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Astrid-Helene Ravn, Jacob P Thyssen, Alexander Egeberg Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark Abstract: Parkinson’s disease (PD) is one of the most common neurodegenerative disorders, characterized by a symptom triad comprising resting tremor, rigidity, and akinesia. In addition, non-motor symptoms of PD are well recognized and often precede the overt motor manifestations. Cutaneous manifestations as markers of PD have long been discussed, and cumulative evidence shows an increased prevalence of certain dermatological disorders in PD. Seborrheic dermatitis is considered to occur as a premotor feature of PD referable to dysregulation of the autonomic nervous system. Also, an increased risk of melanoma has been observed in PD. Light hair color is a known risk factor for melanoma, and interestingly the risk of PD is found to be significantly higher in individuals with light hair color and particularly with red hair. Furthermore, several studies have reported a high prevalence of PD in patients with bullous pemphigoid. Moreover, a 2-fold increase in risk of new-onset PD has been observed in patients with rosacea. Besides the association between PD and various dermatological disorders, the skin may be useful in the diagnosis of PD. Early PD pathology is found not only in the brain but also in extra-neuronal tissues. Thus, the protein α-synuclein, which is genetically associated with PD, is present not only in the CNS but also in the skin. Hence, higher values of α-synuclein have been observed in the skin of patients with PD. Furthermore, an increased risk of PD has been found in the Cys/Cys genotype, which is associated with red hair color. In this review, we summarize the current evidence of the association between PD and dermatological disorders, the cutaneous adverse effects of neurological medications, and describe the potential of skin protein expression and biomarkers in identification of risk and diagnosis of PD. Keywords: Parkinson’s disease, melanoma, rosacea, seborrheic dermatitis, bullous pemphigoid

BackgroundConjunctivitis is common in patients with atopic dermatitis (AD) in general and a commonly reported adverse event in AD clinical trials with dupilumab.ObjectiveTo 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).MethodsElectronic survey and in-person discussion of management strategies.ResultsForty-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.LimitationsThe study relies on expert opinion from dermatologists. Responses from few dermatologists without dupilumab access were not excluded from the survey.ConclusionThe IEC recommends that dermatologists address conjunctivitis in patients with AD, especially during treatment with dupilumab.

BackgroundMost studies on racial disparities in childhood atopic dermatitis (AD) did not consider persistent AD or account for differences in vitamin D status.MethodsAmong 1418 children recruited from a Massachusetts HMO into the pre-birth Project Viva cohort, we examined associations of child’s race/ethnicity with maternal report of child’s AD diagnosis by annual questionnaires. We used multivariable logistic regression adjusted for socio- demographics (maternal education, household income, smoking exposure, parental atopy, breastfeeding duration, child sex) and cord blood 25-hydroxyvitamin D, to estimate odds ratios (OR) of incident AD by early childhood (median age 3.3 years), and, among young children with AD, OR of persistence through mid-childhood (median age 7.7 years).Results68% of children were non-Hispanic white, 13% were black, and 19% were other race/ethnicities. By early childhood, 497/1418 (35%) had incident AD. Among those with both AD and follow- up to mid-childhood, 58/389 (15%) had persistent AD. Black children were more likely than white children to have incident AD (OR 2.21; 95% CI 1.60, 3.04), even after adjustment for socio-demographics (2.64; 1.79, 3.89) and vitamin D levels (1.93; 1.07, 3.48). Black children also had higher odds of persistent AD (3.21; 1.63, 6.32; fully adjusted 4.60; 1.24, 17.13). Children with other race/ethnicities had non-significantly higher risk for AD incidence and persistence than white children.ConclusionIn this cohort, compared with white children, black children and children with other race/ethnicities were at higher risk for incident and persistent AD, even after accounting for differences in socio-demographic characteristics and vitamin D levels.

BACKGROUND AND PURPOSE: It has been speculated that the prevalence of metal allergy may be higher in patients with implant failure. We compared the prevalence and cause of revisions following total hip arthroplasty (THA) in dermatitis patients suspected to have contact allergy and in patients in general with THA. Furthermore, we compared the prevalence of metal allergy in dermatitis patients with and without THA. MATERIALS AND METHODS: The Danish Hip Arthroplasty Registry (DHAR) contained detailed information on 90,697 operations. The Gentofte patch-test database contained test results for patients suspected of having allergic contact dermatitis (n = 18,794). Cases (n = 356) were defined as patch-tested dermatitis patients who also had primary THA performed. Two age- and sex-matched controls (n = 712) from the patch-test database were sought for each case. RESULTS: The prevalence of revision was similar in cases (12%) and in patients from the DHAR (13%). The prevalence of metal allergy was similar in cases and controls. However, the prevalence of metal allergy was lower in cases who were patch-tested after operation (6%) than in those who were patch-tested before operation (16%) (OR = 2.9; 95% CI = 1-8). INTERPRETATION: We found that the risk of surgical revision was not increased in patients with metal allergies and that the risk of metal allergy was not increased in cases who were operated, in comparison to controls. Despite some important study limitations, our observations add to the evidence that the risk of complications in metal allergic patients seems limited. [ABSTRACT FROM AUTHOR]

Background: T helper 2 (Th2) cells crucially contribute to the pathogenesis of atopic dermatitis (AD) by secreting high levels of IL-13 and IL-22. Yet, the upstream regulators that activate Th2 cells in AD skin remain unclear. IL-18 is a putative upstream regulator of Th2 cells as it is implicated in AD pathogenesis and has the capacity to activate T cells., Objective: To decipher the role of IL-18 in Th2 responses in blood and skin of AD patients., Methods: PBMCs and skin biopsies from AD patients and healthy donors were used. Functional assays were performed ex vivo using stimulation or blocking experiments. Analysis was performed using flow cytometry, bead-based multiplex assays, RT-qPCR, RNA-seq, western blotting, and spatial sequencing., Results: IL-18Rα + Th2 cells were enriched in blood and lesional skin of AD patients. Of all the cytokines for which Th2 cells express the receptor, only IL-9 was able to induce IL-18R via an IL-9R-JAK1/JAK3-STAT1 signaling pathway. Functionally, stimulation of circulating Th2 cells with IL-18 induced secretion of IL-13 and IL-22, an effect that was enhanced by co-stimulation with IL-9. Mechanistically, IL-18 induced Th2 cytokines via activation of IRAK4, NF-κB, and AP-1 signaling in Th2 cells, and neutralization of IL-18 inhibited these cytokines in cultured explants of AD skin lesions. Finally, IL-18 protein levels correlated positively with disease severity in lesional AD skin., Conclusion: Our data identify a novel IL-9-IL-18 axis that contributes to Th2 responses in AD. Our findings suggest that both IL-9 and IL-18 could represent upstream targets for future treatment of AD., (Copyright © 2024. Published by Elsevier Inc.)

Background: Treatment optimization may require dosing flexibility. The Phase 3 JADE REGIMEN trial (NCT03627767) evaluated maintenance of abrocitinib 200 mg-induced response in patients with moderate-to-severe atopic dermatitis (AD) randomly assigned to subsequent maintenance with continuous-dose abrocitinib (200 mg), reduced-dose abrocitinib (100 mg) or placebo. Maintenance with continuous-dose abrocitinib was associated with a stronger prevention of disease flares, but also with a higher occurrence of adverse events, compared with the reduced dose., Objective: This post hoc analysis of JADE REGIMEN aimed to identify predictors of not flaring during the maintenance period and to generate tools that can be used to assess probability of not flaring., Methods: Data were analysed from patients who responded to abrocitinib 200 mg induction therapy (12 weeks) and were randomly assigned to receive abrocitinib (200 mg or 100 mg) or placebo in the 40-week maintenance period. Demographic and baseline disease characteristics and level of response to induction were evaluated for association with not flaring using logistic regression. Parameters with a significant (p < 0.15) interaction with the treatment arm were fitted into a multivariable regression model, which was used to assess probability of not flaring., Results: Lower percentage body surface area affected at baseline (p = 0.09), absence of prior exposure to systemic agents (p = 0.02) and greater percentage change in EASI from baseline to randomization (p < 0.001) were identified as predictors of not flaring with abrocitinib. In both abrocitinib arms, percentage change in EASI from baseline to end of induction (Week 12) was the major contributor to the probability of not flaring in the maintenance period., Conclusions: Maintenance of response using reduced-dose abrocitinib 100 mg may be feasible for patients with lower baseline disease severity and strong response to abrocitinib 200 mg induction treatment., (© 2024 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: Upadacitinib has demonstrated high and rapid rates of efficacy in adolescent and adult patients with moderate-to-severe atopic dermatitis (AD) as assessed by the Eczema Area and Severity Index (EASI). This post hoc analysis assessed the EASI response in four anatomical regions for patients with moderate-to-severe AD treated with upadacitinib compared to dupilumab over 24 weeks., Methods: Data from patients randomised 1:1 to receive upadacitinib 30 mg extended-release tablet orally once daily or dupilumab 300 mg by subcutaneous injection every 2 weeks after a loading dose of 600 mg in the Heads Up study were analysed for achievement of ≥75%, ≥90%, or 100% reduction of EASI in four body regions: 1) head and neck, 2) trunk (including genitals), 3) upper limbs, and 4) lower limbs (including buttocks) at each study visit through week 24. Patient response data from the Head and Neck Patient Global Impression of Severity (HN-PGIS) were also analysed at each study visit for comparison of upadacitinib to dupilumab., Results: Greater proportions of patients treated with upadacitinib versus dupilumab achieved skin clearance rates of ≥75% (EASI 75) at week 1 and higher clearance rates of ≥90% (EASI 90) or 100% (EASI 100) by week 4 or earlier in all four body regions. This difference was maintained at each visit through week 24 for both EASI 90 and EASI 100. Patient responses on the HN-PGIS indicated that a greater proportion of patients (nominal p-value <0.05) treated with upadacitinib compared to dupilumab reported that AD symptoms in the head and neck region were absent or minimal as early as week 1., Conclusion: Compared to dupilumab, upadacitinib treatment provided higher rates of rapid, sustained efficacy for the head and neck, trunk, upper limbs, and lower limbs for the treatment of moderate-to-severe AD as measured by the EASI and supported by patient responses., (The Author(s). Published by S. Karger AG, Basel.)

Importance: Hidradenitis suppurativa (HS) is associated with an increased prevalence of cardiovascular diseases compared with the general population. Any association between polygenic risk for HS, risk of incident cardiometabolic outcomes, and the plasma proteome is unclear., Objective: To investigate the genetic correlation between HS and cardiometabolic disease., Design, Setting, and Participants: This cohort study used a polygenic risk score (PRS) for HS to examine the risks of coronary artery disease (CAD) and diabetes and identify changes in the plasma proteome in individuals of European ancestry from the UK Biobank. Participants were enrolled from January 1, 2006, to December 31, 2010. End of follow-up was January 1, 2023. Correlations were assessed between HS susceptibility and cardiometabolic traits using linkage disequilibrium score regression. Odds ratios were assessed in logistic regressions. The risk of incident CAD and diabetes was estimated in cause-specific survival models designed as time-to-event analyses., Exposure: The PRS for HS., Main Outcomes and Measures: Main outcomes were CAD and diabetes diagnosis measured by logistic regressions and incident disease measured by Cox proportional hazards regression models adjusted for sex, age, body mass index, and smoking status., Results: The study included 391 481 individuals (median [IQR] age, 58 [51-64] years; 209 235 [53%] female). Genetic variants for HS correlated significantly with variants associated with CAD, diabetes, and plasma levels of high-density lipoprotein cholesterol, triglycerides, and C-reactive protein. Compared with the low-risk group, a high PRS for HS (≥75th percentile) conferred odds ratios of 1.09 (95% CI, 1.06-1.12; P < .001) for CAD and 1.13 (95% CI, 1.10-1.17; P < .001) for diabetes. Estimates remained consistent when examining only incident CAD and diabetes. The PRS for HS was significantly associated with altered expression of 58 plasma proteins. Integrating this proteomic profile and the PRS for HS in a machine learning model improved prediction of CAD and diabetes compared with a reference model based on sex, age, and body mass index., Conclusions and Relevance: These findings suggest that a high genetic risk of HS is associated with increased risk of subsequent CAD and diabetes and altered composition of the plasma proteome. Additional investigation into the identified proteins and their potential roles as drug targets is warranted.

Real-world data on anatomically localized psoriasis and its response to systemic therapy across different age-groups and sexes is limited. This study aimed to evaluate the severity and distribution of psoriasis over time in female and male patients receiving systemic therapies, categorized by age within the Swiss psoriasis registry (SDNTT). Patient-data was obtained over 11 years through the SDNTT. The localized Psoriasis Area and Severity Index (locPASI) of the head, trunk, upper and lower extremities was analyzed over two years following the start of systemic non-/biologic treatment. A total of 316 female and 517 male patients were analyzed. Male patients had a higher baseline locPASI for legs, trunk and arms (p < 0.001), but not for the head (p = 0.961). The locPASI for the head in younger female patients (18-40 years) had a higher score than those aged 55 + (p = 0.022) and after two years, middle aged (41-54) showed a lower score compared to younger patients (p = 0.045). Younger male patients revealed a lower score after two years of therapy in the leg- and arm-area compared to older (p = 0.018 and p = 0.048, respectively). Female patients on non-biologics had a fast initial response, converging with male patients' scores over 24 months. Over 75% locPASI reduction was observed for female head-area (81.4%), male trunk (82.7%) and legs (76.1%). Absolute locPASI ≤ 2 was achieved 3-6 months for all locations with interleukin (IL)-17, IL-12/23 and IL-23-inhibitors, except for the legs of male patients on anti-IL-17 and female patients on anti-IL-12/23 and -IL-23. After two years, male patients did not achieve a locPASI ≤ 2 for any biologic-treatment in the legs, nor for the arms on anti-TNF-α. Significant disparities in localized PASI were observed between female and male patients. The age, sex and severity of distinct localizations should be considered to optimize treatment goals., (© 2024. The Author(s).)

Skin barrier function (SBF) disorders are a class of pathologies that affect a significant portion of the world population. These disorders cause skin lesions with intense itch, impacting patients' physical and psychological well-being as well as their social functioning. It is in the interest of patients that their disorder be monitored closely while under treatment to evaluate the effectiveness of the ongoing therapy and any potential adverse reactions. Symptom-based assessment techniques are widely used by clinicians; however, they carry some limitations. Techniques to assess skin barrier impairment are critical for understanding the nature of the disease and for helping personalize treatment. This review recalls the anatomy of the skin barrier and describes an atomic-force microscopy approach to quantitatively monitor its disorders and their response to treatment. We review a panel of studies that show that this technique is highly relevant for SBF disorder research, and we aim to motivate its adoption into clinical settings., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The 4th Davos Declaration was developed during the Global Allergy Forum in Davos which aimed to elevate the care of patients with atopic dermatitis (AD) by uniting experts and stakeholders. The forum addressed the high prevalence of AD, with a strategic focus on advancing research, treatment, and management to meet the evolving challenges in the field. This multidisciplinary forum brought together top leaders from research, clinical practice, policy, and patient advocacy to discuss the critical aspects of AD, including neuroimmunology, environmental factors, comorbidities, and breakthroughs in prevention, diagnosis, and treatment. The discussions were geared towards fostering a collaborative approach to integrate these advancements into practical, patient-centric care. The forum underlined the mounting burden of AD, attributing it to significant environmental and lifestyle changes. It acknowledged the progress in understanding AD and in developing targeted therapies but recognized a gap in translating these innovations into clinical practice. Emphasis was placed on the need for enhanced awareness, education, and stakeholder engagement to address this gap effectively and to consider environmental and lifestyle factors in a comprehensive disease management strategy. The 4th Davos Declaration marks a significant milestone in the journey to improve care for people with AD. By promoting a holistic approach that combines research, education, and clinical application, the Forum sets a roadmap for stakeholders to collaborate to improve patient outcomes in AD, reflecting a commitment to adapt and respond to the dynamic challenges of AD in a changing world., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Oral Janus kinase inhibitors (JAKis) have black-box warnings of infections, cancer risk, and cardiovascular and venous thromboembolic events. They may be used off-label for chronic hand eczema (CHE)., Objectives: Assess the prevalence of risk factors potentially impacting oral JAKi safety in CHE patients., Methods: In the Danish Skin Cohort, CHE patients were examined for risk factors affecting oral JAKi use at baseline and followed for 12 months. Data were collected through register linkage (eg, cancer history) and through patient interviews (eg, smoking habits)., Results: Of 941 adults with CHE (66.2% women; mean age 55.5 [SD 13.3] years), 768 (81.6%) patients had at least one risk factor potentially impacting oral JAKi use, of which 682 (72.5%) had nonmodifiable risk factors. Most common risk factors were current or former heavy smoking (62.8%, n  = 591), obesity (28.1%, n  = 264), hypercholesterolemia (21.5%, n  = 202), and hypertension (18.8%, n  = 177). Among patients without any risk factors at baseline ( n  = 173), 20.2% ( n  = 35) developed ≥1 risk factor during the following 12 months., Limitations: Certain risk factors may be underreported., Conclusion: Most CHE patients have risk factors limiting appropriateness of oral JAKi use. Health care providers should assess risk factors in their patients when choosing treatment for CHE., Competing Interests: Outside of the submitted work, Dr Egeberg has received research funding from Almirall, Pfizer, Eli Lilly, Novartis, Bristol-Myers Squibb, AbbVie, Janssen Pharmaceuticals, Boehringer Ingelheim, the Danish National Psoriasis Foundation, the Simon Spies Foundation, and the Kgl Hofbundtmager Aage Bang Foundation. He has received honoraria as consultant and/or speaker from Amgen, AbbVie, Almirall, Leo Pharma, Zuellig Pharma Ltd, Galápagos NV, Sun Pharmaceuticals, Samsung Bioepis Co, Ltd, Pfizer, Eli Lilly and Company, Novartis, Union Therapeutics, Galderma, Dermavant, UCB, Mylan, Bristol-Myers Squibb, McNeil Consumer Healthcare, Horizon Therapeutics, Boehringer Ingelheim, and Janssen Pharmaceuticals. He is currently employed by LEO Pharma. Dr Andersen has received speaker honoraria from Eli Lilly Company. Drs Sieborg and Nymand have nothing to declare. Outside of the submitted work, Dr Thomsen has been a speaker or advisor for Sanofi, AbbVie, LEO Pharma, Pfizer, Eli Lilly, Novartis, UCB Pharma, Symphogen, UNION Therapeutics, Almirall, and Janssen Pharmaceuticals and received research support from Sanofi, AbbVie, LEO Pharma, Novartis, UCB Pharma, and Janssen Pharmaceuticals. Outside of the submitted work, Dr Thyssen has been an advisor for AbbVie, Almirall, Arena Pharmaceuticals, Coloplast, OM Pharma, Aslan Pharmaceuticals, Union Therapeutics, Eli Lilly & Co, LEO Pharma, Pfizer, Regeneron, and Sanofi-Genzyme. He has previously received speaker honoraria from AbbVie, Almirall, Eli Lilly & Co, LEO Pharma, Pfizer, Regeneron, and Sanofi-Genzyme, and has received research grants from Pfizer, Regeneron, and Sanofi-Genzyme. He is currently employed by LEO Pharma. Outside of the submitted work, Dr Torres has been investigator, consultant, and/or speaker: AbbVie, Amgen/Celgene, Almirall, Arena, BIOCAD, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Fresenius-Kabi, Janssen, Leo Pharma, Lilly, Merck, Mylan, Novartis, Pfizer, Samsung-Bioepis, Sandoz, Sanofi Genzyme, and UCB. Outside of the submitted work, Dr Chiricozzi has served as an advisory board member and consultant and has received fees and speaker's honoraria or has participated in clinical trials for AbbVie, Almirall, Bristol Myers Squibb, Boehringer-Ingelheim, Galderma, Leo Pharma, Lilly, Janssen, Novartis, Sanofi Genzyme, and UCB Pharma., (© 2024 by the American Academy of Dermatology, Inc. Published by Elsevier Inc.)

Allergic contact dermatitis is characterized by its appearance of red, raised and infiltrated, scaling or scabbed skin and intense pruritus, and distinguished from irritant contact dermatitis by its specific immune process and histopathology. Many contact allergens are low-molecular- weight chemicals including metals such as nickel, cobalt, and chromium, preservatives, and adhesives. When such materials are used internally in biomedical devices, they are similarly capable of causing sensitization and an inflammatory response. Sometimes, the reaction remains internal, and presents as swelling, pain, stiffness, decreased range of motion, and internal itching around the implant. Such reactions may, in some cases, also extend to include a localized or, rarely, systemic contact dermatitis indicative of the same process. This review will present an overview of reported skin and local internal reactions to orthopedic implants, which are the largest category of implanted internal metal devices. Immune reactions to smaller categories of medical appliances include cardiac devices and vascular stents, neuromodulation devices, diabetic appliances, Nuss bar surgery for pectus excavatum, and dental and spinal implants. We will review the available diagnostic tools, the consensus on interpretation, and reported strategies for treatment., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Cold climate and unique genetic and environmental factors may influence the prevalence of skin diseases in Greenland. However, there is a lack of epidemiological studies on skin diseases in the adult Greenlandic population. To address this unmet need a cross-sectional study, run by dermatologists from Denmark, the UK, and Switzerland estimated the prevalence and clinical manifestations of skin diseases among adults in East Greenland in May 2022. All adults ≥18 years in the town of Tasiilaq were invited, and 295 individuals aged 18-78 years participated (22.5% of the overall adult population in Tasiilaq). Two-hundred and three participants (69%) had visible signs of current skin disease, and among these, 242 cases of dermatoses were identified. The most common skin diseases were hand eczema (22.4%), lichen simplex (9.5%), discoid eczema (7.1%), psoriasis, atopic dermatitis and acne vulgaris (5.8% each). Scabies was the most frequent infectious skin disease (4.4%). No cases of skin cancer were identified. Atopic dermatitis and psoriasis presented with disease that was of limited extent and different from the classical presentations. Skin diseases showed a high prevalence among adults in East Greenland, and some of them were severe. This indicates a noteworthy public health problem that warrants better access to dermatologist support.

Purpose: Topical treatments for mild-to-moderate (MM) atopic dermatitis (AD) include emollients, corticosteroids, calcineurin inhibitors, a Janus kinase inhibitor, and a phosphodiesterase 4 inhibitor, which differ in multiple ways. This study aimed to quantify the conditional relative importance (CRI) of attributes of topical treatments for MM AD among adult and adolescent patients and caregivers of children with MM AD. Materials and methods: A discrete-choice experiment (DCE) survey was administered to US adults and adolescents with MM AD and caregivers of children with MM AD. Each choice task comprised 2 hypothetical topical treatments characterized by efficacy, adverse events, vehicle, and application frequency. Data were analyzed using a random-parameters logit model to calculate the CRI of each attribute. Results and conclusions: 300 adults, 331 adolescents, and 330 caregivers completed the DCE. Avoiding changes in skin color (CRI 29.0) and time until itch improves (26.6) were most important to adults, followed by time until clear/almost clear skin (17.8). Application frequency (3.0) did not have a statistically significant impact on adults' choices. Adolescents were less concerned about changes in skin color than adults or caregivers; caregivers were less concerned about time until clear/almost clear skin than patients. Physicians should consider age-relevant aspects of preferences in treatment discussions with patients and caregivers.

Objective: To explore how the parents of children with atopic dermatitis and allergic diseases such as food allergy, allergic rhinoconjunctivitis, and asthma experience interactions with the Danish healthcare system over time., Design and Methods: A qualitative design with individual in-depth interviews. The analysis was inspired by Systematic Text Condensation., Subjects: Eleven parents of children with atopic dermatitis and allergic diseases who received treatment at hospitals in the Capital Region of Denmark. The families had experiences of cross-sectoral patient care., Results: Despite having the same diseases, the children's care pathways were very different. Mapping demonstrated the intricacy of care pathways for this group of children. We identified three aspects that impacted interaction with healthcare: responsibility, tasks, and roles. The families experienced care when the distribution of tasks and responsibilities associated with treatment and system navigation were consistent with both their expectations and their actual experiences. At the same time, families frequently experienced limited collaboration between healthcare professionals resulting in perceived fragmented care and an extended role for parents as care coordinators. Families felt cared for when healthcare professionals knew both their biomedical and biographical circumstances, and adjusted the level of support and care in accordance with the families' particular needs, expectations, and evolving competences., Conclusion: We suggest that a possible pathway to improve care may be through a partnership approach as part of family-centered care, with general practitioners having a key role in helping to articulate the individual needs and expectations of each family.

Competing Interests: Dr Johansen has been a speaker/consultant for LEO Pharma and UCB and has received research support from UCB, are unrelated to the present manuscript. Dr Egeberg has received research support from AbbVie, Almirall, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Janssen Pharmaceuticals, Novartis, and Pfizer and has been a speaker/consultant for AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Eli Lilly, Galápagos NV, Galderma, Horizon Therapeutics, Janssen, LEO Pharma, McNeil Consumer Healthcare, Mylan, Novartis, Pfizer, Samsung Bioepis Co, Sun Pharmaceuticals, UCB, Union Therapeutics, and Zuellig Pharma Ltd, are unrelated to the present manuscript. Dr Thyssen has received research support from Pfizer, Regeneron, and Sanofi Genzyme, has been a speaker/consultant for AbbVie, Almirall, Arena Pharmaceuticals, OM Pharma, Aslan Pharmaceuticals, Union Therapeutics, Eli Lilly, LEO Pharma, Pfizer, Regeneron, and Sanofi Genzyme, and is currently an employee of LEO Pharma, are unrelated to the present manuscript. Dr Thomsen has received research support from Janssen, LEO Pharma, Novartis, Sanofi and UCB and has been a speaker/consultant for AbbVie, Almirall, Eli Lilly, Galderma, Incyte, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi, Symphogen, UCB, and Union Therapeutics, are unrelated to the present manuscript. Dr Sørensen has no conflicts of interest to declare.

Background: Topical corticosteroid phobia (TOPICOP) is associated with poor treatment adherence and is common among patients with skin disease. Knowledge about corticosteroid phobia and treatment adherence among patients with chronic hand eczema (CHE) is limited., Objectives: To investigate patient-reported outcomes regarding topical corticosteroids (TCSs), and their impact on treatment adherence in patients with CHE., Methods: Patients with CHE from the Danish Skin Cohort answered a questionnaire including the TOPICOP scale and Medication Adherence Report Scale. Response rate was 69.2%., Results: Of 927 with CHE, 75.5% totally or almost agreed that TCS damage the skin, 48.9% totally or almost agreed that TCS would affect their future health and 36.3% reported some degree of fear of TCS although they were unaware of any TCS-associated risks. Most patients (77.9%) always or often stop treatment as soon as possible, whereas 54.8% always or often wait as long as possible before starting treatment. Overall, 38.8% reported that they had taken less medicine than prescribed and 54.0% had stopped treatment throughout a period. Treatment adherence decreased with increasing corticosteroid phobia (P = .004)., Limitations: TOPICOP has not been validated in patients with CHE., Conclusions: Corticosteroid phobia is common among patients with CHE and negatively associated with treatment adherence., Competing Interests: Conflicts of interest Dr Christensen has been a subinvestigator for LEO Pharma, with no relation to this manuscript. Dr Guttman-Yassky is an employee of Mount Sinai, has received research grants from Boehringer Ingelheim, LEO Pharma, Pfizer, Cara Therapeutics, UCB, Kyowa Kirin, RAPT, Amgen, GSK, Incyte, Sanofi, Bristol Meyers Squibb, Aslan, Regeneron, AnaptysBio, Concert, and Janssen, and is a consultant for AbbVie, Almirall, Amgen, AnaptysBio, Apogee Therapeutics, Apollo Therapeutics Limited, Artax Biopharma Inc, AstraZeneca, Bristol Meyers Squibb, Boehringer Ingelheim, Cara Therapeutics, Centrexion Therapeutics Corporation, Connect Biopharm, Eli Lilly, Enveda Biosciences, Escient Pharmaceuticals, Inc, Fairmount Funds Management LLC, FL2022-001, Inc, Galderma, Gate Bio, Google Ventures (GV), GSK Immunology, Horizon Therapeutics USA, Inc, Incyte, Inmagene, Janssen Biotech, Japan Tobacco, Jasper Therapeutics, Kyowa Kirin, LEO Pharma, Merck, Nektar Therapeutics, Novartis Pharmaceuticals Corporation, NUMAB Therapeutics AG, OrbiMed Advisors LLC, OTSUKA Pfizer, Pharmaxis Ltd, Pioneering Medicine VII, Inc, Proteologix US Inc, RAPT, Regeneron Pharmaceuticals, Ribon Therapeutics, Inc, Sanofi, SATO, Schrödinger, Inc, Sun Pharma Advanced Research Company (SPARC), Teva Branded Pharmaceutical Products R&D, Inc, and UCB, with no relation to this manuscript. Dr Ezzedine has been a consultant and speaker and has received funding from AbbVie, Incyte, Lilly, Pfizer, Pierre Fabre, L’Oreal, BMS, and MSD, with no relation to this manuscript. Dr Schlapbach has received honoraria as adviser or speaker for AbbVie, Almirall, BMS, Incyte, LEO Pharma, Lilly, Kiowa Kirin, Novartis, Pfizer, and Sanofi and has received research funding from PPM Services, with no relation to this manuscript. Dr Molin has received honoraria as consultant/adviser or speaker and/or grants from AbbVie, Almirall, Aralez, Arcutis, Basilea, Bausch and Lomb, Bristol Myer Squibb, Boehringer Ingelheim, Evidera, Galderma, GSK, Incyte, LEO Pharma, Lilly, Novartis, Pfizer, Sanofi, Sun Pharma, and UCB, and is currently investigator for Novartis and LEO Pharma, with no relation to this manuscript. Dr Zhang has served on advisory boards and receives honorarium for Pfizer Investment Co, Ltd, Novartis Pharmaceuticals (China), Sanofi China, LEO Pharma (Shanghai) Co, Ltd, GSK (China) Investment Co, Ltd, Eli Lilly and Company (China), Xi’an Janssen Pharmaceutical Ltd, Bristol-Myers Squibb (China) Investment Co, Ltd, Beijing Wenfeng Tianji Pharma Ltd, Keymed Biosciences (Chengdu) Ltd, Akeso Biopharma Co, Ltd, Reistone Biopharma Co, Ltd, and Kintor Pharmaceutical Ltd, with no relation to this manuscript. Dr Zachariae has been a paid speaker for Eli Lilly, Novartis, CSL, and LEO Pharma, and has been a consultant or has served on advisory boards with AbbVie, Janssen Cilag, Novartis, Eli Lilly, LEO Pharma, UCB, Almirall, Takeda, Amgen, and CSL, with no relation to this manuscript. Dr Thomsen has been a speaker or has served on advisory boards for Sanofi, AbbVie, LEO Pharma, Pfizer, Eli Lilly, Novartis, UCB Pharma, Union Therapeutics, Almirall, and Janssen Pharmaceuticals, and has received research support from Sanofi, AbbVie, LEO Pharma, Novartis, UCB Pharma, and Janssen Pharmaceuticals, with no relation to this manuscript. Dr Thyssen is an adviser for AbbVie, Almirall, Arena Pharmaceuticals, Coloplast, OM Pharma, Aslan Pharmaceuticals, Union Therapeutics, Eli Lilly & Co, LEO Pharma, Pfizer, Regeneron, and Sanofi-Genzyme, has a speaker for AbbVie, Almirall, Eli Lilly & Co, LEO Pharma, Pfizer, Regeneron, and Sanofi-Genzyme, received research grants from Pfizer, Regeneron, and Sanofi-Genzyme, and is a full time employee at LEO Pharma. Dr Egeberg has received research funding from Pfizer, Eli Lilly, Novartis, Bristol-Myers Squibb, AbbVie, Janssen Pharmaceuticals, Boehringer Ingelheim, the Danish National Psoriasis Foundation, the Simon Spies Foundation, and the Kgl Hofbundtmager Aage Bang Foundation, has received honoraria as consultant and/or speaker from Amgen, AbbVie, Almirall, LEO Pharma, Zuellig Pharma Ltd, Galápagos NV, Sun Pharmaceuticals, Samsung Bioepis Co, Ltd, Pfizer, Eli Lilly and Company, Novartis, Union Therapeutics, Galderma, Dermavant, UCB, Mylan, Bristol-Myers Squibb, McNeil Consumer Healthcare, Horizon Therapeutics, Boehringer Ingelheim, and Janssen Pharmaceuticals, and is currently employed by LEO Pharma, with no relation to this manuscript. Authors Sieborg and Nymand have no conflicts of interest to declare., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Although rare, allergic reactions to metal implants represent a diagnostic challenge in view of missing guidelines., Objectives: To develop an European expert consensus on characteristics of metal allergy reactions and the utility of various diagnostic tools in suspected metal implant allergy., Methods: A nominal group technique (NGT) was applied to develop consensus statements. Initially an online literature database was created on a secure server to enable a comprehensive information. Twenty-three statements were formulated on potential aspects of metal implant allergy with a focus on diagnostics and grouped into five domains. For the consensus development, the panel of 12 experts initially did refine and reformulate those statements that were ambiguous or had unclear wording. By face-to-face (9/12) or virtual participation (3/12), an anonymous online voting was performed., Results: Consensus (≥80% of agreement) was reached in 20/23 statements. The panel agreed that implant allergy despite being rare should be considered in case of persistent unexplained symptoms. It was, however, recommended to allow adequate time for resolution of symptoms associated with healing and integration of an implant. Obtaining questionnaire-aided standardized medical history and standardized scoring of patient outcomes was also considered an important step by all experts There was broad consensus regarding the utility/performance of patch testing with additional late reading. It was recognized that the lymphocyte transformation test (LTT) has to many limitations to be generally recommended. Prior to orthopaedic implant, allergy screening of patients without a history of potential allergy to implant components was not recommended., Conclusions: Using an expert consensus process, statements concerning allergy diagnostics in suspected metal implant allergy were created. Areas of nonconsensus were identified, stressing uncertainty among the experts around topics such as preoperative testing in assumed allergy, histological correlate of periimplant allergy and in vitro testing, which underscores the need for further research., (© 2024 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: Atopic dermatitis (AD) is mainly driven by type 2 inflammation and often treated with topical agents. Studies comparing differences in biomarkers between these treatments are lacking., Objectives: The aim of this study was to evaluate the effects of topical betamethasone 17-valerate 0.1% and tacrolimus 0.1% ointment on skin barrier function and inflammatory biomarkers in skin and blood in adults with AD., Methods: In this randomized parallel-group double-blind double-dummy active-comparator study design, 36 adults with AD were treated with either whole-body topical corticosteroid (betamethasone ointment 0.1% plus placebo once daily, n = 18) or calcineurin inhibitor (tacrolimus ointment 0.1% twice daily, n = 18). At baseline, after 2 weeks of daily treatment and after further 4 weeks of twice-weekly maintenance treatment, we evaluated AD severity, levels of natural moisturizing factor (NMF) and cytokines in the skin and blood and characterized circulating T cells., Results: Mean AD severity at baseline corresponded to moderate disease and decreased significantly in both groups. Levels of NMF increased significantly in the tacrolimus group after 2 weeks of treatment (p = 0.002) and tended to increase more than betamethasone at week 6 (p = 0.06). Most skin cytokines decreased with both treatments. However, IL-8, IL-18, IL-22, IP-10, MDC, MMP-9 and TARC were significantly more decreased with betamethasone than tacrolimus after 2 weeks, while after 6 weeks this was only the case for IL-8 and MMP-9. Approximate half of the systemic cytokines decreased significantly with both treatments, but betamethasone decreased MDC significantly more after 2 weeks of treatment. T-cell characterization analyses indicated slight differences in the expression and activation of T cells between groups., Conclusion: Topical treatment of AD with betamethasone and tacrolimus ointment effectively reduced disease severity, cutaneous and systemic inflammatory markers. Betamethasone was more effective in decreasing inflammation, but tacrolimus improved skin hydration (NMF levels) more than betamethasone., (© 2024 European Academy of Dermatology and Venereology.)

Background: It is unknown whether the pre-biologic treatment journey affects subsequent biologic drug survival., Objective: To examine the potential impact of a complex treatment journey on subsequent biologic drug survival in patients with psoriasis., Methods: The study utilized longitudinal data from Danish national registries and included all patients who, for the first time, initiated a biological treatment for psoriasis. Maximum follow-up was 5 years and patients were included from 1 January 2010 to 30 June 2021. The study used three definitions of exposure to a complex treatment journey and the following conventional systemic treatments: acitretin, cyclosporine, dimethyl fumarate and methotrexate. The first definition was the cumulative number of treatment series. The second definition comprised the number of unique treatments. The third definition was time from the first conventional systemic treatment to biological therapy. Drug survival for the three definitions were illustrated using Kaplan-Meier curves and compared using log-rank test. The sensitivity analysis largely confirmed these findings by grouping patients according to pharmacotherapy., Results: A total of 2496 patients were included in the study, with 1380 (55.3%) receiving adalimumab, 608 (24.4%) receiving ustekinumab, 271 (10.9%) receiving secukinumab, 166 (6.7%) receiving etanercept and 71 (2.8%) receiving infliximab. The mean age at initiation of biologics was 43.6 years (standard deviation (SD) 15.2 years), and most patients were male (62.9%). During the follow-up of 5477 patient years, 1953 patients (78.2%) reached the main endpoint of discontinuation. Using a log-rank test, the probability of remaining on treatment was unaffected by the three definitions of complexity of the treatment journey., Conclusion: None of the three exposures used to assess the complexity of the pre-biologic treatment journey appeared to impact drug survival. As long as patients experience adequate disease control, these results suggest that conventional systemic treatment do not negatively impact the drug survival of subsequent biologics., (© 2024 The Author(s). Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)