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BACKGROUND: Janus kinase inhibitors (JAKinibs) have the potential to dramatically alter the landscape of atopic dermatitis (AD) management due to their promising efficacy results from phase 3 trials and rapid onset of action. However, JAKinibs are not without risk, and their use is not appropriate for all AD patients, making this a medication class that dermatologists should understand and consider when treating patients with moderate-to-severe AD. OBJECTIVE: This consensus expert opinion statement from the International Eczema Council (IEC) provides a pragmatic approach to prescribing JAKinibs, including choosing appropriate patients, dosing, clinical and lab monitoring, as well as long-term use. METHODS: An international cohort of authors from the IEC with expertise in JAKinibs selected topics of interest and were formed into authorship groups covering 10 subsections. The groups performed topic-specific literature reviews, consulted up-to-date adverse event (AE) data, referred to product labels and provided analysis and expert opinion. The manuscript guidance and recommendations were reviewed by all authors as well as the IEC Research Committee. RESULTS: We recommend JAKinibs be considered for patients with moderate to severe AD seeking the benefits of rapid reduction in disease burden and itch, oral administration, and the potential for flexible dosing. Baseline risk factors should be assessed prior to prescribing JAKinibs, including increasing age, venous thromboembolisms, malignancy, cardiovascular health, kidney/liver function, pregnancy and lactation, and immunocompetence. Patients being considered for JAKinib therapy should be current on vaccinations and we provide a generalized framework for laboratory monitoring, though clinicians should consult individual product labels for recommendations as there are variations among the JAKinib class. Patients who achieve disease control should be maintained on the lowest possible dose, as many of the observed AEs occurred in a dose-dependent manner. Future studies are needed in AD patients to assess the durability and safety of continuous long-term use of JAKinibs, combination medication regimens, and the effects of flexible, episodic treatment over time. CONCLUSIONS: The decision to initiate a JAKinib should be shared among patient and provider, accounting for AD severity and personal risk/benefit assessment, including consideration of baseline health risk factors, monitoring requirements and treatment costs.

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Digital twins, innovative virtual models synthesizing real-time biological, environmental, and lifestyle data, herald a new era in personalized medicine, particularly dermatology. These models, integrating medical-purpose Internet of Things (IoT) devices, deep and digital phenotyping, and advanced artificial intelligence (AI), offer unprecedented precision in simulating real-world physical conditions and health outcomes. Originating in aerospace and manufacturing for system behavior prediction, their application in healthcare signifies a paradigm shift towards patient-specific care pathways. In dermatology, digital twins promise enhanced diagnostic accuracy, optimized treatment plans, and improved patient monitoring by accommodating the unique complexities of skin conditions. However, a comprehensive review across PubMed, Embase, Web of Science, Cochrane, and Scopus until February 5th, 2024, underscores a significant research gap; no direct studies on digital twins' application in dermatology is identified. This gap signals challenges, including the intricate nature of skin diseases, ethical and privacy concerns, and the necessity for specialized algorithms. Overcoming these barriers through interdisciplinary efforts and focused research is essential for realizing digital twins' potential in dermatology. This study advocates for a proactive exploration of digital twins, emphasizing the need for a tailored approach to dermatological care that is as personalized as the patients themselves.

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Background: Dermatology journals play an essential role in the distribution and promotion of scientific and medical information. Despite this, there are little data on governance structure with respect to its editors, owners, and journal boards that oversee the day-to-day operations for these entities. Objective: This study aimed to explore the current governance structure of dermatology journals and best practice recommendations. Methods: The editors-in-chief of the major dermatology journals participated in an online survey of 29 questions to examine general statistics of each journal, open access model, governance structure, and process for editor selection or dismissal. Results: Of the 52 journal responses, 29 (55.8%) are society-owned journals with 19 (65.5%) primarily governed by a society board, while 18 (34.6%) have an advisory committee or alternative body. Most editor(s)-in-chief (56.9%) serve between 3- and 5-year terms, while 84.6% have the option of at least one renewal. Even though the selection, evaluation, and dismissal processes differed between the journals, generalized best practice recommendations were developed to help improve their overall organization and management. Conclusions: The oversight structure of dermatology journals varies, and some do not follow current best practice recommendations. Transparency regarding leadership, governance, and due process is needed to maintain editorial independence and integrity.

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INTRODUCTION: The review article explores the evolving role of Bruton's tyrosine kinase (BTK) inhibitors in immune-mediated dermatological conditions, addressing significant gaps in current treatment approaches. AREAS COVERED: The review comprehensively discusses the mechanisms of action of BTK inhibitors, including irreversible and reversible inhibitors. Clinical applications of BTK inhibitors in dermatological diseases such as pemphigus, chronic spontaneous urticaria (CSU), hidradenitis suppurativa (HS), systemic lupus erythematosus (SLE), and atopic dermatitis are explored, highlighting recent advancements and ongoing clinical trials. Potential advantages of BTK inhibitors over existing therapies and challenges in translating preclinical findings to clinical outcomes are discussed. EXPERT OPINION/COMMENTARY: BTK inhibitors represent a promising therapeutic avenue for immune-mediated dermatological conditions, offering oral administration, targeted pathway inhibition, and a favorable safety profile compared to biologic therapies. Ongoing research and clinical trials hold the potential to address unmet needs and reshape the therapeutic landscape in dermatology.

Our manuscript explores how a new class of medications called Bruton tyrosine kinase (BTK) inhibitors could revolutionize the treatment of skin conditions caused by the immune system. These conditions, like chronic spontaneous urticaria (CSU), pemphigus, and systemic lupus erythematosus (SLE), often lack effective treatments. BTK inhibitors work by targeting specific pathways in the immune system, offering hope for patients with these challenging conditions.We reviewed clinical trials and research studies to understand how BTK inhibitors could benefit patients. One significant advantage of BTK inhibitors is their ability to provide targeted therapy, meaning they can specifically block the faulty immune responses driving these conditions without affecting the entire immune system. This targeted approach could lead to fewer side effects compared to current treatments, such as corticosteroids or immunosuppressants, which can have widespread effects on the body.Overall, BTK inhibitors represent a promising new approach to treating immune-mediated skin conditions. With further research and development, they could offer safer and more effective alternatives to current treatments, improving the lives of patients worldwide.

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BACKGROUND: Pemphigus is a rare autoimmune blistering disease (AIBD) with potentially life-threatening consequences. Establishing minimal clinically important differences (MCIDs) for disease severity scores like the Pemphigus Disease Area Index (PDAI) is crucial for assessing treatment efficacy. OBJECTIVE: To calculate MCIDs for both improvement and deterioration in PDAI scores in patients with pemphigus vulgaris (PV) and pemphigus foliaceous (PF) using the anchor-based method. METHODS: A total of 41 pemphigus patients were recruited, with 35 meeting the MCID analysis criteria. The anchor-based method was employed to calculate MCIDs for PDAI scores against the 15-point Likert scale and the Physician Global Assessment Visual Analogue Scale (PGA-VAS) anchors. Receiver operating characteristic (ROC) curves were employed to determine optimal MCID cutpoints with the highest Youden Index (J). The 15-point Likert scale scores the change in disease severity spanning from -7 to +7, designed to quantify the extent of disease improvement/deterioration since the preceding visit. RESULTS: The MCID for improvement in PDAI activity scores was 2.65 points using the 15-point Likert scale (78.7% correct classification; sensitivity 75.9%; specificity 73.5%) and 2.5 points using the PGA-VAS as the anchor (78.0% correct classification; sensitivity 84.4%; specificity 68.2%). Given the slightly higher correct classification rate using the 15-point Likert scale anchor, the MCID of 2.65 points was selected for PDAI activity score improvement. In contrast, MCID for deterioration consistently remained at 2.5 points for the 15-point Likert scale anchor (81.0% correct classification; sensitivity 72.7%; specificity 81.0%) and 2.5 points for the PGA-VAS anchor (70.9% correct classification; sensitivity 69.6%; specificity 76.9%). CONCLUSION: This study marks the inaugural attempt at MCID determination for PDAI scores in pemphigus, filling a critical knowledge gap. The study's calculated MCIDs provide essential benchmarks for clinical trials, treatment evaluation, and research design optimisation. Future studies should explore international collaborations to examine potential cross-cultural variations in MCIDs.

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Physicians and surgeons have a threefold increased risk of glioblastoma compared with population controls. We discuss the potential role of dermatology neurotoxin and carcinogenic occupational exposure, particularly to formalin/formaldehyde; how to reduce those exposures; and the ethical imperative for dermatologists to protect themselves, their staff, and their patients.

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OBJECTIVES: To describe disease burden in individuals with moderate-to-severe atopic dermatitis (AD) in Australia and New Zealand (ANZ) and compare it with other geographic regions. METHODS: This multicentre, cross-sectional, observational study (MEASURE-AD) recruited consecutive adolescent and adult patients attending dermatology clinics in 28 countries. Data collected included scores of pruritus, disease severity, sleep, pain, disease control, work and quality of life. RESULTS: This study included 112 ANZ participants (Australia n = 72; New Zealand n = 40) from December 2019 to December 2020. Treatments included topicals (85.7% of patients), non-biologic systemic therapy (28.6%), phototherapy (9.8%) and dupilumab (4.5%). Mean Eczema Area and Severity Index (EASI) score was 22.3 (95% CI 19.6-25.0) and Patient-Oriented Eczema Measurement (POEM) score was 18.4 (95% CI 16.8-20.0). Pruritus Numerical Rating Scale (NRS) was 6.0 (95% CI 5.5-6.6) (50% had severe pruritus) and Dermatology Life Quality Index (DLQI) 14.3 (95% CI 12.8-15.8). ADerm-Impact sleep domain score was 15.1 (95% CI 13.2-16.9). ADerm-Symptom Scale worst skin pain domain score was 5.0 (95% CI 4.3-5.6). Work Productivity and Activity Impairment (WPAI) percentages indicated work and productivity impairment. Inadequately controlled AD was self-reported by 41%, with 9.7 flares in the past 6 months. Scores of pruritus, disease severity, sleep, pain, disease control and quality of life in ANZ were often the highest of all the geographic regions studied. CONCLUSION: ANZ patients with AD have a high disease burden, which extends across multiple facets of daily life. Many are inadequately controlled with existing therapies.

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Hereditary hemochromatosis (HH) is a genetic disorder leading to excessive iron absorption, impacting multiple organs, notably the skin, nails and mucosae. The objective of this study is to elucidate the dermatologic manifestations, associated symptoms, pathophysiology and management recommendations of HH. We searched five primary databases (PubMed, Embase, Cochrane Library, Scopus and Web of Science) up to April 2023. Non-English articles were included to minimize language bias. The studies were evaluated using Oxford Centre for Evidence-based Medicine standards, with adherence to PRISMA guidelines. Inaccessible articles were directly sourced from authors. Out of the initial 1582 publications from 1904 to 2023, 22 studies (19 in English, 2 in French and 1 in German) were selected. Most reports were from the USA, UK and France and were predominantly case reports, covering 148 patients with skin symptoms related to hereditary hemochromatosis. We collected data on the cutaneous findings and, when available, their histopathological features. The current study highlights the scope, variety and traits of dermatologic symptoms in hereditary hemochromatosis, pinpointing research gaps and areas for future exploration. Our review accentuates the diverse dermatological manifestations of hereditary hemochromatosis, notably hyperpigmentation, hypertrichosis and resistant pruritus, often linked to excessive iron deposition and subsequent impairment of skin cell function. We also found controversial evidence indicating that skin cancers seem to be associated with hereditary hemochromatosis. Porphyria cutanea tarda and hereditary hemochromatosis were frequently reported together. Given hereditary hemochromatosis's genetic nature, early identification in one individual can substantially guide familial care and preemptive interventions. Clinicians should prioritize hereditary hemochromatosis as a differential when patients present with specific dermatological symptoms, especially in sun-exposed regions. A rigorous assessment ensures accurate diagnosis, facilitating optimal management for both the patient and their family.

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Efforts to achieve gender equity of health professionals should be a priority in all fields of medicine, including academic dermatology. This review aimed, first, to summarize available evidence about the status of gender equity in various domains of academic dermatology-headship positions, salary, editor and editorial board appointments, publications, conference presentations, receipt of research grants and academic prizes-second, to identify challenges to achieving gender equity and, third, to articulate the components of a multifaceted strategy for gender parity. A variety of databases were searched. Manual searching of reference lists and searching of grey literature were also undertaken. It was found that, despite improvements in some domains, the gender inequity persists in all of the above-mentioned areas of academic dermatology. Challenges to achieve gender parity include time in pregnancy, disproportionate participation in childrearing and domestic tasks compared with men, suboptimal legislation in many jurisdictions for parenting and childcare leave, and unconscious biases about women. Elements of a multipronged approach include strengthening women's dermatology societies that advocate for women in academia; celebrating the careers of distinguished female academic dermatologists; mentoring; promoting leadership courses; striving for a greater representation of women among editors-in-chief, authors, and conference presenters, among others; seeking better pay, leave conditions and other work entitlements; conducting high-quality research about gender inequity in academic dermatology; imposing sanctions for violations of gender equity; supporting dermatologists' health; and learning from the experience of other fields of academic medicine.

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BACKGROUND: Inherited epidermolysis bullosa (EB) is a clinically and genetically heterogeneous group of skin fragility disorders characterized by blister formation following minor trauma. Four major types are distinguished based on the level of cleavage within the skin. Most EB forms present severely disabling cutaneous and systemic signs and symptoms. Management relies on daily time-consuming and distressing topical medications, and symptomatic treatment of systemic findings. Disease manifestations, symptoms, and daily care strongly affect patient and caregiver quality of life (QoL). To date, there are two validated EB-specific questionnaires, the "Quality of Life in Epidermolysis Bullosa" (QOLEB) and the "Epidermolysis Bullosa Burden of Disease" (EB-BoD) for the evaluation of patient and family disease burden, respectively. The aim of our study was to develop an Italian translation of the two questionnaires and to pilot-test them. METHODS: The guidelines for translation and cross-cultural adaptation of health-related QoL measures were followed. Initially, two separate translations were generated for each questionnaire, and subsequently reconciled by an expert committee. This was followed by a back-translation process. The original texts and all translations underwent revision by the expert committee, resulting in definitive versions. The final versions were then tested in a pilot study involving cognitive debriefing in a group of 17 families, representative of all EB major types. RESULTS: The translation and reconciliation process led to minor changes to obtain semantic/idiomatic/cultural equivalence of the Italian versions with the original ones and to reconcile the questions with the answer options. The cognitive debriefing process showed a good understanding and did not require text modifications. CONCLUSIONS: The Italian versions of the QOLEB and EB-BoD provide valuable tools in everyday clinical practice of reference centers, and they allow the participation in multicenter international real-life observational studies as well as in controlled clinical trials. They enable the identification of disease-specific psychological and socioeconomic challenges for EB patients and their families, guiding targeted interventions to ensure appropriate and timely care.

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TRIAL DESIGN: Pemphigus is a rare but life-threatening autoimmune disease requiring long-term treatment that minimizes corticosteroid (CS) exposure while providing consistent disease control. The phase 2 pemphigus study of oral, reversible, covalent Bruton tyrosine kinase inhibitor rilzabrutinib demonstrated rapid and sustained efficacy with well-tolerated safety. METHODS: Adults (aged 18-80 years) were randomized 1:1 to 400 mg rilzabrutinib (n = 65) or placebo (n = 66) twice daily (with CS ≤ 0.5 mg/kg/d) for 37 weeks in the phase 3 PEGASUS study in moderate-to-severe pemphigus vulgaris/pemphigus foliaceus. RESULTS: The primary endpoint of complete remission from week 29 to week 37 with the amended endpoint CS dose ≤10 mg/d was not significant for 13 of 54 (24%) rilzabrutinib versus 10 of 55 (18%) placebo patients with PV (P = .45). Secondary endpoints showed numerical but nonsignificant improvements with rilzabrutinib (vs placebo) in reduced CS use, prolonged complete remission duration, and faster time to first complete remission. CONCLUSIONS: Overall, rilzabrutinib was well-tolerated, with similar adverse events reported in both groups. Using minimal CS dose ≤10 mg/d and excluding remote observations, the primary efficacy endpoint was not met. However, results from a prespecified sensitivity analysis using CS dose ≤5 mg/d, considering all observations, and including all patients support Bruton tyrosine kinase inhibition as a viable therapeutic approach for pemphigus.

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This review aims to present a comprehensive synthesis of the existing treatment modalities for keratosis pilaris (KP) and evaluate their therapeutic efficacy. KP is a prevalent chronic dermatological condition typified by its unique 'chicken skin appearance', with the cheeks being the most commonly involved sites. Numerous therapeutic interventions have emerged, given its substantial prevalence and impact on skin aesthetics and psychological wellbeing. Nonetheless, a consistent therapeutic response has been challenging to achieve. This review endeavours to collate and critically appraise the current treatment landscape for KP. An exhaustive literature search was performed using databases such as Ovid, PubMed and Scopus. From an initial count of 459 articles identified after deduplication, 52 were selected for inclusion after a thorough full-text examination for articles with concrete outcome data highlighting the efficacies of different therapeutic modalities; articles that lacked data or were tangential to the core focus on KP treatment were excluded. The included articles were then catalogued based on the nature of treatment strategies and their respective outcomes. Among the various therapeutic interventions, laser and light modalities appear to be supported by the most substantial evidence base. Notably, the Nd:YAG (neodymium-doped yttrium-aluminium-garnet) laser, attributed to its longer wavelength, emerged as a preferred option. While other therapeutic avenues have also exhibited notable improvements in skin texture and discolouration relative to baseline, the inconsistency in outcome measures underscores the need for a standardized, KP-specific scoring system to foster a more coherent comparison across treatments. Based on the current evidence, Nd:YAG laser therapy demonstrates promising effectiveness with a relatively favourable side-effect profile. However, the landscape of KP treatment is multifaceted, and further studies are essential to solidify recommendations.

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BACKGROUND: Bullous pemphigoid (BP) is a rare, autoimmune, blistering skin disease associated with high disease burden, profoundly decreased quality of life and increased morbidity. Emerging evidence supports an important role for type 2 inflammation in disease pathogenesis. Current management relies on topical and/or systemic corticosteroids, non-selective immunosuppressants and antibiotics with anti-inflammatory properties, which are all limited by side effects and toxicities. Therefore, targeted, efficacious and safe therapies are needed. Dupilumab blocks the shared receptor component for interleukin (IL)-4 and IL-13, key and central drivers of type 2 inflammation. Several reports of patients successfully treated with dupilumab have been published; however, dupilumab has not been formally assessed in a double-blind, placebo-controlled trial. OBJECTIVES: We report the design of LIBERTY-BP ADEPT, a multicenter, randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of dupilumab in adults with BP. METHODS: LIBERTY-BP ADEPT comprises a 35-day screening, 52-week treatment and 12-week follow-up period. Approximately 98 adults aged 18-90 years with moderate-to-severe BP are being enrolled at 51 sites on 4 continents and randomized 1:1 to subcutaneous dupilumab or placebo every 2 weeks. All participants will receive concomitant oral corticosteroids (OCS). PLANNED OUTCOMES: The primary endpoint is the proportion of patients achieving complete remission off steroid therapy at week 36. Key secondary endpoints include total cumulative OCS dose to week 36, percent change and proportion of patients with ≥ 4-point reduction in the weekly average of daily Peak Pruritus Numerical Rating Scale from baseline to week 36 and percent change in Bullous Pemphigoid Area Index score from baseline to week 36. CONCLUSION: The trial results will provide evidence on whether the efficacy and safety of dupilumab support its use as a potential novel treatment approach for BP and will provide new insights into the role of type 2 inflammation in BP pathogenesis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04206553.

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