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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.)

Background: Hidradenitis suppurativa (HS) affects different patient populations that require unique considerations in their management. However, no HS guidelines for these populations exist., Objective: To provide evidence-based consensus recommendations for patients with HS in seven special patient populations: i) pregnancy, ii) breastfeeding, iii) pediatrics, iv) malignancy, v) tuberculosis infection, vi) hepatitis B or C infection, and vii) HIV disease., Methods: Recommendations were developed using the Grading of Recommendations Assessment, Development and Evaluation system to ascertain level of evidence and selected through a modified Delphi consensus process., Results: 119 expert consensus statements are provided for the management of patients with HS across these seven special patient populations., (Copyright © 2024. Published by Elsevier Inc.)

Background: International Dermatology Outcome Measures (IDEOM) is a non-profit organization whose mission is to improve the availability of evidence-based, consensus-driven outcome measures for dermatological diseases. IDEOM facilitates collaboration between stakeholders from various backgrounds, including researchers, patients, physicians, and industry representatives, to develop objective benchmark metrics that enable better treatment and management of dermatologic conditions., Summary: The 2023 IDEOM Annual Meeting was held June 23-24, 2023. Workgroups in psoriatic disease, hidradenitis suppurativa, geriatric dermatology, connective tissue disease, vitiligo, itch, actinic keratosis, acne, and cutaneous T-cell lymphoma discussed the progress of their respective outcome-measures research. This report summarizes each workgroup’s updates since the 2022 annual meeting and their next steps as established during the 2023 IDEOM Annual Meeting. J Drugs Dermatol. 2024;23(12):1114-1120. doi:10.36849/JDD.8363.

Hidradenitis suppurativa (HS) is an inflammatory skin disease associated with high morbidity and disability that has limited treatment options. People from racial and ethnic minority groups may experience greater disease severity and delay to diagnosis. This study assessed the impact of race/ethnicity on HS diagnosis and management in real-world clinical settings. Data were derived from the Adelphi Real World Hidradenitis Suppurativa Disease Specific Programme, a survey of dermatologists and their consulting HS patients in five European countries and the USA in 2020/2021. Dermatologists returned demographic and clinical data, and treatment goals and satisfaction for their next five to seven consulting patients. Patients completed a questionnaire on disease history and diagnosis, disease burden, and treatment satisfaction. Groups were compared with bivariate tests. In total, 312 physicians returned data on 1787 patients; 57.6% were female and 77.7% White. People from racial and ethnic minority groups were younger than White patients (32.9 ± 11.6 vs. 34.9 ± 12.4, mean ± standard deviation) and reported symptoms at a younger age (23.3 ± 10.8 vs. 26.2 ± 11.1), but their time to first consultation was longer than for White patients (2.6 ± 5.7 vs. 1.2 ± 2.5 years). People from racial and ethnic minority groups took longer to receive a correct diagnosis following first consultation (2.7 ± 5.3 vs. 1.5 ± 4.1 years) and were more likely to be misdiagnosed with boils (73.5% vs. 40.4%). People from racial and ethnic minority groups had a greater disease awareness at diagnosis and reported wanting greater support. People from racial and ethnic minority groups reported a greater impact on life, more severe pain, and a greater level of activity impairment in the Work Productivity and Activity Impairment: General Health (27.0 ± 25.2 vs. 20.0 ± 20.6). All P values were ≤0.05. These data show evidence of delayed diagnosis and higher HS symptom burden amongst people from racial and ethnic minority groups, highlighting health disparities in HS., (© 2024 Eli Lilly and Company. Adelphi Real World and The Author(s). The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Skin color classification can have importance in skin health, pigmentary disorders, and oncologic condition assessments. It is also critical for evaluating disease course and response to a variety of therapeutic interventions and aids in accurate classification of participants in clinical research studies. A panel of dermatologists conducted a literature review to assess the strengths and limitations of existing classification scales, as well as to compare their preferences and utilities. We identified 17 skin classification systems utilized in dermatologic settings. These systems include a range of parameters such as UV light reactivity, race, ethnicity, and degree of pigmentation. The Fitzpatrick skin type classification is most widely used and validated. However it has numerous limitations including its conflation with race, ethnicity, and skin color. There is a lack of validation data available for the remaining scales. There are significant deficiencies in current skin classification instruments. Consensus-based initiatives to drive the development of validated and reliable tools are critically needed., Competing Interests: Conflicts of interest Dr Harvey has served as a consultant for L’Oréal and SkinCeuticals and on advisory boards for AbbVie, Lilly, Bristol-Myers Squibb, and Johnson & Johnson. Dr Alexis has received grants (funds to institution) from LEO Pharma, Novartis, Almirall, Bristol-Myers Squibb, Amgen, Vyne, Galderma, Valeant (now Bausch Health), Cara Therapeutics, Arcutis, Dermavant, AbbVie, and Castle; on advisory board or as a consultant for LEO Pharma, Galderma, Pfizer, Sanofi-Regeneron, Dermavant, Beiersdorf, Ortho, L’Oréal, BMS, Bausch Health, UCB, Vyne, Arcutis, Janssen, Allergan, Almirall, AbbVie, Amgen, VisualDx, Eli Lilly, Swiss American, Cutera, Cara Therapeutics, EPI Health, Incyte, Castle, Apogee, Alphyn, and Canfield; as a speaker for Regeneron, Sanofi-Genzyme, Pfizer, and BMS; and has received royalties from Springer, Wiley-Blackwell, and Wolters Kluwer Health. Dr McKinley-Grant has served as a consultant for Janssen and Determi-Nation. Dr Taylor has served as a consultant/advisor/speaker for AbbVie, Arcutis Biotherapeutics, Inc, Armis Scientific, Avita Medical, Beiersdorf, Inc, Biorez, Inc, Bristol-Myers Squibb, Cara Therapeutics, Dior, Eli Lilly, EPI Health, Evolus, Inc, Galderma Laboratories, LP, GloGetter, Hugel America, Inc, Johnson & Johnson Consumer Products Company, L’Oréal USA, Medscape/WebMD, MJH LifeSciences, Pfizer, Piction Health, Sanofi, Scientis US, UCB, and Vichy Laboratoires; as an author at McGraw-Hill; on the Editorial Board for Practical Dermatology, Cutis, and Archives in Dermatologic Research and a peer reviewer for the British Journal of Dermatology; and as an investigator for Allergan Aesthetics, Concert Pharmaceuticals, Croma-Pharma GmbH, Eli Lilly, and Pfizer. Dr Desai has served as an investigator and/or consultant for Galderma, Pfizer, Lilly, Dermavant, AbbVie, and many other companies; he also holds multiple leadership positions in national and other organizations. Dr Jaleel has received grants from Pfizer, Skin of Color Society, Dermatology Foundation, and the NIH; as a consultant for UCB, Eli Lilly, Novartis, and ChemoCentryx. Dr Kang has served on the advisory board and/or as a consultant for Amore Pacific, CeraVe, Galderma, Eli Lilly, and Jeune. Dr Vashi has served as a consultant for Janssen Biotech, L’Oréal, and Canfield. Dr Elbuluk has served as a consultant for Avita, Scientis, Beiersdorf, Incyte, VisualDx, La Roche Posay, Beiersdorf, and Unilever; on advisory boards for Allergan, Eli Lily, Galderma, Incyte, Janssen, La Roche Posay, and L’Oréal; as speaker for Estee Lauder, La Roche Posay, Scientis, Medscape, Beiersdorf, and Dior; and as an investigator for Avita. Dr Hamzavi has served as a consultant to AbbVie, Pfizer, Incyte, UCB, Boehringer Ingelheim, Sonoma, Union therapeutics, Novartis, Janssen, Avita, Galderma, Almirall, and Vimela; as an investigator for Lenicura, Pfizer, Incyte, Avita, Loreal/Laroche Posay, Clinuvel, ITN, Chemocentyx, Ferndale Laboratories, Inc, Unigen, Inc, and Arcutis; and as a board member and Past-president of the HS Foundation and Global Vitiligo Foundation. Dr Kwatra has served as an advisory board member/consultant for AbbVie, Amgen, Arcutis Biotherapeutics, Aslan Pharmaceuticals, Cara Therapeutics, Castle Biosciences, Celldex Therapeutics, Galderma, Genzada Pharmaceuticals, Incyte Corporation, Johnson & Johnson, LEO Pharma, Novartis Pharmaceuticals Corporation, Pfizer, Regeneron Pharmaceuticals, and Sanofi; and as an investigator for Galderma, Incyte, Pfizer, and Sanofi. Dr Kholi has served as an investigator for Ferndale, Estée Lauder, La Roche Posay Dermatologique, Unigen, Johnson & Johnson, Allergan, Pfizer, Sciton, and Bayer; received support from the American Skin Association for a vitiligo project; was a consultant for Pfizer, Johnson & Johnson, Beiersdorf (previously known as Bayer), and ISDIN; and received salary support from the Dermatology Foundation through a research career development award. Dr Callender has served as an investigator and/or received grants from AbbVie/Allergan, Almirall, Aerolase, Arcutis, Avava, Beiersdorf, Eirion, Eli Lilly, Janssen, L’Oréal, Pfizer, Prollineum, skinbetter science, Symatese, and Teoxane; as a consultant or advisor for Acne Store, Aerolase, Arcutis, Avita Medical, Beiersdorf, Cutera, Dermavant, EPI Health, Jeune Aesthetics, L’Oréal, OrthoDerm, Scientis, Sente, SkinCeuticals, and UCB; as a speaker for Eli Lilly, L’Oréal, and SkinCeuticals; and has received royalties from Elsevier and UpToDate. Author Okeke, Dr Heath, Dr Lester, Dr Vasquez, Dr Rodriguez, Dr Sundaram, Author Brown, and Author Cobb have no conflicts of interest to declare., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of interest W.W.L. is supported by the National Institutes of Health (NIH) (F30 DK122712). T.J. is an investigator for AbbVie, Eli Lilly and UCB; she reports consulting for ChemoCentryx, Novartis, and Eli Lilly and receiving honoraria; she has received funds from Pfizer and UCB for research fellow support; from the Dermatology Foundation, Duke Strong Start Physician Scientist Award, NIH (grant no. K12 HD043446) and Skin of Color Society; she is also a board member for the Skin of Color Society. The remaining authors declare that the research was conducted in the absence of any financial relationships that could be construed as a potential conflict of interest.

Purpose The purpose of this study is to examine the impact of the timing of the steroid switch on both visual and anatomical outcomes in diabetic macular edema (DME) eyes that have shown an inadequate response to multiple intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections. In the treatment of DME, anti-VEGF injections are typically the initial course of action. However, in cases where DME persists despite anti-VEGF treatment, intravitreal dexamethasone implants (Ozurdex ® , Allergan Inc., Irvine, CA) are often utilized. Despite this, there remains a lack of consensus regarding the optimal timing for transitioning to steroid treatment. This study aims to shed light on the potential benefits of adjusting the timing of the steroid switch in cases of recalcitrant DME.  Methods The eyes (n = 105) of 77 patients with recalcitrant DME were included in this retrospective, interventional, comparative study comprising three groups: participants switched to steroid implants after three anti-VEGF injections (Group I), four to six anti-VEGF injections (Group II), and more than six anti-VEGF injections (Group III). Anti-VEGF treatment failure was defined as a central retinal thickness (CRT) of ≥300 microns and/or a lack of visual improvement (≤1 line of visual gain according to Snellen acuity). The last follow-up took place after 10-12 weeks of Ozurdex ® injections. Results Improvement was observed in 19 eyes (46%), 17 eyes (50%), and 10 eyes (33%) in Groups I, II, and III, respectively, after switching to dexamethasone implants. The best overall results (an improvement in vision and stabilization) were seen in Group II (32 eyes, 94%). The decrease in CRT was statistically significant in all three groups.  Conclusion Intravitreal dexamethasone implants improved functional and morphological outcomes in anti-VEGF-resistant DME eyes. After four to six anti-VEGF injections, switching to a steroid implant resulted in the best functional results., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Al Bahar Institutional Review Board issued approval (AIRB/021/2021). Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Raizada et al.)

Introduction: Skin involvement in patients with psoriatic arthritis (PsA) worsens the severity and burden of disease. Ixekizumab (IXE), a selective interleukin (IL)-17A antagonist, was compared to placebo (PBO) in the SPIRIT-P1 (NCT01695239) and SPIRIT-P2 (NCT02349295) studies in patients with PsA and evidence of plaque psoriasis. This post hoc analysis reports musculoskeletal, skin, and nail outcomes through week 24 in patients from SPIRIT-P1 and SPIRIT-P2, stratified by mild, moderate, or psoriasis at baseline., Methods: This post hoc analysis pooled patients from SPIRIT-P1 and SPIRIT-P2 who were randomly assigned to PBO or IXE 80 mg every 4 weeks (Q4W) or every 2 weeks (Q2W). Efficacy outcomes were analyzed through week 24 by baseline psoriasis severity, defined by percent body surface area (BSA) affected; mild = BSA < 3%, moderate = 3% ≤ BSA ≤ 10%, severe = BSA > 10%. The primary outcomes assessed were the proportion of patients achieving American College of Rheumatology (ACR)20, ACR50, and ACR70 responses. Secondary outcomes included musculoskeletal, disease activity, skin and nail, and health-related quality-of-life measures., Results: Similar proportions of patients achieved ACR20/ACR50/ACR70 over time across all severity subgroups and treatment arms. More than one-third of IXE-treated patients achieved ACR20 at week 4, or ACR50 at week 24, with no significant differences according to psoriasis severity at baseline. Disease activity outcomes were similar through week 24 with both IXEQ4W and IXEQ2W, regardless of psoriasis severity at baseline. There were no significant differences over 24 weeks in the proportions of IXE-treated patients with mild, moderate, or severe baseline psoriasis who achieved Minimal Disease Activity (MDA). Across all severity subgroups, IXE demonstrated Psoriasis Area Severity Index 100 response as early as week 4, and approximately one-third of IXE-treated patients achieved total skin clearance at week 24., Conclusion: IXE demonstrated rapid and consistent efficacy in joint, skin, and nail for patients with PsA, regardless of baseline psoriasis severity., Trial Registration: SPIRIT-P1 (NCT01695239), SPIRIT-P2 (NCT02349295)., (© 2024. The Author(s).)

Importance: Clinical trials remain the cornerstone for determining the safety and efficacy of an intervention. A diverse participant pool in dermatology clinical trials is critical to ensure that results are generalizable among the patient population who will ultimately depend on the efficacy of the intervention. The Skin of Color Society hosted the inaugural Meeting the Challenge Summit: Diversity in Dermatology Clinical Trials in Washington, DC, from June 10 to 11, 2022. The summit was an interactive and collaborative effort to advance discussions regarding the need for broader inclusion of racial and ethnic minority patients in dermatology clinical trials., Observations: The summit focused on 3 principal areas: (1) understanding the current clinical trials landscape; (2) breaking down patient, clinician, industry, and regulatory barriers; and (3) effecting change through a diversity-focused strategy. The program hosted thought-provoking panel talks and discussions with various stakeholder groups, including a keynote presentation from the family of Henrietta Lacks., Conclusions and Relevance: Panel discussions and insightful presentations from physicians, industry leaders, community trailblazers, and patients fostered new collaborations. The summit provided recommendations and suggested strategies for future initiatives designed to increase the representation of minority individuals in dermatology clinical trials.

Competing Interests: Conflicts of interest T.J. is an investigator for UCB and Eli Lilly. She reports consulting for Eli Lilly and Chemocentryx and receiving honoraria. She has received funds from Pfizer for research fellow support. The remaining authors declare that the research was conducted in the absence of any financial relationships that could be construed as a potential conflict of interest. She also has received funds from Dermatology Foundation, and Skin of Color Society, and NIH K12 (grant number: K12HD043446).

Background: Hidradenitis suppurativa (HS) is associated with comorbidities that contribute to poor health, impaired life quality, and mortality risk., Objective: To provide evidence-based screening recommendations for comorbidities linked to HS., Methods: Systematic reviews were performed to summarize evidence on the prevalence and incidence of 30 comorbidities in patients with HS relative to the general population. The screening recommendation for each comorbidity was informed by the consistency and quality of existing studies, disease prevalence, and magnitude of association, as well as benefits, harms, and feasibility of screening. The level of evidence and strength of corresponding screening recommendation were graded by using the Strength of Recommendation Taxonomy (SORT) criteria., Results: Screening is recommended for the following comorbidities: acne, dissecting cellulitis of the scalp, pilonidal disease, pyoderma gangrenosum, depression, generalized anxiety disorder, suicide, smoking, substance use disorder, polycystic ovary syndrome, obesity, dyslipidemia, diabetes mellitus, metabolic syndrome, hypertension, cardiovascular disease, inflammatory bowel disease, spondyloarthritis, and sexual dysfunction. It is also recommended to screen patients with Down syndrome for HS. The decision to screen for specific comorbidities may vary with patient risk factors. The role of the dermatologist in screening varies according to comorbidity., Limitations: Screening recommendations represent one component of a comprehensive care strategy., Conclusions: Dermatologists should support screening efforts to identify comorbid conditions in HS., Competing Interests: Conflicts of interest Dr Garg has served as a consultant for AbbVie, Amgen, Boehringer Ingelheim, Incyte, Janssen, Novartis, Pfizer, UCB, and Viela Bio; has received honoraria from AbbVie, Amgen, Boehringer Ingelheim, Incyte, Janssen, Novartis, Pfizer, UCB, and Viela Bio; and has received grants: from AbbVie and the National Psoriasis Foundation. Dr Alavi has served as a consultant for AbbVie, Boehringer Ingelheim, Incyte, Janssen, Pfizer, UCB, Actelion, Celgene, Galderma, GlaxoSmithKline, Leo Pharma, Novartis, Sanofi-Genzyme, Kymera, Eli Lily, InflaRx, Sanofi, and Bausch; has received honoraria from AbbVie, Boehringer Ingelheim, Incyte, Janssen, Pfizer, UCB, Actelion, Celgene, Galderma, GlaxoSmithKline, Leo Pharma, Novartis, Genzyme, Kymera, Eli Lily, Sanofi, and Bausch; has received grants from AbbVie; and has received donations of medical equipment from Galderma and Swift. Dr Alhusayen has served as a consultant for AbbVie, Janssen, Leo Pharma, Hidramed Solutions and has received honoraria from AbbVie, and Eli Lilly. Dr Daveluy has served as a consultant for AbbVie; has received honoraria from AbbVie; has served on the speakers bureau for AbbVie; and has received grants from AbbVie, InflaRx, Regeneron, and Pfizer. Dr Delorme has served as a consultant for AbbVie, Celgene, Eli-Lilly, Janssen, Novartis, and Sanofi-Genzyme; has received honoraria from AbbVie, Amgen, Avene, Celgene, Eli Lilly, Janssen, Novartis, and UCB Pharma; has served on the speakers bureau for AbbVie, Bausch Health, Celgene, Eli Lilly, Janssen, Novartis, and Sanofi Genzyme; and has received grants from AbbVie, InflaRx, Regeneron, and Pfizer. Dr Gulliver has served as a consultant for AbbVie, Amgen, Bausch Health, Celgene, Cipher, Eli Lilly, Janssen, LEO Pharma, Novartis, PeerVoice, Pfizer, Sanofi-Genzyme, UCB, and Valeant; has received honoraria from AbbVie, Amgen, Bausch Health, Celgene, Cipher, Eli Lilly, Janssen, LEO Pharma, Novartis, PeerVoice, Pfizer, Sanofi-Genzyme, UCB, and Valeant; and has received grants from AbbVie, Amgen, Eli Lilly, Novartis, and Pfizer. Dr Hamzavi has served as a consultant for Incyte, UCB, and Pfizer and has received grants from Lenicura and Boehringer Ingelheim. Dr Jaleel has served as a consultant for Eli Lilly and ChemoCentryx/IQVIA and has received grants from the Dermatology Foundation and Skin of Color Society. Dr Kimball has served as a consultant for AbbVie, Janssen, Lilly, Novartis, Pfizer, UCB, and Kymera; has received honoraria from AbbVie, Janssen, Lilly, Novartis, Pfizer, UCB, and Kymera; and has received royalties from Pfizer, Trifecta, and UCB. Dr Kirby has served as a consultant for AbbVie, ChemoCentryx, Incyte, Novartis, and UCB; has received honoraria from AbbVie, Incyte, and Viela Bio; and has served on the speakers bureau for AbbVie. Dr Kirchhof has served as a consultant for AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Sanofi-Genzyme; has served on the speakers bureau for AbbVie, Janssen, Novartis, Pfizer, UCB, and Sanofi-Genzyme; and has received grants from the Canadian Dermatology Foundation. Dr Lev-Tov has served as a consultant for Pfizer, Mölnlycke, and NextScience; has received honoraria from Essity; has received grants from NextScience and Essity; and has received donations of medical equipment from Essity, Mölnlycke, and NextScience. Dr Lowes has served as a consultant for AbbVie, Janssen, Viela Bio, Almirall, BSN, Incyte, Janssen, Kymera, and XBiotech. Dr Naik has served as a consultant for Boehringer Ingelheim, Janssen, and 23andme and has received grants from AbbVie, Hidradenitis Suppurativa Foundation. Dr Orenstein has received a Hidradenitis Suppurativa Foundation Danby Research Grant. Dr Piguet has served as a consultant for Pfizer, AbbVie, Janssen, UCB, Novartis, Almirall, and Celgene; has received honoraria from Kyowa Kirin Co Ltd, AbbVie, and Novartis; has received grants from AbbVie, Bausch Health, Celgene, Janssen, LEO Pharma, Lilly, NAOS, Novartis, Pfizer, Pierre-Fabre, and Sanofi; and has received a donation of medical equipment from La Roche-Posay. Dr Sayed has served as a consultant for UCB, InflaRx, and AbbVie; has received honoraria from UCB and AbbVie; and has served on the speakers bureau for AbbVie and Novartis. Dr Tan has served as a consultant for Almirall, Bausch, Boots/Walgreens, Botanix, Cipher, Galderma, Incyte, L’Oréal, Novartis, Pfizer, Promius, Sun, and UCB; has received honoraria from Almirall, Bausch, Boots/Walgreens, Botanix, Galderma, L’Oréal, Novartis, Pfizer, Promius, and Sun; has served on the speakers bureau for Galderma and L’Oréal; and has received grants from Incyte and UCB. Drs Alikhan and Goldfarb, Author Lester, Drs Malviya and Micheletti, and Authors Strunk and Wright have no conflicts of interest to declare., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent abscesses, nodules, and sinus tracts in areas of high hair follicle and sweat gland density. These sinus tracts can present with purulent drainage and scar formation. Dysregulation of multiple immune pathways drives the complexity of HS pathogenesis and may account for the heterogeneity of treatment response in HS patients. Using transcriptomic approaches, including single-cell sequencing and protein analysis, we here characterize the innate inflammatory landscape of HS lesions. We identified a shared upregulation of genes involved in interferon (IFN) and antimicrobial defense signaling through transcriptomic overlap analysis of differentially expressed genes (DEGs) in datasets from HS skin, diabetic foot ulcers (DFUs), and the inflammatory stage of normal healing wounds. Overlap analysis between HS- and DFU-specific DEGs revealed an enrichment of gene signatures associated with monocyte/macrophage functions. Single-cell RNA sequencing further revealed monocytes/macrophages with polarization toward a pro-inflammatory M1-like phenotype and increased effector function, including antiviral immunity, phagocytosis, respiratory burst, and antibody-dependent cellular cytotoxicity. Specifically, we identified the STAT1/IFN-signaling axis and the associated IFN-stimulated genes as central players in monocyte/macrophage dysregulation. Our data indicate that monocytes/macrophages are a potential pivotal player in HS pathogenesis and their pathways may serve as therapeutic targets and biomarkers in HS treatment., Competing Interests: AM consulted for Silab and received a project grant from Silab to support her lab. Silab did not have any insight into the current data and had no decision in publishing or ownership. AM served as a SEC member of the LEO Foundation in the recent past and is currently employed by Janssen. The spouse of AM was employed by Precision Biosciences and holds stock and stock options. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mariottoni, Jiang, Prestwood, Jain, Suwanpradid, Whitley, Coates, Brown, Erdmann, Corcoran, Gregory, Jaleel, Zhang, Harris-Tryon and MacLeod.)

Background: Hidradenitis suppurativa (HS) and atopic dermatitis (AD) are both chronic inflammatory skin diseases. An association between these 2 conditions can have important potential implications for elucidating pathogenesis, disease course, and treatment., Objective: To investigate the association between AD and HS., Methods: We performed a retrospective cohort study of patients seen at Duke University Medical Center from 2007 to 2017 who had AD compared with a control group without an AD diagnosis. The association of AD and HS was evaluated using a logistic regression model after adjusting for other confounders including age, sex, and race., Results: Of 28,780 patients with an AD diagnosis, 325 (1.1%) were diagnosed with HS compared with 76 (0.2%) within the 48,383 patients in the non-AD group. An adjusted logistic regression model demonstrated an increased odds ratio of having HS diagnosis in the AD group as compared with the control non-AD group (odds ratio: 5.57, 95% confidence interval: 4.30-7.21, P  < .001)., Limitations: This was a retrospective study performed at a single institution with the possibility of surveillance bias being present., Conclusions: Patients with AD are more likely to be diagnosed with HS than patients without AD. Further research is needed to understand the pathophysiologic mechanism and potential treatment implications., Competing Interests: Dr Macleod consulted for Silab when she was an employee at Duke. The MacLeod laboratory has previously received funds from Silab Company; funding from this partnership was not directly used for this study. Silab did not have any influence on the content of this project. Dr Macleod is also consulting for the LEO Foundation. The spouse of Dr Macleod is employed at Precision Biosciences and has stock options. Dr Jaleel is an investigator for UCB and reported consulting for Eli Lilly and Chemocentryx and receiving honoraria. None of the content or the decision to publish has been affected by the authors' involvement with Eli Lilly, Silab, Chemocentryx, Precision Biosciences or the LEO foundation. Drs Kaakati, Tanaka, Liu, Ward, and Green have no conflicts of interest to declare., (© 2021 by the American Academy of Dermatology, Inc. Published by Elsevier Inc.)

Hidradenitis suppurativa (HS) is an inflammatory disease of the skin with a chronic, relapsing-remitting course. The pathogenesis of the disease is poorly understood and involves multiple factors, including genetics, environment, host-microbe interactions, and immune dysregulation. In particular, the composition of the cutaneous microbiome shifts as the disease progresses, although it is unclear whether this is a primary or secondary process. Trials with immunomodulatory therapy elucidate the role of specific immune pathways and cytokine signaling in disease mechanism, such as TNF-α, IL-1β, IL-12, IL-17, IL-23, and complement. Future studies should continue examining the causes of and contributing factors to microbial changes and immune dysregulation in HS pathogenesis., (© 2021 The Authors.)

Poorly controlled and long-standing hidradenitis suppurativa (HS) increases the risk of squamous cell carcinoma (SCC). We report a 54-year-old woman with an over 20-year history of HS, who had previously undergone wide perineal excision with secondary intention healing and presented with a painful verrucous vulvar plaque and proximal non-healing perineal wound. The patient had four perineal scouting biopsies performed and excisional biopsy with no evidence of high-grade dysplasia or carcinoma on histology. Chromogenic in situ hybridization was negative for HPV 16 and 18 mRNA; the patient's HIV and HSV PCR were also negative. Our patient was treated with interferon alfa-2b with notable clinical improvement. There is currently no standardized stepwise approach to monitoring verrucous lesions in HS patients with significant risk factors for SCC. Our report highlights a vigilant approach to monitoring. If scouting biopsies are negative, complete testing for high risk HPV strains (HPV 16 and 18) is warranted. If negative, we recommend follow up every 6 months with no further biopsies except if overt clinical changes are observed. We also recommend treatment of verrucous changes to decrease risk of possible malignant conversion. Interferon alfa-2b was effective in decreasing the verrucous lesion burden in our patient and may be considered.

Hidradenitis suppurativa is a chronic inflammatory disorder affecting hair follicles, with profoundly negative impact on patient quality of life. Evidence informing ideal evaluation and management of patients with hidradenitis suppurativa is still sparse in many areas, but it has grown substantially in the last decade. Part I of this evidence-based guideline is presented to support health care practitioners as they select optimal management strategies, including diagnostic testing, comorbidity screening, and both complementary and procedural treatment options. Recommendations and evidence grading based on the evidence available at the time of the review are provided., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Hidradenitis suppurativa is a severe and debilitating dermatologic disease. Clinical management is challenging and consists of both medical and surgical approaches, which must often be combined for best outcomes. Therapeutic approaches have evolved rapidly in the last decade and include the use of topical therapies, systemic antibiotics, hormonal therapies, and a wide range of immunomodulating medications. An evidence-based guideline is presented to support health care practitioners as they select optimal medical management strategies and is reviewed in this second part of the management guidelines. A therapeutic algorithm informed by the evidence available at the time of the review is provided., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: This pilot retrospective study examined the role of continuous low-dose maintenance immunomodulatory treatment (IMT) as an adjunct to rituximab (RTX) rescue therapy in severe pemphigus vulgaris (PV) and pemphigus foliaceus (PF) after a complete response (CR) to RTX was achieved. Materials and methods: Ten severe pemphigus patients who received RTX rescue therapy were evaluated after achieving CR. The post-RTX clinical course and long-term follow up was compared between patients who adhered to a low recommended dose (LRMD) to patients who were non-compliant with LRMD. Results: Five patients relapsed due to discontinuing or tapering their LRMD therapy, whereas the five patients who adhered to their maintenance therapy did not experience a relapse after the initial post-RTX CR. A combination of increasing or adding IMTs and initiating subsequent RTX cycles was used to regain control in relapsed patients. Conclusions: We propose an alternative treatment strategy utilizing RTX as a rescue agent in combination with long-term LRMD as a means to maintain a sustained long-term CR post-RTX therapy in severe pemphigus patients. This strategy could prevent disease flares and the need for additional RTX cycles and higher dosages of immunomodulatory therapies.

Hidradenitis suppurativa (HS) is a debilitating chronic inflammatory skin disease resulting in non-healing wounds affecting body areas of high hair follicle and sweat gland density. The pathogenesis of HS is not well understood but appears to involve dysbiosis-driven aberrant activation of the innate immune system leading to excessive inflammation. Marked dysregulation of antimicrobial peptides and proteins (AMPs) in HS is observed, which may contribute to this sustained inflammation. Here, we analyzed HS skin transcriptomes from previously published studies and integrated these findings through a comparative analysis with a published wound healing data set and with immunofluorescence and qPCR analysis from new HS patient samples. Among the top differently expressed genes between lesional and non-lesional HS skin were members of the S100 family as well as dermcidin, the latter known as a sweat gland-associated AMP and one of the most downregulated genes in HS lesions. Interestingly, many genes associated with sweat gland function, such as secretoglobins and aquaporin 5, were decreased in HS lesional skin and we discovered that these genes demonstrated opposite expression profiles in healing skin. Conversely, HS lesional and wounded skin shared a common gene signature including genes encoding for S100 proteins, defensins, and genes encoding antiviral proteins. Overall, our results suggest that the pathogenesis of HS may be driven by changes in AMP expression and altered sweat gland function, and may share a similar pathology with chronic wounds., Competing Interests: ASM received research support from Silab and is now consulting for this company. This relationship does not confer any conflict of interest. This role as consultant does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Eczema is a skin condition which affects up to 10% to 20% of people worldwide. Previous literature finds that low vitamin D levels may be a risk factor for eczema, but the association is not clear., Methods: We used the cross-sectional data from U.S. National Health and Nutrition Examination Survey 2005-2006. Adults were defined as 20 years and older. The association between eczema and serum 25-hydroxyvitamin D [25(OH)D] was estimated using multivariate logistic regression models adjusted for patient demographics, lifestyle variables, stress, and medical comorbidities. Restricted cubic spline analyses were performed to explore nonlinear relationship. We also stratified by race., Results: A total of 3921 adults were included in the analysis. The prevalence of ever-report of eczema was 7.94% in US adults. Reports of eczema were higher in people with higher socioeconomic status, depressive symptoms, previous history of asthma and hay fever, female, sampled in summer, and nonHispanic white. The logistic regression found higher odds ratio of eczema in vitamin D deficiency group (<50 nmol/L) compared to sufficiency group (>75 nmol/L) (OR = 1.81, 95% CI: 1.09-3.01, P = 0.02). The spline analysis found an inverted U-shaped relationship between eczema and serum 25(OH)D level. Eczema risk reached the highest at around 45 nmol/L, with decreasing risk in both directions away from this value. This relationship was absent in nonHispanic black population., Conclusion: Vitamin D is associated with reports of eczema in nonHispanic white population, but not in the nonHispanic black population in the United States., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Secukinumab (also known as AIN-457) is a human monoclonal antibody targeting IL-17A, which has been recently FDA-approved for the treatment of moderate to severe psoriasis and psoriatic arthritis with coexistent moderate to severe plaque psoriasis based on clinical trials demonstrating excellent efficacy. This review will address the rationale for targeting the IL-23/Th17/IL-17 axis, the role of IL-17 and Th17 cells in psoriasis and other chronic inflammatory diseases, and will examine pre-clinical studies, pharmacologic properties, clinical efficacy, and the safety profile of secukinumab.

Some blistering eruptions are self-limited, but others are life threatening, and prompt diagnosis and management are critical. The clinical presentation of vesicles and bullae suggests a broad differential and this article (1) highlights some common diagnoses that may be encountered by primary care physicians and subspecialists; (2) provides a possible systematic diagnostic approach to such patients, including history, physical examination, and relevant work-up., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective. We report a rare case of keloidal scleroderma and provide an analysis of similar cases. Results. A 41 year-old woman presented with dark brown, indurated, exophytic nodules over the chest along with smaller hyperpigmented plaques scattered over the abdomen, with concomitant sclerodactyly. The clinical, laboratory, and pathological findings were consistent with a diagnosis of keloidal scleroderma. The patient was treated with methotrexate, resulting in reduced firmness of her plaques and no new lesions. A literature review of previously reported cases was performed using keywords including keloidal morphea, keloidal scleroderma, nodular morphea, and nodular scleroderma. In our review, the majority of patients were African American and female. 91% of cases had nodular lesions with distribution on the trunk. The majority of patients exhibited sclerodactyly and pulmonary involvement was reported in 28%1. The majority of patients were ANA positive (63%) and only 10% demonstrated anti-SCL-70 positivity. Conclusion. Keloidal scleroderma is a rare presentation, which can often be clinically confused with keloid and scar formation. Due to this being a rare variant, our knowledge of treatment options and efficacy is limited. Methotrexate could be considered as an initial treatment option for patients with progressive keloidal scleroderma.

UVB radiation is a potent immunosuppressive agent that inhibits cell-mediated immune responses. The mechanisms by which UVB radiation influences cell-mediated immune responses have been the subject of extensive investigation. However, the role of innate immunity on photoimmunological processes has received little attention. The purpose of this study was to determine whether Toll-like receptor-4 (TLR4) contributed to UV-induced suppression of contact hypersensitivity (CHS) responses. TLR4⁻/⁻ and wild type C57BL/6 (TLR4+/+) mice were subjected to a local UVB immunosuppression regimen consisting of 100 mJ/cm² UVB radiation followed by sensitization with the hapten DNFB. Wild type TLR4+/+ mice exhibited significant suppression of contact hypersensitivity response, whereas TLR4⁻/⁻ developed significantly less suppression. The suppression in wild type TLR4+/+ mice could be adoptively transferred to naïve syngeneic recipients. Moreover, there were significantly fewer Foxp3 expressing CD4+CD25+ regulatory T-cells in the draining lymph nodes of UV-irradiated TLR4⁻/⁻ mice than TLR4+/+ mice. When cytokine levels were compared in these two strains after UVB exposure, T-cells from TLR4+/+ mice produced higher levels of IL-10 and TGF-β and lower levels of IFN-γ and IL-17. Strategies to inhibit TLR4 may allow us to develop immunopreventive and immunotherapeutic approaches for management of UVB induced cutaneous immunosuppression., (Copyright © 2011. Published by Elsevier Inc.)

Objective: To evaluate the effects and mechanisms of action of vitamin D on human uterine leiomyoma (HuLM) cell proliferation in vitro., Design: Laboratory study., Setting: University hospitals., Patients(s): Not applicable., Interventions(s): Not applicable., Main Outcome Measure(s): HuLM cells were treated with 1,25-dihydroxyvitamin D3 (vitamin D), and cell proliferation was assayed by the methylthiazolyl tetrazolium technique. proliferating cell nuclear antigen (PCNA), BCL-2, BCL-w, cyclin-dependent kinase (CDK) 1, and catechol-O-methyltransferase (COMT) protein levels were analyzed by Western blotting. COMT mRNA and enzyme activity were assayed by quantitative reverse-transcription polymerase chain reaction (RT-PCR) and high-performance liquid chromatography analysis, respectively. The role of COMT was evaluated in stable HuLM cells by silencing COMT expression., Result(s): Vitamin D inhibited the growth of HuLM cells by 47±0.03% at 1 μM and by 38±0.02% at 0.1 μM compared with control cells at 120 hours of treatment. Vitamin D inhibited extracellular signal-regulated kinase activation and down-regulated the expression of BCL-2, BCL-w, CDK1, and PCNA. Western blot, RT-PCR, and enzyme assay of COMT demonstrated inhibitory effects of vitamin D on COMT expression and enzyme activity. Silencing endogenous COMT expression abolished vitamin D-mediated inhibition of HuLM cell proliferation., Conclusion(s): Vitamin D inhibits growth of HuLM cells through the down-regulation of PCNA, CDK1, and BCL-2 and suppresses COMT expression and activity in HuLM cells. Thus, hypovitaminosis D appears to be a risk factor for uterine fibroids., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Proteomic analysis of murine skin has shown that a variety of heat shock proteins (HSPs) are constitutively expressed in the skin. Using murine allergic contact hypersensitivity as a model, we investigated the role of two heat shock proteins, HSP27 and HSP70, in the induction of cutaneous cell-mediated immune responses. Immunohistochemical examination of skin specimens showed that HSP27 was present in the epidermis and HSP70 was present in both the epidermis and dermis. Inhibition of HSP27 and HSP70 produced a reduction in the 1-fluoro-2,4-dinitrobenzene contact hypersensitivity response and resulted in the induction of Ag-specific unresponsiveness. Treatment of dendritic cell cultures with recombinant HSP27 caused in the up-regulation of IL-1beta, TNF-alpha, IL-6, IL-12p70, and IL-12p40 but not IL-23p19, which was inhibited when Abs to HSP27 were added. The 1-fluoro-2,4-dinitrobenzene-conjugated dendritic cells that had been treated with HSP27 had an increased capacity to initiate contact hypersensitivity responses compared with control dendritic cells. This augmented capacity required TLR4 signaling because neither cytokine production by dendritic cells nor the increased induction of contact hypersensitivity responses occurred in TLR4-deficient C3H/HeJ mice. Our findings indicate that a cascade of events occurs following initial interaction of hapten with the skin that includes increased activity of HSPs, their interaction with TLR4, and, in turn, increased production of cytokines that are known to enhance Ag presentation by T cells. The results suggest that HSPs form a link between adaptive and innate immunity during the early stages of contact hypersensitivity.