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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.

Pyoderma Gangrenosum is a severe ulcerative disease with a great need for novel therapies. A major barrier to the development of novel therapies is a lack of understanding of disease pathogenesis. We present the results of a proof-of-concept open label clinical trial of IL-23p19 antagonism with Tildrakizumab ion Pyoderma Gangrenosum. Gene expression analysis identified pro-inflammatory genes associated with interferon responses and dendritic cell activity including IFI27, XBP1, SAA1 LGALS3 and STAT3 significantly downregulated in lesional tissue after 12 weeks of therapy. Immunohistochemistry confirmed reduction in IL-17A and IL-17 F positive cells as well as reduction in TNF-a, C5a and IL-1B positive cells in week 12 samples compared to baseline. Significant reduction in serum inflammation was observed via serum proteomics, with IL-8, IL-6, and CASP-8 levels reduced comparable to healthy controls at Week 12. Clinical outcomes demonstrated significant reduction in ulcer size, pain, itch and quality of life outcomes in line with the molecular findings. Differential expression of key inflammatory cytokines such as IL-8, CXCL5, PD-L1, SPP1 and MMP1 were observed in tissue and serum when stratified by clinical responders and non-responders. This data provides insights into the clinical relevance of alterations in molecular markers in pyoderma gangrenosum and the potential for the identification of clinically relevant biomarkers of disease activity., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background/objectives: Caucasian and Asian patients with hidradenitis suppurativa demonstrate significant differences with regard to age, gender and body mass index. Demographic characteristics are known to influence the efficacy and drug survival of hidradenitis suppurativa therapeutics including biologic therapies. What remains unknown is the impact of ethnicity upon the efficacy of therapeutics once demographic and disease characteristics have been taken into account. This is an important question given the expansion of biologic therapies for HS into the global patient community., Methods: We assessed 170 patients from a single HS specialist centre in Australia stratified by patient-identified ethnicity including those identifying as either Caucasian or Asian., Results: Asian patients demonstrated lower BMI, higher rates of smoking and greater odds of Hurley stage 3 disease with tunnels than Caucasian patients in line with the reported literature. There was no significant difference between percentage of individuals achieving HiSCR50 or IHS4-55 at Week 16. Significant differences were seen in median time to secondary loss of response, and Kaplan-Meier curve analysis showed a significant difference between curves when stratified by patient-reported ethnicity. Cox regression analysis demonstrated after accounting for age, gender, BMI, smoking and Hurley stage, the significance of ethnicity in influencing time to secondary loss of response disappears., Conclusions: Caucasian or Asian ethnicity does not influence response to adalimumab treatment on patients with hidradenitis suppurativa., (© 2024 The Author(s). Australasian Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Australasian College of Dermatologists.)

Background/objectives: Surgical deroofing is an essential part of ongoing management of Hidradenitis Suppurativa, including persistent lesions non-responsive to medical therapy. The variables associated with delayed wound healing after surgical deroofing are contradictory within the literature due to the inclusion of heterogeneous surgical intervention methods. We aimed to assess the predictors of time to wound healing after surgical deroofing in HS., Methods: Patients who underwent in-office surgical deroofing between 2020 and 2024 at a single tertiary HS referral centre were included in analysis. Demographic, disease and blood variables were collected as per standard of care. Statistical analysis was performed using univariate correlation, with multiple regression performed to explore the interactions between variables and identify variables predictive of time to wound healing., Results: A total of 270 individuals were included in the analysis. The median time to wound healing was 9.6 weeks with a range from 4 to 22 weeks. Kaplan-Meier curves demonstrated significant differences with the log rank test when comparing biologic use versus no use, normal versus abnormal CRP and normal versus abnormal haemoglobin. Cox regression analysis identified biologic use with a significant hazard ratio compared to no biologic therapy (HR = 2.512, p < 0.0001) along with baseline CRP (HR = 0.968, p < 0.0001) and baseline haemoglobin (HR = 1.052, p < 0.001)., Conclusions: Time to wound healing after in-office deroofing can be decreased with prior biologic therapy and markers of systemic inflammation in blood are also significantly associated with delays in healing. This correlates well with the existing literature promoting concurrent medical and surgical therapy to improve patient outcomes in HS., (© 2024 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.)

Competing Interests: The authors made the following disclosures: J.W.F. has conducted advisory work for Janssen, Boehringer-Ingelheim, Pfizer, Kyowa Kirin, LEO Pharma, Regeneron, Chemocentryx, Abbvie, Azora, Novartis, and UCB, participated in trials for Pfizer, UCB, Boehringer-Ingelheim, Eli Lilly, CSL, and Azora, and received research support from Ortho Dermatologics, Sun Pharma, LEO Pharma, UCB, and La Roche Posay. The remaining authors have no conflicts of interest to disclose.

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a considerable disease burden. Existing treatment options are limited and often suboptimal; a high unmet need exists for effective targeted therapies., Objectives: To explore the effects of spesolimab treatment in patients with HS., Methods: This randomized double-blind placebo-controlled proof-of-clinical-concept (PoCC) study was conducted at 25 centres across 12 countries from 3 May 2021 to 21 April 2022. Patients had moderate-to-severe HS for ≥ 1 year before enrolment. Patients were randomized (2 : 1) to receive a loading dose of 3600-mg intravenous spesolimab (1200 mg at weeks 0, 1 and 2) or matching placebo, followed by maintenance with either 1200-mg subcutaneous spesolimab every 2 weeks from weeks 4 to 10 or matching placebo. The primary endpoint was the percentage change from baseline in total abscess and inflammatory nodule (AN) count at week 12. Secondary endpoints were the absolute change from baseline in the International Hidradenitis Suppurativa Severity Score System (IHS4), percentage change from baseline in draining tunnel (dT) count, the proportion of patients achieving a dT count of 0, absolute change from baseline in the revised Hidradenitis Suppurativa Area and Severity Index (HASI-R), the proportion of patients achieving Hidradenitis Suppurativa Clinical Response (HiSCR50), the proportion of patients with ≥ 1 flare (all at week 12) and patient-reported outcomes., Results: In this completed trial, randomized patients (n = 52) received spesolimab (n = 35) or placebo (n = 17). The difference vs. placebo in least squares mean is reported. At week 12, the percentage change in total AN count was similar between treatment arms: -4.1% [95% confidence interval (CI) -31.7 to 23.4]. There was greater numerical improvement in the spesolimab arm, as measured by IHS4 (13.9, 95% CI -25.6 to -2.3); percentage change from baseline in dT count (-96.6%, 95% CI -154.5 to -38.8); and the proportion of patients achieving a dT count of 0 (18.3%, 95% CI -7.9 to 37.5). Spesolimab treatment also improved HASI-R and HiSCR50 vs. placebo. Spesolimab demonstrated a favourable safety profile, similar to that observed in trials in other diseases., Conclusions: This exploratory PoCC study supports the development of spesolimab as a new therapeutic option in HS., Competing Interests: Conflicts of interest A.A. is a consultant for AbbVie, Almirall, Boehringer Ingelheim, Incyte, InflaRx, Kymera, Novartis and UCB; and an investigator for Boehringer Ingelheim and Processa Pharmaceuticals. E.P. is a consultant and advisory board member for, and has received speaker fees from, AbbVie, Janssen, Novartis and UCB; and his institution has received grant support from AbbVie, Celgene, the Centre for Human Drug Research, Janssen, Novartis, Pfizer and UCB. A.B.K. declares receiving consultant fees from AbbVie, Alumis, Bayer, Boehringer Ingelheim, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer, Priovant, Sanofi, Sonoma Bio, Target RWE and UCB; serves on the board of directors for Almirall; and her institution has received grant support from AbbVie, Admirx, AnaptysBio, Aristea, Bristol Myers Squibb, Eli Lilly, Incyte, Janssen, MoonLake, Novartis, Pfizer, Prometheus, Sonoma Bio and UCB. J.W.F. declares receiving research support from Ortho Dermatologics and Sun Pharmaceutical Industries; has conducted advisory work for AbbVie, Boehringer Ingelheim, Chemocentryx, Janssen, Kyowa Kirin, LEO Pharma, Pfizer, Regeneron and UCB; and has participated in clinical trials for Boehringer Ingelheim, CSL, Eli Lilly, Pfizer and UCB. J.G.K. declares receiving consultant fees/honoraria from AbbVie, Aclaris Therapeutics, Allergan, Almirall, Amgen, Arena, Aristea, Asana BioSciences, Aurigene, Bausch Health, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Escalier Biosciences, Galapagos, Janssen, MoonLake, Nimbus, Novartis, Pfizer, Sanofi, Sienna Biopharmaceuticals, Sun Pharmaceutical Industries, TARGET PharmaSolutions, UCB and Ventyx Biosciences; and his institution has received grant support from AbbVie, Akros, Allergan, Amgen, Avillion, Biogen, Botanix, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Exicure, Incyte, Innovaderm Research, Janssen, Kyowa Kirin, Nimbus Lakshmi, Novan, Novartis, Parexel, Pfizer, Regeneron, UCB and Vitae Pharmaceuticals. C.C.Z. declares receiving disease-relevant consultancy fees/honoraria from Boehringer Ingelheim, Eli Lilly, Idorsia, Incyte, Novartis, Pfizer, Sanofi, and UCB; has received speaker fees from Novartis, Pfizer and UCB; is President of the European Hidradenitis Suppurativa Foundation, Coordinator of the ALLOCATE skin group of European Reference Network Skin, and Chair of the Acne, Rosacea and Hidradenitis Suppurativa Task Force group of the European Academy of Dermatology and Venereology; is Editor of the European Academy of Dermatology and Venereology News and co-copyright holder of IHS4 on behalf of the European Hidradenitis Suppurativa Foundation; and his institution has received disease-relevant grants from Boehringer Ingelheim, InflaRx, Novartis and UCB. S.M., U.R., N.B.I. and A.C.H.D. are employees of Boehringer Ingelheim International GmbH; H.G. is an employee of Boehringer Ingelheim Shanghai Pharmaceuticals Co. Ltd., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions characterised by keratinocyte apoptosis, necroptosis and epidermal detachment. Several cytokines and cytotoxic proteins have been shown to be elevated in the blood and skin of SJS/TEN sufferers and biologics such as intravenous immune globulin and tumour necrosis factor (TNF)-alpha inhibitors have demonstrated good therapeutic potential. The exact pathogenic model of SJS/TEN however remains elusive. This systematic review aimed to evaluate the case-control studies of cytokines and cytotoxic proteins in the blister fluid and skin of adults with Stevens Johnson syndrome and/or toxic epidermal necrolysis. This review was registered with INPLASY and conducted in accordance with the PRISMA reporting guidelines. Potential bias was assessed using the NIH criteria. Eleven articles describing results from 96 cases and 170 controls were included. Fas, Fas ligand, Interleukin (IL)-8 and B-cell lymphoma (Bcl)-2 were elevated in SJS/TEN blister fluid and skin tissue, compared with healthy controls. IL-2, IL-6, TNF-alpha, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon-gamma and matrix metalloproteinase-2 were elevated in SJS/TEN blister fluid compared with fluid sampled from lesional controls. Granulysin, IL-33, TGF-beta-1 and IL-13 were elevated in SJS/TEN skin tissue compared with lesional lichen planus tissue, as was IL-13, IFN-gamma, IL-2 and IL-5, when compared with erythema multiforme tissue. A wide array of cytokines and cytotoxic proteins are present at higher concentrations in the blister fluid and skin tissue of SJS/TEN patients compared with healthy and lesional controls. Our findings suggest that these proteins may be pathogenic, as well as possibly markers for diagnosis, disease severity and course. They may also prove to be useful therapeutic targets. More research is needed., (© 2024 The Author(s). Australasian Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Australasian College of Dermatologists.)

Methods for describing and reporting the clinical and histologic characteristics of cutaneous tissue samples from patients with hidradenitis suppurativa (HS) are not currently standardized, limiting clinicians' and scientists' ability to uniformly record, report, and communicate about the characteristics of tissue used in translational experiments. A recently published consensus statement outlined morphological definitions of typical HS lesions, but no consensus has been reached regarding clinical characterization and examination of HS tissue samples. In this study, we aimed to establish a protocol for reporting histopathologic and clinical characteristics of HS tissue specimens. This study was conducted from May 2023 to August 2023. Experts in clinical care, dermatopathology, and translational research were recruited, and a modified Delphi technique was used to develop a protocol for histologic reporting and clinical characterization of submitted tissue specimens from patients with HS. A total of 27 experts participated (14 dermatologists, 3 fellowship-trained dermatopathologists, 3 plastic surgeons, 3 general surgeons, and 4 research scientists) in creating and reviewing protocols for the clinical and histopathological examination of HS tissue specimens. The protocols were formatted as a synoptic report and will help to consistently classify specimens in biobanks on the basis of histologic features and more accurately report and select samples used in translational research projects., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests statement:The authors declare no competing interest.

Importance: The HLA-B*15:02 allele has been associated with an increased risk of carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in specific Asian populations (including Han Chinese, Malaysian, Thai, and Vietnamese individuals). While HLA-B*15:02 genotype testing in Asian populations is recommended by several international prescribing guidelines, it is not subsidized by the Medicare Benefits Schedule in Australia., Objective: To evaluate the cost-effectiveness of HLA-B*15:02 genotyping in Asian Australian patients with epilepsy., Design, Setting, and Participants: A model with components of decision analysis and Markov simulation was developed to simulate clinical trajectories of adult Asian Australian patients with newly diagnosed epilepsy being considered for carbamazepine treatment. Cost-effectiveness and cost-utility analyses over a lifetime time horizon were conducted from the perspective of the Australian health care sector. The study was conducted in May 2023 and data analysis was performed from August 2023 to November 2023., Intervention: No HLA-B*15:02 genotyping and the empirical initiation of treatment with carbamazepine vs HLA-B*15:02 genotyping and the initiation of treatment with valproate in allele carriers., Main Outcomes and Measures: Life-years (LYs), quality-adjusted life-years (QALYs), and costs in 2023 Australian dollars (A$); incremental cost-effectiveness ratios., Results: HLA-B*15:02 screening was associated with an additional mean cost of A$114 (95% CI, -A$83 to A$374; US$76; 95% CI, -US$55 to US$248) and a reduction in 0.0152 LYs (95% CI, 0.0045 to 0.0287 LYs) but improvement by 0.00722 QALYs (95% CI, -0.0247 to -0.01210) compared with no screening, resulting in an incremental cost-effectiveness ratio of A$15 839 per QALY gained (US$10 523 per QALY). Therefore, universal genotyping for Asian Australian individuals was cost-effective compared with current standards of practice at the A$50 000 per QALY willingness-to-pay threshold. Sensitivity analyses demonstrated that the intervention remained cost-effective across a range of costs, utilities, transition probabilities, and willingness-to-pay thresholds. At the A$50 000 per QALY willingness-to-pay threshold, universal screening was the preferred strategy in 88.60% of simulations., Conclusions and Relevance: The results of this economic evaluation suggest that HLA-B*15:02 screening represents a cost-effective choice for Asian Australian patients with epilepsy who are being considered for treatment with carbamazepine.

Background: The hidradenitis suppurativa (HS) clinical response (HiSCR) has come under scrutiny as several HS clinical trials failed to meet primary endpoints with high placebo responses. This may be due to limitations of the tool and raters' ability to accurately characterize and count lesions, rather than lack of efficacy of the studied drug. Due to HS lesion complexity and potential differences in rater training, it was hypothesized that there would be discrepancies in how providers characterize and count lesions for HS clinical trials., Objective: To evaluate how HS providers and patients name and count HS lesions and to identify discrepancies among providers to initiate the development of consensus-driven guidance for HS rater training., Methods: An online survey was distributed to the members of HIdradenitis SuppuraTiva cORe outcomes set International Collaboration (HISTORIC). Respondents were asked to classify lesion images composed of multiple and different morphology types and answer questions regarding inclusion of associated dermatological conditions., Results: Forty-seven HISTORIC members responded (29 providers; 18 patients). There was variability in how respondents classified HS lesions. Of 12 questions containing images, four had ≥50% of respondents choosing the same answer. With an image of a lesion composed of different morphologies, 45% of providers counted it as a single lesion and 45% counted it as multiple distinct lesions. With an image of multiple interconnected draining tunnels, 7% of providers classified it as a single draining tunnel while 79% categorized it as multiple draining tunnels with the number estimated by visual inspection. There was also variability in deciding whether lesions occurring in associated conditions should be considered separately or included in HS lesion counts. Patient responses were also variable., Conclusions: The result of the current study reaffirms the gap in how providers characterize and count HS lesions for clinical trials and the need to develop consensus-driven rater training related to HS outcome measures., (© 2024 European Academy of Dermatology and Venereology.)

Hidradenitis suppurativa is a disease in great need of novel therapies. Given the heterogeneous nature of the disease and the variable response to therapies, biomarkers are essential to predict response to therapies and increase our understanding of disease pathogenesis. Our recent phase 2 clinical trial of spleen tyrosine kinase antagonism using fostamatinib in hidradenitis suppurativa demonstrated a 75% clinical response, with the greatest benefit in individuals with elevated serum inflammation and IgG. In this study, we present results of an in-depth serum proteomic analysis in this patient cohort identifying downregulation of IL-12B as well as B-cell-associated proteins CCL19 and CCL20 and IFN-γ-mediated proteins CXCL10 and CX3CL1. Clinical responders demonstrated greater reduction in serum IL-17A, IL-6, IL-8, and CX3CL1 compared with clinical nonresponders. Baseline levels of CCL28 were associated with clinical response to fostamatinib therapy at week 12. Overall, this suggests that fostamatinib, by targeting B-cell receptor and Fc receptor activity in B cells, monocytes, and macrophages, has a significant molecular impact on the inflammatory serum proteome of hidradenitis suppurativa. In addition, potential therapeutic biomarkers may aid in patient selection for targeted therapy., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Several registries for hidradenitis suppurativa (HS) already exist in Europe and the USA. There is currently no global consensus on a core dataset (CDS) for these registries. Creating a global HS registry is challenging, owing to logistical and regulatory constraints, which could limit opportunities for global collaboration as a result of differences in the dataset collected. The solution is to encourage all HS registries to collect the same CDS of information, allowing registries to collaborate., Objectives: To establish a core set of items to be collected by all HS registries globally. The core set will cover demographic details, comorbidities, clinical examination findings, patient-reported outcome measures and treatments., Methods: Beginning in September 2022, 20 participants - including both clinicians with expertise in HS and patient advocates - from eight countries across three continents participated in a Delphi process consisting of four rounds of voting, with all participants completing each round. A list of potential items for inclusion in the core set was generated from the relevant published literature, including systematic reviews of comorbidities in HS, clinical and examination findings, and epidemiology. For disease severity and progression items, the Hidradenitis SuppuraTiva Core outcome set International Collaboration (HiSTORIC) core set and other relevant instruments were considered for inclusion. This resulted in 47 initial items. Participants were invited to suggest additional items to include during the first round. Anonymous feedback was provided to inform each subsequent round of voting to encourage consensus., Results: The eDelphi process established a CDS of 48 items recommended for inclusion in all HS registries globally., Conclusions: The routine adoption of this CDS in current and future HS registries should allow registries in different parts of the world to collaborate, enabling research requiring large numbers of participants., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Current infectious disease screening recommendations for hidradenitis suppurativa (HS) are adopted from recommendations in chronic plaque psoriasis. No HS-specific guidelines for infectious disease screening prior to immunomodulatory therapy have been developed., Objectives: The aim of the study was to establish an expert Delphi consensus of recommendations regarding infectious disease screening prior to systemic immunomodulatory therapy in HS., Methods: Participants were identified via recent publications in the field and were sent a questionnaire regarding infectious diseases encountered in the setting of HS, and opinions regarding infectious disease screening prior to various systemic immunomodulatory therapies. All questions were informed by a systematic literature review regarding infections exacerbated or precipitated by immunomodulatory therapy. Questionnaire responses were followed by round-table discussion with a core group of 8 experts followed by a final round of questionnaires resulting in achievement of consensus., Results: 44 expert HS physicians from 12 countries on 5 continents participated in the development of the expert consensus recommendations. Consensus recommendations include screening for hepatitis B, hepatitis C and tuberculosis in all individuals with HS prior to therapy. All immunomodulatory therapies (biologic and systemic immunosuppressant therapy) should be preceded by infectious disease screening including patient and location-specific considerations for endemic local diseases and high-risk activities and occupations. Clinical assessment has a significant role in determining the need for laboratory screening in the setting of many uncommon or tropical diseases such as leprosy, leishmaniasis and strongyloidiasis., Conclusions: The presented consensus recommendations are the first specifically developed for pre-treatment infectious disease screening in HS., (© 2023 S. Karger AG, Basel.)

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/plasma 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., (© 2023 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)

Melanoma accounts for the majority of skin cancer-related mortality, highlighting the need to better understand melanoma initiation and progression. In-depth molecular analysis of neoplastic melanocytes in whole tissue biopsies may be diluted by inflammatory infiltration, which may obscure gene signatures specific to neoplastic cells. Thus, a method is needed to precisely uncover molecular changes specific to tumor cells from a limited sample of primary melanomas. Here, we performed laser capture microdissection (LCM) and gene expression profiling of patient-derived frozen sections of pigmented lesions and primary cutaneous melanoma. Compared to bulk tissue analysis, analysis of LCM-derived samples identified 9528 additional differentially expressed genes (DEGs) including melanocyte-specific genes like PMEL and TYR, with enriched of pathways related to cell proliferation. LCM methodology also identified potentially targetable kinases specific to melanoma cells that were not detected by bulk tissue analysis. Taken together, our data demonstrate that there are marked differences in gene expression profiles depending on the method of sample isolation. We found that LCM captured higher expression of melanoma-related genes while whole tissue biopsy identified a wider range of inflammatory markers. Taken together, our data demonstrate that LCM is a valid approach to identify melanoma-specific changes using a relatively small amount of primary patient-derived melanoma sample., (© 2023 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.)

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 that provide durable responses in chronic immune-mediated skin diseases, even after cessation. In this review, we summarize 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, the available data on the potential for existing and novel treatments to affect the development or survival of cT-RMs in the skin are synthesized. The data 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., Competing Interests: Conflicts of interest J.W.F. has conducted advisory work for Janssen, Boehringer Ingelheim, Pfizer, Kyowa Kirin, LEO Pharma, Regeneron, ChemoCentryx, AbbVie and UCB; has participated in trials for Pfizer, UCB, Boehringer Ingelheim, Eli Lilly and CSL; and has received research support from Ortho Dermatologics and Sun Pharma., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., Competing Interests: JWF has conducted advisory work for Janssen, Boehringer-Ingelheim, Pfizer, Kyowa Kirin, LEO Pharma, Regeneron, Chemocentryx, Abbvie and UCB, participated in trials for Pfizer, UCB, Boehringer-Ingelheim, Eli Lilly, CSL, Abbvie, Janssen, and received research support from Ortho Dermatologics and Sun Pharma and La Roche Posay. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Flora et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Hidradenitis suppurativa (HS) is an autoinflammatory disorder of keratinization with a prominence of B cells and plasma cells. Fostamatinib is a spleen tyrosine kinase inhibitor targeting B cells and plasma cells., Objectives: To assess the safety, tolerability, and clinical response at week 4 and week 12 of fostamatinib in moderate-to-severe HS., Methods: Twenty participants were administered fostamatinib 100 mg twice a day for 4 weeks, escalating to 150 mg twice a day thereafter until week 12. Participants were assessed for adverse events and clinical response assessed by HiSCR (Hidradenitis Suppurativa Clinical Response Score) and IHS4 (International Hidradenitis Suppurativa Severity Score) as well as other outcomes including DLQI (Dermatology Life Quality Index), visual analog scale, and physician global assessment., Results: All 20 participants completed the week 4 and week 12 endpoints. Fostamatinib was well tolerated in this cohort with no grade 2/3 adverse events reported. A total of 85% achieved HiSCR at week 4 and 85% at week 12. The greatest reduction in disease activity was seen at weeks 4/5 with worsening in a proportion of patients thereafter. Significant improvements were seen in pain, itch, and quality of life., Conclusions: Fostamatinib was well tolerated in this HS cohort with no serious adverse events and improvement in clinical outcomes. Targeting B cells/plasma cells may be a viable therapeutic strategy in HS and requires further exploration., Competing Interests: Conflicts of interest Dr Frew has conducted advisory work for Janssen, Boehringer-Ingelheim, Pfizer, Kyowa Kirin, LEO Pharma, Regeneron, Chemocentryx, Abbvie, Azora, Novartis, and UCB; participated in trials for Pfizer, UCB, Boehringer-Ingelheim, Eli Lilly, CSL, and Azora; and received research support from Ortho Dermatologics, Sun Pharma, LEO Pharma, UCB and La Roche Posay. Jepsen, Edwards, Flora, and Kozera have no conflicts of interest to declare., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Conflicts of interest: D.M. has received research funding from: Bioderma, Avene, LEO Pharma, La Roche Posay. J.W.F. has conducted advisory work for Janssen, Boehringer-Ingelheim, Pfizer, Kyowa Kirin, LEO Pharma, Regeneron, Chemocentryx, AbbVie, Azora, Novartis and UCB, participated in trials for Pfizer, UCB, Boehringer-Ingelheim, Eli Lilly, CSL, Azora and received research support from Ortho Dermatologics, Sun Pharma, LEO Pharma, UCB and La Roche Posay. The other authors declare they have no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: Conflicts of interest J.W.F. has conducted advisory work for Janssen, Boehringer-Ingelheim, Pfizer, Kyowa Kirin, LEO Pharma, Regeneron, ChemoCentryx, AbbVie, Azora, Novartis, and UCB; participated in trials for Pfizer, UCB, Boehringer-Ingelheim, Eli Lilly, CSL, and Azora; and received research support from Ortho Dermatologics, Sun Pharma, LEO Pharma, UCB, and La Roche Posay.

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 individuals 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., (© 2023 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)

Introduction: 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., Methods: 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., Results: 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., Conclusion: 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., (© 2023 The Authors. Australasian Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Australasian College of Dermatologists.)

Background: 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, individuals 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., Objective: The aim of this study was to assess the effect of biological therapy in psoriasis vulgaris in individuals with well-controlled HIV on CD4 + cell counts, CD4 + proportion and HIV viral load over 12 months., Methods: This retrospective cohort study was conducted at a tertiary referral centre in Sydney, Australia and included 36 HIV-positive individuals with psoriasis treated with biological therapy, compared with 144 age-, gender- and HAART-matched individuals without psoriasis seen between 2010 and 2022. Outcomes of interest included HIV viral load, CD4 + cell count and incidence of infections., Results: No statistically significant difference was seen in baseline HIV viral load and CD4 + count between individuals 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., Conclusions: In individuals 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., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Competing Interests: Conflicts of interest JWF has conducted advisory work for Janssen, Boehringer-Ingelheim, Pfizer, Kyowa Kirin, LEO Pharma, Regeneron, Chemocentryx, Abbvie, Azora, Novartis and UCB, participated in trials for Pfizer, UCB, Boehringer-Ingelheim, Eli Lilly, CSL, Azora and received research support from Ortho Dermatologics, Sun Pharma, LEO Pharma, UCB and La Roche Posay.

Competing Interests: Dr. Frew has conducted advisory work for Janssen, Boehringer-Ingelheim, Pfizer, Kyowa Kirin, LEO Pharma, Regeneron, Chemocentryx, AbbVie, Azora, Novartis, and UCB; participated in trials for Pfizer, UCB, Boehringer-Ingelheim, Eli Lilly, CSL, Azora; and received research support from Ortho Dermatologics, Sun Pharma, LEO Pharma, UCB, and La Roche-Posay. Drs Selvaraj and Stewart have no conflicts of interest to declare.

Competing Interests: Conflicts of interest: J.W.F. has conducted advisory work for Janssen, Boehringer-Ingelheim, Pfizer, Kyowa Kirin, LEO Pharma, Regeneron, Chemocentryx, AbbVie and UCB, participated in trials for Pfizer, UCB, Boehringer-Ingelheim, Eli Lilly and CSL, and received research support from Ortho Dermatologics and Sun Pharma. None declared by the other authors.

Competing Interests: Conflicts of interest Dr Frew has conducted advisory work for Janssen, Boehringer-Ingelheim, Pfizer, Kyowa Kirin, LEO Pharma, Regeneron, Chemocentryx, AbbVie, and UCB; participated in trials for Pfizer, UCB, Boehringer-Ingelheim, Eli Lilly, and CSL; and received research support from Ortho Dermatologics and Sun Pharma. Authors Kozera, Flora, Stewart, Gill, Xu, and De La Vega have no conflicts of interest to declare.

Altered gut microbiota composition has been observed in individuals 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 samples from participants with HS prior to and 12 weeks after commencing adalimumab therapy. HS individuals 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., (© 2022 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)