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Rosacea, a common chronic, predominantly centro‐facial dermatosis, has previously been classified into distinct subtypes with a range of morphological signs that overlap with other inflammatory skin disorders. Recently, there has been a move towards diagnosis of clinical phenotypes, largely driven by a better understanding of the pathophysiology of rosacea and clinical trial endpoints. Despite this, treatment remains a challenge. The Australasian Medical Dermatology Group held a Rosacea workshop in November 2022 to develop a practical narrative. Eighteen recommendations were agreed upon using a modified eDelphi process in the first round, including a rosacea treatment algorithm. [ABSTRACT FROM AUTHOR]

This article emphasizes the need for concrete descriptions of supervision to promote diversity-competent group work and presents an application of the supervision of group work model (SGW) to this end. The SGW, a supervision model adapted from the discrimination model, is uniquely suited for promoting diversity competence in group work, since it allows integration of awareness of self, awareness of client's worldview, and diversity-appropriate interventions with the individual, interpersonal, and group-as-a-whole dimensions of group work. Strategies to prepare for and conduct supervision, and a case analysis that highlights key issues for diversity-competent group work supervision and illustrates a potential supervision process, are presented. Implications for supervisors, group workers, and future research are also provided. [ABSTRACT FROM AUTHOR]

Hidradenitis Suppurativa is a burdensome inflammatory skin disease with significant quality of life impact. These management guidelines were developed to direct appropriate clinical management in the Australasian context. A systematic review was used for the basis of the consensus guidelines. Thirteen clinical experts were involved in a modified Delphi consensus process to develop the guidelines and treatment algorithms. Overall management strategies include appropriate severity assessment of disease and comorbidities, multimodal therapy with systemic and local treatments, and evidence-based progression along the therapeutic ladder in the event of inadequate response. Sequential monotherapy with antibiotics and/or single agent therapy is discouraged and aggressive treatment of moderate to severe disease to capture the window of opportunity is highly emphasised. Specific considerations in the setting of disease comorbidities, pregnancy and breastfeeding are also addressed. Overall, the complex nature of HS requires a complex and multimodal therapeutic response with medical, physical and surgical therapies to achieve best patient outcomes., (© 2024 The Author(s). Australasian Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Australasian College of Dermatologists.)

Background: Hidradenitis suppurativa (HS) is a debilitating chronic inflammatory disease with significant impact upon quality of life. Generic quality-of-life measures suffer from decreased face validity and content validity, leading to the development of disease-specific quality-of-life measures such as the Hidradenitis Suppurativa Quality of Life (HiSQOL) outcome measure. The aim of this study was to validate the use of the HiSQOL in the Australian population and evaluate the quality-of-life impact in HS patients in Australia., Methods: A total of 301 patients were recruited and consented to be involved in this study. All participants were invited to complete the HiSQOL questionnaire along with basic demographic and disease information, the DLQI and HADS anxiety and depression scale. Participants were then asked to repeat the questionnaires 14 days later to assess test-retest reliability., Results: The mean HiSQOL score was 46.5 out of a possible total score of 76 (SD = 24.2) indicating a very large impact on quality of life. Based upon the published validity bands this corresponds to a very large impact on quality of life. Validation statistics indicated a high degree of internal consistency (Cronbach's alpha = 0.956) with expected levels of convergent validity and excellent test-retest reliability (p = 0.95). Multiple regression analysis indicated individuals with a younger age of onset and positive family history had significantly greater quality-of-life impact as measured by the HiSQOL., Conclusions: The HiSQOL is a valid, reliable measure for assessing the quality-of-life impact of HS. Significant factors influencing quality of life include age of onset and family history. Longitudinal measurements will enable evaluation of the impact of therapy upon QOL in the Australian context., (© 2024 Australasian College of Dermatologists.)

Introduction: Alport syndrome (AS) is a hereditary type IV collagen disease. It starts shortly after birth, without clinical symptoms, and progresses to end-stage kidney disease early in life. The earlier therapy starts, the more effectively end-stage kidney disease can be delayed. Clearly then, to ensure preemptive therapy, early diagnosis is an essential prerequisite., Methods: To provide early diagnosis, we searched for protein biomarkers (BMs) by mass spectrometry in dogs with AS stage 0. At this very early stage, we identified 74 candidate BMs. Of these, using commercial enzyme-linked immunosorbent assays (ELISAs), we evaluated 27 in dogs and 28 in children, 50 with AS and 104 healthy controls., Results: Most BMs from blood appeared as fractions of multiple variants of the same protein, as shown by their chromatographic distribution before mass spectrometry. Blood samples showed only minor differences because ELISAs rarely detect disease-specific variants. However, in urine , several proteins, individually or in combination, were promising indicators of very early and preclinical kidney injury. The BMs with the highest sensitivity and specificity were collagen type XIII, hyaluronan binding protein 2 (HABP2), and complement C4 binding protein (C4BP)., Conclusion: We generated very strong candidate BMs by our approach of first examining preclinical AS in dogs and then validating these BMs in children at early stages of disease. These BMs might serve for screening purposes for AS before the onset of kidney damage and therefore allow preemptive therapy., (© 2023 International Society of Nephrology. Published by Elsevier Inc.)

Understanding the role of the immune microenvironment in modulating intratumor heterogeneity is essential for effective cancer therapies. Using multicolor lineage tracing in genetically engineered mouse models and single-cell transcriptomics, we show that slowly progressing tumors contain a multiclonal landscape of relatively homogeneous subpopulations within a well-organized tumor microenvironment. In more advanced and aggressive tumors, however, the multiclonal landscape develops into competing dominant and minor clones accompanied by a disordered microenvironment. We demonstrate that this dominant/minor landscape is associated with differential immunoediting, in which minor clones are marked by an increased expression of IFNγ-response genes and the T cell-activating chemokines Cxcl9 and Cxcl11. Furthermore, immunomodulation of the IFNγ pathway can rescue minor clones from elimination. Notably, the immune-specific gene signature of minor clones exhibits a prognostic value for biochemical recurrence-free survival in human prostate cancer. These findings suggest new immunotherapy approaches for modulating clonal fitness and tumor progression in prostate cancer., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Col4a3 -/- Alport mice serve as an animal model for renal fibrosis. MicroRNA-21 (miR-21) expression has been shown to be increased in the kidneys of Alport syndrome patients. Here, we investigated the nephroprotective effects of Lademirsen anti-miR-21 therapy. We used a fast-progressing Col4a3 -/- mouse model with a 129/SvJ background and an intermediate-progressing F1 hybrid mouse model with a mixed genetic background, with angiotensin-converting enzyme inhibitor (ACEi) monotherapy in combination with anti-miR-21 therapy. In the fast-progressing model, the anti miR-21 and ACEi therapies showed an additive effect in the reduction in fibrosis, the decline of proteinuria, the preservation of kidney function and increased survival. In the intermediate-progressing F1 model, the anti-miR-21 and ACEi therapies individually improved kidney pathology. Both also improved kidney function and survival; however, the combination showed a significant additive effect, particularly for survival. RNA sequencing (RNA-seq) gene expression profiling revealed that the anti-miR-21 and ACEi therapies modulate several common pathways. However, anti-miR-21 was particularly effective at normalizing the expression profiles of the genes involved in renal tubulointerstitial injury pathways. In conclusion, significant additive effects were detected for the combination of anti-miR-21 and ACEi therapies on kidney function, pathology and survival in Alport mouse models, as well as a strong differential effect of anti-miR-21 on the renal expression of fibrotic factors. These results support the addition of anti-miR-21 to the current standard of care (ACEi) in ongoing clinical trials in patients with Alport syndrome.

Background: Factors beyond the Psoriasis Area and Severity Index (PASI) contribute to disease severity in psoriasis and potentially affect treatment responses., Objective: This subset analysis of data from two phase 3 clinical studies assessed baseline parameters in patients with different degrees of psoriasis severity in order to determine treatment responses to ixekizumab and safety outcomes., Methods: This study used integrated data from the UNCOVER-2 and -3 trials involving 2709 patients with chronic plaque psoriasis to assess the efficacy and safety of ixekizumab in three subgroups of patients, defined by PASI > 15 (group 1), PASI > 15 and history of ≥3 non-biologic systemic therapies (group 2), or PASI = 12-15 (group 3)., Results: In groups 1 and 2, additional baseline features were identified that could influence treatment responses, including age at disease onset, Dermatology Life Quality Index, and work productivity. Irrespective of subgroup, ixekizumab demonstrated high PASI responses at weeks 12 and 60, which were evident as early as week 2. Adverse events did not differ across subgroups., Conclusion: Our data support the efficacy, early onset of action, and maintained response of ixekizumab as observed in previous trials, and highlight the complexity of comprehensively defining disease severity in psoriasis.

Introduction: The aim of this work is to perform a systematic review and meta-analysis of anti-tumor necrosis factor (anti-TNF) and anti-interleukin-17 (anti-IL-17) trials for spondyloarthritis, psoriatic arthritis, and psoriasis comparing rates of inflammatory bowel disease (IBD) events compared to placebo., Methods: MEDLINE, EMBASE, and The Cochrane Library were searched for double-blind, randomized placebo-controlled anti-TNF and anti-IL-17 trials of included diseases. Inflammatory bowel disease events from the RCT period were pooled and meta-analyzed using statistical methods suitable for low-event-rate meta-analysis (Peto's, Mantel-Haenszel, hypergeometric-normal model, and Shuster-Guo-Skyler). When observed data were insufficient, we performed an exploratory sensitivity analysis to compare methods., Results: We identified 9551 original papers, and included 96 publications: 65 anti-TNF and 31 anti-IL-17 trials, containing 21 new and 12 flare IBD events in 28,209 participants. New IBD on anti-IL-17 occurred 0.23/100 patient-years (PY) in psoriasis, 0.61/100 PY in PsA and 1.63/100 PY in spondyloarthritis, rates similar to observational cohorts, and less commonly on anti-TNF (0/100 PY, 0/100 PY, 0.32/100 PY, respectively). No evidence of difference between groups was found, with wide CI from many pooled counts of zero, especially in placebo arms., Conclusions: IBD events were rare, occurring at rates similar to biologic-naive groups. We could not find statistically significant differences in risk of new or recurrent IBD between treatment and control groups using selected meta-analytical methods for low event rate scenarios. Meta-analyses of this topic require more IBD events, ideally without pooling heterogeneous groups. Larger, thoroughly reported trials with systematic and detailed safety reporting are required to improve risk estimation and to make accurate inferences., (© 2021. The Author(s).)

Background: Autosomal recessive Alport syndrome (ARAS) is caused by pathogenic variants in both alleles of either COL4A3 or COL4A4 genes. Reports on ARAS are rare due to small patient numbers and there are no reports on renin-angiotensin-aldosterone system (RAAS) inhibition therapy in ARAS., Methods: Retrospective study in 101 patients with ARAS from Chinese Registry Database of Hereditary Kidney Diseases and European Alport Registry. Genotype-phenotype correlations and nephroprotective effects of RAAS inhibition in ARAS were evaluated., Results: Median age was 15 years (range 1.5-46 years). Twelve patients progressed to stage 5 chronic kidney disease (CKD5) at median age 20.5 years. Patients without missense variants had both higher prevalence and earlier onset age of hearing loss, nephrotic-range proteinuria, more rapid decline of eGFR, and earlier onset age of CKD5 compared to patients with 1 or 2 missense variants. Most patients (79/101, 78%) currently are treated with RAAS inhibitors; median age at therapy initiation was 10 years and mean duration 6.5 ± 6.0 years. Median age at CKD5 for untreated patients was 24 years. RAAS inhibition therapy delayed CKD5 onset in those with impaired kidney function (T-III) to median age 35 years, but is undefined in treated patients with proteinuria (T-II) due to low number of events. No treated patients with microalbuminuria (T-I) progressed to CKD5. ARAS patients with 1 or 2 missense variants showed better response to treatment than patients with non-missense-variants., Conclusions: Our study provides the first evidence for early use of RAAS inhibition therapy in patients with ARAS. Furthermore, genotype in ARAS correlates with response to therapy in favor of missense variants., (© 2021. The Author(s).)

Angiotensin-converting enzyme inhibitors (ACEi) delay progression of the inherited renal disease Alport syndrome. However, the effect of ACEis weakens gradually due to an "aldosterone escape". Here, we investigate if an aldosterone antagonist can counteract loss of ACEi-efficacy. COL4A3-/- mice were treated with ramipril (ACEi), starting at 4.5 weeks of age, and spironolactone was added at 7 weeks of age. Lifespan until renal failure, as well as kidney function parameters, were investigated. Dual therapy decreased proteinuria levels compared to ACEi monotherapy. Matrix accumulation, as well as tubulointerstitial and glomerular scar-tissue formation, were significantly reduced compared to untreated mice and ACEi-monotherapy at 75 and 100 days. Lifespan in dual treated mice was extended compared to untreated mice. However, lifespan was not superior to ACEi monotherapy-despite improved urea-nitrogen levels in the dual therapy group. In conclusion, adding the aldosterone-antagonist spironolactone to ACEi therapy further improved kidney function and reduced proteinuria and fibrosis. However, survival was not improved further, possibly due to premature death from side effects of dual therapy such as hyperkalemia. Thus, dual therapy could offer an effective therapy option for Alport syndrome patients with progressive proteinuria. However, the risks of adverse events require close monitoring.

Chronic hand/foot eczemas are common, but treatment is often challenging, with widespread dissatisfaction over current available options. Detailed history is important, particularly with regard to potential exposure to irritants and allergens. Patch testing should be regarded as a standard investigation. Individual treatment outcomes and targets, including systemic therapy, should be discussed early with patients, restoring function being the primary goal, with clearing the skin a secondary outcome. Each new treatment, where appropriate, should be considered additive or overlapping to any previous therapy. Management extends beyond mere pharmacological or physical treatment, and requires an encompassing approach including removal or avoidance of causative factors, behavioural changes and social support. To date, there is little evidence to guide sequences or combinations of therapies. Moderately symptomatic patients (e.g. DLQI ≥ 10) should be started on a potent/super-potent topical corticosteroid applied once or twice per day for 4 weeks, with tapering to twice weekly application. If response is inadequate, consider phototherapy, and then a 12-week trial of a retinoid (alitretinoin or acitretin). Second line systemic treatments include methotrexate, ciclosporin and azathioprine. For patients presenting with severe symptomatic disease (DLQI ≥ 15), consider predniso(lo)ne 0.5-1.0 mg/kg/day (or ciclosporin 3 - 5 mg/kg/day) for 4-6 weeks with tapering, and then treating as for moderate disease as above. In non-responders, botulinum toxin and/or iontophoresis, if associated with hyperhidrosis, may sometimes help. Some patients only respond to long-term systemic corticosteroids. The data on sequencing of newer agents, such as dupilumab or JAK inhibitors, are immature., (© 2020 The Australasian College of Dermatologists.)

Background/objectives: The prevalence of atopic dermatitis (AD) has increased significantly in industrialised countries in recent decades but data about the incidence or prevalence of AD in Australia are sparse. We aimed to determine the prevalence and incidence of AD among patients seen in Australian general practice and the use of specified medicines., Methods: This was a cross-sectional study of 2.1 million patients attending 494 general practices in the MedicineInsight program from 1 January 2017 to 31 December 2018. We assessed the prevalence (lifetime and current), incidence, management and severity of AD., Results: The lifetime (ever diagnosed) prevalence of AD in this general practice population was 16.4% and was greater in females (17.3%) than males (15.3%). One in five patients with AD were classified as having moderate-to-severe disease. Prevalence over the last two years was 6.3%. The incidence of AD in 2018 was 2.0% and was greater in females (2.2%) and for patients aged 0-4 years (3.9%). Patients with AD had an increased risk of insomnia, anxiety and depression, compared to those with no recorded AD. For AD patients, topical corticosteroids were the most commonly prescribed AD medication (36.5%) and topical calcineurin inhibitors the least (0.1%), with systemic corticosteroids (15.6%) more commonly prescribed than other immunosuppressants (0.9%)., Conclusions: Our findings provide important insights into the epidemiology of AD and its management in Australian general practice. This information is likely to be useful in planning effective interventions to support GPs in the optimal management of patients with AD., (© 2020 The Authors. Australasian Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Australasian College of Dermatologists.)

Background/objectives: Atopic dermatitis (AD) has significant negative impact on health-related quality of life, mood, sleep, work productivity and everyday activities. Research into the use of new drugs in the management of AD continues to develop, and international updates and recommendations have been published. However, questions remain in the Australian setting. This consensus aims to provide evidence-based insights and practical advice on the management of adult AD in Australia., Methods: A panel (five dermatologists and one clinical immunologist) met to review the literature, critically examine clinical questions of relevance to Australian healthcare practitioners and develop a series of recommendation statements. A consensus panel, comprising the initial panel plus nine additional members, used a 2-round Delphi voting process to determine a set of final guidance statements., Consensus: ≥75% agreement in the range 7-9., Results: Round 1 voting comprised 66 guidance statements. Of these, consensus was reached on 26, which were retained, and five were removed. The remainder (35) were modified and one new guidance statement was added for inclusion in round 2 voting. After round 2, consensus was reached on 35, which were retained, and one was removed (considered redundant). The 61 guidance statements upon which consensus was reached were then used to support a series of core consensus recommendations and a management flow chart., Conclusions: Expert consensus recommendations providing practical guidance of clinical relevance to specialists and primary care physicians in Australia have been developed. Dissemination of this guidance and evaluation of its impact on patient outcomes remain to be undertaken., (© 2019 The Australasian College of Dermatologists.)

The level of faecal contamination in urban public spaces depends on the behaviour of dogs's owners as well as on dog abundance. The aims of the present study were to explore patterns of the relative abundance of dogs, the canine faecal contamination, the behaviour of owners and dog walkers towards their pets, and their relationship with human demographic/economic variables in Buenos Aires city. We carried out a cross sectional study that included 67 randomly selected sampling sites (street corners). Each sampling site was evaluated one only time by two trained students under our supervision and all sighted dogs between 7 and 11 a.m. in both sidewalks of each corner were counted (spring 2013, 23 days of sampling). Data about dogs and people were obtained by using a standardized questionnaire and by direct observation. Feces censuses in 242 sidewalks were carried out. The sidewalks were randomly selected and its characteristics were registered (i.e. number of shops, trees). GIS was loaded with the city´s cartography and the values for nine variables used as demographic/economic indicators were obtained disaggregated by demographic units (National Census). Generalized linear models were used to identify the environmental and demographic variables related to the number of dogs sighted per site and feces per sidewalk. Explanatory variables per site included human density, number of inhabitants, households, precarious housing, proportion of children, maximum educational level and drinking water provision. For the sidewalks number of shops, trees, tree pits, broken sectors and total length were added. Also, variables regarding dog's owners and dog walkers behaviour were compared. A total of 1193 dog's owners, 234 dog walkers and 2835 dogs were sighted. The number of observed pets and that of people sighted with dogs showed a positive relationship with the economic level and the human density. The stool number per sidewalk increased with the higher number of broken sectors, higher number of tree pits per meter of sidewalk and the lower number of shops on it. The stool number per sidewalk was lower when 40% or more people with dogs carried waste bag to clean dogs' feces. Our results indicate that dog walkers compared to owners showed different behavioural patterns towards the pets (bag to remove dog's fouling, leash use, use of the green spaces, etc)., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The Australasian Psoriasis Collaboration has developed a clinical practice narrative with respect to the relationship between psoriasis, its treatment and infection. The cutaneous microbiome of patients with psoriasis is different to those without psoriasis, although the significance of this is unclear. Whilst a wide range of microorganisms has been associated with psoriasis (including β-haemolytic streptococci, Staphylococcus aureus, Porphyromonas gingivalis, Candida albicans, Chlamydia psittaci, human immunodeficiency virus and hepatitis C virus), there is limited evidence that antimicrobial therapy is of direct benefit in preventing flares of psoriasis. Psoriasis is independently associated with an increased risk of serious infection, but the absolute risk is low. The risk of serious infections is further increased with immune-modulatory treatments. The decision whether to, and when to, stop or resume immune-modulatory treatment after a serious infection has occurred depends on risk assessment for that patient, taking into account the infection being treated, the risk of recurrent infection, any interventions that can modify the risk and the need for psoriasis control. Live vaccines (e.g. MMR, varicella, zoster and yellow fever) are generally contraindicated in patients with psoriasis on immune-modulatory agents, but this depends on the degree of immune suppression and individual risk factors. Wound healing in psoriasis is normal. Treatment with infliximab, adalimumab, etanercept, methotrexate and ciclosporin can safely be continued through low-risk surgical procedures. For moderate- and high-risk surgeries, a case-by-case approach should be taken based on the patient's individual risk factors and comorbidities., (© 2018 The Australasian College of Dermatologists.)

Background: Hidradenitis Suppurativa (HS) is a painful, chronic inflammatory skin disease. Global estimates of prevalence vary between 0.03% and 4% of the population. Our main aim was to determine HS prevalence in the Australian adult population focussing on the demographics, management pathways and diagnosis rate of individuals living with HS., Methods: In this population-based cross-sectional study, 17,050 individuals representative of the Australian adult population were asked through face-to-face household interviews to answer a previously validated HS screening questionnaire with high diagnostic power. Individuals who screened positive were asked additional questions, including previous diagnosis of HS and number/type of physicians consulted regarding their condition., Results: 11,433 Australian residents answered the HS questionnaire, 88 screening positive for HS (0.77%; 95% CI 0.62-0.95). Considering the previously reported sensitivity (0.97) and positive predictive value (0.85) of the screening questionnaire, HS prevalence was estimated to be 0.67% (95% CI 0.53%-0.84%). 6 of 88 suspected HS individuals reported a pre-existing HS diagnosis (6.8%; 95% CI 3.2%-14.1%). 25.6% of the undiagnosed individuals suspected of having HS had not seen any clinicians regarding their boils; the remaining ones had consulted General Practitioners (96.7%), and clinicians from different specialties. Comparisons of individuals who screened positive for HS versus those who screened negative demonstrated statistically significant differences in gender (p = 0.0046), age (p<0.0001), BMI (p = 0.0307), smoking status (p<0.0001), employment status (p<0.0001) and income (p = 0.0321)., Conclusions: The prevalence of HS in Australia was estimated to be 0.67% (95% CI 0.53%-0.84%). The diagnosis rate amongst the suspected HS cases was low, which appeared to be due to a combination of patients not seeking help and decentralization of care. Individuals suspected of having HS were more likely to be females, young, obese, smokers, unemployed or at home duties and having lower annual personal income in comparison with individuals not suspected of having HS., Competing Interests: AbbVie Pty Ltd funded the research for these studies and participated in the studies design; studies research; analysis and interpretation of data; and writing, reviewing and approving of this publication. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials. M Calao, JL Wilson, A Watts receive a salary as employees of AbbVie and may also receive AbbVie stock and/or stock grants. D Rubel is principal investigator for the following HS studies: M11-810 and M12-555, HS registry H13-147, HS validation study 10610, and HS epidemiology study 10756, as well as M13-674 Adalimumab nail psoriasis study; and has served on the Advisory Boards for Abbvie, Eli Lilly, Celgene, Galderma, GlaxoSmithKline, Janssen, Leo Pharma, Novartis, and Sanofi. L Spelman has served on the advisory Boards for Abbvie, Eli Lilly, Novartis and Sanofi; and undertakes sponsored clinical research for AbbVie, Amgen, Ascend Biopharmaceuticals, Australian Wool Innovation Limited, Celgene, Dermira, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, Leo Pharma, Merck, Novartis, Phosphagenics, Regeneron, and has received sponsored travel from AbbVie, Novartis, and Janssen- Cilag. GB Jemec disclosures are as follows: AbbVie: Adboard, consultant, investigator, speaker, unrestricted grant. Coloplast: Consultant, speaker. Leo pharma: Consultant, investigator, speaker, unrestricted grant. Galderma: Speaker. Janssen-Pharma: Adboard MSD: Adboard. Novartis: Adboard, consultant, investigator, unrestricted grant. Regeneron: Investigator. UCB: Consultant and investigator. InflaRX: Consultant and investigator. L Billot is an employee of The George Institute for Global Health which has received payment from AbbVie for the conduct and analysis of the prevalence study.