, fibroblasts, and fibroblast-like cells such as mesenchymal stromal cells, are prime candidates for cell-based DEB therapies. An alternative for management of disorders caused by defects in proteins with relatively low turnover rate is to introduce the protein de novo to the tissue by direct application of the protein. CVII is long-lived and expressed in moderate amounts in the skin this makes injection of collagen VII protein a realistic approach for the treatment of DEB. Here we present methods and protocols that we are using for fibroblast- and recombinant CVII-based therapies of DEB in our model of this disease, the CVII hypomorphic mouse. These protocols are directed towards management of DEB but they can be easily adapted for the treatment of other skin fragility disorders.
Publisher: No publisher found
Date: 2012
Publisher: Wiley
Date: 26-05-2021
DOI: 10.1111/AJD.13611
Abstract: The BIOCHIP is an indirect immunofluorescence diagnostic investigation which identifies multiple autoantibodies with a mosaic panel of target antigen‐specific substrates in a single incubation field. The EUROIMMUN Dermatology Profile ELISA allows simultaneous investigation of the six most important autoantibodies in bullous autoimmune dermatoses. Evaluation of the BIOCHIP Mosaic 7, compared to that of the EUROIMMUN Dermatology Profile ELISA, when used as a diagnostic investigation in pemphigus and pemphigoid, was undertaken in an Australian cohort. The serum of 27 patients was analysed including patients with pemphigus vulgaris ( n = 10), pemphigus foliaceous ( n = 4), bullous pemphigoid ( n = 8), mucous membrane pemphigoid ( n = 3) and negative controls ( n = 2). Results of the BIOCHIP were compared with the EUROIMMUN Dermatology Profile ELISA, as well as with histology, direct immunofluorescence and indirect immunofluorescence. In pemphigus vulgaris, sensitivity & specificity for the BIOCHIP Mosaic 7 were 100% and 94.1%, comparable to that of the EUROIMMUN Dermatology Profile ELISA with 80% sensitivity and 100% specificity. In bullous pemphigoid, sensitivity of the BIOCHIP was 87.5% and sensitivity of the EUROIMMUN Dermatology ELISA profile was 75%, whilst specificities for both diagnostic methods were 100% in our limited cohort. There was substantial or almost perfect concordance between the BIOCHIP Mosaic 7 and EUROIMMUN Dermatology Profile ELISA for pemphigus vulgaris and bullous pemphigoid. The BIOCHIP Mosaic 7 is a rapid, reliable diagnostic investigation in pemphigus and bullous pemphigoid. Results indicate it is comparable to the EUROIMMUN Dermatology Profile ELISA, whilst also providing additional testing with salt split skin, on one field.
Publisher: No publisher found
Date: 2013
Publisher: Elsevier BV
Date: 10-2005
Publisher: No publisher found
Date: 2013
Publisher: Elsevier BV
Date: 2010
DOI: 10.1016/J.DET.2009.10.007
Abstract: Collagen XVII has been identified as having a role in inherited junctional epidermolysis bullosa non-Herlitz (JEB-other, MIM #226650). The role of collagen XVII in both autoimmune and genetic blistering disorders demonstrates its relevance to dermal-epidermal adhesion. Collagen XVII is a major structural component of the hemidesmosome (HD), a highly specialized multiprotein complex that mediates the anchorage of basal epithelial cells to the underlying basement membrane in stratified, pseudostratified, and transitional epithelia. This article examines the genetic and pathological features of collagen XVII.
Publisher: Wiley
Date: 18-05-2021
DOI: 10.1111/AJD.13630
Abstract: This is the largest study of Aboriginal and Torres Strait Islander dermatologic presentations to an urban specialist clinic within a community‐controlled health organisation. It adds to our understanding of Aboriginal and Torres Strait Islander dermatoepidemiology. Patient files were reviewed over the five‐year audit period, with age, gender, Indigenous status, diagnosis, disease category, ‘new’ or ‘review consultation’ and ‘did not attend’ (DNA) data recorded. Our study shows that eczema and benign, pre‐malignant or malignant neoplasms are the most common presentations for urban Aboriginal and Torres Strait Islander patients. Lupus erythematosus and cutaneous infections were less prominent in comparison to data from rural and remote populations. Overall, a broad casemix of dermatologic presentations was observed. Similar to other studies, adult male patients were under‐represented. Most skin malignancies were diagnosed in this cohort this, therefore, identifies a possible target for public health intervention. A high ratio of new to review patients is consistent with the clinic offering a consultation model of care facilitated by primary health‐care providers’ support within Aboriginal Community‐Controlled Health Service. DNA rates in this study were lower than hospital outpatient rates in a comparative study and may be attributed to specialist dermatology care being offered in a more culturally sensitive environment. The dermatology clinic at the Victorian Aboriginal Health Services (VAHS) provides a good breadth of specialist dermatology care. The community health‐care model could be replicated in centres elsewhere, including interstate, to help overcome barriers to specialist dermatology care experienced by Aboriginal and Torres Strait Islander populations. Additionally, this model improves trainee exposure and understanding of Aboriginal and Torres Strait Islander health.
Publisher: No publisher found
Date: 2012
Publisher: Wiley
Date: 18-02-2023
DOI: 10.1111/AJD.14004
Publisher: Medical Journals Sweden AB
Date: 2013
Publisher: Wiley
Date: 05-2010
Publisher: Medical Journals Sweden AB
Date: 2013
Publisher: EMBO
Date: 2013
DOI: 10.1038/MSB.2013.17
Publisher: Elsevier BV
Date: 10-2012
DOI: 10.1038/JID.2012.166
Abstract: Acral peeling skin syndrome (APSS) is an autosomal recessive skin disorder characterized by acral blistering and peeling of the outermost layers of the epidermis. It is caused by mutations in the gene for transglutaminase 5, TGM5. Here, we report on clinical and molecular findings in 11 patients and extend the TGM5 mutation database by four, to our knowledge, previously unreported mutations: p.M1T, p.L41P, p.L214CfsX15, and p.S604IfsX9. The recurrent mutation p.G113C was found in 9 patients, but also in 3 of 100 control in iduals in a heterozygous state, indicating that APSS might be more widespread than hitherto expected. Using quantitative real-time PCR, immunoblotting, and immunofluorescence analysis, we demonstrate that expression and distribution of several epidermal differentiation markers and corneodesmosin (CDSN) is altered in APSS keratinocytes and skin. Although the expression of transglutaminases 1 and 3 was not changed, we found an upregulation of keratin 1, keratin 10, involucrin, loricrin, and CDSN, probably as compensatory mechanisms for stabilization of the epidermal barrier. Our results give insights into the consequences of TGM5 mutations on terminal epidermal differentiation.
Publisher: No publisher found
Date: 2013
Publisher: Oxford University Press (OUP)
Date: 07-2008
DOI: 10.1111/J.1365-2133.2008.08760.X
Abstract: The Kindler syndrome (KS) protein kindlin-1 is a member of a protein complex that links cortical actin to integrins on the surface of basal keratinocytes. Loss of kindlin-1 leads to abnormalities of cell adhesion and motility, and to skin blistering and progressive poikiloderma as clinical symptoms. Here we investigated a severely affected patient, disclosed the mutation that caused the disease and delineated its biological consequences. Mutation screening of the kindlin-1 gene, KIND1 (now called FERMT1), was performed with polymerase chain reaction (PCR) lification of all exons and sequencing. Mutated kindlin-1 was characterized by reverse transcriptase (RT)-PCR and immunoblotting, and genotype-phenotype correlations were analysed using immunohistochemical staining of skin biopsies and keratinocytes from the patient's skin. Cell adhesion and motility were assessed with functional tests. We disclosed a splice site mutation in the first position of intron 13 of the FERMT1 gene, which caused skipping of exon 13. The short transcript partially escaped nonsense-mediated mRNA decay and was translated into a truncated protein. A C-terminally truncated kindlin-1 in keratinocytes could not function correctly even if it were expressed.
Publisher: Informa UK Limited
Date: 03-10-2019
Publisher: Oxford University Press (OUP)
Date: 11-2009
DOI: 10.1111/J.1365-2133.2009.09333.X
Abstract: Dystrophic epidermolysis bullosa (DEB) is a severe genetic skin blistering disorder caused by mutations in the gene COL7A1, encoding collagen VII. Recently, the MMP1 promoter single nucleotide polymorphism (SNP) rs1799750, designated as 1G 2G, was shown to be involved in modulation of disease severity in patients with recessive DEB (RDEB), and was proposed as a genetic modifier. To identify the molecular basis of DEB in 103 in iduals and to replicate the results of the MMP1 promoter SNP analysis in an independent patient group, as verification is necessary in such a rare and heterogeneous disorder. To determine the molecular basis of the disease, we performed COL7A1 mutation screening, reverse transcription-polymerase chain reaction (PCR) and real-time quantitative PCR. The status of the MMP1 SNP was analysed by PCR and restriction enzyme digestion and verified by sequencing. We disclosed 42 novel COL7A1 mutations, including the first large genomic deletion of 4 kb affecting only the COL7A1 gene, and three apparently silent mutations affecting splicing. Even though the frequency of the high-risk allele was increased in patients with RDEB, no statistically significant correlation between disease severity and genotype could be made. Also, no correlation was observed with development of squamous cell carcinoma, a severe complication of DEB. Taken together, the results suggest that the MMP1 SNP is not the sole disease modifier in different forms of DEB, and other genetic and environmental factors contribute to the clinical phenotype.
Publisher: Elsevier BV
Date: 09-2009
DOI: 10.1038/MT.2009.144
Publisher: No publisher found
Date: 2013
Publisher: Wiley
Date: 03-02-2012
DOI: 10.1111/J.1610-0387.2011.07840.X
Abstract: No consistent data are available on the currently employed diagnostic tools for autoimmune bullous diseases in Germany. The aim of this survey was to describe currently performed diagnostic methods for bullous autoimmune diseases in German dermatology departments. A standardized questionnaire evaluated the available diagnostic methods i. e. direct immunofluorescence microscopy (IFM), indirect IFM, commercial ELISA systems, and non-commercial serological tests as well as the number of s les per year in all 34 university and 39 non-university dermatology departments. The overall return rate was 89 %, 100 % and 79 % for the university and non-university departments, respectively. Direct IFM was the most frequently used method and was applied in 98 % of the responding departments. In 74 % of the responding departments, indirect IFM was used mainly on monkey esophagus and human salt-split skin. Commercial ELISA systems were employed in 58 % of the clinics all of them used anti-desmoglein ELISA, while anti-BP180 and anti-BP230 ELISA were established in 49 % and 48 % of departments, respectively. Non-commercial analytic methods were only performed in 22 % of the departments. The high return rate of this survey allows a relatively precise description of the current diagnostic methods used in German dermatology departments. Standard diagnostic tests are available nationwide and in bullous pemphigoid and pemphigus, the antigen-specific detection of autoantibodies is routinely performed in half of the departments. Rare disorders may be diagnosed by cooperation with some specialized centers.
Publisher: Oxford University Press (OUP)
Date: 13-11-2018
DOI: 10.1111/BJD.17146
Publisher: Wiley
Date: 29-07-2022
DOI: 10.1111/AJD.13900
Abstract: Onychopapilloma is an uncommon tumour of the nailbed and the distal nail matrix. To date, only 19 case reports and case series have been reported in the literature. This article includes literature review on all reported cases and provides the first case series of onychopapilloma in an Australian population, evaluating the clinical features and histopathological diagnosis of patients with onychopapilloma in an Australian subspecialty nail clinic.
Publisher: Oxford University Press (OUP)
Date: 20-10-2023
DOI: 10.1093/BJD/LJAC001
Abstract: Epidermolysis bullosa (EB) is a heterogeneous group of rare, difficult-to-treat, inherited multisystem diseases affecting epithelial integrity. Patients with EB are affected by mechanical fragility of epithelial surfaces including the skin and, as a result, extensive recurrent blistering is a characteristic of the condition. Chronic wounds predispose patients with EB to the development of squamous cell carcinoma, which is a major cause of premature death. EASE was a double-blind, randomized, vehicle-controlled, phase III study to determine the efficacy and safety of the topical gel Oleogel-S10 (birch triterpenes) in EB. EASE was funded by Amryt Research Limited. Patients with dystrophic EB, junctional EB or Kindler EB and a target partial-thickness wound lasting ≥ 21 days and & 9 months that was 10–50 cm2, were enrolled and randomized via computer-generated allocation tables 1 : 1 to Oleogel-S10 or control gel – both with standard-of-care dressings. Study gel was applied to all wounds at least every 4 days. The primary endpoint was the proportion of patients with first complete closure of target wound within 45 days. A total of 223 patients were enrolled and treated (109 treated with Oleogel-S10, 114 with control gel). The primary endpoint was met Oleogel-S10 resulted in 41·3% of patients with first complete target wound closure within 45 days, compared with 28·9% in the control gel arm (relative risk 1·44, 95% confidence interval (CI) 1·01–2·05 P = 0·013). Adverse events (AEs) occurred with similar frequency for Oleogel-S10 (81·7%) compared with control gel (80·7%). AEs were predominantly of mild-to-moderate intensity (4·6% were severe). Oleogel-S10 is the first therapy to demonstrate accelerated wound healing in EB. Oleogel-S10 was well tolerated.
Publisher: Public Library of Science (PLoS)
Date: 23-05-2013
Publisher: No publisher found
Date: 2013
Publisher: S. Karger AG
Date: 2012
DOI: 10.1159/000339328
Abstract: We describe an otherwise healthy 7-year-old boy who developed confetti-like hypopigmented macules on the dorsal aspects of the hands and feet, spreading to the palms and soles a few months after birth. In 1964 Siemens introduced the term acromelanosis albo-punctata to describe the skin features of a patient who has remained the only reported case in the literature so far and who strongly resembles our patient. By genetic testing we excluded mutations in genes known to be involved in diseases with acral hypo- or hyperpigmentation. We review the differential diagnosis of acral localized spotty dyspigmentation and conclude that acromelanosis albo-punctata may represent a distinct entity.
Publisher: Elsevier BV
Date: 02-2013
Publisher: Wiley
Date: 26-05-2010
No related grants have been discovered for Johannes S Kern.