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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., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

The Eczema Area and Severity Index is an investigator-assessed instrument reporting clinical signs of atopic dermatitis. The instrument is extensively validated in both adult and paediatric populations and recommended as a core outcome measure to assess clinical signs by the Harmonising Outcome Measures for Eczema initiative in clinical trials and was recently recommended as an option to measure signs in clinical practice. Here, we review the validation of the instrument using standard assessment criteria, explore controversies and challenges to its universal applicability and highlight future electronic adaptations. We find that the instrument demonstrates adequate performance in the measurement properties recommended by the COnsensus-based Standards for the selection of health Measurement INstruments initiative for instruments reporting clinical signs, is clinically interpretable, and is suitable for all atopic dermatitis severities. Some validation gaps remain. Information reporting on its performance in diverse populations, with emphasis on deeply pigmented skin, is promising though limited. Technological adaptations are demonstrating promising initial validation results and may facilitate remote and/or automated assessments assisting clinical care and decentralized clinical trials in the future. We find no strong evidence limiting its use in trials or clinical practice although questions pertaining to the effect of investigator training remain. We recommend that the Eczema Area and Severity Index be used in all interventional atopic dermatitis trials and be considered alongside other recommended clinical practice severity instruments., (© 2024 European Academy of Dermatology and Venereology.)

Importance: Outcome measurement is an essential component of value-based health care and can aid patient care, quality improvement, and clinical effectiveness evidence generation. The Harmonising Outcome Measures for Eczema Clinical Practice initiative aims to identify a list of validated, feasible, outcome measurement instruments recommended to measure atopic dermatitis (AD) in the clinical practice setting. The clinical practice set is a list of instruments that clinicians can pick and choose from to suit their needs in the context of clinical care., Objective: To recommend instruments to measure clinical signs of AD in clinical practice., Evidence Review: Following the predefined roadmap, a mixed methods design was implemented and incorporated systematic reviews and qualitative consensus methods. Previous systematic reviews identified few clinical signs instruments with sufficient validation for recommendation. An updated systematic review evaluating the validity of clinical signs instruments informed an international meeting to reach consensus on recommended instruments to measure AD clinical signs in clinical practice. Consensus was defined as less than 30% disagreement. An in-person consensus exercise was held in Montreal, Canada, on October 16, 2022. The 34 attendees included patient and patient advocate research partners, health care professionals, researchers, methodologists, and industry representatives., Findings: The updated systematic review found that the Eczema Area and Severity Index (EASI), Scoring Atopic Dermatitis, and objective Scoring Atopic Dermatitis were the only instruments that demonstrated sufficient performance in all assessed measurement properties. The modified EASI and Signs Global Assessment × Body Surface Area instruments were also recommended. The EASI, Validated Investigator Global Assessment, and Investigator's Global Assessment multiplied by or measured concurrently with a body surface area measure achieved consensus in criteria and were adopted., Conclusions and Relevance: This consensus statement by the Harmonising Outcome Measures for Eczema initiative suggests that when assessing and documenting clinical signs of AD, there are several valid and feasible instruments that can best fit a clinician's specific practice needs. These instruments should improve and standardize the documentation of signs severity, help determine the effect of treatment, facilitate the generation of clinical effectiveness evidence, and enhance the implementation of value-based health care.

Background: Atopic dermatitis (AD) and inflammatory bowel disease (IBD) share genetic susceptibility loci with immune regulation functions. Atopic dermatitis was associated with IBD mostly in database studies., Objective: To assess whether AD is associated with an increased prevalence of IBD in a tertiary dermatology clinic., Methods: A retrospective cross-sectional analysis using medical records of adults with verified AD followed up at an AD clinic, compared with age- and sex-matched (1:2) controls from the general dermatology clinic in the same hospital., Results: Overall, 9/364 (2.47%) of patients with AD had verified IBD, compared with 7/725 (0.97%) of controls (p = 0.0512). In multivariable logistic regression adjusting for age, gender and smoking, the association became significant (adjusted OR = 3.89, 95% CI: 1.28-11.85). Stratified for AD severity, only moderate-to-severe AD was associated with IBD (p = 0.035), with an adjusted OR of 4.45 (95% CI: 1.43-13.90). Mild AD was not associated with IBD, but the study was not powered for this sub-analysis. In the AD group, older age was associated with IBD (p = 0.0172)., Conclusion: This study, in a robustly verified cohort of patients, supports an association between AD, especially the moderate-to-severe forms, and IBD. A multidisciplinary approach for patients with moderate-to-severe AD should extend to consider IBD., (© 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.)

Introduction: Atopic dermatitis (AD) is characterized by intense itch and other symptoms that negatively impact quality of life (QoL). This study evaluates the effect of upadacitinib (an oral selective Janus kinase inhibitor) monotherapy on patient-reported outcomes (PROs) among adults and adolescents with moderate-to-severe AD over 16 weeks., Methods: This integrated analysis of the double-blind, placebo-controlled periods of phase 3 monotherapy clinical trials Measure Up 1 (NCT03569293) and Measure Up 2 (NCT03607422) assessed itch (Worst Pruritus Numerical Rating Scale [WP-NRS] and SCORing Atopic Dermatitis [SCORAD]), skin pain and symptom severity (AD Symptom Scale), symptom frequency (Patient-Oriented Eczema Measure), sleep (AD Impact Scale [ADerm-IS] and SCORAD), daily activities and emotional state (ADerm-IS), QoL (Dermatology Life Quality Index [DLQI] and Children's DLQI), mental health (Hospital Anxiety and Depression Scale), and patient impressions (Patient Global Impression of Severity, Patient Global Impression of Change, and Patient Global Impression of Treatment)., Results: Data from 1683 patients (upadacitinib 15 mg, n = 557; upadacitinib 30 mg, n = 567; placebo, n = 559) were analyzed. A greater proportion of patients receiving upadacitinib versus placebo experienced improvements in itch (≥ 4-point improvement on WP-NRS) by week 1 (upadacitinib 15 mg, 11.2%; upadacitinib 30 mg, 17.7%; placebo, 0.5%; P < 0.001), with response rates sustained through week 16 (upadacitinib 15 mg, 47.1%; upadacitinib 30 mg, 59.8%; placebo, 10.4%; P < 0.001). Improvements were similar for PROs assessing skin pain/symptoms, sleep, daily activities, QoL, emotional state, mental health, and patient impressions of disease severity and treatment. Responses generally improved rapidly (within 1-2 weeks), increased through weeks 4-6, and were maintained through week 16., Conclusions: Once-daily oral upadacitinib monotherapy improved response rates across PROs compared with placebo. Upadacitinib therapy resulted in rapid, sustained improvements in PROs measuring symptom burden and QoL in adults and adolescents with moderate-to-severe AD., Trial Registration: ClinicalTrials.gov identifiers, NCT03569293 and NCT03607422., (© 2024. The Author(s).)

Background: The Harmonising Outcome Measures for Eczema (HOME) initiative has agreed upon the Core Outcome Set (COS) for use in atopic dermatitis (AD) clinical trials, but additional guidance is needed to maximize its uptake., Objectives: To provide answers to some of the commonly asked questions about using the HOME COS; to provide data to help with the interpretation of trial results; and to support sample size calculations for future trials., Methods and Results: We provide practical guidance on the use of the HOME COS for investigators planning clinical trials in patients with AD. It answers some of the common questions about using the HOME COS, how to access the outcome measurement instruments, what training/resources are needed to use them appropriately and clarifies when the COS is applicable. We also provide exemplar data to inform sample size calculations for eczema trials and encourage standardized data collection and reporting of the COS., Conclusions: By encouraging adoption of the COS and facilitating consistent reporting of outcome data, it is hoped that the results of eczema trials will be more comprehensive and readily combined in meta-analyses and that patient care will subsequently be improved., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Treat-to-target (T2T) is a pragmatic therapeutic strategy being gradually introduced into dermatology after adoption in several other clinical areas. Atopic dermatitis (AD), one of the most common inflammatory skin diseases, may also benefit from this structured and practical therapeutic approach. We aimed to evaluate existing data regarding the T2T approach in dermatology, with a specific focus on AD, as well as the views of International Eczema Council (IEC) members on the potential application of a T2T approach to AD management. To do so, we systematically searched for peer-reviewed publications on the T2T approach for any skin disease in the PubMed and Scopus databases up to February 2022 and conducted a survey among IEC members regarding various components to potentially include in a T2T approach in AD. We identified 21 relevant T2T-related reports in dermatology, of which 14 were related to psoriasis, five to AD, one for juvenile dermatomyositis and one for urticaria. In the IEC member survey, respondents proposed treatable traits (with itch, disease severity and sleep problems getting the highest scores), relevant comorbidities (with asthma being selected most commonly, followed by anxiety and depression in adults), recommended specialists that should define the approach in AD (dermatologists, allergists and primary care physicians were most commonly selected in adults), and applicable assessment tools (both physician- and patient-reported), in both adult and paediatric patients, for potential future utilization of the T2T approach in AD. In conclusion, while the T2T approach may become a useful tool to simplify therapeutic goals and AD management, its foundation in AD is only starting to build. A multidisciplinary approach, including a wide range of stakeholders, including patients, is needed to further define the essential components needed to utilize T2T in AD., (© 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.)

Background: Core outcome sets (COS) are consensus-driven sets of minimum outcomes that should be measured and reported in all clinical trials. COS aim to reduce heterogeneity in outcome measurement and reporting, and selective outcome reporting. Implementing COS into clinical trials is challenging. Guidance to improve COS uptake in dermatology is lacking., Objectives: To develop a structured practical guide to COS implementation., Methods: Members of the Harmonising Outcome Measurement for Eczema (HOME) executive committee developed an expert opinion-based roadmap founded on a combination of a review of the COS implementation literature, the Core Outcome Measures in Effectiveness Trials (COMET) initiative resources, input from HOME members and experience in COS development and clinical trials., Results: The data review and input from HOME members was synthesized into themes, which guided roadmap development: (a) barriers and facilitators to COS uptake based on stakeholder awareness/engagement and COS features; and (b) key implementation science principles (assessment-driven, data-centred, priority-based and context-sensitive). The HOME implementation roadmap follows three stages. Firstly, the COS uptake scope and goals need to be defined. Secondly, during COS development, preparation for future implementation is supported by establishing the COS as a credible evidence-informed consensus by applying robust COS development methodology, engaging multiple stakeholders, fostering sustained and global engagement, emphasizing COS ease of use and universal applicability, and providing recommendations on COS use. Thirdly, incorporating completed COS into primary (trials) and secondary (reviews) research is an iterative process starting with mapping COS uptake and stakeholders' attitudes, followed by designing and carrying out targeted implementation projects. Main themes for implementation projects identified at HOME are stakeholder awareness/engagement; universal applicability for different populations; and improving ease-of-use by reducing administrative and study burden. Formal implementation frameworks can be used to identify implementation barriers/facilitators and to design implementation strategies. The effect of these strategies on uptake should be evaluated and implementation plans adjusted accordingly., Conclusions: COS can improve the quality and applicability of research and, so, clinical practice but can only succeed if used and reported consistently. The HOME implementation roadmap is an extension of the original HOME roadmap for COS development and provides a pragmatic framework to develop COS implementation strategies., Competing Interests: Conflicts of interest Y.A.L. has received honoraria or fees from AbbVie, Sanofi, Genentech, Regeneron, Pfizer and Dexcel Pharma, an independent research grant from AbbVie and has – without personal compensation – provided investigator services for Eli Lilly, Pfizer and AbbVie, all unrelated to this study. E.L.S. reports personal fees from Advances in Cosmetic Medical Derm Hawaii, AbbVie, Amgen, AOBiome, Arcutis Biotherapeutics, Arena Pharmaceuticals, Aslan Pharma, Boehringer Ingelheim USA, Boston Consulting Group, Bristol Myers Squibb, Collective Acumen (CA), CorEvitas, Dermira, Eli Lilly, Evelo Biosciences, Evidera, ExcerptaMedica, FIDE, Forte Bio RX, Galderma, GlaxoSmithKline, Incyte, Janssen, Johnson & Johnson, Kyowa Kirin Pharmaceutical Development, LEO Pharma, Medscape, Merck, MauiDerm, MLG Operating, MJH Holding, Pfizer, Physicians World, PRImE, Regeneron, Revolutionizing Atopic Dermatitis, Roivant, Sanofi-Genzyme, Trevi Therapeutics, Valeant, Vindico Medical Education and WebMD. He also reports grants (or serves in a Principal Investigator role for) from AbbVie, Acrotech Biopharma, Amgen, Arcutis, Aslan, Castle Biosciences, CorEvitas, Dermavant, Dermira, Eli Lilly, Incyte, Kymab, Kyowa Kirin, National Jewish Health, LEO, Pfizer, Regeneron, Sanofi and Target RWE. These potential conflicts of interest have been reviewed and managed by Oregon Health & Science University. C.A. has received institutional funding from the Dr Wolff Group and Bionorica, and consultancy fees or honoraria from the Dr Wolff Group, Bionorica, Sanofi, LEO Pharma and RHEACELL. He was also involved in the development and testing of one of the HOME core outcome instruments [Recap of atopic eczema (RECAP)]. P.I.S. has received departmental independent research grants for the TREAT NL registry from pharma since December 2019; is involved in performing clinical trials with many pharmaceutical industries that manufacture drugs used for the treatment of, for example, psoriasis and atopic dermatitis, for which financial compensation is paid to the department/hospital; is Chief Investigator of the systemic and phototherapy atopic eczema registry (TREAT NL) for adults and children; and was involved in the development of one of the HOME core outcome instruments (RECAP). K.S.T. was involved in the development and testing of one of the HOME core outcome instruments (RECAP). J.S. reports institutional grants for investigator-initiated research from the German Federal Joint Committee (G-BA), the Federal Ministry of Health (BMG), Federal Ministry of Research and Education (BMBF), European Union, Federal State of Saxony, Novartis, Sanofi, ALK and Pfizer. He has also participated in advisory board meetings as a paid consultant for Sanofi, Eli Lilly and ALK. L.H. has received consultation fees from the University of Oxford on an educational grant funded by Pfizer, unrelated to the submitted work, and was involved in the development of the RECAP instrument. N.K. has received honoraria as a speaker/consultant for Sanofi, Maruho, AbbVie, Eli Lilly Japan, Mitsubishi Tanabe Pharma, Janssen Pharma, Taiho Pharmaceutical, Torii Pharmaceutical, Kyowa Kirin, Celgene Japan and LEO Pharma; and has received grants as an investigator from Maruho, Eli Lilly Japan, Sun Pharma, Taiho Pharmaceutical, Torii Pharmaceutical, Boehringer Ingelheim Japan, Kyowa Kirin, Jansen Pharma, Boehringer Ingelheim Japan, A2 Healthcare, AbbVie and LEO Pharma. H.C.W. chaired the HOME core outcome set initiative from 2008 to 2021 and was involved in the development of the Patient Oriented Eczema Measure (POEM). H.C.W., K.S.T. and L.H. are employed at the research centre where the POEM was developed. The University of Nottingham owns copyright to license POEM – chargeable for commercial users. L.A.A.G. and M.E.J. declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritus, skin pain, and sleep impacts, which are only reportable by patients themselves. The goal of this research is to evaluate the reliability, validity, and interpretability of the scores from three patient-reported outcome measures within the context of a clinical trial for adolescents and adults with moderate to severe AD., Methods: Data from a Phase 3 randomized, double-blind, placebo-controlled, multinational clinical trial for individuals 12-75 years of age with moderate to severe AD (AD Up [ClinicalTrials.gov NCT03568318]) were used to assess the reliability, validity, and interpretability of scores on the Worst Pruritus Numerical Rating Scale (NRS) and the Atopic Dermatitis Symptom and Impact Scales (ADerm-SS and ADerm-IS). Analyses were conducted separately for the adult and adolescent subgroups., Results: Of the 882 participants included in the psychometric analyses, the majority were adults ( n  = 769, 87.2%), male ( n  = 536, 60.8%), and white ( n  = 630, 71.4%). Multi-item scores from the ADerm-SS and ADerm-IS had good internal consistency reliability, and most scores demonstrated acceptable test-retest reliability. Scores from the three questionnaires demonstrated adequate validity, exhibiting correlations with other conceptually related outcome assessments and score differences between clinically distinct subgroups. Finally, the score interpretation analyses provide estimates for meaningful within-person change and between-groups difference thresholds that may be useful for future research in adults and adolescents with moderate to severe AD., Conclusions: These results provide evidence that the scores produced by the Worst Pruritus NRS, ADerm-SS, and ADerm-IS are reliable and construct-valid when completed by adults and adolescents with moderate to severe AD in a clinical trial setting. The results presented here expand upon the previous qualitative evidence of these tools and provide further support for their use in future clinical studies. While results are specific to clinical trials, next steps would be to evaluate the use of these questionnaires in clinical practice. This can provide clinicians and dermatologists a window into the patient's disease experience outside of the clinic, aid in shared decision making, and support a patient-centric approach to management of moderate to severe AD.

Competing Interests: Conflicts of interest: see Appendix S1.

Introduction: Three patient-reported outcome (PRO) questionnaires-Worst Pruritus Numerical Rating Scale (WP-NRS), Atopic Dermatitis Symptom Scale (ADerm-SS), and Atopic Dermatitis Impact Scale (ADerm-IS)-were developed to assess the symptoms and impacts of atopic dermatitis (AD). Severity strata for these PROs are needed to aid in their interpretation., Methods: Using data from a global, randomized, double-blind, placebo-controlled, phase 3 clinical trial (NCT03568318) of patients with moderate-severe AD (age ≥ 12 years), equipercentile linking analyses were conducted to define severity strata applying the Patient Global Impression of Severity as an anchor. Analyses were conducted separately for adults and adolescents, and then harmonized between the two age groups., Results: The sample included 769 adults and 113 adolescents. For the WP-NRS, 0 was associated with absent, 1-2 with minimal, 3 with mild, 4-7 with moderate, and 8-10 with severe. For the ADerm-SS Skin Pain, 0 was associated with absent, 1 with minimal, 2 with mild, 3-6 with moderate, and 7-10 with severe. For ADerm-SS 7-Item Total Symptom Score (TSS-7), 0-1 was associated with absent, 2-11 with minimal, 12-22 with mild, 23-47 with moderate, and 48-70 with severe. For ADerm-IS Sleep, 0 was associated with absent, 1-3 with minimal, 4-6 with mild, 7-20 with moderate, and 21-30 with severe. For ADerm-IS Daily Activities, 0 was associated with absent, 1-2 with minimal, 3-7 with mild, 8-25 with moderate, and 26-40 with severe. For ADerm-IS Emotional State, 0 was associated with absent, 1-2 with minimal, 3-8 with mild, 9-22 with moderate, and 23-30 with severe., Conclusions: These severity strata provide score interpretations of the WP-NRS, ADerm-SS, and ADerm-IS, translating these scores to simple and intuitive outcomes, which can inform clinical studies and clinical practice., Trial Registration Number: NCT03568318., (© 2022. The Author(s).)

Importance: Measuring outcomes in clinical practice can aid patient care, quality improvement, and real-world evidence generation. The Harmonising Outcome Measures for Eczema (HOME) Clinical Practice initiative is developing a list of validated, feasible instruments to measure atopic eczema in clinical care. Prior work identified symptoms and long-term control as the most important domains to measure in clinical practice. The Patient-Oriented Eczema Measure (POEM) and the Patient-Oriented Scoring Atopic Dermatitis Index (PO-SCORAD) were recommended by consensus to measure symptoms in clinical practice, but a need for instruments to measure itch intensity specifically was recognized. The HOME group also previously decided that long-term control should be captured by repeated measurements of eczema control. Recommended instruments to measure eczema control in clinical practice have not been defined., Objective: To recommend instruments to measure eczema control and itch intensity in patients with atopic eczema in clinical practice., Evidence Review: Available instruments to measure eczema control and itch intensity were identified through systematic reviews, informing a consensus process held at the HOME VIII virtual online meeting (October 6 and October 9, 2020). Feasibility aspects were highlighted to optimize instrument selection for the clinical practice. Consensus on an instrument was reached if fewer than 30% of the voters disagreed., Findings: Of 7 identified instruments, the Recap of Atopic Eczema (RECAP) and Atopic Dermatitis Control Tool (ADCT) were the recommended instruments to measure eczema control (3 of 63 [5%] and 7 of 69 [10%] of voters disagreed, respectively). A single-question patient global assessment garnered support, but the current available instrument did not reach consensus. Six available itch-intensity instruments were identified. Of them, 3 instruments were recommended by consensus: a peak 24-hour numeric rating scale (NRS)-itch, and 1-week NRS-itch instruments from the Patient-Reported Outcomes Measurement Information System (PROMIS) Itch Questionnaire, measuring average and peak itch (11 of 63 [17%], 14 of 63 [22%], and 16 of 59 [27%] voters disagreed, respectively)., Conclusions and Relevance: Clinicians and patients are encouraged to incorporate these well-validated, quick-to-perform, and easy-to-use instruments into their clinic, selecting the instruments that best fit their need. These assessments are meant to enhance, not replace, the patient-clinician encounter, and to support real-world research and health care improvement.

Background: Patients with atopic dermatitis (AD) are susceptible to infectious and inflammatory cutaneous comorbidities., Objective: The aim of the study was to describe the prevalence of cutaneous comorbidities associated with AD, including their relationship with AD severity., Methods: A retrospective cross-sectional analysis was performed using the Israeli Maccabi Healthcare Services database. Prevalent AD cases on December 31, 2017, were diagnosed with AD at any time since 1998 and had 1 or more recent (2013-2017) AD diagnoses. Dispensed AD treatments within 5 or fewer years served as a surrogate for AD severity. Cutaneous comorbidities in AD cases were compared with non-AD controls matched 1:1 on age, sex, and residential area. Among adults, comorbidities were compared across AD severity using multinomial logistic regression., Results: The eligible population included 94,483 patients with mild (57.7%), moderate (36.2%), or severe (6.1%) AD, and 94,483 matched non-AD controls. Skin infections, inflammatory skin conditions, cutaneous manifestations of AD, and sweat gland disorders were more prevalent ( P < 0.001) in patients with AD than in controls. Most cutaneous comorbidities that were more prevalent in adult patients with AD were also significantly ( P < 0.001) associated with AD severity., Conclusions: This study suggests that AD is associated with many infectious and inflammatory cutaneous comorbidities and highlights the relationship between AD severity and comorbidity prevalence., Competing Interests: Y.A.L. has received honoraria or fees as a consultant from AbbVie, Sanofi, and Genentech and as an advisory board member from Sanofi and Regeneron Pharmaceuticals, Pfizer, and Dexcel Pharma and has, without personal compensation, provided investigator services for Eli Lilly, Pfizer, and AbbVie. D.B.A. has received consultant fees from AbbVie. P.B.S. is a former employee of AbbVie and may own AbbVie stock and/or stock options. H.L., H.W., B.C., and A.D. are full-time employees of AbbVie and may own AbbVie stock and/or stock options. The other authors have no funding or conflicts of interest to declare., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Contact Dermatitis Society.)

Background: Data on Demodex in the immunosuppressed state is limited, focusing mainly on patients with human immunodeficiency virus and hematological malignancies. The aim of this study was to describe the manifestations of facial demodicosis in diverse immunosuppressive states., Methods: The medical records of all patients followed at a Demodex outpatient clinic of a tertiary medical center from January 2008 to November 2020 were retrospectively reviewed. Data on patients who were immunosuppressed while with demodicosis were retrieved., Results: The cohort included 28 patients (17 women and 11 men; median age, 58 years). Types of immunosuppression included treatments with hydroxyurea for polycythemia vera/essential thrombocytosis, mycophenolic acid, tacrolimus, and prednisone for liver and/or kidney transplantation, prednisone with cyclosporine/methotrexate/azathioprine/rituximab mainly for autoimmune diseases, mercaptopurine with/without anti-tumor necrosis factor alpha (TNF-α) for Crohn's disease, chemotherapy for neoplasms, anti-TNF-α for psoriasis, and Cushing's syndrome. The clinical types of demodicosis included: papulopustular, erythematotelangiectatic and fulminant rosacea, hyperpigmented, pityriasis folliculorum, pustular folliculitis, and dermatitis. The diverse clinical presentations led to various differential diagnoses. Topical treatment with ivermectin (monotherapy/combination with other treatments) was effective., Conclusion: Clinicians treating immunosuppressed patients should be familiar with the different forms of demodicosis and include them in the differential diagnosis of facial eruptions., (© 2022 the International Society of Dermatology.)

Actinic keratoses are common cutaneous lesions with a potential to progress to invasive squamous cell carcinoma. Therefore, treatment is crucial. The Tixel® is a noninvasive thermomechanical device designed to transfer heat to the upper dermis in a controlled manner according to a predetermined setting. This study aimed to evaluate the safety and efficacy of a thermomechanical fractional skin resurfacing technology for the treatment of facial and scalp actinic keratoses. A prospective, open-label, before-after study was conducted in a tertiary medical centre from May 2020 to April 2021. Patients presenting with facial/scalp actinic keratoses of mild-to-moderate thickness underwent 2 or 3 Tixel treatments (depending on clinical improvement), 3-4 weeks apart. The reduction in lesion count and overall improvement in appearance were assessed by clinical examination and digital photography. Findings were compared between baseline and follow-up at 3 months after the last treatment session. Patient satisfaction was evaluated by questionnaire, and adverse effects were documented. A total of 20 patients participated in the study. All completed 2-3 treatments and follow-up visits. Assessment of digital photographs was performed by 2 assessors blinded to the timepoint at which each photo was taken (before or after treatment). The average number of lesions at baseline was 9.8 (± 4.8) and the mean reduction in lesion count was 7.9 (± 4.4) (80.6%). Complete clearance was observed in 31.6% of patients. No adverse effects were noted during treatment and follow-up. Most patients reported being "very satisfied" or "satisfied" with the treatment results (85%) and experience (95%). Treating facial and scalp actinic keratoses with the Tixel device was found to be effective and safe., (© 2022. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Background: Real-life efficacy data on the recently approved once daily application of chlormethine gel (CG) for mycosis fungoides (MF) is limited, and detailed characterization of the side effects and their management are strikingly sparse., Objective: To evaluate the efficacy and particularly the side effect profile of CG in early-stage MF patients in a real-life setting., Methods: We performed a single-center retrospective analysis of 66 early-stage MF adult patients treated with CG in 2016-2019., Results: Treatment with a once-daily application (52%), or at lower frequencies (48%), in some with topical corticosteroids (TCS) (40%), resulted in an overall response rate of 50%, with no significant difference between stage IA and IB. Cutaneous side effects (56%) included irritant or allergic contact dermatitis (36%, mostly mild/moderate and manageable by reducing application frequency and/or adding TCS or interrupting treatment), unmasking effect (9%), hyperpigmentation (14%), and pruritus (9%). Withdrawal due to side effects occurred in 19.6% of patients (15% for contact dermatitis)., Conclusion: In real-life management, flexible regimens of CG sometimes with TCS, show efficacy in early-stage MF and may reduce the rate of contact dermatitis, the main treatment-limiting side effect. Practical recommendations with emphasis of the types, time of appearance, and management of side effects are provided.

Introduction: Real-world data on the epidemiology and economic burden of atopic dermatitis (AD) are limited. Here we describe the epidemiology and economic burden of AD using electronic healthcare data from Israel., Methods: A retrospective study was performed using the Maccabi Healthcare Services database. AD incidence in 2008-2017 and point prevalence (AD prev ) on 31 December 2017 were described using diagnosis codes for overall patients, and sex and age subgroups. For AD prev , severity was defined using recently dispensed treatments for AD. Annual healthcare resource utilization in AD prevalent patients was compared with non-AD matched controls using generalized linear modelling. Direct annual costs were estimated also., Results: AD incidence was 7.0/1000 person-years; overall prevalence was 4.4% (female patients 4.5%, male patients 4.3%; age 0 to less than 6 months, 0.9%; 6 months to less than 12 years, 11.0%; 12 to less than 18 years, 5.8%; 18 years or older, 2.2%). Among AD prev (n = 94,483), mild, moderate, and severe AD comprised 57.7%, 36.2%, and 6.1% (adults 43.8%, 46.3%, 9.9%), respectively. Dermatologist and allergist visits and hospitalization rates (at least one) were 40.7%, 6.6%, and 3.8% in 2017. Compared with controls, overall and moderate-to-severe AD were associated with 36% and 52% increases in annual per-person costs (incremental costs $126 and $190)., Conclusions: AD epidemiology in Israel is comparable with other real-world database studies. AD imposes an economic burden that increases with disease severity., (© 2022. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Core outcome sets are critically important outcomes that should be measured in clinical trials. Their absence in atopic dermatitis is a form of research waste and impedes combining evidence to inform patient care. Here, we articulate the rationale for core outcome sets in atopic dermatitis and review the work of the international Harmonising Outcome Measures for Eczema group from its inception in Munich, 2010. We describe core domain determination (what should be measured), to instrument selection (how domains should be measured), culminating in the complete core outcome measurement set in Tokyo, 2019. Using a "road map," Harmonising Outcome Measures for Eczema includes diverse research methods including Delphi and nominal group techniques informed by systematic reviews of properties of candidate instruments. The 4 domains and recommended instruments for including in all clinical trials of atopic dermatitis are patient symptoms, measured by Patient-Oriented Eczema Measure and peak Numerical Rating Scale 11 for itch intensity over 24 hours, clinical signs measured using the Eczema Area and Severity Index, quality of life measured by the Dermatology Life Quality Index series for adults, children, and infants, and long-term control measured by either Recap of atopic eczema or Atopic Dermatitis Control Tool., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Rituximab is the front-line therapy for pemphigus disease. Although very effective, relapse rates are high. We assessed factors associated with disease remission and early relapse following the first rituximab cycle. A single center, retrospective cohort study of patients with pemphigus treated with rituximab (1000 mg 0, 14 days) at the Autoimmune Bullous Disease Clinic of the Division of Dermatology in Rabin Medical Center, Israel, between January 1, 1995 and March 31, 2020. The cohort included 99 patients with a median follow-up of 37 months (range 12-155). After a single rituximab cycle, 74 patients (75%) achieved remission. Increased time to rituximab was associated with decreased remission rates (OR, 0.98 per month; 95% CI, 0.97-0.998). Of patients in remission with sufficient follow-up, 15/69 (22%) experienced an early relapse (≤12 months from remission). Prolonged time to rituximab and increased baseline disease severity, were associated with early relapse (OR, 1.02 per month; 95% CI, 1.001-1.04; OR, 1.04 per point; 95% CI, 1.01-1.08, accordingly). Initiating rituximab early following diagnosis is recommended. Maintenance rituximab infusions, especially for patients with severe baseline disease, should be further investigated., (© 2022 Wiley Periodicals LLC.)

Abstract: Atopic dermatitis is a chronic inflammatory skin condition that affects approximately 18 million people in the United States. Assessing the extent and severity of atopic dermatitis is critical for determining baseline disease burden and treatment effectiveness for both investigators and clinicians. Considerable efforts over the past several decades have been made in developing a highly validated instrument called the Eczema Area and Severity Index (EASI). Although several guides exist for the EASI, questions continue to arise regarding its use and interpretation. This review was developed to serve as the definitive guide for the EASI and to address commonly asked questions., Competing Interests: E.L.S. reports personal fees from AbbVie, Amgen, Arena Pharmaceuticals, Aslan Pharma, Boston Consulting Group, Collective Acumen, LLC (CA), Dermira, Eli Lilly, Evidera, ExcerptaMedica, Forte Bio RX, Galderma, GlaxoSmithKline, Incyte, Janssen, Kyowa Kirin Pharmaceutical Development, Leo Pharm, Medscape LLC, Pfizer, Physicians World LLC, Regeneron, Sanofi-Genzyme, Trevi Therapeutics, and WebMD. He also reports grants (or principal investigator role) from AbbVie, Amgen, Arcutis, Aslan, Corevita, Dermira, Eli Lilly, Incyte, Kyowa Hakko Kirin, Leo Pharmaceuticals, Merck, Novartis, Pfizer, Regeneron, Sanofi, and TARGET-DERM. These potential conflicts of interest have been reviewed and managed by OHSU. The other authors have no funding or conflicts of interest to declare., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Contact Dermatitis Society.)

Background: The coexistence of hidradenitis suppurativa (HS) and atopic dermatitis (AD) had been reported but, to our knowledge, was not investigated in controlled studies., Objective: To evaluate the bidirectional association between HS and AD., Methods: A population-based retrospective cohort study was conducted to compare the incidence rate of AD among patients with HS (n = 6779) and age-, sex-, and ethnicity-matched control individuals (n = 33,260). Adjusted hazard ratios (HRs) and adjusted odds ratios were estimated., Results: The incidence of AD was 2.51 (95% confidence interval [CI], 2.07-3.02) and 1.24 (95% CI, 1.10-1.40) per 1000 person-years among patients with HS and control individuals, respectively. Patients with HS were twice as likely to develop AD as control individuals (HR, 2.06; 95% CI, 1.64-2.58). Furthermore, the prevalence of pre-existing AD was higher in patients with HS than in control individuals (2.5% vs 1.8%, respectively; P < .001). A history of AD was associated with a 40% increase in the odds of HS (odds ratio, 1.41; 95% CI, 1.19-1.67). Relative to patients with isolated HS, those with a dual diagnosis of HS and AD were younger and had a female predominance, lower prevalence of smoking, and lower body mass index., Limitations: Retrospective data collection., Conclusions: A bidirectional association between HS and AD was observed. Dermatologists should be aware of this association., Competing Interests: Conflicts of interest Dr Tzur Bitan has received a research grant from Pfizer. Dr Cohen has received research grants from Janssen, Novartis, AbbVie, and Sanofi and has served as a consultant, advisor, or speaker for AbbVie, Amgen, Boehringer Ingelheim, Dexcel Pharma, Janssen, Kamedis, Lilly, Neopharm, Novartis, Perrigo, Pfizer, Rafa, Samsung Bioepis, Sanofi, Sirbal, and Taro. Drs Sherman, Kridin, Leshem, and Hodak have no conflicts of interest to declare., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Although the clinical hair changes that occur under treatment with epidermal growth factor receptor inhibitors (EGFRIs) are documented, their trichoscopic features have not been reported., Objective: To evaluate the trichoscopic findings in scalp and facial hair, induced by EGFRI treatment., Methods: Patients treated with EGFRIs at a tertiary oncodermatology clinic in 2015 through 2017 were evaluated for macroscopic and trichoscopic changes., Results: The cohort included 23 patients (13 women; median age, 68 years) treated with EGFRIs for an average of 13 months (range, 2-40 months). Macroscopically, 18 patients (78%) had dry, lusterless, coarse, kinky, brittle scalp hair, and 17 (74%) had trichomegaly of the eyebrows/eyelashes. Trichoscopic findings were of hair shaft anomalies including pili torti, affecting scalp hair in 20 patients (87%), eyebrows in 6 (26%), and eyelashes in 8 (50%), and asymmetric hyperpigmented fusiform widening of hair scalp in 3 (13%), eyebrows in 10 (43%), and eyelashes in 4 (25%). Dermoscopic findings of the peri- and interfollicular skin were scale, whitish erythematous structureless areas, and branching vessels., Limitations: Lack of trichoscopic-histologic correlation, lack of baseline examination., Conclusion: The trichoscopic correlates of the macroscopic hair changes under EFGRI treatment include pili torti, and asymmetric hyperpigmented fusiform widening, with dermoscopic cutaneous manifestations of scale, whitish erythematous structureless areas, and branching vessels., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Solar urticaria is a well-recognized photodermatosis, sometimes accompanied by angioedema. However, isolated solar angioedema (ISA) is a rare and unrecognized entity. The purpose of our work was to systematically review the available data on ISA. Therefore, a systematic review of studies evaluating ISA was performed. Additionally, a case of a 21-years-old patient from our photodermatosis service is presented. The search yielded 421 publications, with 3 eligible for review. Together with our case, 5 cases were included overall. All patients were female. Four out of 5 patients first experienced ISA at childhood or early adulthood (age range 6-22 years). UVA photoprovocation was positive in the 3 out of the 4 patients who were tested. Improvement was noted following NB-UVB hardening (2 out of 5 patients) or a short course of oral prednisone (3 out of 5 patients) combined with regular sunscreen application. To conclude, ISA is an extremely rare entity, although it may be underdiagnosed due to lack of awareness. The clinician must consider ISA in the differential diagnosis of angioedema since it can have a detrimental effect on quality of life. Besides sun avoidance, there is no consensus regarding treatment., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Multiple studies have reported on dermoscopic structures in basal cell carcinoma (BCC) and its subtypes, with varying results., Objective: To systematically review the prevalence of dermoscopic structures in BCC and its subtypes., Methods: Databases and reference lists were searched for relevant trials according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were assessed for the relative proportion of BCC dermoscopic features. Random-effects models were used to estimate summary effect sizes., Results: Included were 31 studies consisting of 5950 BCCs. The most common dermoscopic features seen in BCC were arborizing vessels (59%), shiny white structures (49%), and large blue-grey ovoid nests (34%). Arborizing vessels, ulceration, and blue-grey ovoid nests and globules were most common in nodular BCC; short-fine telangiectasia, multiple small erosions, and leaf-like, spoke wheel and concentric structures in superficial BCC; porcelain white areas and arborizing vessels in morpheaform BCC; and arborizing vessels and ulceration in infiltrative BCC., Limitations: Studies had significant heterogeneity. Studies reporting BCC histopathologic subtypes did not provide clinical data on pigmentation of lesions., Conclusion: In addition to arborizing vessels, shiny white structures are a common feature of BCC. A constellation of dermoscopic features may aid in differentiating between BCC histopathologic subtypes., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Early-stage mycosis fungoides (MF) includes involvement of dermatopathic lymph nodes (LNs) or early lymphomatous LNs. There is a lack of unanimity among current guidelines regarding the indications for initial staging imaging in early-stage presentation of MF in the absence of enlarged palpable LNs., Objectives: To investigate how often imaging is performed in patients with early-stage presentation of MF, to assess the yield of LN imaging, and to determine what disease characteristics promoted imaging., Methods: A review of clinicopathologically confirmed newly diagnosed patients with cutaneous patch/plaque (T1/T2) MF from PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) data., Results: PROCLIPI enrolled 375 patients with stage T1/T2 MF: 304 with classical MF and 71 with folliculotropic MF. Imaging was performed in 169 patients (45%): 83 with computed tomography, 18 with positron emission tomography-computed tomography and 68 with ultrasound. Only nine of these (5%) had palpable enlarged (≥ 15 mm) LNs, with an over-representation of plaques, irrespectively of the 10% body surface area cutoff that distinguishes T1 from T2. Folliculotropic MF was not more frequently imaged than classical MF. Radiologically enlarged LNs (≥ 15 mm) were detected in 30 patients (18%); only seven had clinical lymphadenopathy. On multivariate analysis, plaque presentation was the sole parameter significantly associated with radiologically enlarged LNs. Imaging of only clinically enlarged LNs upstaged 4% of patients (seven of 169) to at least IIA, whereas nonselective imaging upstaged another 14% (24 of 169). LN biopsy, performed in eight of 30 patients, identified N3 (extensive lymphomatous involvement) in two and N1 (dermatopathic changes) in six., Conclusions: Physical examination was a poor determinant of LN enlargement or involvement. Presence of plaques was associated with a significant increase in identification of enlarged or involved LNs in patients with early-stage presentation of MF, which may be important when deciding who to image. Imaging increases the detection rate of stage IIA MF, and identifies rare cases of extensive lymphomatous nodes, upstaging them to advanced-stage IVA2., (© 2020 British Association of Dermatologists.)

Background: A combined regimen of rituximab with corticosteroids for the treatment of pemphigus was effective in a prospective randomized controlled trial., Objective: To assess real-life response to rituximab in patients with pemphigus., Methods: A retrospective cohort of patients with pemphigus treated with ≥1 rituximab cycles (1,000 mg on days 0 and 14). The primary outcome was remission rate after 1 cycle. For efficacy analyses, a minimal 6-month follow-up was required. Adverse events were assessed in all patients., Results: The cohort included 117 patients for safety analysis, 108 for efficacy analysis (median follow-up of 33 months). All but one received concomitant corticosteroids, a third also received adjuvants. Overall, 80/108 patients (74%) achieved remission after the first rituximab cycle at a median of 5.5 months. Relapses occurred in 39 patients (49%) at a median of 18 months. Repeating treatment in relapsed patients increased remission rates to 75 and 88% after the second and third cycles, respectively. Adverse events were similar to those of previous publications. Two elderly patients died of infections attributable to rituximab combined with high-dose corticosteroids., Conclusion: In a large real-life long-term cohort, rituximab with corticosteroids ± adjuvants induced remission in most patients with pemphigus, with relatively favorable safety. Repeating treatment following relapse or remission failure was beneficial., (© 2021 S. Karger AG, Basel.)

Introduction: In a randomized prospective trial, adjuvant rituximab was more efficacious than corticosteroids alone in the treatment of pemphigus; however, real-life data are limited. Rituximab treatment for pemphigus has only recently been introduced to the Israeli health basket. Previously, patients received rituximab if they paid out of pocket or through private insurance, separating patients into 2 treatment groups, mostly based on economic capability., Methods: A retrospective cohort study of the 12-month clinical response of pemphigus vulgaris/foliaceus patients. We compared patients after a single cycle (1,000 mg on days 0 and 15 or weekly 375 mg/m2 for 4 weeks) of adjuvant rituximab with systemic corticosteroids ± steroid-sparing agents, to patients who were prescribed rituximab, could not obtain it, and received systemic corticosteroids ± steroid-sparing agents., Results: Forty-five patients were included (adjuvant rituximab, n = 29; immunosuppression alone, n = 16). At baseline, rituximab patients had a higher mean pemphigus disease area index (PDAI) (p = 0.07) and higher mean daily dosages of prednisone (1.51 vs. 1.16 mg/kg, p = 0.39). All patients but 1 in the rituximab group continued systemic steroids, and 31% in the rituximab group versus 50% in the immunosuppression-alone group received systemic adjuvants. At 12 months, partial or complete remission rates (on or off maximum 40 mg/day prednisone equivalent) were nonsignificantly higher in the rituximab group (62 vs. 50%, p = 0.53); however, patients on rituximab showed faster remissions (3.4 ± 1.9 vs. 5.9 ± 3.6 months; p = 0.03) with a trend for a greater PDAI reduction (p = 0.051). Adverse events were comparable., Conclusions: In this real-life study, a single cycle of rituximab achieved more remissions and sooner compared to conventional immunosuppression, but the differences were not significant, probably due to a small sample size and severe baseline disease in the rituximab group. Future real-life studies on larger groups are needed., (© 2020 S. Karger AG, Basel.)

Background: The incidence of epidermal growth factor receptor inhibitor (EGFRI)-induced papulopustular rash is 60-85%., Objective: To investigate prophylactic topical treatment for EGFRI-induced rash., Methods: A single-center, randomized, double-blind, placebo-controlled trial. Adult cancer patients initiating treatment with EGFRIs were randomized to receive facial topical treatment with chloramphenicol 3% + prednisolone 0.5% (CHL-PRED) ointment, chloramphenicol 3% (CHL) ointment, or aqua cream (AQUA). The primary end points were the incidence of ≥grade 3 rash using the Common Terminology Criteria for Adverse Events (CTCAE), on days 14 and 30. A subanalysis was conducted for incidence of a protocol-specified significant rash, defined as ≥10 facial papulopustular lesions., Results: The per-protocol analysis on day 14 included 69 patients, who received CHL-PRED (21), CHL (23), or AQUA (25). The incidence of CTCAE ≥grade 3 rash was not statistically significant between arms; however, the incidence of the protocol-specified significant rash was: CHL-PRED 14%, CHL 39%, and AQUA 48% (p = 0.03, CHL-PRED vs. AQUA). At 30 days, the CTCAE ≥grade 3 incidence was similar, but the incidences of protocol-specified significant rash were 6%, 16%, and 43% (p = 0.03, CHL-PRED vs. AQUA). No significant differences were found between CHL and CHL-PRED and between CHL and AQUA., Conclusions: Prophylactic topical CHL-PRED was efficacious when compared to AQUA, in the treatment of EGFRI-induced facial papulopustular rash., (© 2020 S. Karger AG, Basel.)

Photodynamic therapy (PDT), traditionally used in patients with nonmelanoma skin cancer, has been found to be effective for various inflammatory skin conditions. Daylight-activated PDT (DL-PDT), in which the sun serves as the light source, is substantially less painful than conventional PDT. This study aimed to determine the safety and efficacy of DL-PDT in a series of patients with chronic hand eczema (CHE). A proof-of-concept prospective design was used. Eight patients diagnosed with CHE at a tertiary dermatology clinic underwent DL-PDT. The first treatment was administered at the clinic and subsequent treatments (up to four total) were self-administered at home at 2-week intervals. Outcome was evaluated with the Investigator Global Assessment (IGA; score 0-4), Dermatology Life Quality Index (DLQI; score 0-24), and blinded review of clinical photographs (graded on a quartile scale by percent improvement). There were six male and two female patients of mean age 35 years. All underwent at least three treatments. The IGA score improved by 2.5 points at 1 month, 2.7 at 3 months, and 2.2 at 6 months post-treatment, and the DLQI score improved by 7.9, 6.6, and 6.1 points, respectively. Clinical photograph grades improved by 2.9 points at 3 months. Side effects were mild and transient. All patients had some degree of recurrence after 6 months of treatment. The self-administered DL-PDT is easy to perform, moderately effective, and safe to use in patients with CHE. Repeated treatments might be required to maintain remission., (© 2020 Wiley Periodicals LLC.)

Background: Moisturizers possibly improve atopic dermatitis (AD) by restoration of skin barrier, although some have detrimental effects., Objective: The aim of the study was to estimate the effects of several routine moisturizers on barrier functions., Methods: This is a randomized, forearm-controlled, observer-blind study. Patients older than 12 years with clear to moderate AD were randomized to 1 of 4 moisturizers (Cetaphil Cream, Aveeno Eczema Therapy Moisturizing Cream, CeraVe Moisturizing Cream, Vaseline) applied to nonlesional skin of 1 forearm and no moisturizer to the opposite forearm for 4 weeks. Transepidermal water loss (TEWL), capacitance, pH, and TEWL after tape stripping were evaluated at weeks 0 and 4. In addition, participants without AD underwent baseline measurements only., Results: Twenty patients with AD completed the study. Baseline measurements between the AD group and 10 non-AD controls were similar. After the intervention (AD group), mean TEWL improved in the treated forearm and worsened in the untreated one, but the difference was not significant. There was no significant change in pH or in TEWL after tape stripping. Capacitance significantly improved in the moisturizer forearm. The study was underpowered as recruitment fell short., Conclusions: The effects of moisturizers on nonlesional AD skin were small and need to be addressed when powering future studies. Broadening investigations beyond the classic barrier properties might be useful in future studies.

Aim: To identify risk factors for the development of dupilumab-induced ocular surface disease (DIOSD) in adult patients with atopic dermatitis (AD) and describe outcomes of treatment., Methods: A retrospective institutional cohort study performed at the Rabin Medical Center, Petach Tikva, Israel. Adult patients with AD who received dupilumab from March 2018 to June 2019 were included. Demographics, AD severity scores, blood IgE levels, previous atopic keratoconjunctivitis (AKC), dermatological response to dupilumab, ophthalmological evaluation and treatment were noted. Univariate and multivariate analyses were used to identify risk factors for DIOSD., Results: Sixteen of 37 patients who were included in the study (43%) had new or exacerbated symptoms of ocular surface disease starting at 2 weeks following the first treatment. Three patients reported transient dry eye sensation which lasted 2 weeks; nine patients reported chronic dry eye sensation, and four patients (25%) had marked blepharoconjunctivitis. The presence of severe AD was the strongest predictor of DIOSD. Not a single patient with moderate AD had DIOSD. In multivariate analysis, prior AKC was a risk factor for DIOSD (R 2 =15.78, OR=23.28, p=0.005) while a family history of atopy was protective of DIOSD (R 2 =6.22, OR=0.13, p=0.05). All four patients with blepharoconjunctivitis had resolution of signs, and symptoms within days of starting periocular 0.03%-0.1% tacrolimus ointment., Conclusions: DIOSD is common in patients with AD receiving dupilumab. While most cases are mild, some patients can develop blepharoconjunctivitis which responds well to tacrolimus ointment. AD severity, and previous AKC are risk factors for DIOSD., Competing Interests: Competing interests: EH and YAL were scientific advisors and speakers for Sanofi/Regeneron. Other authors declare no competing interests., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Measuring patient-centered outcomes in clinical practice is valuable for monitoring patients and advancing real-world research. A new initiative from the Harmonising Outcome Measures for Eczema (HOME) group aims to recommend what might be recorded for atopic eczema patients in routine clinical care., Objectives: Prioritize outcome domains to measure atopic eczema in clinical practice and select valid and practical outcome measurement instruments for the highest-priority domain., Methods: An online survey of HOME members identified and ranked 21 possible health domains. Suitable instruments were then selected for the top-prioritized domain at the HOME VI meeting, using established consensus processes informed by systematic reviews of instrument quality., Results: Patient-reported symptoms was the top-prioritized domain. In accordance with psychometric properties and feasibility, there was consensus that the recommended instruments to measure atopic eczema symptoms in clinical practice are the POEM, the PO-SCORAD index, or both. The numeric rating scale for itch received support pending definition and validation in atopic eczema., Conclusion: Following the first step of the HOME Clinical Practice initiative, we endorse using the POEM, the PO-SCORAD index, or both for measuring atopic eczema symptoms in clinical practice. Additional high-priority domains for clinical practice will be assessed at subsequent HOME meetings., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Disorders of the umbilicus are commonly seen in infancy, including hernias, infections, anomalies, granulomas, and malignancies. Meticulous inspection of the umbilicus at birth might reveal a persisting embryonic remnant, such as an omphalomesenteric duct (OMD), manifested by a variety of cutaneous signs, such as an umbilical mass, granulation tissue, or discharge., Objective: To systematically review the available data regarding the presence and management of OMD remnant with cutaneous involvement to suggest a practical approach for diagnosis and treatment., Methods: A systematic review of the literature evaluating OMD anomalies presenting with cutaneous symptoms was performed. In addition, an index case of an 11-month-old patient is presented., Results: We included 59 publications reporting 536 cases; 97% of the patients whose age was noted were infants (mean age 11 months). In 7.5% of the cases, diagnosis was established only after treatment failure. In 6.4% of patients, nonlethal complications were reported, and in 10.3%, the outcome was death, partly due to delayed diagnosis or mismanagement., Limitations: Limited quality of the collected data, reporting bias., Conclusion: OMD is relatively rare; however, the clinician must consider this remnant while examining patients with umbilical abnormalities because mismanagement could cause severe morbidity and mortality., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The association between body mass index (BMI) and acne is unclear., Objective: To determine the association between BMI and acne in youths., Methods: A nationwide, population-based, cross-sectional study was conducted in 2002-2015 by using medical data on 600,404 youths during compulsory military service. BMI was measured at age 17 years. Acne was diagnosed by dermatologists. Unadjusted and adjusted odds ratios (aORs) of acne in relation to BMI (stratified into 8 groups) were calculated, with the low-normal group (18.5≤ BMI ≤21.99 kg/m 2 ) serving as the reference., Results: The study included 299,163 males (49.9%) and 301,241 females (50.1%) with a mean age of 18.9 years (standard deviation, 0.6) and 18.7 years (standard deviation, 0.5), respectively, at recruitment. Acne was diagnosed in 55,842 males (18.7%) and 48,969 females (16.3%). The proportion of participants with acne decreased gradually from the underweight to the severely obese group (males, from 19.9% to 13.9%; females, from 16.9% to 11.3%). The findings on multivariable analysis were similar to the unadjusted analysis results, showing the lowest odds of acne in severely obese participants (aOR for males, 0.53; 95% confidence interval, 0.42-0.64; aOR for females, 0.5; 95% confidence interval, 0.37-0.62). The findings persisted in the sensitivity analyses., Limitations: Information was lacking on potential confounders and acne severity., Conclusion: In youths, overweight and obesity are inversely associated with acne in a dose-dependent manner., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Conjunctivitis is common in patients with atopic dermatitis (AD) in general and a commonly reported adverse event in AD clinical trials with dupilumab., Objective: To survey opinions and experience about conjunctivitis occurring in AD, including those during dupilumab treatment in a group of AD experts from the International Eczema Council (IEC)., Methods: Electronic survey and in-person discussion of management strategies., Results: Forty-six (53.5%) IEC members from 19 countries responded to the survey. Consensus was reached for several statements regarding diagnostic workup, referral and treatment. IEC members suggest that patients with AD should (i) routinely be asked about ocular complaints or symptoms, (ii) obtain information about the potential for conjunctivitis before starting dupilumab therapy and (iii) if indicated, be treated with dupilumab despite previous or current conjunctivitis. In cases of new-onset conjunctivitis, there was consensus that dupilumab treatment should be continued when possible, with appropriate referral to an ophthalmologist., Limitations: The study relies on expert opinion from dermatologists. Responses from few dermatologists without dupilumab access were not excluded from the survey., Conclusion: The IEC recommends that dermatologists address conjunctivitis in patients with AD, especially during treatment with dupilumab., (© 2019 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.)

Background: Dermoscopy is a noninvasive technique for the diagnosis of skin lesions. Its accuracy for basal cell carcinoma (BCC) has not been systematically studied., Objective: We sought to systematically investigate the accuracy of dermoscopy for the diagnosis of BCC compared with examination with the naked eye., Methods: A systematic review of studies reporting the accuracy of naked eye examination and dermoscopy for the diagnosis of BCC was conducted. A meta-analysis for sensitivity and specificity was performed using a bivariate mixed-effects logistic regression modeling framework., Results: Seventeen studies were identified. The pooled sensitivity and specificity of dermoscopy for the diagnosis of BCC were 91.2% and 95%, respectively. In studies comparing test performance, adding dermoscopy to naked eye examination improved sensitivity from 66.9% to 85% (P = .0001) and specificity from 97.2% to 98.2% (P = .006). The sensitivity and specificity of dermoscopy were higher for pigmented than nonpigmented BCC. Sensitivity increased when dermoscopy was performed by experts and when the diagnosis was based on in-person dermoscopy as opposed to dermoscopic photographs., Limitations: Significant heterogeneity among studies with a medium-to-high risk of bias., Conclusion: Dermoscopy is a sensitive and specific add-on tool for the diagnosis of BCC. It is especially valuable for pigmented BCC., (Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: As novel systemic therapeutics for patients with atopic dermatitis (AD) are developed, ethical and methodological concerns regarding placebo-controlled-trials (PCT) have surfaced., Objective: To guide the design and implementation of PCT in AD, focusing on trials with systemic medications., Methods: A subgroup of the International Eczema Council (IEC) developed a consensus e-survey, which was disseminated to IEC members., Results: The response rate was 43/82 (52%). Consensus was reached on 24/27 statements and on 3/11 options from multiple-selection statements, including: performing monotherapy studies in proof-of-concept phases; avoiding concomitant topical corticosteroids or calcineurin inhibitors until a predefined timepoint as rescue (borderline consensus); selection of sites and assessors with recognized expertise in AD clinical trials; clear definition and identification of baseline disease severity; minimizing time and proportion of patients on placebo; using daily emollients with several options provided; instigating open-label extension studies for enrolment after a predefined timepoint; and including outcomes which set a higher bar for disease clearance., Conclusion: Conducting PCT in AD requires balancing several, sometimes opposing principles, including ethics, methodology, regulatory requirements and real-world needs. This paper can provide a framework for conducting PCT with systemic medications for patients with AD., (© 2019 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.)

Background: Psychological stress has long been linked with the exacerbation/onset of psoriasis., Objectives: To determine if antecedent psychological stress is associated with the exacerbation/onset of psoriasis., Methods: A search of the PubMed, PsycINFO, Cochrane library and ClinicalTrials.gov databases was performed. Surveys evaluating beliefs about stress reactivity were analysed separately. Suitable studies were meta-analysed., Results: Thirty-nine studies (32 537 patients) were included: 19 surveys, seven cross-sectional studies, 12 case-control studies and one cohort study. Forty-six per cent of patients believed their disease was stress reactive and 54% recalled preceding stressful events. Case-control studies evaluating stressful events rates prior to the exacerbation (n = 6) or onset (n = 6) of psoriasis varied in time lag to recollection (≤ 9 months to ≥ 5 years). Pooling five studies evaluating stressful events preceding onset of psoriasis gave an odds ratio (OR) of 3·4 [95% confidence interval (CI) 1·8-6·4; I 2 = 87%]; the only study evaluating a documented stress disorder diagnosis reported similar rates between patients and controls (OR 1·2, 95% CI 0·8-1·8). Four studies evaluating stressful events prior to psoriasis exacerbation reported comparable rates with controls, whereas two found more frequent/severe preceding events among patients with psoriasis. A small prospective cohort study reported a modest association between stress levels and exacerbation of psoriasis (r = 0·28, P < 0·05)., Conclusions: The association between preceding stress and exacerbation/onset of psoriasis is based primarily on retrospective studies with many limitations. No convincing evidence exists that preceding stress is strongly associated with exacerbation/onset of psoriasis., (© 2017 British Association of Dermatologists.)

This is the report from the fifth meeting of the Harmonising Outcome Measures for Eczema initiative (HOME V). The meeting was held on 12-14 June 2017 in Nantes, France, with 81 participants. The main aims of the meeting were (i) to achieve consensus over the definition of the core domain of long-term control and how to measure it and (ii) to prioritize future areas of research for the measurement of the core domain of quality of life (QoL) in children. Moderated whole-group and small-group consensus discussions were informed by presentations of qualitative studies, systematic reviews and validation studies. Small-group allocations were performed a priori to ensure that each group included different stakeholders from a variety of geographical regions. Anonymous whole-group voting was carried out using handheld electronic voting pads according to predefined consensus rules. It was agreed by consensus that the long-term control domain should include signs, symptoms, quality of life and a patient global instrument. The group agreed that itch intensity should be measured when assessing long-term control of eczema in addition to the frequency of itch captured by the symptoms domain. There was no recommendation of an instrument for the core outcome domain of quality of life in children, but existing instruments were assessed for face validity and feasibility, and future work that will facilitate the recommendation of an instrument was agreed upon., (© 2018 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Current systemic treatments for atopic dermatitis (AD) offer limited efficacy and are often restricted by safety concerns. Biologics may address the unmet need for improved AD therapeutics., Objective: The aim of this study was to evaluate the efficacy and safety of biologic agents in AD., Methods: A systematic review and meta-analysis of studies evaluating AD patients treated with biologics was performed. The primary outcome was the Eczema Area and Severity Index (EASI)-75 response, while secondary outcomes were SCOring Atopic Dermatitis (SCORAD)-75, EASI-50, SCORAD-50, Investigator Global Assessment 0/1 responses, change in responses from baseline, and adverse events., Results: We included 13 randomized controlled trials (RCTs) and 10 observational studies evaluating nine biologics. High-quality evidence was available for dupilumab, nemolizumab and ustekinumab. Pooling five studies, at weeks 12-16 dupilumab 300 mg every week to every 2 weeks achieved EASI-75 responses of 55%, superior to placebo [relative risk (RR) 3.3, 95% confidence interval (CI) 2.9-3.6]. Nemolizumab had similar EASI-75 responses as placebo, but significantly improved pruritus. In online reports, lebrikizumab demonstrated superior EASI-50 responses versus placebo (RR 1.3, 95% CI 1.04-1.7), while tralokinumab had superior SCORAD-50 responses versus placebo, with borderline significance (RR 1.7, 95% CI 0.97-3.1). In two RCTs each, omalizumab and ustekinumab were comparable with placebo, while antithymic stromal lymphopoietin receptor, infliximab, and rituximab lacked adequate evidence of efficacy. All medications had a comparable safety profile to placebo., Limitations: Lack of RCTs and the use of variable outcome measures limited conclusions., Conclusion: Dupilumab is currently the only biologic with robust evidence of efficacy in AD. Nemolizumab, lebrikizumab, and tralokinumab show promise but further data are needed. Longer follow-up and larger studies will establish their safety profile.

The verrucous epidermal nevus (VEN) is the most common type of epidermal nevi. As lesions can be disfiguring, treatment is often sought. Many therapeutic approaches have been reported, with variable efficacy and safety. Picosecond (PS) lasers are novel laser devices designated to target small chromophores. A side effect of these lasers is blistering due to epidermal-dermal separation. We aimed to harness this side effect of the PS lasers to treat patients with VEN. The purpose of this study was to report our experience treating VEN using a PS 532-nm laser. We present a retrospective case series of six patients with large VEN who were treated using a PS 532-nm laser (2-6 treatments, 8-10 weeks apart). Response in clinical photographs was assessed by two independent dermatologists and graded on a scale of 0 (exacerbation) to 4 (76-100% improvement). Patient satisfaction was recorded on a scale of 1-5. All patients demonstrated significant improvement. Average improvement was 3.7 on the quartile scale of improvement. Patient satisfaction rate averaged 4.7. The PS 532-nm laser is a promising novel modality for the treatment of large VEN.

Importance: Pneumocystis pneumonia (PCP) is a potentially lethal opportunistic infection that primary prophylaxis can help prevent. The risk of prophylactic therapy must be weighed against the incidence of PCP in the patient population. Prophylaxis most frequently involves trimethoprim-sulfamethoxazole, with second-line therapies, including atovaquone, dapsone, and pentamide. The indication for prophylaxis in immunocompromised patients without HIV is less well defined. Previously, an incidence of at least 3.5% has been proposed as a cutoff to justify prophylaxis., Objective: To assess the incidence of PCP in patients with autoimmune blistering diseases receiving no routine prophylaxis., Design, Setting, and Participants: This was a retrospective analysis of patient medical records to determine the incidence of PCP infections. The multicenter study was performed at tertiary care centers that provide care for patients with autoimmune blistering disease in Germany, Italy, Singapore, Israel, and the Netherlands. Patients had a confirmed diagnosis of pemphigus vulgaris/foliaceus, bullous pemphigoid, epidermolysis bullosa acquisita, mucous membrane pemphigoid/cicatricial pemphigoid, or anti-p200 pemphigoid., Main Outcomes and Measures: To determine the incidence of PCP defined as patients with the International Classification of Diseases, Ninth Revision (ICD-9), code 136.3, for PCP, or free text documentation of PCP occurring based on characteristic radiographic findings with elevated lactate dehydrogenase, or hospitalization for pneumonia with bronchioalveolar lavage demonstrating Pneumocystis jiroveci on confirmatory stains., Results: A total of 801 patients with autoimmune blistering diseases were included in this study; their mean (SD) age was 66.5 (17.6) years, and a total of 465 (58%) were female. Only 1 patient developed PCP, resulting in an incidence rate of 0.1%. This incidence significantly fell below the recommended threshold of 3.5% (0.1% vs 3.5%, χ21 = 27.0; P < .001). This incidence was significantly lower than the previously reported incidence of PCP in all immunosuppressed dermatologic patients (0.1% vs 1.3%; χ21 = 8.2; P = .004)., Conclusions and Relevance: Routine Pneumocystis prophylaxis for patients with autoimmune blistering diseases does not seem to be warranted. Patients with autoimmune blistering disease seem to have a lower risk of PCP than the general population of immunosuppressed dermatology patients. Risks of routine prophylaxis include hyperkalemia, hypoglycemia, photosensitivity, thrombocytopenia, and more rare adverse reactions.

Background: Studies evaluating whether malignancy rate is increased in patients with bullous pemphigoid (BP) have reached conflicting results., Objective: We sought to determine whether BP is associated with malignancy., Method: Medline, EMBASE, the Cochrane library, and reference lists of included studies were searched for comparative studies that evaluated the relationship between BP and malignancy. Data were analyzed on the basis of study design: cross-sectional, case control, and cohort. A meta-analysis was performed by using a random effects model to estimate pooled odds ratio., Results: The review included 8 studies. No association between BP and overall cancer was found for any of the study designs. Although a single cohort study reported an association with lymphoid leukemia and kidney and larynx cancer, a pooled analysis of case-control studies did not. A pooled analysis of cross-sectional studies found a significant association between BP and hematologic malignancies., Limitations: The paucity of well-designed studies hindered the possibility of proving or disproving the BP-cancer association., Conclusion: We did not find an association of BP with overall malignancy, but a possible association with hematologic malignancy was observed., (Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Venous thromboembolism (VTE) has been reported to be a significant cause of death in patients with pemphigus., Objective: We sought to assess the incidence and characteristics of VTE in patients with pemphigus., Methods: A retrospective study following a cohort of 172 patients with newly diagnosed pemphigus for the development of VTE was conducted., Results: Over a mean follow-up time of 4 years, 10 patients (6%) had development of VTE at a median of 4 months from pemphigus diagnosis. The highest risk was found in the first year, at 5 VTE events per 100 patient-years or a 5% VTE risk for that first year. Five patients had deep vein thromboses, 4 had pulmonary embolisms, and 1 had both. Age and gender were not related to the VTE risk. Most patients had VTE risk factors, either hereditary or acquired as the result of pemphigus treatments and their complications, including hospitalization, immobilization, and infections., Limitations: The use of existing health records limited the assessment of asymptomatic VTE and VTE risk factors; a matched control population was not studied., Conclusions: VTEs are not rare in patients with pemphigus, more so in the first year after diagnosis. VTE risk must be assessed in all patients, especially when hospitalized, and thrombo-prophylaxis should be initiated in qualifying cases., (Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Opportunistic infections (OIs) are a dreaded adverse effect of immunosuppressive therapy, leading to the use of opportunistic infection prophylaxis (OIP) in many immunosuppressed conditions. However, guidelines for OIP in pemphigus are lacking., Objective: Our objective was to evaluate the approach of leading pemphigus experts towards OIP., Methods: We conducted an online survey of OIP trends., Results: The survey was completed by 33 experts. Prior to initiation of immunosuppressive therapy, 75% routinely screened for hepatitis viruses, and at least half screened for HIV or tuberculosis. Most experts (76%) prescribed OIP but to <10% of their patients, and the most frequent drugs of choice were sulfamethoxazole/trimethoprim and acyclovir. Most experts agreed that treatment with three or more immunosuppressive agents or a previous history of OIs would lead to the use of OIP that was then discontinued with cessation of immunosuppression. The arguments against OIP were the lack of evidence for its necessity and concern about side effects or emergence of resistant pathogens. The surveyed experts treated patients with severe disease in a tertiary care setting, which may have led to an overestimation of the use of OIP. Infectious disease specialists were not included., Conclusion: Substantial disparities exist in approaches to OIP for patients with pemphigus, including the decision to treat, type of treatment, and risk stratification among pemphigus experts.

This article is a report of the fourth meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in Malmö, Sweden on 23-24 April 2015 (HOME IV). The aim of the meeting was to achieve consensus over the preferred outcome instruments for measuring patient-reported symptoms and quality of life for the HOME core outcome set for atopic eczema (AE). Following presentations, which included data from systematic reviews, consensus discussions were held in a mixture of whole group and small group discussions. Small groups were allocated a priori to ensure representation of different stakeholders and countries. Decisions were voted on using electronic keypads. For the patient-reported symptoms, the group agreed by vote that itch, sleep loss, dryness, redness/inflamed skin and irritated skin were all considered essential aspects of AE symptoms. Many instruments for capturing patient-reported symptoms were discussed [including the Patient-Oriented SCOring Atopic Dermatitis index, Patient-Oriented Eczema Measure (POEM), Self-Administered Eczema Area and Severity Index, Itch Severity Scale, Atopic Dermatitis Quickscore and the Nottingham Eczema Severity Score] and, by consensus, POEM was selected as the preferred instrument to measure patient-reported symptoms. Further work is needed to determine the reliability and measurement error of POEM. Further work is also required to establish the importance of pain/soreness and the importance of collecting information regarding the intensity of symptoms in addition to their frequency. Much of the discussion on quality of life concerned the Dermatology Life Quality Index and Quality of Life Index for Atopic Dermatitis; however, consensus on a preferred instrument for measuring this domain could not be reached. In summary, POEM is recommended as the HOME core outcome instrument for measuring AE symptoms., (© 2016 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)