Phase 3 Trial of Nemolizumab in Patients with Prurigo Nodularis.

BACKGROUND: Prurigo nodularis is a chronic, debilitating, and severely pruritic neuroimmunologic skin disease. Nemolizumab, an interleukin-31 receptor alpha antagonist, down-regulates key pathways in the pathogenesis of prurigo nodularis. METHODS: In this phase 3, double-blind, multicenter, randomized trial, we assigned adults with moderate-to-severe prurigo nodularis to receive an initial 60-mg dose of nemolizumab followed by subcutaneous injections of 30 mg or 60 mg (depending on baseline weight) every 4 weeks for 16 weeks or matching placebo. The primary end points were an itch response (a reduction of ≥4 points on the Peak Pruritus Numerical Rating Scale [PP-NRS; scores range from 0 to 10, with higher scores indicating more severe itch]) and an Investigator's Global Assessment (IGA) response (a score of 0 [clear] or 1 [almost clear] on the IGA [scores range from 0 to 4] and a reduction from baseline to week 16 of ≥2 points). There were five key secondary end points. RESULTS: A total of 274 patients underwent randomization; 183 were assigned to the nemolizumab group, and 91 to the placebo group. Treatment efficacy was shown with respect to both primary end points at week 16; a greater percentage of patients in the nemolizumab group than in the placebo group had an itch response (56.3% vs. 20.9%; strata-adjusted difference, 37.4 percentage points; 95% confidence interval [CI], 26.3 to 48.5), and a greater percentage in the nemolizumab group had an IGA response (37.7% vs. 11.0%; strata-adjusted difference, 28.5 percentage points; 95% CI, 18.8 to 38.2) (P<0.001 for both comparisons). Benefits were observed for the five key secondary end points: itch response at week 4 (41.0% vs. 7.7%), PP-NRS score of less than 2 at week 4 (19.7% vs. 2.2%) and week 16 (35.0% vs. 7.7%), and an improvement of 4 or more points on the sleep disturbance numerical rating scale (range, 0 [no sleep loss] to 10 [unable to sleep at all]) at week 4 (37.2% vs. 9.9%) and week 16 (51.9% vs. 20.9%) (P<0.001 for all comparisons). The most common individual adverse events were headache (6.6% vs. 4.4%) and atopic dermatitis (5.5% vs. 0%). CONCLUSIONS: Nemolizumab monotherapy significantly reduced the signs and symptoms of prurigo nodularis. (Funded by Galderma; ClinicalTrials.gov number, NCT04501679; EudraCT number, 2019-004789-17.).

Road-traffic-related air pollution contributes to skin barrier alteration and growth defect of sensory neurons.

The effects of air pollution on health are gaining increasing research interest with limited data on skin alterations available. It was suggested that air pollution is a trigger factor for sensitive skin (SS). However, this data was based on surveys with a lack of experimental data. SS is related to altered skin nerve endings and cutaneous neurogenic inflammation. TTe present study was to assess the in vitro effect of particulate matter (PM) on epidermis and nerve ending homeostasis. PM samples were collected according to a validated protocol. Reconstructed human epidermis (RHE, Episkin®) was exposed to PM and subsequently the supernatants were transferred to a culture of PC12 cells differentiated into sensory neurons (SN). Cell viability, axonal growth and neuropeptide-release were measured. The modulation of the expression of different inflammatory, keratinocytes differentiation and neurites growth markers was assessed. PM samples contained a high proportion of particles with a size below 1 µm and a complex chemical composition. Transcriptomic and immunohistochemical analyses revealed that PM altered keratinocytes terminal differentiation and induced an inflammatory response. While viability and functionality of the SN were not modified, their outgrowth was significantly decreased after incubation with PM-exposed Episkin® supernatants. This was closely related to the modification of nerve growth factor/semaphorin 3A balance. This study showed that air pollutants have negative effects on keratinocytes and sensory nerve endings including inflammatory responses. These effects are probably involved in the SS pathophysiology and might be involved in inflammatory skin disorders.

International study on prevalence of itch: examining the role of itch as a major global public health problem.

BACKGROUND: Very few studies evaluated the global prevalence of pruritus. OBJECTIVE: To assess its prevalence according to age, gender, ethnicity, and geographic regions. METHODS: An international cross-sectional study was conducted in 20 countries from January to April 2023. Participants were asked to complete a questionnaire on sociodemographics, confirm the presence or absence of a skin disease in the last 12 months and the presence or absence of pruritus in the last 7 days. RESULTS: The studied sample included 50552 individuals. The worldwide prevalence of pruritus was 39.8%. The age group ≥65 had the highest prevalence (43.3%). The prevalence was 40.7% among women and 38.9% among men (p<0.001). There was no significant difference between ethnicities (p=0.14). Compared to North America (41.6%), the prevalence of pruritus was significantly lower in Europe (35.9%, p<0.001), Australia (38.4%, p=0.017), East Asia (40.2%, p=0.04), and Latin America (36.5%, p<0.001), and higher in Africa (45,7%, p=0.007). No significant difference was found with the Middle East (40.2%, p=0.36). The prevalence was 40.3% in developed countries and 38.7% in BRICS countries 40.7% (p<10-3). LIMITATIONS: No information about the severity or type (acute, chronic) of pruritus. CONCLUSION: Global prevalence of pruritus revealed age, gender, and geographic region differences, with no ethnic differences.

Effectiveness of a nurse-led one-to-one education programme in addition to standard care in children with atopic dermatitis: a multicentre randomized control trial.

BACKGROUND: Therapeutic patient education (TPE) is recommended for children with atopic dermatitis (AD), but no consensus has been reached on the optimal tailoring of delivery. While repeated multidisciplinary group education sessions have shown effectiveness, the benefits of one-on-one educational interventions led by nurses for children with AD have not yet been assessed. OBJECTIVES: To assess the benefits of additional, well-structured, 1-h nurse-led individual TPE interventions in children with AD and their families compared with standard care alone. METHODS: Children with moderate-to-severe AD and their parents were randomized to receive a 1-h nurse-led education session in addition to standard care vs. standard care alone. The primary outcome was the area under the curve (AUC) of the SCORing of Atopic Dermatitis index (SCORAD) from baseline to week 24 (lower AUC values represent better long-term control of the disease). RESULTS: In our study, 176 patients were randomized across 11 centres, and 153 were included in the full analysis set. The mean (SD) age was 4.47 (4.57) years. By week 24, there were no significant differences in the AUCs of the SCORAD between the two groups (P = 0.3). Secondary outcomes including patient-reported severity and quality of life [AUCs of the patient-oriented SCORAD (PO-SCORAD) and Infants' Dermatitis Quality of Life Index (IDLQI), Children's Dermatitis Quality of Life Index (CDLQI) and Family Dermatitis Quality of Life Index (FDLQI)] were not significantly different between the two groups. The only significant change observed in the intervention group, when compared with the one receiving standard care, was a decrease in topical steroid phobia, as assessed by the topical corticosteroid phobia (TOPICOP) score. Prespecified subgroup analyses showed that disease severity in the intervention group was significantly lower throughout the study, compared with the standard-care group when participants had moderate AD at baseline (n = 47); while participants with severe AD at baseline (n = 106) did not show benefit from the intervention. Participants showed no additional benefit from the intervention regardless of age group. CONCLUSIONS: This study did not show any additional effectiveness, in long-term severity control, of a 1-h nurse-led TPE intervention in children with AD treated with standard care, compared with those treated with standard care alone. However, it should be noted that the intervention reduced the fear of using topical steroids and may be beneficial for patients in the subgroup with moderate AD.

Abrocitinib Provides Rapid and Sustained Improvement in Skin Pain and Is Associated with Improved Quality of Life Outcomes in Adult and Adolescent Patients with Moderate-to-Severe Atopic Dermatitis.

BACKGROUND: Skin pain in atopic dermatitis (AD) increases with disease severity and is associated with substantial quality of life (QoL) burden. OBJECTIVES: The aim of the study was to evaluate abrocitinib efficacy on skin pain and QoL in adults and adolescents with moderate-to-severe AD. METHODS: This post hoc analysis included data with abrocitinib administered as monotherapy (pooled phase 2b [NCT02780167] and phase 3 JADE MONO-1 [NCT03349060] and JADE MONO-2 [NCT03575871]) or in combination with topical therapy (phase 3 JADE COMPARE [NCT03720470] and JADE TEEN [NCT03796676]). Patients received oral, once-daily abrocitinib 200 mg, abrocitinib 100 mg, or placebo for 12 or 16 weeks (JADE COMPARE). Skin pain was rated using the Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) skin pain Numerical Rating Scale (NRS) item ("How painful was your skin over the past 24 h?") on a scale from 0 (not painful) to 10 (extremely painful). Itch (Peak Pruritus NRS) and QoL (Dermatology Life Quality Index or Children's Dermatology Life Quality Index) were assessed. Least squares mean (LSM) change from baseline was analyzed using mixed-effects repeated measures modeling. RESULTS: A total of 1,822 patients (monotherapy pool, n = 942; JADE COMPARE, n = 595; and JADE TEEN, n = 285) were analyzed. LSM change from baseline in PSAAD skin pain score was significantly greater with abrocitinib versus placebo from week 2 through week 12 or 16 across all 3 study populations and occurred in a dose-dependent manner. A greater proportion of patients achieved a ≥4-point improvement from baseline in PSAAD skin pain score with abrocitinib (200 mg and 100 mg) versus placebo in the monotherapy pool (56% and 38% vs. 12%; week 12), JADE COMPARE (72% and 52% vs. 26%; week 16), and JADE TEEN (51% and 60% vs. 31%; week 12). Additionally, a greater proportion of patients achieved a stringent threshold of skin pain improvement (PSAAD skin pain score <2) with abrocitinib versus placebo. Adults and adolescents who achieved a ≥4-point improvement in skin pain reported greater QoL improvement than those who did not achieve a ≥4-point improvement. A positive correlation (≥0.3) was observed between skin pain and QoL and separately between skin pain and itch across the 3 study populations. CONCLUSION: Abrocitinib as monotherapy or in combination with topical therapy improved skin pain and was associated with improved QoL in both adults and adolescents with moderate-to-severe AD across all evaluated studies.

Baricitinib treatment rapidly improves the four signs of atopic dermatitis assessed by Eczema Area and Severity Index (EASI) clinical subscores.

BACKGROUND: Baricitinib treatment in adults with moderate-to-severe atopic dermatitis (AD) has demonstrated rapid improvements in itch as well as AD sign severity and affected body surface area as assessed by the Eczema Area and Severity Index (EASI) total score, whether administered as monotherapy or in combination with topical corticosteroids (TCS). As EASI clinical signs differ in time course and associated antecedents, the effects of baricitinib on each individual clinical sign are of interest. OBJECTIVES: In this post hoc analysis, we aimed to investigate the effects of baricitinib on individual EASI subscores, namely excoriation, oedema/papulation, erythema and lichenification, in both monotherapy and TCS combination therapy trials. METHODS: We analysed the percent change from baseline in individual EASI subscores from three phase-III, double-blind, 16-week trials of baricitinib in monotherapy (BREEZE-AD1/BREEZE-AD2) and TCS combination therapy (BREEZE-AD7) cohorts via mixed model repeated measures (MMRM). RESULTS: Baricitinib 4 mg showed rapid and sustained improvements in all four clinical signs in both cohorts. Significant effects emerged at week 1 for excoriation, oedema/papulation and erythema scores in monotherapy (p < 0.001) and TCS combination therapy (p < 0.001, p < 0.01, p < 0.001), plateaued at week 4, and remained significant versus placebo through week 16. The effect on lichenification scores also emerged early, at week 1 in monotherapy (p < 0.05) and week 2 in combination therapy (p < 0.001), with scores continuously improving without a clear plateau. Effect magnitude was highest in excoriation scores, exhibiting near-maximal reduction in week 1 of monotherapy and remaining highest across all timepoints in combination therapy. CONCLUSIONS: Rapid and sustained improvements were observed across clinical signs of inflammation and particularly on excoriation following baricitinib treatment. Our findings suggest that selective inhibition of janus kinases 1 and 2 leads to rapid and sustained control of skin inflammation, and that rapid reductions in itch translate into early disruption of the itch-scratch cycle.

Classification of psychodermatological disorders: Proposal of a new international classification.

INTRODUCTION: Several classifications of psychodermatology disorders have been proposed, with most of them based on two to four main disorder category groups. However, there is, to date, no classification that has resulted from a consensus established by psychodermatology experts. The DSM-5-TR (Diagnostic and statistical manual of mental disorders (5th ed.), Text Revision) and the ICD-11 (International classification of diseases (11th revision)) also do not provide a systematized approach of psychodermatology disorders. Taking into consideration that classifications are a key pillar for a comprehensive approach to the pathologies of each branch of medicine, the proposal of a classification in psychodermatology appeared as a central need for the recognition of psychodermatological disorders, in an attempt to improve their recognition and, in that sense, to find a common language for the development of this subspecialty that crosses dermatology and psychiatry. METHODS: Previously published classifications in psychodermatology were critically reviewed and discussed by expert opinion from an international multidisciplinary panel of 16 experts in psychodermatology and a new classification system is proposed, considering classical concepts in general dermatology and psychopathology. RESULTS: Two main categories of disorders are presented (a main group related to primary mental health disorders and another main group related to primary skin disorders), which are subsequently subdivided into subgroups considering pathophysiological and phenomenological similarities, including key aspects of dermatological examination, namely the presence of visible skin lesions (primary and secondary skin lesions) and psychopathological correlates. CONCLUSION: This new classification aims to unify previous classifications, systematize the disorders that belong to psychodermatology and highlight their tenuous boundaries, to improve their management. It has been built and approved by the Psychodermatology Task Force of the European Academy of Dermatology and Venereology (EADV), the European Society for Dermatology and Psychiatry (ESDaP) and the Association for Psychoneurocutaneous Medicine of North America (APMNA).

Basic mechanisms of itch.

Pruritus (or itch) is an unpleasant sensation leading to a desire to scratch. In the epidermis, there are selective C or Aδ epidermal nerve endings that are pruriceptors. At their other ends, peripheral neurons form synapses with spinal neurons and interneurons. Many areas in the central nervous system are involved in itch processing. Although itch does not occur solely because of parasitic, allergic, or immunologic diseases, it is usually the consequence of neuroimmune interactions. Histamine is involved in a minority of itchy conditions, and many other mediators play a role: cytokines (eg, IL-4, IL-13, IL-31, IL-33, and thymic stromal lymphopoietin), neurotransmitters (eg, substance P, calcitonin gene-related peptide, vasoactive intestinal peptide, neuropeptide Y, NBNP, endothelin 1, and gastrin-releasing peptide), and neurotrophins (eg, nerve growth factor and brain-derived neurotrophic factor). Moreover, ion channels such as voltage-gated sodium channels, transient receptor potential vanilloid 1, transient receptor ankyrin, and transient receptor potential cation channel subfamily M (melastatin) member 8 play a crucial role. The main markers of nonhistaminergic pruriceptors are PAR-2 and MrgprX2. A notable phenomenon is the sensitization to pruritus, in which regardless of the initial cause of pruritus, there is an increased responsiveness of peripheral and central pruriceptive neurons to their normal or subthreshold afferent input in the context of chronic itch.

Trial of Nemolizumab in Moderate-to-Severe Prurigo Nodularis.

BACKGROUND: Prurigo nodularis is a chronic pruritic skin disease with multiple nodular skin lesions. Nemolizumab is a monoclonal antibody targeting the interleukin-31 receptor, which is involved in the pathogenesis of prurigo nodularis. METHODS: We conducted a 12-week, randomized, double-blind, phase 2 trial of nemolizumab (at a dose of 0.5 mg per kilogram of body weight) administered subcutaneously at baseline, week 4, and week 8, as compared with placebo, in patients with moderate-to-severe prurigo nodularis and severe pruritus. Moderate-to-severe prurigo nodularis was defined as 20 or more nodules, and severe pruritus was defined as a mean score of at least 7 for the worst daily intensity of pruritus on the numerical rating scale (scores range from 0 [no itch] to 10 [worst itch imaginable]). The primary outcome was the percent change from baseline in the mean peak score for pruritus on the numerical rating scale at week 4. Secondary outcomes included additional measures of itching and disease severity. Safety assessments were performed through week 18. RESULTS: A total of 70 patients were randomly assigned in a 1:1 ratio to receive nemolizumab (34 patients) or placebo (36). The initial pruritus score on the numerical rating scale was 8.4 in each group. At week 4, the peak pruritus score on the numerical rating scale was reduced from baseline by 4.5 points (change, -53.0%) in the nemolizumab group, as compared with a reduction of 1.7 points (change, -20.2%) in the placebo group (difference, -32.8 percentage points; 95% confidence interval, -46.8 to -18.8; P<0.001). Results for secondary outcomes were in the same direction as for the primary outcome. Nemolizumab was associated with gastrointestinal symptoms (abdominal pain and diarrhea) and musculoskeletal symptoms. CONCLUSIONS: Nemolizumab resulted in a greater reduction in pruritus and severity of skin lesions than placebo in patients with prurigo nodularis but was associated with adverse events. Larger and longer trials are needed to determine the durability and safety of nemolizumab for the treatment of prurigo nodularis. (Funded by Galderma; ClinicalTrials.gov number, NCT03181503.).

Do Merkel complexes initiate mechanical itch?

Itch is a common sensation which is amenable to disabling patients' life under pathological and chronic conditions. Shared assertion easily limits itch to chemical itch, without considering mechanical itch and alloknesis, its pathological counterpart. However, in recent years, our understanding of the mechanical itch pathway, particularly in the central nervous system, has been enhanced. In addition, Merkel complexes, conventionally considered as tactile end organs only responsible for light touch perception due to Piezo2 expressed by both Merkel cells and SA1 Aß-fibres - low threshold mechanical receptors (LTMRs) -, have recently been identified as modulators of mechanical itch. However, the tactile end organs responsible for initiating mechanical itch remain unexplored. The consensus is that some LTMRs, either SA1 Aß- or A∂- and C-, are cutaneous initiators of mechanical itch, even though they are not self-sufficient to finely detect and encode light mechanical stimuli into sensory perceptions, which depend on the entire hosting tactile end organ. Consequently, to enlighten our understanding of mechanical itch initiation, this article discusses the opportunity to consider Merkel complexes as potential tactile end organs responsible for initiating mechanical itch, under both healthy and pathological conditions. Their unsuspected modulatory abilities indeed show that they are tuned to detect and encode light mechanical stimuli leading to mechanical itch, especially as they host not only SA1 Aß-LTMRs but also A∂- and C-fibres.

New human in vitro co-culture model of keratinocytes and sensory neurons like cells releasing substance P with an evaluation of the expression of ZIKV entry receptors: A potent opportunity to test Zika virus entry and to study Zika virus' infection in neurons?

During the course of acute ZIKV infection, pruritus is a cardinal symptom widely documented in the literature. Its frequent association with dysesthesia and several dysautonomic manifestations, suggests a pathophysiological mechanism involving the peripheral nervous system. The aim of this study was to develop a functional human model to potentially able to be infected by ZIKV: by demonstrating the functionality on a new human model of co-culture of keratinocyte and sensory neuron derived from induced pluripotent stem cells using a classical method of capsaicin induction and SP release, and verify the presence of ZIKV entry receptor in these cells. Depending of cellular type, receptors of the TAMs family, TIMs (TIM1, TIM3 and TIM4) and DC-SIGN and RIG1 were present/detected. The cells incubations with capsaicin resulted in an increase of the substance P. Hence, this study demonstrated the possibility to obtain co-cultures of human keratinocytes and human sensory neurons that release substance P in the same way than previously published in animal models which can be used as a model of neurogenic skin inflammation. The demonstration of the expression of ZIKV entry receptors in these cells allows to considerate the potent possibility that ZIKV is able to infect cells.

Pain Management in Dermatology.

BACKGROUND: The dermatologist has to deal with many situations where the patient feels pain and must therefore know how to manage it. SUMMARY: The aim of this review was to explore the treatments available to manage pain in dermatology in different circumstances, with an emphasis on pharmacological and non-pharmacological interventions specifically studied in dermatology.

Emergence of New Concepts in Skin Physiopathology through the Use of in vitro Human Skin Explants Models.

BACKGROUND: This review summarizes uses and new applications for dermatological research of in vitro culture models of human skin explants (HSEs). In the last decade, many innovations have appeared in the literature and an exponential number of studies have been recorded in various fields of application such as process culture engineering, stem cell extractions methodology, or cell-to-cell interaction studies under physiological and pathological conditions, wound-healing, and inflammation. Most studies also concerned pharmacology, cosmetology, and photobiology. However, these topics will not be considered in our review. SUMMARY: A better understanding of the mechanisms driving intercellular relationships, at work in the maintenance of 3D tissue architectures has led to the improvement of cell culture techniques. Many papers have focused on the physiological ways that govern in vitro tissue maintenance of HSEs. The analysis of the necessary mechanical stress, intercellular and cell-matrix interactions, allows the maintenance and prolonged use of HSEs in culture for up to 15 days, regardless of the great variability of study protocols from one laboratory to another and in accordance with the objectives set. Because of their close similarities to fresh skin, HSEs are increasingly used to study skin barrier repair and wound healing physiology. Easy to use in co-culture, this model allows a better understanding of the connections and interactions between the peripheral nervous system, the skin and the immune system. The development of the concept of an integrated neuro-immuno-cutaneous system at work in skin physiology and pathology highlighted by this article represents one of the new technical challenges in the field of in vitro culture of HSE. This review of the literature also reveals the importance of using such models in pathology. As sources of stem cells, HSEs are the basis for the development of new tissue engineering models such as organoids or optical clearing tissues technology. This study identifies the main advances and cross-cutting issues in the use of HSE.

Psychopathology Associated with Chronic Pruritus: A Systematic Review.

There are no previous studies of the psychopathology associated with different aetiologies of chronic pruritus. A systematic review was performed of cohort and case-control studies comparing healthy controls with patients with chronic pruritus related to primary dermatoses, systemic diseases, psychogenic pruritus, idiopathic pruritus, prurigo nodularis and/or lichen simplex chronicus. The review was registered in PROSPERO and performed according to the PRISMA statement, which allowed the inclusion of 26 studies. The quality of eligible studies was assessed using the modified Newcastle-Ottawa Scale. Most of the studies concern primary dermatoses and systemic diseases. Sleep disorders are a common comorbidity interrelated with pruritus, anxiety and depressive symptoms, in primary dermatoses. Sleep disorders are linked with pruritus and depressive symptoms in end-stage renal disease and hepatobiliary disease. Depressive and anxiety symptoms are associated with psychogenic pruritus. Psychogenic pruritus, lichen simplex chronicus and some primary dermatoses are linked with personality characteristics. Further studies are required to explore in depth the psychopathology linked with psychogenic pruritus and prurigo nodularis, as well as psychopathology linked with other primary dermatoses and systemic disorders associated with chronic pruritus, and to better differentiate psychogenic pruritus from psychopathological characteristics linked with other aetiologies of chronic pruritus, in order to improve the management of patients with chronic pruritus.

Impact of Atopic Dermatitis on Patients and their Partners.

Atopic dermatitis is a chronic, relapsing and inflammatory skin disease. The impact of atopic dermatitis on the partners living with patients has been poorly investigated. The objective of this study was to evaluate the impact of atopic dermatitis in the daily lives of adult patients and to assess the burden of the disease on their partners. A population-based study was conducted on a representative sample of the general population of French adults aged 18 years of age using stratified, proportional sampling with a replacement design. Data were collected on 1,266 atopic dermatitis patient-partner dyads (mean age of patients 41.6 years, 723 (57.1%) women). The mean age of partners was 41.8 years. Patient burden, measured by the Atopic Dermatitis Burden Scale for Adults (ABS-A) score, was closely related to the objective atopic dermatitis severity: the mean score in the mild group (29.5) was significantly lower than in the moderate (43.9) and severe groups (48.6) (p < 0.0001). Partner burden, measured by the EczemaPartner score, was highly related to atopic dermatitis severity (p < 0.0001). Daytime sleepiness, measured by the Epworth Sleepiness Scale, showed a mean score of 9.24 in patients and 9.01 in their partners, indicating impaired sleep. Atopic dermatitis was found to decrease sexual desire in 39% and 26% of partners and patients respectively.

Perceived Stigmatization among Dermatological Outpatients Compared with Controls: An Observational Multicentre Study in 17 European Countries.

Perceived stigmatization places a large psychosocial burden on patients with some skin conditions. Little is known about the experience of stigmatization across a wide range of skin diseases. This observational cross-sectional study aimed to quantify perceived stigmatization and identify its predictors among patients with a broad spectrum of skin diseases across 17 European countries. Self-report questionnaires assessing perceived stigmatization and its potential predictors were completed by 5,487 dermatology outpatients and 2,808 skin-healthy controls. Dermatological diagnosis, severity, and comorbidity were clinician-assessed. Patients experienced higher levels of perceived stigmatization than controls (p < 0.001, d = 0.26); patients with psoriasis, atopic dermatitis, alopecia, and bullous disorders were particularly affected. Multivariate regression analyses showed that perceived stigmatization was related to sociodemographic (lower age, male sex, being single), general health-related (higher body mass index, lower overall health), disease-related (higher clinician-assessed disease severity, presence of itch, longer disease duration), and psychological (greater distress, presence of suicidal ideation, greater body dysmorphic concerns, lower appearance satisfaction) variables. To conclude, perceived stigmatization is common in patients with skin diseases. Factors have been identified that will help clinicians and policymakers to target vulnerable patient groups, offer adequate patient management, and to ultimately develop evidence-based interventions.

In vivo transepidermal water loss: Validation of a new multi-sensor open chamber water evaporation system Tewameter TM Hex.

BACKGROUND: Instrumentation technology for transepidermal water loss measurements has not been substantially modified since its introduction by Nilsson in 1977. Recent progress in sensor development allowed a new sensor arrangement using a matrix of 30 sensors. Raw measurement values are processed with spatial statistical analysis. We aimed to compare the new, multi-sensor probe (Tewameter TM Hex) with the established Tewameter TM 300 probe and to gain reference data for the new parameters of transepidermal energy loss and water vapor concentration on skin. MATERIAL AND METHODS: Baseline measurements and repeated measurements on the volar forearm and assessment on eight different anatomical locations were performed on 24 healthy volunteers (both gender) with the TM Hex and the TM 300. RESULTS: A significant correlation (p < 0.001; R-coefficient = 0.9) between TM Hex and the TM 300 with a low coefficient of variance (CV) 11% for TM Hex and 19% for TM 300, could be assessed. The CV ranged between 7% (right inner upper arm) and 14% (palms). Average transepidermal heat loss ranged from 12 W/m2 on the lower leg to 38.8 W/m2 on the palm. CONCLUSION: The correlation between TM Hex and TM 300 along with the robustness of the measurements with the TM Hex shows that the new probe for assessment of epidermal barrier function is comparable to the TM 300. In most conditions, TM Hex provides more accurate measurements than TM 300. New parameters open the field to studying skin's water and energy balance.

Differences between aquagenic and non-aquagenic pruritus in myeloproliferative neoplasms: An observational study of 500 patients.

BACKGROUND: Pruritus is a frequent symptom experienced by patients with myeloproliferative neoplasms (MPN). Aquagenic pruritus (AP) is the most common type. The Myeloproliferative Neoplasm-Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) self-report questionnaires were distributed to MPN patients before consultations. OBJECTIVES: The aim of this study was to assess clinical incidence (phenotypical evolution and response to treatment) of pruritus, especially AP, in MPN patients during their follow-ups. PATIENTS AND METHODS: We collected 1444 questionnaires from 504 patients [54.4% essential thrombocythaemia (ET) patients, 37.7% polycythaemia vera (PV) patients, and 7.9% primary myelofibrosis (PMF) patients]. RESULTS: Pruritus was reported by 49.8% of the patients, including 44.6% of AP patients, regardless of type of MPN or driver mutations. Patients suffering from pruritus were more symptomatic and had a higher rate of evolution into myelofibrosis/acute myeloid leukaemia (19.5% vs. 9.1%, OR = 2.42 [1.39; 4.32], p = 0.0009) than MPN patients without pruritus. Patients with AP had the highest pruritus intensity values (p = 0.008) and a higher rate of evolution (25.9% vs. 14.4%, p = 0.025, OR = 2.07) than patients with non-AP. Disappearance of pruritus was observed in only 16.7% of AP cases, compared to 31.7% of cases with other types of pruritus (p < 0.0001). Ruxolitinib and hydroxyurea were the most effective drugs to reduce AP intensity. CONCLUSIONS: In this study, we demonstrate the global incidence of pruritus across all MPN. Pruritus, especially AP, which is a major constitutional symptom observed in MPN, should be assessed in all MPN patients due to higher symptom burden and higher risk of evolution.

Patient Unique Stigmatization Holistic tool in dermatology (PUSH-D): Development and validation of a dermatology-specific stigmatization assessment tool.

BACKGROUND: The skin plays an important role in establishing interpersonal relationships, and thus visible skin disorders, which have a significant impact on physical appearance, influence other people's behaviours and attitudes. OBJECTIVE: To develop and validate a dermatologic-specific questionnaire to evaluate stigmatization in individuals with visible skin conditions. METHODS: Items were generated by a verbatim report based on qualitative interviews with patients with various dermatologic conditions. Subsequently, a study was implemented for psychometric analysis. A dermatology-specific stigmatization questionnaire (PUSH-D) was refined via item reduction according to inter-question correlations, consensus among experts and exploratory factor analysis. Internal consistency was determined by calculating Cronbach's α. Concurrent validity was determined by calculating the correlation between PUSH-D and the Dermatology Life Quality Index (DLQI) and the Rosenberg Self-Esteem Scale (RSES). RESULTS: From a primary list of 22 items, PUSH-D was reduced to a 17-item questionnaire, covering two pertinent dimensions based on the exploratory factor analysis. Construct validity was demonstrated, and PUSH-D showed good internal consistency (Cronbach's α = 0.9). PUSH-D correlated strongly with the DLQI 0.72 (p < 0.001) and moderately with the RSES 0.49 (p < 0.001). CONCLUSION: PUSH-D allows a comprehensive view of the degree of stigmatization in visible skin disorders, as well as the comparability of stigmatization levels across various skin conditions.

White paper on psychodermatology in Europe: A position paper from the EADV Psychodermatology Task Force and the European Society for Dermatology and Psychiatry (ESDaP).

Psychodermatology is a subspecialty of dermatology that is of increasing interest to dermatologists and patients. The case for the provision of at least regional psychodermatology services across Europe is robust. Psychodermatology services have been shown to have better, quicker and more cost-efficient clinical outcomes for patients with psychodermatological conditions. Despite this, psychodermatology services are not uniformly available across Europe. In fact many countries have yet to establish dedicated psychodermatology services. In other countries psychodermatology services are in development. Even in countries where psychodermatolgy units have been established, the services are not available across the whole country. This is especially true for the provision of paediatric psychodermatology services. Also whilst most states across Europe are keen to develop psychodermatology services, the rate at which this development is being implemented is very slow. Our paper maps the current provision of psychodermatology services across Europe and indicates that there is still very much more work to be done in order to develop the comprehensive psychodermatology services across Europe, which are so crucial for our patients.