ORCID Profile
0000-0001-5042-3632
Current Organisations
University of New South Wales
,
Rockefeller University Hospital
,
Rockefeller University
,
Liverpool Hospital
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Publisher: Elsevier BV
Date: 2010
DOI: 10.1016/J.DET.2009.10.019
Abstract: Quality of life (QOL) evaluation in epidermolysis bullosa (EB) has important applications in clinical management, patient advocacy, clinical research, and the development of new treatments. Several new quantitative and qualitative QOL measurement tools were developed recently, providing insight into the impact EB has on in iduals and their family members. Selection of the most appropriate QOL tool for patients who have EB depends on not only the type of information required but also the general or specific cohort being examined. EB-specific quantitative tools possess the highest level of content validity and statistical accuracy. However, generic dermatologic tools may also be appropriate in some circumstances. Overall, QOL evaluation in EB is still a developing area of research that may help improve patient management and assess emerging treatment modalities for their efficacy in improving the QOL of patients with EB.
Publisher: Elsevier BV
Date: 12-2013
DOI: 10.1016/J.JAAD.2013.08.014
Abstract: Chronic wounds are a major source of morbidity and mortality in generalized severe recessive dystrophic epidermolysis bullosa (RDEB-GS). This was a phase II double-blinded randomized controlled trial of intralesional allogeneic cultured fibroblasts in suspension solution versus suspension solution alone for wound healing in RDEB-GS. Adult patients with RDEB-GS were screened for chronic ulcers and reduced collagen VII expression. Up to 6 pairs of symmetric wounds were measured and biopsied at baseline, then randomized to cultured allogeneic fibroblasts in a crystalloid suspension solution with 2% albumin or suspension solution alone. Ulcer size, collagen VII protein and messenger RNA expression, anchoring fibril numbers, morphology, and inflammatory markers were measured at 2 weeks and at 3, 6, and 12 months. All wounds healed significantly more rapidly with fibroblasts and vehicle injections, with an area decrease of 50% by 12 weeks, compared with noninjected wounds. Collagen VII expression increased to a similar degree in both study arms in wounds from 3 of 5 patients. The number of patients with RDEB-GS who met inclusion criteria was a limitation, as was 1 trial center rather than multicenter. The injection of both allogeneic fibroblasts and suspension solution alone improved wound healing in chronic nonhealing RDEB-GS wounds independently of collagen VII regeneration. This may provide feasible therapy for wound healing in patients with RDEB-GS.
Publisher: Oxford University Press (OUP)
Date: 09-2018
DOI: 10.1111/BJD.16811
Publisher: Elsevier BV
Date: 02-2021
Publisher: Oxford University Press (OUP)
Date: 03-2021
DOI: 10.1111/BJD.19805
Publisher: Oxford University Press (OUP)
Date: 15-06-2021
DOI: 10.1111/BJD.20513
Publisher: Wiley
Date: 30-11-2021
DOI: 10.1111/EXD.14224
Publisher: Elsevier BV
Date: 2021
DOI: 10.1016/J.JACI.2021.05.027
Abstract: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease presenting with erse manifestations ranging from nodules and abscesses to draining tunnels. Whether the underlying inflammation from lesions extends to relatively healthy-appearing adjacent perilesional and distant nonlesional skin has not been systematically evaluated. We sought to characterize lesional, perilesional, and nonlesional skin in patients with HS. Skin biopsy s les were collected under ultrasound guidance from patients with active, untreated moderate-to-severe HS. Site-matched control biopsy s les from healthy volunteers were used for comparison. RNA sequencing demonstrated that HS skin clustered separately from healthy control skin, with perilesional and lesion skin clustering together and away from nonlesional skin. Immunohistochemistry analysis identified psoriasiform hyperplasia with keratin 16 positivity in both perilesional and lesional skin, with comparable levels of CD3 Perilesional HS skin has a transcriptomic and molecular profile comparable to that of lesional skin. HS can be grouped into 2 distinct subtypes based on molecular levels of LCN2 in the skin, with the LCN2-high subtype exhibiting an overall higher inflammatory burden and an upregulation of targetable cytokines. To our knowledge, this is the first study to characterize a unique HS subtype (and a potential endotype) that may guide future therapeutic targets.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2021
Publisher: Oxford University Press (OUP)
Date: 02-11-2021
DOI: 10.1111/BJD.20750
Abstract: Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease of the hair follicle defined by recurrent nodules, tunnels and scarring involving the intertriginous regions. HS is associated with microbial dysbiosis and immune dysregulation. In HS, an increasing number of studies have investigated antimicrobial peptides (AMPs). To provide an overview of the literature on AMPs in HS, and to discuss the potential role of AMPs in the pathogenesis of HS. PubMed, Embase and the Cochrane Library were searched. The titles, abstracts and full texts of all articles were manually screened. Additionally, the reference lists of the included articles were screened and hand searched for relevant studies. The final literature s le comprised 18 retrospective and prospective studies (no reviews or commentaries) published between 2009 and 2020. This review demonstrates the multitude of AMPs in HS. Although the methodology of the studies varied, the included studies indicate a consistent overexpression of human β-defensin (hBD)-2, S100A7, S100A8 and S100A9 at both the mRNA and protein levels, and a decreased expression of hBD-1. Overall, the studies point to a dysregulation of AMPs in both lesional and nonlesional HS skin.
Publisher: Oxford University Press (OUP)
Date: 12-2009
DOI: 10.1111/J.1365-2133.2009.09347.X
Abstract: Epidermolysis bullosa (EB) has a profound effect on quality of life (QOL) however, generic QOL assessments are poor indicators of the impact of EB. To develop a valid and reliable EB-specific QOL tool for use in measuring the effects of disease impact and interventions. Open, nonstructured interviews were conducted with 26 patients with EB, along with 33 family members and 11 health professionals (70 in iduals) for item generation. A pilot questionnaire was compiled, refined and distributed to 130 patients with EB. From the 115 returned questionnaires a principal axis factor analysis was undertaken producing a 17-item final questionnaire. Discriminative validity was assessed by differences in scores between EB subtypes. Content validity was assessed by expert ranking of items in terms of importance. Construct validity was evaluated by correlation with existing QOL tools. Test-retest reliability and internal consistency were evaluated. Factor analysis was performed. A 17-item questionnaire was developed: the QOLEB questionnaire. This gave distinguishing QOL scores to different EB subtypes, and correlated highly with existing QOL instruments. The QOLEB questionnaire is the first EB-specific QOL measurement tool, and is a valid and reliable measurement tool for the quantification of QOL in patients with various subtypes of EB. In addition, the QOLEB has potential as a sensitive instrument to monitor QOL, and to identify dimensions of QOL as targets for interventions and research.
Publisher: Wiley
Date: 08-2010
DOI: 10.1111/J.1440-0960.2010.00666.X
Abstract: Epidermolysis bullosa with pyloric atresia is a form of junctional epidermolysis bullosa associated with gastrointestinal abnormalities, which may include pyloric atresia. Genotype phenotype correlation is poorly understood and prognosis is difficult, if not impossible, to predict. Immunoflourescence mapping is an ideal candidate for developing a broad prognostic indicator for epidermolysis bullosa with pyloric atresia without the need for genetic mutation analysis. However, the tool developed in this paper does have limitations due to the small number of cases available and the effects of deleterious mutations in highly conserved cysteine residues on the predicted length of survival.
Publisher: Elsevier BV
Date: 03-2013
DOI: 10.1016/J.JAAD.2012.08.018
Abstract: Diffuse melanosis cutis (DMC) is a rare presentation of metastatic melanoma characterized by a progressive blue-gray discoloration of the skin and mucous membranes. To foster a better understanding of the clinical presentation, histological findings, and pathophysiology underlying DMC. A systematic review of the literature was completed utilizing MEDLINE, CINAHL, Embase, and Google. Data were extracted using a protocol-driven spread sheet with all statistical analyses completed using SPSS. The review identified 68 original cases of DMC. The mean time from diagnosis of melanoma until development of DMC was 11.48 months (95% confidence interval [CI]: 0-48.16). The mean time to death following the onset of DMC was 4.43 months (95% CI: 0.00-11.11). Histological findings were relatively consistent demonstrating intracellular and extracellular melanin deposition in the dermis, with a pronounced perivascular distribution. The pathophysiological mechanisms underlying DMC could not be definitively elucidated however, it is hypothesized that the melanin precursors, melanin, and melanosomes liberated by cytolytic metastatic melanoma deposits are phagocytosed by dermal histiocytes, manifesting clinically as diffuse melanosis. The cross-sectional nature of case reports, paucity of cases of DMC, and heterogeneity in reporting limit any conclusions being drawn regarding the pathophysiology of DMC definitively. DMC heralds a poor prognosis for patients with metastatic melanoma and affected patients should be made aware of the implications of this condition on survival.
Publisher: Elsevier BV
Date: 07-2020
Publisher: Elsevier BV
Date: 05-2020
Publisher: American Medical Association (AMA)
Date: 10-2021
Publisher: Springer Berlin Heidelberg
Date: 2015
Publisher: SAGE Publications
Date: 05-2018
Publisher: Elsevier BV
Date: 10-2011
DOI: 10.1016/J.DET.2011.07.001
Abstract: Treatment modalities in pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are many and varied, although level 1 evidence supporting their use is limited. To date, only 2 systematic reviews exist to support the use of different treatment modalities to control this group of conditions. Overall, within the literature, the quality of trials comparing treatment modalities is poor. Cohort sizes are small, methodologies are varied, and standardized outcome measurements are lacking. The authors aim to present a comprehensive view of the level 1 evidence that exists for common treatment modalities used in PV and PF.
Publisher: Elsevier BV
Date: 04-2012
DOI: 10.1016/J.DET.2011.11.008
Abstract: Both congenital and acquired bullous dermatoses have the potential to impose a significant burden of disease, and the impact exerted on the quality of life (QOL) of patients is often multifaceted. The qualitative and quantitative studies reviewing QOL in patients with bullous dermatoses have all reported a significant decrease in QOL scores compared with the greater population using a range of patient-based measures. Formal evaluation of QOL in the setting of bullous dermatoses facilitates the assessment of disease severity and mapping of disease trajectory and can capture outcomes of therapeutic intervention relevant to the patient.
Publisher: Elsevier BV
Date: 03-2022
Publisher: Oxford University Press (OUP)
Date: 31-10-2013
DOI: 10.1111/BJD.12623
Abstract: Treatments for autoimmune blistering diseases have significant risk of medical complications and quality of life impacts during treatment, and it is difficult to differentiate these impacts from disease burden or the effects of treatment. To develop a quality of life instrument specific to the effects of treatments used in patients with autoimmune bullous disease (AIBD). A comprehensive item generation process was used to build a 45-item pilot Autoimmune Bullous Disease Quality of Life (ABQOL) questionnaire, distributed to 70 patients with AIBD. Experts in bullous disease refined the pilot ABQOL, selecting only those questions pertaining to the treatment effects. This pilot Treatment of Autoimmune Bullous Disease Quality of Life (TABQOL) questionnaire was administered to 70 patients, before factor analysis was performed to yield the final questionnaire of 17 questions. Validity and reliability were evaluated across a range of indices. Face and content validity were established through a comprehensive patient interview process, expert review and summaries of treatments used. The questionnaire was found to have appropriate correlation with the Dermatology Life Quality Index (r = 0.64) and the level of treatments used (P < 0.01), and was found to be responsive to overall variations in treatment burden. The TABQOL was also found to be a reliable instrument as evaluated by internal consistency (Cronbach α = 0.892) and test-retest reliability (r = 0.99). We have shown that the TABQOL questionnaire is a valid and reliable instrument that may to be used to measure treatment burden in AIBD and serve as an end point in clinical trials.
Publisher: Elsevier BV
Date: 02-2021
Publisher: Wiley
Date: 20-10-2020
DOI: 10.1111/IJD.14697
Abstract: Several case reports and case series have recently explored the association between hidradenitis suppurativa (HS) and inflammatory bowel disease (IBD). We performed a systematic review and meta-analysis of case-control studies to determine (i) the pooled prevalence of IBD in HS cohorts, and (ii) whether HS is more strongly associated with Crohn's disease or ulcerative colitis. Electronic searches were performed using five databases, from their inception to August 2018. Case-control studies reporting the proportion of IBD cases in HS cohorts were included and meta-analysis performed. From six included studies, a significant association between HS and IBD after pooling of adjusted effect sizes was identified (OR 2.12 95% CI 1.62-2.77 P = 0.03). Subgroup analysis demonstrated a significant association between HS and Crohn's disease (OR 2.25 95% CI 1.52-3.32 P < 0.0001, I Studies reviewed were observational by design which are susceptible to bias and lack of randomization. Our results indicate a statistically significant association between HS and IBD. Our results highlight that all patients with HS should be clinically screened for symptoms of IBD and symptomatic patients referred for further investigations.
Publisher: Oxford University Press (OUP)
Date: 22-03-2019
DOI: 10.1111/CED.13954
Publisher: Oxford University Press (OUP)
Date: 21-10-2021
DOI: 10.1111/BJD.20642
Abstract: Hidradenitis suppurativa (HS) is now recognized as a systemic inflammatory disease, sharing molecular similarities with psoriasis. Direct comparison of the systemic inflammation in HS with psoriasis is lacking. To evaluate the serum proteome of HS and psoriasis, and to identify biomarkers associated with disease severity. In this cross-sectional study, 1536 serum proteins were assessed using the Olink Explore (Proximity Extension Assay) high-throughput panel in patients with moderate-to-severe HS (n = 11), patients with psoriasis (n = 10) and age- and body mass index-matched healthy controls (n = 10). HS displayed an overall greater dysregulation of circulating proteins, with 434 differentially expressed proteins (absolute fold change ≥ 1·2 P ≤ 0·05) in patients with HS vs. controls, 138 in patients with psoriasis vs. controls and 503 between patients with HS and patients with psoriasis. Interleukin (IL)-17A levels and T helper (Th)1/Th17 pathway enrichment were comparable between diseases, while HS presented greater tumour necrosis factor- and IL-1β-related signalling. The Th17-associated markers peptidase inhibitor 3 (PI3) and lipocalin 2 (LCN2) were able to differentiate psoriasis from HS accurately. Both diseases presented increases of atherosclerosis-related proteins. Robust correlations between clinical severity scores and immune and atherosclerosis-related proteins were observed across both diseases. HS and psoriasis share significant Th1/Th17 enrichment and upregulation of atherosclerosis-related proteins. Despite the greater body surface area involved in psoriasis, HS presents a greater serum inflammatory burden.
Publisher: Wiley
Date: 29-08-2023
DOI: 10.1111/JDV.18543
Publisher: Wiley
Date: 24-08-2011
DOI: 10.1111/J.1440-0960.2010.00684.X
Abstract: Bullous dermolysis of the newborn is an inherited mechano-bullous disorder classed as a rare subtype of dystrophic epidermolysis bullosa. Fewer than 30 cases of bullous dermolysis of the newborn have been reported in the literature and the pathogenesis of the disease is poorly understood. Only a minority of cases have had pathogenic mutations identified. We present a case of a neonate born to non-consanguineous Caucasian parents with an exon 54 (c.5017G > A, p.G1673R) mutation reported as one mutant allele in a case of recessive dystrophic epidermolysis bullosa (generalized other).
Publisher: Elsevier BV
Date: 08-2020
Publisher: Informa UK Limited
Date: 16-04-2020
Publisher: Oxford University Press (OUP)
Date: 02-06-2022
DOI: 10.1111/BJD.21060
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2021
Publisher: Springer Berlin Heidelberg
Date: 2015
Publisher: Wiley
Date: 21-01-2018
DOI: 10.1111/AJD.12770
Abstract: Hidradenitis suppurativa is a chronic, painful, autoinflammatory condition resulting in nodules, abscesses and sinus tracts. We present an evidence-based review providing new understanding of the pathogenesis of hidradenitis suppurativa and associated comorbidities. By the nature of their speciality, dermatologists are uniquely positioned to investigate and treat patients with this condition. Data collected from a subspecialty hidradenitis suppurativa clinic (N = 106) and experiences thereof are discussed in this review.
Publisher: Oxford University Press (OUP)
Date: 08-2019
DOI: 10.1111/CED.13980
Abstract: Pachyonychia congenita (PC) describes a group of genodermatoses manifesting as thickened nails, palmoplantar keratoderma (PPK) and increased risk of cutaneous infections. PC tarda (PCT) describes late-onset PC, and associated genetic polymorphisms have been identified. There has been discussion that PCT may not be a distinct entity but rather misdiagnosed ectodermal dysplasia (ED) or PPK. Clarification of this is important for appropriate diagnosis, management and patient and genetic counselling. We aimed to conduct a systematic review of all reported cases of PCT in the published literature and collate evidence of genetic polymorphisms and clinical features to compare with known features of PC, ED and PPK. PubMed (1946 to 1 July 2018), Scopus (1955 to 1 July 2018) and Web of Science (1990 to 1 July 2018) databases were searched for case reports of PCT with no search restrictions on date or language. The search strategy included the terms pachyonychia congenita tarda OR pachyonychia congenita AND (late onset OR delayed OR PCT). In total, 13 reports describing 19 in idual cases of PCT were identified. Of the three identified genetic polymorphisms, the earliest identified has been shown to be highly probably pathogenic, with the second likely to result in a benign amino acid change, while the third has since been shown to be nonpathogenic,. No epigenetic studies have been performed on any reported cases. Previous authors have suggested that a number of cases of PCT may be misdiagnosed ED or PPK. The findings of our review cannot refute this suggestion, and highlight the need for thorough clinical documentation of suspected cases of PCT and thorough genetic screening of kindred to identify causative genetic polymorphisms. Further high-quality datasets and reporting are needed to give further insight into the nature of PCT as a unique entity.
Publisher: Elsevier BV
Date: 07-2011
DOI: 10.1016/J.DET.2011.03.018
Abstract: Paraneoplastic pemphigus is a rare condition with extremely high rates of mortality. Although its pathogenesis is incompletely understood, its pathologic findings have significant overlap with other autoimmune blistering diseases, such as pemphigus vulgaris, bullous pemphigoid, erythema multiforme and erosive lichen planus. A universally accepted consensus definition is needed to firmly define the condition. This would aid in identification of paraneoplastic pemphigus and the institution of timely and appropriate treatment to avoid rapid patient deterioration as well as recruitment for trials to further examine the pathogenesis and new therapeutic modalities. This article reviews the varied clinical presentations and pathologic characteristics pertaining to paraneoplastic pemphigus.
Publisher: Wiley
Date: 22-03-2022
DOI: 10.1111/JDV.18075
Publisher: Wiley
Date: 18-08-2021
DOI: 10.1111/JDV.17536
Publisher: Elsevier BV
Date: 06-2207
Publisher: Oxford University Press (OUP)
Date: 21-08-2023
DOI: 10.1093/BJD/LJAD303
Abstract: Resident memory T-cells (T-RMs) remain in epithelial barrier tissues after antigen exposure and the initial effector phase. These T-RMs provide effective antimicrobial and anticancer immunity, however pathogenic T-RMs have been shown to mediate various chronic inflammatory disorders in a variety of tissue types. In the skin, T-RMs are referred to as resident cutaneous memory T-cells (cT-RMs). Understanding the mechanisms leading to the development and establishment of these cT-RMs populations may allow for targeted treatments providing durable responses in chronic immune-mediated skin diseases, even after cessation. In this Review, we summarise the evidence on cT-RMs as drivers of chronic inflammatory dermatoses including psoriasis, vitiligo, atopic dermatitis, cutaneous lupus erythematosus and alopecia areata, among others. Data from in-vitro, animal model, and ex-vivo human studies are presented – with a focus on the potential for cT-RMs to trigger acute disease flares as well as recurrent disease by establishing an immune ‘memory’ in the skin. Furthermore, available data on the potential for existing and novel treatments to affect the development or survival of cT-RMs in the skin are synthesised. These suggest a dynamic and rapidly growing area in the field of dermatology however we also discuss areas in need of greater research to allow for optimal treatment selection for long-term disease control.
Publisher: Oxford University Press (OUP)
Date: 02-2023
DOI: 10.1093/BJD/LJAD027
Publisher: The Royal Australian College of General Practitioners
Date: 05-2022
Publisher: Oxford University Press (OUP)
Date: 21-08-2023
DOI: 10.1093/BJD/LJAD301
Publisher: Wiley
Date: 29-12-2017
DOI: 10.1111/AJD.12767
Publisher: Elsevier BV
Date: 2021
Publisher: Oxford University Press (OUP)
Date: 19-04-2019
DOI: 10.1111/BJD.17695
Publisher: Oxford University Press (OUP)
Date: 06-08-2019
DOI: 10.1111/BJD.18300
Publisher: Oxford University Press (OUP)
Date: 12-05-2023
DOI: 10.1093/CED/LLAD182
Abstract: Hidradenitis suppurativa (HS) is a chronic, inflammatory condition of the pilosebaceous unit. The typical patient with HS is characterized as someone with obesity, who smokes and who has nodules, abscesses and/or draining tunnels predominantly distributed in intertriginous skin. It has been established that lifestyle and genetic factors are the main pathophysiological drivers of HS. In this critical review, we explore the interrelatedness of meta-inflammation, obesity and HS and discuss if and how this relationship may be manipulated for a therapeutic end.
Publisher: Elsevier BV
Date: 09-2009
DOI: 10.1016/J.JAAD.2008.12.004
Abstract: The Dystrophic Epidermolysis Bullosa (EB) Research Association (DebRA) of New Zealand has run 3 adventure c s specifically geared to the unique and specific needs of teenagers and young adults with EB. We sought to describe how the 2007 winter c was organized, funded, and run for teenagers and young adults with a range of EB severities. Planning and fundraising by DebRA of New Zealand began 1 year before the c . Nurses and international medical personnel volunteered as c staff. Instructors qualified to assist persons with disabilities were hired to provide c activities. The 5-day adventure c was held at a national park on the North Island of New Zealand. The 2007 c included 5 c ers (aged 21-35 years) with recessive dystrophic EB, 3 of whom used wheelchairs, and two teenagers with EB simplex. All c ers were male. Twelve international volunteers assisted with daily dressing changes and c activities, which included skiing, whitewater rafting, and fly-fishing. Challenges included difficulty in recruiting new c ers each year, particularly female c ers. The c allowed c ers to challenge themselves both physically and mentally, while developing lifelong friendships. It was immensely rewarding for all the volunteers. This c demonstrated that it is possible to provide such activities safely to severely affected patients.
Publisher: Oxford University Press (OUP)
Date: 24-09-2021
DOI: 10.1111/BJD.19478
Publisher: Oxford University Press (OUP)
Date: 29-08-2019
DOI: 10.1111/BJD.18309
Publisher: Wiley
Date: 27-03-2023
DOI: 10.1111/AJD.14025
Abstract: Academic dermatologists in Australia and New Zealand provide high‐quality and meaningful contributions to the understanding of disease and therapeutic translational research. Concerns have been raised by the Australian Medical Association regarding the decline of clinical academics in Australia as a whole, however, such trends in scholarly output have not previously been analysed for Australasian dermatologists. A bibliometric analysis of dermatologists in Australia and New Zealand was conducted in January and February 2023. Available Scopus profiles for all dermatologists were used to measure lifetime H index, scholarly output, citation counts and field‐weighted citation impact (FWCI) in the last 5 years (2017–2022). Trends in output over time were measured using non‐parametric tests. Differences in output between subgroups stratified by gender and academic leadership positions (associate professor or professor) were measured using Wilcoxon rank‐sum and one‐way ANOVA tests. The scholarly output of recent College graduates was also analysed as a subgroup, comparing the same bibliographic variables in the 5 years preceding and 5 years following awarding of their fellowships. From the 463 practising dermatologists in Australia and New Zealand, 372 (80%) were successfully matched to Scopus researcher profiles. Of these dermatologists, 167 were male (45%) and 205 (55%) were female, and 31 (8%) held academic leadership positions. Most dermatologists (67%) published at least one paper in the last 5 years. The median lifetime H index was 4, and between 2017 and 2022 median scholarly output was 3, the median citations were 14 and the median FWCI was 0.64. There was a non‐significant trend towards fewer publications per year, however, citation count and FWCI decreased significantly. By subgroups, female dermatologists published significantly more papers between 2017 and 2022, and other bibliographic variables were comparable to male dermatologists. However, women were underrepresented in positions of academic leadership—comprising only 32% of this cohort despite representing 55% of dermatologists. Professors were also significantly more likely to have higher bibliographic outcomes than associate professors. Finally, analysis of recent College graduates highlighted a significant decline in bibliometric outcomes pre‐ and post‐fellowship. Overall, our analysis identifies a trend towards decreased research output by dermatologists in Australia and New Zealand in the last 5 years. Strategies to support dermatologists in research endeavours, particularly women and recent graduates, will be essential in maintaining strong scholarly output among Australasian dermatologists and thereby sustaining optimal evidence‐based patient care.
Publisher: Oxford University Press (OUP)
Date: 26-05-2020
DOI: 10.1111/CED.14264
Publisher: Oxford University Press (OUP)
Date: 08-2022
DOI: 10.1111/CED.15232
Publisher: Oxford University Press (OUP)
Date: 03-2016
DOI: 10.1111/BJD.14349
Abstract: Linked Article: Xiao et al. Br J Dermatol 2016 174:522–532.
Publisher: Wiley
Date: 23-05-2017
DOI: 10.1111/AJD.12641
Abstract: The Australasian Psoriasis Collaboration has reviewed the evidence for managing moderate to severe psoriasis in those who are pregnant or are breast-feeding, or planning a family. The severity of the psoriasis, associated comorbidities and specific anti-psoriasis treatment, along with other exposures, can have a deleterious effect on pregnancy outcomes. Psoriasis itself increases the risk of preterm and low birthweight babies, along with spontaneous and induced abortions, but no specific birth defects have been otherwise demonstrated. The baseline risk for a live born baby to have a major birth defect is 3%, and significant neuro-developmental problem is 5%. In Australia, pregnant women with psoriasis are more likely to be overweight or obese, depressed, or smoke in their first trimester, and are also less likely to take prenatal vitamins or supplements. Preconception counselling to improve maternal, pregnancy and baby health is therefore strongly encouraged. The topical and systemic therapies commonly used in psoriasis are each discussed separately, with regards to pregnancy exposure, breast-feeding and effects on male fertility and mutagenicity. The systemic therapies included are acitretin, adalimumab, apremilast, certolizumab, ciclosporin, etanercept, infliximab, ixekizumab, methotrexate, NBUVB, prednisone, PUVA, secukinumab and ustekinumab. The topical therapies include dithranol (anthralin), calcipotriol, coal tar, corticosteroids (weak, potent and super-potent), moisturisers, salicylic acid, tacrolimus, and tazarotene. As a general recommendation, effective drugs that have been widely used for years are preferable to newer alternatives with less foetal safety data. It is equally important to evaluate the risks of not treating, as severe untreated disease may negatively impact both mother and the foetus.
Publisher: Wiley
Date: 06-2021
DOI: 10.1111/EXD.14338
Abstract: The registration of the tumour necrosis factor‐α inhibitor adalimumab in 2015 was a major step forward in the treatment of hidradenitis suppurativa/acne inversa (HS). However, it soon became evident that the effectiveness of adalimumab in daily practice was highly variable. A significant unmet medical need of HS patients remained, and the search for novel therapeutic targets was intensified. During the 10th European Hidradenitis Suppurativa Foundation (EHSF) e.V. Conference, reknown international HS investigators virtually presented and discussed the published data on these potential target molecules for future HS treatment. This article addresses the most promising molecules currently under investigation from a pathophysiological and clinical point of view. With phase III trials ongoing, the anti‐ interleukin (IL)‐17 biologics bimekizumab and secukinumab are in the most advanced stage of clinical development showing promising results. In addition, targeting IL‐1α with bermekimab has shown encouraging results in two clinical trials. Directing treatment at neutrophil recruitment and activation by targeting IL‐36 with spesolimab fits well in the pathogenic concept of HS and clinical phase II trial results are pending. In contrast to in situ evidence, Complement 5a (C5a) and C5a receptor blockade have only shown greater clinical benefit in patients with severe HS. Inhibition of Janus kinase (JAK) 1 signalling in HS showed clinical efficacy only in the highest dosage, highlighting that careful surveillance of the balance between safety and efficacy of JAK inhibition is warranted. Overall, clinical efficacies of all novel treatments reported so far are modest. To guide drug development, more and better‐defined translational data on the pathogenesis of this severe and enigmatic inflammatory skin disease are required.
Publisher: Frontiers Media SA
Date: 19-09-2019
Publisher: Wiley
Date: 12-2020
DOI: 10.1111/EXD.14214
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2015
Publisher: Elsevier BV
Date: 03-2022
DOI: 10.1016/J.JID.2021.08.400
Abstract: Hidradenitis suppurativa is considered to be a T helper 17-mediated inflammatory disorder. However, the role of prominent B-cell and plasma cell infiltrates has not been incorporated into pathogenic understanding of the disease. In their new article in the Journal of Investigative Dermatology, Carmona-Rivera et al. (2021) present new insights regarding autoantibody-mediated macrophage activation, which bridges the link between the innate and adaptive immune responses in severe hidradenitis suppurativa.
Publisher: Wiley
Date: 29-11-2020
DOI: 10.1111/EXD.14056
Abstract: Complement inhibition has been identified as a potential therapeutic target for multiple inflammatory disorders including Hidradenitis Suppurativa (HS). It is currently unclear how complement integrates into our current model of molecular pathogenesis in HS and whether it represents a central component of pathogenesis, or a neutrophil-associated bystander. Levels of C5a in serum and tissue correlate with disease activity and degree of neutrophilic infiltrates in HS. C5a has been associated with Th17 immune axis activation in psoriasis, rheumatoid arthritis and Crohn's disease with strong similarities to TH17 activation in HS. Porphyromonas species (which are identified in the HS microbiome) are able to cleave inactive C5 into C5a implicating the cutaneous microbiome as an activator of complement. C3a and C5a are associated with activation of the NLRP3 inflammasome, implicated in the inflammatory drive in HS. Complement receptors are present upon dendritic cells, monocytes, fibroblasts and adipocytes, which may broaden the potential contribution of complement to multiple aspects of HS pathogenesis. Dysregulation of complement receptor pathways has been documented in obesity, insulin resistance and polycystic ovarian syndrome leading to the possibility that complement may explain the epidemiological associations between these conditions and HS. The therapeutic potential of complement inhibitors in HS may be related to the therapeutic target (complement receptor or complement subunit) and the presence of alternate receptors (such as C5aR2) or ligands (including C3a, PAMPs and DAMPs). Integrating complement into the known pathogenesis of HS may aid in explaining the contradictory results between Phase 2 studies of C5a antagonists. It also allows for the identification of existing knowledge gaps to target further clinical investigation and research.
Publisher: Wiley
Date: 12-07-2022
DOI: 10.1111/JDV.18403
Publisher: Oxford University Press (OUP)
Date: 10-2022
DOI: 10.1111/BJD.21673
Abstract: Prolonged systemic antibiotic treatment is often a part of management of hidradenitis suppurativa (HS). Although biologic therapies are now available, the patient’s treatment journey leading to biologic therapy is unclear. To examine treatment patterns and duration of systemic treatment use in patients with HS preceding biologic therapy. We identified all patients with HS receiving treatment with biologics in the Danish National Patient Registry from 2010 to 2018 and extracted their entire prescription history of specific systemic treatments from the Danish National Prescription Registry since its inception in 1995. The patients’ treatment journeys are graphically displayed through Sankey diagrams and box plots generated to show temporal distributions. Descriptive patient characteristics were presented as frequencies with percentages for categorical variables and as means with SDs or medians with interquartile ranges (IQRs) for continuous variables. A total of 225 patients with HS were included. Patients had most frequently been treated with penicillin (n = 214 95·1%), dicloxacillin (n = 194 86·2%), tetracycline (n = 145 64·4%) and rif icin/clindamycin (n = 111 49·3%), as well as the retinoids isotretinoin and acitretin, and dapsone. Prior to biologic therapy, patients received a mean of 4·0 (SD 1·3) different systemic therapies, across a mean of 16·9 (SD 11·3) different treatment series. The mean time from first systemic therapy until biologic therapy was initiated was 15·3 (SD 5·1) years [8·2 (SD 5·9) years when excluding penicillin and dicloxacillin]. Patients with HS who receive biologic therapy have long preceding treatment histories with multiple drug classes and treatment series, many of which are supported by relatively weak evidence in HS. Delay in the initiation of biologic therapy may represent a missed opportunity to prevent disease progression. What is already known about this topic? The treatment journey leading to biologic therapy in patients with HS has not previously been investigated. What does this study add? Our data from 225 patients with HS illustrate that patients who receive biologic therapy have long preceding treatment histories with multiple drug classes and treatment series, many of which are supported by relatively weak evidence in HS.
Publisher: Elsevier BV
Date: 10-2013
Publisher: Hindawi Limited
Date: 2014
DOI: 10.1111/DTH.12003
Abstract: Dermatological disease is commonly associated with psychological morbidity because of its visible nature. The burden of living with a chronic dermatological illness can contribute to the development of psychiatric illness and conversely, such conditions can result in the exacerbation of preexisting dermatological disease. It may also reduce a patient's compliance to treatment, result in loss to follow-up and a decreased level of functioning and quality of life. In dermatological patients who suffer from psychiatric symptoms, medical management used in their treatment may have significant interactions with systemic medications used to treat their dermatological condition. A well-known ex le of this is lithium's ability to exacerbate psoriasis. Such interactions can result in suboptimal treatment of their psychiatric and/or dermatological condition. The present paper aimed to review the literature for documented interactions and the level of clinical significance between dermatological and psychoactive medications. Such information is clinically relevant to the practicing dermatologist in order to minimize adverse effects and drug-drug interactions in dermatological patients.
Publisher: American Medical Association (AMA)
Date: 04-2021
Publisher: Elsevier BV
Date: 11-2020
Publisher: Oxford University Press (OUP)
Date: 20-09-2017
DOI: 10.1111/BJD.15441
Abstract: Hidradenitis suppurativa (HS) is a severe chronic inflammatory disorder characterized by recurrent painful deep-seated nodules with a predilection to the apocrine-bearing areas of skin. A minority of cases of HS are due to mutations in the γ-secretase complex. Contention exists surrounding the pathogenicity of sequence variants and their effects upon Notch signalling. This systematic review was registered with PROSPERO (CRD42016041425) and was conducted in line with the PRISMA statement. Eligibility criteria for this review included published case reports, case series and reviews that identified sequence variants or protein or functional studies from patients with HS. Sixty-two articles were identified reporting a total of 41 sequence variants - heterozygous missense (nine), splice site (nine), insertion resulting in frameshift (one), premature termination codon (19) and promoter region PSTPIP1 (three) - with 18 associated protein or functional studies. The American College of Medical Genetics and Genomics standards and guidelines on the interpretation of sequence variants were applied to each identified variant to assess evidence for pathogenicity. Twenty-three variants were assessed as likely pathogenic, 17 of uncertain significance and one benign. The large number of variants of 'uncertain significance' is largely due to the variable number of functional studies. Four studies used Notch as a proxy for γ-secretase function, with conclusions of nonpathogenicity based on the assumption of Notch signalling as the sole pathogenic process. The role of Notch-independent signalling mechanisms requires further research. Limitations to this study include identification of variants of Mendelian inheritance and not complex polygenic traits.
Publisher: Elsevier BV
Date: 06-2023
Publisher: Oxford University Press (OUP)
Date: 04-09-2020
DOI: 10.1111/BJD.18436
Publisher: Wiley
Date: 24-05-2021
DOI: 10.1111/AJD.13600
Abstract: Hidradenitis Suppurativa is a chronic inflammatory disease manifesting in painful nodules, abscesses and malodorous draining tunnels with a pre‐disposition to flexural regions of skin. Traditional surgical interventions include excision of clinically visible lesions and in severe cases – excision down to fascia of entire anatomical regions (axilla, groin) and repair with split‐thickness grafting or skin substitutes. However, such techniques are plagued by long healing times (up to several months), extensive tissue loss and high recurrence rates given that a large proportion of disease is not clinically visible. Deroofing is a tissue‐saving surgical technique, ideal for Hurley Stage 2 disease, which when combined with bedside pre‐operative sonography can allow for the accurate identification and removal of occult dermal tunnels whilst minimising the risks of pain, infection, minimising healing times and can be safely conducted in the setting of immunomodulatory therapy.
Publisher: Wiley
Date: 11-12-2017
DOI: 10.1111/AJD.12754
Publisher: Oxford University Press (OUP)
Date: 03-12-2020
DOI: 10.1111/BJD.18556
Publisher: Frontiers Media SA
Date: 06-11-2019
Publisher: Wiley
Date: 09-03-2015
DOI: 10.1111/EXD.12648
Publisher: Oxford University Press (OUP)
Date: 17-12-2019
DOI: 10.1111/BJD.17426
Publisher: Wiley
Date: 03-07-2019
DOI: 10.1111/EXD.13978
Publisher: Wiley
Date: 18-03-2023
DOI: 10.1111/JDV.19020
Abstract: Psoriasis is a chronic immune‐mediated inflammatory disorder that also occurs in the setting of human immunodeficiency virus (HIV). Biological therapy has transformed the treatment landscape for psoriasis however, in iduals with HIV are excluded from clinical trials. The impact of biological therapy on blood parameters in HIV is unclear and is only observed in small case series. The aim of this study was to assess the effect of biological therapy in psoriasis vulgaris in in iduals with well‐controlled HIV on CD4 + cell counts, CD4 + proportion and HIV viral load over 12 months. This retrospective cohort study was conducted at a tertiary referral centre in Sydney, Australia and included 36 HIV‐positive in iduals with psoriasis treated with biological therapy, compared with 144 age‐, gender‐ and HAART‐matched in iduals without psoriasis seen between 2010 and 2022. Outcomes of interest included HIV viral load, CD4 + cell count and incidence of infections. No statistically significant difference was seen in baseline HIV viral load and CD4 + count between in iduals with and without psoriasis. No significant change in CD4 + count or HIV viral load was seen over the 12‐month period of analysis in the HIV cohort without psoriasis. The HIV cohort treated with biological therapy for psoriasis also did not demonstrate any significant change in HIV viral load and CD4 + counts over the 12‐month period examined. Stratification by type of biological therapy used did not identify any significant changes in these parameters. Rates of infections and adverse events were also not significantly different between cohorts. It is possible that minor blips seen in the biologics cohort may be a risk factor for future virological failure, and future prospective longitudinal studies are required. In in iduals with well‐controlled HIV, the use of biological therapy for psoriasis does not significantly impact HIV viral load, CD4 + cell count, CD4 + proportion and rates of infection over the first 12 months of therapy.
Publisher: Wiley
Date: 18-03-2023
DOI: 10.1111/EXD.14789
Abstract: Hidradenitis suppurativa is a complex inflammatory disease in which predicting therapeutic response remains challenging. IL‐23 interacts with sex hormones but the relationships between the two in HS remains uninvestigated. To assess whether baseline clinical, hormonal or molecular markers are associated with clinical response to IL‐23 antagonism with risankizumab in hidradenitis suppurativa. Twenty six in iduals with Hurley stage 2/3 disease were administered risankizumab 150 mg Week 0, 4, 12. Baseline sex hormones and skin biopsies were taken. Clinical response at Week 16 assessed by the HiSCR, and differences between responders and non‐responders assessed. Eighteen of 26 participants achieved HiSCR50 at week 16 (69.2%). Clinical response to IL‐23 antagonism was associated with male gender, elevated total serum testosterone and decreased levels of FSH. Stratification by clinical responders/nonresponders identified differentially expressed genes including PLPP4 and MAPK10 . Immunohistochemistry identified elevated numbers of CD11c, IL‐17A and IL‐17F positive cells compared to nonresponders. CD11c + cells significantly correlated with serum levels of total testosterone and inversely correlated with serum FSH. Clinical response to IL‐23 antagonism in HS is associated with serum sex hormones, Th17 polarized inflammation in lesional tissue and CD11c + cells. These potential therapeutic biomarkers require further validation in larger cohorts but may suggest potential targeted HS therapy.
Publisher: Elsevier BV
Date: 07-2023
Publisher: Wiley
Date: 16-09-2022
DOI: 10.1111/IJD.15910
Abstract: Hidradenitis suppurativa (HS) is a chronic, suppurative condition of the pilosebaceous unit. Patients suffering from HS demonstrate a molecular profile in keeping with a state of systemic inflammation and are often found to fit the criteria for a diagnosis of metabolic syndrome (MetS). In this paper, we review the literature with regards to established data on the prevalence of MetS in HS patients and revise the odds ratio of comorbid disease. Furthermore, we attempt to draw parallels between inflammatory pathways in HS and MetS and evaluate how convergences may explain the risk of comorbid disease, necessitating the need for multidisciplinary care.
Publisher: S. Karger AG
Date: 2017
DOI: 10.1159/000464140
Publisher: Mucosa
Date: 29-09-2019
Abstract: Objective The Quality of Life in Epidermolysis Bullosa (QOLEB) score is an Epidermolysis Bullosa (EB) specific quality of life (QoL) measurement tool. It is a statistically valid and reliable questionnaire which has benefits over generic QoL tools in QoL evaluation in EB. It also has important implications in the evaluation of the clinical efficacy of new interventions in EB. The utility of this score would be increased if the clinical relevance of in idual scores and changes in QOLEB scores could be further understood.Methods In order to achieve this, the minimal clinically important difference (MCID) was calculated using both anchor-based and distribution-based techniques. Banding techniques were also applied to the QOLEB questionnaire in order to stratify scores into “very mild”, “mild”, “moderate”, “severe” and “very severe” categories.Results Using these methodologies, the MCID for the QOLEB score was calculated at a 6 point change in QOLEB scores, and the QOLEB bands were calculated as: 0-4 points for ‘very mild’, 5-9 points for ‘mild’, 10-19 points for ‘moderate’, 20-34 points for ‘severe’ and 35-51 points for ‘very severe’ impact on QoL.Conclusions Calculating the MCID and clinical bands for the QOLEB questionnaire increases the breadth of clinical applications for the QOLEB questionnaire. It now has direct utility in determining the clinical significance of interventions in EB by evaluating changes in QOLEB scores and how they correlate to the MCID and clinical bands.
Publisher: Wiley
Date: 30-08-2022
DOI: 10.1111/EXD.14665
Abstract: Altered gut microbiota composition has been observed in in iduals with hidradenitis suppurutiva (HS) and many other inflammatory diseases, including obesity, type 1 and type 2 diabetes. Here, we addressed whether adalimumab, a systemic anti‐inflammatory therapy, may impact the microbiota biochemical profile, particularly on beneficial metabolites such as short‐chain fatty acids (SCFAs). We conducted an observational single‐arm pilot trial to assess gut microbiota composition by 16S rRNA gene sequence analysis and to detect metabolite signatures by gas chromatography in stool s les from participants with HS prior to and 12 weeks after commencing adalimumab therapy. HS in iduals that better responded to adalimumab treatment showed a shift in the composition and function of the gut microbiota with significantly increased SCFA acetate and propionate compared to age, gender and BMI‐matched healthy controls. A positive correlation was observed between propionate with Prevotella sp and Faecalibacterium prausnitsii. Increased SCFAs, changes in gut microbiota composition, function and metabolic profile following 12 weeks of adalimumab suggest that targeting SCFAs may be considered a potential biomarker to be evaluated as a complementary protective factor or as a diagnostically relevant signal in HS.
Publisher: Wiley
Date: 22-11-2019
DOI: 10.1111/PHPP.12436
Abstract: Australia has the highest incidence of cutaneous melanoma worldwide. Previous studies have identified some body areas (forearms and dorsal hands) have lower rates of melanoma than expected when compared with other similarly exposed areas, leading to the suggestion that endogenous immunological protective mechanisms in certain body sites may exist. We hypothesise that examination of melanoma by body site in a regional Australian setting would demonstrate no significant variation in the incidence of melanoma across highly sun exposed areas including the head and neck and upper limbs. Results were stratified by body site and further examined by univariate correlation analysis by gender, age, body site, Breslow thickness and subtype. Polytomous logistic regression was used to test the difference in risk factors by location of melanoma. A total of 772 melanomas were included in the analysis. Melanomas of the upper limb were more likely to affect females (OR = 2.415 95%CI: 1.433-4.072) and more likely to be thinner than other body sites. Compared to other international studies, statistically significant decreased rates of melanoma were seen on the upper limb compared to other areas of the body (X Our study was limited by its retrospective nature, and the findings require validation in a larger prospective cohort. Further exploration of such mechanisms may lead to new insights into the immunological mechanisms surrounding cutaneous melanoma.
Publisher: Elsevier BV
Date: 10-2011
DOI: 10.1016/J.DET.2011.06.004
Abstract: Corticosteroids, while providing rapid remission and ongoing control of symptoms of autoimmune blistering diseases (AIBD), have numerous potentially serious acute and long-term side effects. Evidence-based medicine has reevaluated the various types of corticosteroids and forms of corticosteroid delivery in AIBD to ascertain whether any advantages of specific delivery systems or regimens exist. Careful monitoring of patients and simple preventive measures are effective in minimizing the adverse outcomes associated with their use. This article outlines the current level of evidence for corticosteroid use in AIBDs, and discusses appropriate investigations and interventions to minimize or prevent the associated adverse effects.
Publisher: Cold Spring Harbor Laboratory
Date: 26-02-2023
DOI: 10.1101/2023.02.22.23286201
Abstract: Hidradenitis Suppurativa is a complex inflammatory disease in which predicting therapeutic response remains challenging. IL-23 interacts with sex hormones but the relationships between the two in HS remains uninvestigated. To assess whether baseline clinical, hormonal, or molecular markers are associated with clinical response to IL-23 antagonism with Risankizumab in Hidradenitis Suppurativa. 26 in iduals with Hurley Stage 2/3 disease were administered Risankizumab 150mg Week 0,4,12. Baseline sex hormones and skin biopsies were taken. Clinical response at Week 16 assessed by the HiSCR, and differences between responders and non-responders assessed. 18 of 26 participants achieved HiSCR50 at week 16 (69.2%). Clinical response to IL-23 antagonism was associated with male gender, elevated total serum testosterone, and decreased levels of FSH. Stratification by clinical responders/non responders identified differentially expressed genes including PLPP4 and MAPK10 . Immunohistochemistry identified elevated numbers of CD11c, IL-17A and IL-17F positive cells compared to non-responders. CD11c+ cells significantly correlated with serum levels of total testosterone and inversely correlated with serum FSH. Clinical response to IL-23 antagonism in HS is associated with serum sex hormones, Th17 polarized inflammation in lesional tissue and CD11c+ cells. These potential therapeutic biomarkers require further validation in larger cohorts but may suggest potential targeted HS therapy.
Publisher: Springer Science and Business Media LLC
Date: 12-2017
Publisher: Wiley
Date: 11-08-2021
DOI: 10.1111/EXD.14141
Abstract: Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic inflammatory skin disease with still largely unknown pathogenesis. While infectious organisms have been identified in lesions of the disease since the 1980s, questions remain over the role that bacteria and microbiome play. Recent studies using 16S ribosomal RNA gene sequencing and larger culture‐based studies have begun to paint a clearer picture of the microbial world of HS. With this systematic review, we summarize all the work that has been done to date in HS bacteriology, analyse potential pitfalls and limitations of the current studies, and address future directions of investigation. This systematic review attempted to collate and analyse all bacteriology studies done to date. This review was prospectively registered with PROSPERO (1670769) performed in line with the PRISMA checklist. Twenty two studies were identified comprising 862 in idual HS patients for culture studies and 206 HS patients for 16S rRNA gene sequencing studies. Methodology tended to be varied, with different s ling, culturing and sequencing methods as well as amount of analysis and stratification of patients. Bacteria identified as elevated in HS lesions in sequencing studies as well as grown from HS lesions in culture studies are identified and discussed. These primarily included the anerobic Gram‐negative bacilli Prevotella , Porphyromonas and Fusibacterium , the Gram‐positive bacilli Corynebacterium , and the Gram‐positive cocci Staphylococcus , Streptococcus and Parvimonas. Potential interactions, as well as work in other disease models with related bacteria are also discussed. Areas of further investigation include in vitro studies of interactions between bacteria and keratinocytes, gut and oral microbiome studies and deep sequencing studies for virulence and phage factors.
Publisher: Elsevier BV
Date: 07-2020
Publisher: S. Karger AG
Date: 2022
DOI: 10.1159/000521268
Abstract: b i Introduction: /i /b Hidradenitis suppurativa (HS) patients may be at increased risk of COVID-19 infection and complications from their medications and comorbidities. There is a lack of expert consensus on recommendations for the COVID-19 vaccine for HS patients. Herein, we aim to provide expert-driven consensus recommendations regarding COVID-19 vaccinations in HS patients. b i Methods: /i /b A modified Delphi consensus survey developed by a core committee of 7 dermatologist HS experts consisting of 4 demographic questions and 12 practice statements was distributed to the US HS Foundation-sponsored provider listserv. Participants were attending physician HS experts. Survey results were to be reviewed by the core group and revised and resubmitted until consensus (≥70% agreement) was achieved. b i Results: /i /b Among the 33 survey participants, there were 30 (87%) dermatologists, 1 general surgeon, 1 plastic surgeon, and 1 rheumatologist. Consensus for all 12 statements on vaccine counseling and HS treatment counseling was achieved after the first round. b i Discussion/Conclusion: /i /b For now, this consensus can serve as a resource for clinicians discussing COVID-19 vaccination with their HS patients. These recommendations will need to be updated as new evidence on COVID-19 emerges.
Publisher: Elsevier BV
Date: 06-2021
Publisher: Frontiers Media SA
Date: 06-03-2019
Publisher: Frontiers Media SA
Date: 25-02-2019
Publisher: Elsevier BV
Date: 05-2019
Publisher: Elsevier BV
Date: 06-2022
Publisher: Wiley
Date: 26-07-2017
DOI: 10.1111/AJD.12582
Publisher: Medical Journals Sweden AB
Date: 2014
Abstract: Defining the health-related quality of life (HRQoL) in patients suffering from the heritable blistering disease epidermolysis bullosa (EB) is important in assessing the efficacy of new treatments. The quality of life in EB questionnaire (QOLEB) is an English 17-item EB-specific HRQoL measurement tool. The aim of this study was to develop a validated and reliable QOLEB in Dutch and assess the HRQoL in Dutch EB patients. The QOLEB was translated to Dutch according to protocol. Fifty-five adult patients across 4 EB subtypes participated. The QOLEB had excellant correlation with the Skindex-29 (ρs = 0.86), good correlation with the SF-36 physical score (ρs = -0.75), and moderate correlation with the SF-36 mental score (ρs = -0.43). The discriminative validity between the 4 different EB subtypes was significant (p = 0.002). The internal consistency was excellent (α = 0.905), and the test-retest reliability strong (ρs = 0.88). In conclusion, the Dutch QOLEB is a reliable and valid instrument for the assessment of the HRQoL in adult EB patients.
Publisher: Elsevier BV
Date: 05-2012
DOI: 10.1016/J.IAC.2012.04.008
Abstract: Corticosteroids, while providing rapid remission and ongoing control of symptoms of autoimmune blistering diseases (AIBD), have numerous potentially serious acute and long-term side effects. Evidence-based medicine has reevaluated the various types of corticosteroids and forms of corticosteroid delivery in AIBD to ascertain whether any advantages of specific delivery systems or regimens exist. Careful monitoring of patients and simple preventive measures are effective in minimizing the adverse outcomes associated with their use. This article outlines the current level of evidence for corticosteroid use in AIBDs, and discusses appropriate investigations and interventions to minimize or prevent the associated adverse effects.
Publisher: Frontiers Media SA
Date: 22-06-2021
Abstract: Elevated BMI in Hidradenitis Suppurativa is associated with decreased response to Adalimumab therapy. BMI is proposed to segregate distinct disease subtypes. It remains unresolved whether a threshold BMI exists above which increased dosages may provide clinical benefit. In idual patient data from 578 PIONEER Phase 3 participants were analyzed. Descriptive, multivariable regression analysis and receiver operating characteristic (ROC) curves were calculated to assess the relationship between BMI and clinical outcome measures using R v3.5.3. Participants in the overweight and obese BMI category had reduced odds (58 and 67%, respectively) of achieving HiSCR [OR = 0.42 (95%CI −0.19, 0.91) p = 0.03], [OR = 0.33 (95%CI 0.16, 0.67) p = 0.002] compared to participants with BMI & 25. Reduction in AN count and IHS4 score was not significantly associated. ROC analysis did not reveal any cut off value predictive of treatment outcome. No correlation between BMI and baseline disease activity or covariate interactions were identified. These findings suggest BMI is a significant covariate in the setting of lower baseline disease activity, supporting the concept of disease heterogeneity and differential therapeutic response to Adalimumab.
Publisher: Oxford University Press (OUP)
Date: 19-04-2022
DOI: 10.1111/BJD.21019
Abstract: Dupilumab associated head and neck dermatitis is incompletely understood. This prospective multicentre prospective study identified baseline Malassezia-specific IgE as associated with the development of Dupilumab associated head and neck dermatitis.
Publisher: Oxford University Press (OUP)
Date: 22-10-2020
DOI: 10.1111/CED.14448
Publisher: Elsevier BV
Date: 2018
Publisher: Wiley
Date: 16-04-2015
DOI: 10.1111/JDV.13169
Publisher: F1000 Research Ltd
Date: 17-06-2019
DOI: 10.12688/F1000RESEARCH.17268.2
Abstract: Background: Hidradenitis suppurativa (HS) is a chronic inflammatory disease with significant morbidity and impact on quality of life. Our understanding of the pathophysiology is incomplete, impairing efforts to develop novel therapeutic targets. Immunohistochemistry studies have produced conflicting results and no systematic evaluation of study methods and results has been undertaken to date. Methods: This systematic review aimed to collate and describe all reports of immunohistochemical staining in HS. This systematic review was registered with PROSPERO and conducted in line with the PRISMA reporting guidelines. Potential bias was assessed using the NIH Criteria and antibodies used across various studies were tabulated and compared. Results : A total of 22 articles were identified describing results from 494 HS patients and 168 controls. 87 unique immunohistochemical targets were identified. The overall quality of studies was sub-optimal with staining intensity confounded by active treatment. Conflicting data was identified and able to be reconciled through critical evaluation of the study methodology. Conclusions : Keratinocyte hyperplasia with loss of cytokeratin markers co-localizes with inflammation comprising of dendritic Cells, T-lymphocytes and macrophages, which are known to play central roles in inflammation in HS. Primary follicular occlusion as a pathogenic paradigm and the principal driver of HS is unclear based upon the findings of this review. Inflammation as a primary driver of disease with secondary hyperkeratosis and follicular occlusion is more consistent with the current published data.
Publisher: F1000 Research Ltd
Date: 11-12-2018
DOI: 10.12688/F1000RESEARCH.17268.1
Abstract: Background: Hidradenitis suppurativa (HS) is a chronic inflammatory disease with significant morbidity and impact on quality of life. Our understanding of the pathophysiology is incomplete, impairing efforts to develop novel therapeutic targets. Immunohistochemistry studies have produced conflicting results and no systematic evaluation of study methods and results has been undertaken to date. Methods: This systematic review aimed to collate and describe all reports of immunohistochemical staining in HS. This systematic review was registered with PROSPERO and conducted in line with the PRISMA reporting guidelines. Potential bias was assessed using the NIH Criteria and antibodies used across various studies were tabulated and compared. Results : A total of 22 articles were identified describing results from 494 HS patients and 168 controls. 87 unique immunohistochemical targets were identified. The overall quality of studies was sub-optimal with staining intensity confounded by active treatment. Conflicting data was identified and able to be reconciled through critical evaluation of the study methodology. Conclusions : Keratinocyte hyperplasia with loss of cytokeratin markers co-localizes with inflammation comprising of dendritic Cells, T-lymphocytes and macrophages, which are known to play central roles in inflammation in HS. Primary follicular occlusion as a pathogenic paradigm and the principal driver of HS is not consistent with the findings of this review. Inflammation as a primary driver of disease with secondary hyperkeratosis and follicular occlusion is more consistent with the current published data.
Publisher: SAGE Publications
Date: 2019
Abstract: Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the skin, manifesting in chronic, recurrent painful pustules, nodules, boils and purulent draining abscesses. Our current understanding of the pathogenesis of the disease is incomplete. This review aims to identify available treatment options in HS and discuss the pharmacological mechanisms through which such agents function. Identifying common pathways may inform our understanding of the pathogenesis of HS as well as identify future therapeutic targets. The pharmacological mechanisms implicated in topical therapies, antibiotic, hormonal, systemic immunomodulatory and biologic therapies for HS are discussed. Significant differences exist between agents and implicated pathways in therapy for mild and severe disease. This is an expression of the possible dichotomy in inflammatory pathways (and treatment responses) in HS. Studies involving monoclonal antibodies provide the greatest insight into what these specific mechanisms may be. Their variable levels of clinical efficacy compared with placebo bolsters the suggestion that differential inflammatory pathways may be involved in different presentations and severity of disease. Nuclear factor kappa B (NF-κB), tumor necrosis factor (TNF)-α and other innate immune mechanisms are strongly represented in treatments which are effective in mild to moderate disease in the absence of scarring or draining fistulae, however complex feed-forward mechanisms in severe disease respond to interleukin (IL)-1 inhibition but are less likely to respond to innate immune inhibition (through NF-κB or TNF-α) alone. It is unclear whether IL-17 inhibition will parallel TNF-α or IL-1 inhibition in effect, however it is plausible that small molecule targets (Janus kinase1 and phosphodiesterase 4) may provide effective new strategies for treatment of HS.
Publisher: Elsevier BV
Date: 02-2021
Publisher: Wiley
Date: 10-2009
Publisher: Oxford University Press (OUP)
Date: 11-2020
DOI: 10.1111/BJD.19504
Publisher: Elsevier BV
Date: 08-2020
Publisher: Oxford University Press (OUP)
Date: 06-09-2202
DOI: 10.1111/BJD.19343
Publisher: Wiley
Date: 22-07-2015
DOI: 10.1111/AJD.12215
Publisher: Oxford University Press (OUP)
Date: 02-08-2020
DOI: 10.1111/BJD.19345
Publisher: Oxford University Press (OUP)
Date: 21-10-2023
DOI: 10.1093/BJD/LJAC060
Abstract: The utility of Strongyloidiasis screening in the setting of Dupilumab therapy is unknown. Our retrospective cohort study identifies a low prevalence of Strongyloidiasis with no cases of disseminated disease in the setting of Dupilumab therapy. Baseline IgE and Eosinophil levels were not associated with Strongyloidiasis and screening is likely of low utility.
Publisher: Elsevier BV
Date: 08-2023
Publisher: Elsevier BV
Date: 2022
Publisher: American Medical Association (AMA)
Date: 03-2022
Publisher: Elsevier BV
Date: 12-2020
Publisher: Elsevier BV
Date: 06-2018
Publisher: Wiley
Date: 20-05-2020
DOI: 10.1111/IJD.14960
Publisher: Oxford University Press (OUP)
Date: 15-02-2010
Publisher: Wiley
Date: 30-07-2015
DOI: 10.1111/IJD.12945
Abstract: The xanthodermatoses consist of a heterogeneous group of cutaneous disorders characterized by the macroscopic yellow hue seen on examination. This hue is attributable to the chemical structure of the accumulating substances within the skin or surrounding tissues. The most common culprits are lipids (cholesterol and triglycerides), elastin, and bilirubin. Exogenous sources of yellow pigment include yellow dyes (including hennas) and metal salts. This article will focus on recognition of these entities, classified in terms of morphology and the site of initial eruption, in order to support the recognition and diagnosis of these widely variable conditions.
Publisher: American Medical Association (AMA)
Date: 10-2013
DOI: 10.1001/JAMADERMATOL.2013.4972
Abstract: Quality-of-life (QOL) evaluation is an increasingly important outcome measure in dermatology, with disease-specific QOL instruments being the most sensitive to changes in disease status. To develop a QOL instrument specific to autoimmune bullous disease (AIBD). A comprehensive item generation process was used to build a 45-item pilot Autoimmune Bullous Disease Quality of Life (ABQOL) questionnaire, distributed to 70 patients with AIBD. Experts in bullous disease refined the pilot ABQOL before factor analysis was performed to yield the final ABQOL questionnaire of 17 questions. We evaluated validity and reliability across a range of indices. Australian dermatology outpatient clinics and private dermatology practices. PATIENTS AND EXPOSURE: Patients with a histological diagnosis of AIBD. The development of an AIBD-specific QOL instrument. Face and content validity were established through the comprehensive patient interview process and expert review. In terms of convergent validity, the ABQOL was found to have a moderate correlation with scores on the Dermatology Life Quality Index (R = 0.63) and the General Health subscale of the 36-Item Short Form Health Survey (R = 0.69 P = .009) and low correlation with the Pemphigus Disease Area Index (R = 0.42) and Autoimmune Bullous Disease Skin Disorder Intensity Score (R = 0.48). In terms of discriminant validity, the ABQOL was found to be more sensitive than the Dermatology Life Quality Index (P = .02). The ABQOL was also found to be a reliable instrument evaluated by internal consistency (Cronbach α coefficient, 0.84) and test-retest reliability (mean percentage variation, 0.92). The ABQOL has been shown to be a valid and reliable instrument that may serve as an end point in clinical trials. Future work should include incorporating patient weighting on questions to further increase content validity and translation of the measure to other languages. anzctr.org.au Identifier: ACTRN12612000750886.
Publisher: AMPCo
Date: 09-2015
DOI: 10.5694/MJA15.00098
Publisher: Oxford University Press (OUP)
Date: 02-2018
DOI: 10.1111/BJD.16162
Publisher: Cold Spring Harbor Laboratory
Date: 23-02-2023
DOI: 10.1101/2023.02.23.529664
Abstract: Hidradenitis Suppurativa is a chronic inflammatory disease of which the pathogenesis is incompletely understood. Dermal fibroblasts have been previously identified as a major source of inflammatory cytokines, however information pertaining to the characteristics of subpopulations of fibroblasts in HS remains unexplored. Using in silico-deconvolution of whole-tissue RNAseq, Nanostring gene expression panels and confirmatory immunohistochemistry we identified fibroblast subpopulations in HS tissue and their relationship to disease severity and lesion morphology. Gene signatures of SFRP2+ fibroblast subsets were increased in lesional tissue, with gene signatures of SFRP1+ fibroblast subsets decreased. SFRP2+ and CXCL12+ fibroblast numbers, measured by IHC, were increased in HS tissue, with greater numbers associated with epithelialized tunnels and Hurley Stage 3 disease. Pro-inflammatory CXCL12+ fibroblasts were also increased, with reductions in SFRP1+ fibroblasts compared to healthy controls. Evidence of Epithelial Mesenchymal Transition was seen via altered gene expression of SNAI2 and altered protein expression of ZEB1, TWIST1, Snail/Slug, E-Cadherin and N-Cadherin in HS lesional tissue. The greatest dysregulation of EMT associated proteins was seen in biopsies containing epithelialized tunnels. The use of the oral Spleen tyrosine Kinase inhibitor Fostamatinib significantly reduced expression of genes associated with chronic inflammation, fibroblast proliferation and migration suggesting a potential role for targeting fibroblast activity in HS.
Publisher: Cold Spring Harbor Laboratory
Date: 03-04-2023
DOI: 10.1101/2023.04.02.23287928
Abstract: Mast cells have traditionally been associated with allergic inflammatory responses however they play important roles in cutaneous innate immunity and wound healing. The Hidradenitis Suppurativa tissue transcriptome is associated with alterations in innate immunity and wound healing associated pathways, however the role of Mast cells in the disease is unexplored. We demonstrate that Mast cell associated gene expression (using whole tissue RNAseq) is upregulated, and in-silico cellular deconvolution identifies activated mast cells upregulated and resting mast cells downregulated in lesional tissue. Tryptase/Chymase positive Mast cells (identified using IHC) localize adjacent to epithelialised tunnels, fibrotic regions of the dermis and at perivascular sites associated with Neutrophil Extracellular Trap formation and TNF-alpha production. Treatment with Spleen Tyrosine Kinase antagonist (Fostamatinib) reduces the expression of mast cell associated gene transcripts, associated biochemical pathways, and number of tryptase/chymase positive mast cells in lesional hidradenitis suppurativa tissue. This data indicates that although Mast cells are not the most abundant cell type in Hidradenitis Suppurativa tissue, the dysregulation of mast cells is associated with B cell lasma cell inflammation, inflammatory epithelialized tunnels and epithelial budding. This provides an explanation as to the mixed inflammatory activation signature seen in HS, the correlation with dysregulated wound healing and potential pathways involved in the development of epithelialized tunnels.
Publisher: Springer Science and Business Media LLC
Date: 21-08-2019
DOI: 10.1038/S41598-019-48226-W
Abstract: Hidradenitis suppurativa (HS) is a chronic inflammatory disorder characterized by painful nodules, sinus tracts, and scars occurring predominantly in intertriginous regions. The prevalence of HS is currently 0.053–4%, with a predominance in African-American women and has been linked to low socioeconomic status. The majority of the reported literature is retrospective, population based, epidemiologic studies. In this regard, there is a need to establish a repository of biospecimens, which represent appropriate gender and racial demographics amongst HS patients. These efforts will diminish knowledge gaps in understanding the disease pathophysiology. Hence, we sought to outline a step-by-step protocol detailing how we established our HS biobank to facilitate the formation of other HS tissue banks. Equipping researchers with carefully detailed processes for collection of HS specimens would accelerate the accumulation of well-organized human biological material. Over time, the scientific community will have access to a broad range of HS tissue biospecimens, ultimately leading to more rigorous basic and translational research. Moreover, an improved understanding of the pathophysiology is necessary for the discovery of novel therapies for this debilitating disease. We aim to provide high impact translational research methodology for cutaneous biology research and foster multidisciplinary collaboration and advancement of our understanding of cutaneous diseases.
Publisher: Oxford University Press (OUP)
Date: 02-12-2019
DOI: 10.1111/BJD.17414
Publisher: Wiley
Date: 20-01-2022
DOI: 10.1002/DER2.113
Abstract: Hidradenitis suppurativa is a complex inflammatory skin disease with the molecular pathogenesis of disease incompletely understood. Recent observational and experimental insights into disease pathogenesis are challenging long‐held beliefs regarding the causes and mechanisms of disease. The most effective treatments to date are anti‐inflammatory in nature suggesting inflammation is the major driver of disease activity. This study critically evaluates the existing literature regarding the mechanisms of disease pathogenesis. Specifically, it questions the role of follicular occlusion as the central driver of disease activity and reframes hidradenitis suppurativa as a complex autoinflammatory and autoimmune disorder. Ongoing efforts to understand the mechanisms of disease will no doubt lead to more efficacious therapeutics to control this burdensome disabling disease.
Publisher: Oxford University Press (OUP)
Date: 03-10-2019
DOI: 10.1111/BJD.18468
Publisher: Wiley
Date: 28-01-2016
DOI: 10.1111/AJD.12287
Publisher: Oxford University Press (OUP)
Date: 23-04-2019
DOI: 10.1111/BJD.17934
Publisher: Wiley
Date: 2019
DOI: 10.1111/EXD.13849
Publisher: AMPCo
Date: 02-2016
DOI: 10.5694/MJA15.00802
Publisher: Wiley
Date: 15-02-2022
DOI: 10.1111/EXD.14534
Abstract: Pyoderma gangrenosum is a painful recurrent ulcerative neutrophilic dermatosis in which the pathogenesis is incompletely defined. Current evidence suggests that PG is associated with dysregulation of components of both the innate and adaptive immune system with dysregulation of neutrophil function and contribution of the Th17 immune axis. PG can be present in numerous heterogeneous clinical presentations and be associated with multiple inflammatory conditions including rheumatoid arthritis, inflammatory bowel disease and hidradenitis suppurativa. However, no critical evaluation of the observed molecular characteristics in PG studies in association with their clinical findings has been assessed. Additionally, emerging evidence suggests a potential role for other cell types and immune pathways including B cells, macrophages, autoantibodies and the complement system in PG, although these have not yet been integrated into the pathogenesis of disease. This systematic review aims to critically evaluate the current molecular observations regarding the pathogenesis of PG and discuss associations with clinical characteristics as well as the evidence supporting novel cell types and immune pathways in PG.
Publisher: Elsevier BV
Date: 11-2020
Publisher: F1000 Research Ltd
Date: 13-12-2018
DOI: 10.12688/F1000RESEARCH.17267.1
Abstract: Background: The pathogenesis of hidradenitis suppurativa (HS) remains unclear. In order to develop effective treatment strategies, a deeper understanding of pathophysiology is needed. This is impaired by multiple small studies with inconsistent methodologies and the impact of co-occurring pro-inflammatory conditions such as smoking and obesity. Methods: This systematic review aimed to collate all published reports of cytokine studies in tissue, blood, serum and exudate. It was registered with PROSPERO (Registration number CRD42018104664) performed in line with the PRISMA checklist. Results: 19 studies were identified comprising 564 in idual HS patients and 198 control patients examining 81 discrete cytokines. Methodology was highly varied and the quality of studies was generally low. There was a large degree of variance between the measured levels of cytokines. 78.2% of cytokines demonstrated heterogeneity by the chi-squared test for homogeneity and hence meta-analysis was not deemed appropriate. However, a strong and significant IL-17 signalling component was identified. Conclusions: Cytokines consistently elevated in lesional, peri-lesional and unaffected tissue are identified and discussed. Areas for further investigation include the role of dendritic cells in HS the contribution of obesity, smoking, diabetes and the microbiome to cytokine profiles in HS and examining the natural history of this disease through longitudinal measurements of cytokines over time.
Publisher: Wiley
Date: 31-07-2023
DOI: 10.1111/EXD.14894
Abstract: Mast cells have traditionally been associated with allergic inflammatory responses however, they play important roles in cutaneous innate immunity and wound healing. The Hidradenitis Suppurativa tissue transcriptome is associated with alterations in innate immunity and wound healing‐associated pathways however, the role of mast cells in the disease is unexplored. We demonstrate that mast cell‐associated gene expression (using whole tissue RNAseq) is upregulated, and in‐silico cellular deconvolution identifies activated mast cells upregulated and resting mast cells downregulated in lesional tissue. Tryptase/Chymase positive mast cells (identified using IHC) localize adjacent to epithelialized tunnels, fibrotic regions of the dermis and at perivascular sites associated with Neutrophil Extracellular Trap formation and TNF‐alpha production. Treatment with Spleen Tyrosine Kinase antagonist (Fostamatinib) reduces the expression of mast cell‐associated gene transcripts, associated biochemical pathways and the number of tryptase/chymase positive mast cells in lesional hidradenitis suppurativa tissue. This data indicates that although mast cells are not the most abundant cell type in Hidradenitis Suppurativa tissue, the dysregulation of mast cells is paralleled with B cell lasma cell inflammation, inflammatory epithelialized tunnels and epithelial budding. This provides an explanation as to the mixed inflammatory activation signature seen in HS, the correlation with dysregulated wound healing and potential pathways involved in the development of epithelialized tunnels.
Publisher: Elsevier BV
Date: 10-2011
DOI: 10.1016/J.DET.2011.06.016
Abstract: Paraneoplastic pemphigus (PNP) or paraneoplastic autoimmune multiorgan syndrome (PAMS) is a life-threatening autoimmune blistering disease commonly associated with lymphoproliferative neoplasms. This article focuses on current management strategies in PNP/PAMS, and reported instances of their treatment successes and failures. Due to the rarity of the condition and the high rates of treatment failure, no randomized control trials exist to guide the evidence-based treatment of this condition all evidence to date on the efficacy of therapeutic modalities has been gained from in idual case reports, small case series, and expert recommendations.
Publisher: Elsevier BV
Date: 08-2021
Publisher: Wiley
Date: 04-2019
DOI: 10.1111/JDV.15572
Publisher: Oxford University Press (OUP)
Date: 25-11-2020
DOI: 10.1111/BJD.18593
Publisher: Wiley
Date: 17-03-2020
DOI: 10.1111/EXD.14092
Publisher: F1000 Research Ltd
Date: 03-01-0025
DOI: 10.12688/F1000RESEARCH.17664.1
Abstract: Background: Cutaneous langerhans cell histiocytosis (LCH) is a rare disorder characterized by proliferation of cells with phenotypical characteristics of Langerhans cells. Although some cases spontaneously resolve, no consistent variables have been identified that predict which cases will manifest with systemic disease later in childhood. Methods: A systematic review (Pubmed, Embase, Cochrane database and all published abstracts from 1946-2018) was undertaken to collate all reported cases of cutaneous LCH in the international literature. This study was registered with PROSPERO ( CRD42016051952 ). Descriptive statistics and correlation analyses were undertaken. Bias was analyzed according to GRADE criteria. Results: A total of 83 articles encompassing 128 cases of cutaneous LCH were identified. Multiple lesions were weakly associated with an increased length of survival (R=0.304 (p .05)), Worse prognosis was associated with internal organ involvement with a statistically significant chi squared statistic (χ 2 =14.96, 2DF p .001) and an elevated odds ratio ((OR)= 12.30 95% CI=2.67-56.74). Vesicular lesions (OR=10.8 95% CI=2.83-41.26), but not ulceration (OR=0.53 95% CI 0.12-2.05) were associated with greater risk of mortality. Conclusions: Congenital and neonatal LCH most commonly presents as multiple lesions in multiple anatomical sites at birth. Significant differences, including the associations of mortality with lesion morphology and number were seen in this neonatal cohort compared to overall pediatric LCH. These findings require validation in a large prospective cohort.
Publisher: Elsevier BV
Date: 09-2021
Publisher: Springer Berlin Heidelberg
Date: 2015
No related grants have been discovered for John Frew.