Acceptability and perceived benefits of validated pruritus assessment instruments in the dermatological office and clinic: The perspectives of patients and physicians.

BACKGROUND: Several patient-reported outcome measures (PROMs) have been developed for research to assess the multiple dimensions of chronic pruritus (CP). The acceptability and perceived benefits of their use in clinical practice remain unknown. OBJECTIVES: To assess the acceptability and perceived benefits of validated PROMs from the perspective of patients and physicians in dermatological offices and clinics. METHODS: Patients with CP due to atopic dermatitis, psoriasis, chronic prurigo or chronic urticaria were recruited at 10 dermatological offices and two dermatological clinics in Germany. Patients completed a set of validated PROMs on pruritus intensity (numerical rating scale, NRS), symptom control (itch-controlled days, ItchCD), quality of life (Dermatology Life Quality Index, DLQI; 5-pruritus life quality, 5PLQ) and general health status (EuroQol, EQ-VAS). Acceptability (relevance, difficulty of completion, length) and benefits (usefulness, feasibility) of these tools were assessed on a NRS (0-10) by patients and physicians, respectively. Data were analysed descriptively. Linear regression was used to study potential associations between age, sex, occupation, office versus clinic, change of therapy and physician-reported benefits. RESULTS: N = 523 patients (46% male, average age: 53.5 years) participated. Acceptability of PROMs by patients was high, indicated by low difficulty (Md = 0, IQR = 0-1 for all PROMs) and high relevance (Md = 8, IQR = 4-10 for all PROMs). Also, most patients (89-95%) rated length of the questionnaires as 'exactly right'. Physicians rated the NRS as the most beneficial instrument (feasibility: Md = 8, IQR = 6-10; usefulness: Md = 9, IQR = 7-10). Hierarchical linear regression revealed that only recruitment site (dermatological office vs. clinic) was significantly associated with usefulness and feasibility (higher ratings for clinical context; ßs = 0.149-0.258, ps <0.05; except feasibility for EQ5d, ß = ns). CONCLUSIONS: PROMs are welcomed by patients, while physicians consider instruments measuring pruritus intensity and impairment of quality of life as beneficial for the clinical routine. Widespread implementation of PROMs in daily clinical work is needed to improve care.

A cross-sectional study on gender differences in body dysmorphic concerns in patients with skin conditions in relation to sociodemographic, clinical and psychological variables.

BACKGROUND: Dysmorphic concern is an overconcern with an imagined or slight defect in physical appearance that can be a symptom of body dysmorphic disorder (BDD). Appearance-related concerns are frequently reported by people with dermatological conditions. However, relatively little remains known about the relationship between dysmorphic concern and other variables within persons with different skin conditions. OBJECTIVES: The aim of this multicentre, cross-sectional study was to investigate gender differences regarding dysmorphic concern and the prevalence of BDD in a large sample of patients with skin conditions, in relation to sociodemographic, clinical and psychological variables. METHODS: Participants aged ≥18 years with skin conditions were consecutively enrolled in dermatological clinics of 22 European centres. Dysmorphic concern and the possible presence of BDD were measured using the Dysmorphic Concern Questionnaire (DCQ) and compared between men and women in relation to sociodemographic, clinical and psychological variables, and separately for each skin condition. RESULTS: The DCQ questionnaire was completed by 5290 dermatological patients. In all categories, mean scores were significantly higher in women than in men. Mean DCQ scores were also higher in women for most skin conditions, with the highest effect size in vitiligo. The percentage of patients who screened positive for BDD on the DCQ was 10.5%, 7.7% of men and 12.7% of women. The prevalence of BDD positive was 6.9% in patients with mild clinical severity, 11.1% for moderate and 19.1% for severe condition. In the multivariate model in patients with mild skin condition, the presence of BDD was positively associated with stress and stigma both in men and in women. CONCLUSIONS: Dysmorphic concern and BDD were more frequent in women than in men with skin conditions. Both received and actual stigmatization might have an impact on body-related concerns, in particular in women, who may be more at risk for sociocultural reasons.

[Patient survey on the use of video consultation in the outpatient treatment of chronic pruritus]. / Patientenbefragung zum Einsatz von Videosprechstunden in der ambulanten Behandlung von chronischem Pruritus.

BACKGROUND: Analyses of patient evaluations and barriers to the implementation of teledermatology procedures are still rare. The aim of this study was to determine whether administrative processes have an influence on the patient evaluation of telephone and video consultations. METHODS: With the help of a patient survey, assessments of the processes and organisation surrounding the outpatient appointment were asked. These were then compared to the assessment of whether the telephone or video consultation is an alternative to on-site consultation. RESULTS: In all, 1538 patients took part in the survey. Significant correlations were found between the evaluation of the telephone or video consultation and the distance between the place of residence and the outpatient clinic, whether the patient had already been seen several times or for the first time, as well as the evaluation of the waiting time for the appointment, the organisation before the appointment and the waiting time in the outpatient clinic. CONCLUSIONS: The study shows that even after the Coronavirus pandemic, telephone and video consultations remain an important tool for patients to contact their physician. However, patients' perceptions of the processes around the outpatient appointment have an influence on their willingness to participate in a digital consultation.

[Treatment of chronic prurigo: update and perspectives]. / Therapie der chronischen Prurigo: Update und Perspektive.

BACKGROUND: Despite the high burden in patients with chronic prurigo (CPG), the first and so far only approved systemic therapy for this disease, dupilumab, has only been available since 2022. Therefore, treatment is mostly based on expert recommendations for off-label therapies. We aim to provide an overview of current therapies and possible future therapeutic drugs for CPG patients, which are currently in clinical trials. MATERIALS AND METHODS: For this review, a systematic literature and clinical trial search was conducted via PubMed and Clinical Trials using the terms "chronic prurigo", "chronic nodular prurigo", "prurigo nodularis" and "therapy". CONCLUSION: Multiple new therapeutic agents are currently under investigation in clinical trials, providing promising results for future treatment options. Moreover, an annotated checklist was developed recently to improve therapeutic decision-making in daily clinical practice with CPG patients.

EADV Task Force Pruritus White Paper on chronic pruritus and chronic prurigo: Current challenges and future solutions.

Chronic pruritus (CP) is frequent in general medicine and the most common complaint in general dermatology. The prevalence of CP is expected to rise in the future due to the ageing population. The clinical presentation, underlying aetiology and treatment strategy of CP are heterogeneous. Also, individual treatment aims and physical, psychic and economic burdens of patients might vary. Chronic prurigo (CPG) is the most severe disease in the chronic pruritus spectrum, being associated with long-standing scratch-induced skin lesions and a therapy refractory itch-scratch-cycle. It is thus important to raise disease awareness for CP and CPG in the general public and among decision-makers in the health system. Further, there is a need to support a rational clinical framework to optimize both diagnostics and therapeutics. Currently, there is still a shortcoming regarding approved therapies and understanding CP/CPG as severe medical conditions. Therefore, the EADV Task Force Pruritus decided to publish this white paper based on several consensus meetings. The group consented on the following goals: (a) ensure that CP is recognized as a serious condition, (b) increase public awareness and understanding of CP and CPG as chronic and burdensome diseases that can greatly affect a person's quality of life, (c) clarify that in most cases CP and CPG are non-communicable and not caused by a psychiatric disease, (d) improve the support and treatment given to patients with CP to help them manage their disease and (e) publicize existing therapies including current guidelines. We aim to point to necessary improvements in access and quality of care directed to decision-makers in health policy, among payers and administrations as well as in practical care.

Dermatological patients with itch report more stress, stigmatization experience, anxiety and depression compared to patients without itch: Results from a European multi-centre study.

BACKGROUND: Itch as the most common symptom in dermatology has been shown to be related to psychological factors such as stress, anxiety and depression. Moreover, associations were found between perceived stigmatization and itch. However, studies investigating the differences between patients with dermatoses with and without itch regarding perceived stress, stigmatization, anxiety and depression are missing. Therefore, one of the aims of the second study of the European Society for Dermatology and Psychiatry (ESDaP study II) was to investigate these relationships in a large cohort of patients with different itchy dermatoses. RESULTS: 3399 patients with 14 different itchy dermatoses were recruited at 22 centres in 17 European countries. They filled in questionnaires to assess perceived stigmatization, stress, signs of clinically relevant anxiety or depression, itch-related quality of life, the overall health status, itch duration, frequency and intensity. The most significant association between the severity of itching and the perception of stress was observed among individuals with rosacea (correlation coefficient r = 0.314). Similarly, the strongest links between itch intensity and experiences of stigmatization, anxiety, and depression were found in patients with seborrheic dermatitis (correlation coefficients r = 0.317, r = 0.356, and r = 0.400, respectively). Utilizing a stepwise linear regression analysis, it was determined that within the entire patient cohort, 9.3% of the variation in itch intensity could be accounted for by factors including gender, levels of anxiety, depression, and perceived stigmatization. Females and individuals with elevated anxiety, depression, and perceived stigmatization scores reported more pronounced itch intensities compared to those with contrary attributes. CONCLUSION: This study underscores the connection between experiencing itch and its intensity and the psychological strain it places on individuals. Consequently, psychological interventions should encompass both addressing the itch itself and the interconnected psychological factors. In specific cases, it becomes imperative for dermatologists to direct individuals towards suitable healthcare resources to undergo further psychological assessment.

Personal, financial and time burden in inherited ichthyoses: A survey of 144 patients in a university-based setting.

BACKGROUND: Patients with inherited ichthyosis suffer from scaling due to mutations affecting the epidermal barrier. Symptomatic treatment with ointments, bathing and mechanical scale removal can alleviate the disease, but therapy is time and cost intensive. OBJECTIVES: We investigated costs, time and disease burden of ichthyoses. The study addresses difficulties of the healthcare situation for patients with ichthyoses and reveals potential improvements. MATERIALS AND METHODS: We developed a questionnaire addressing time and financial effort for the treatment. Additionally, we collected data of the Dermatology Life Quality Index (DLQI) and the Pruritus Life Quality (5PLQ) questionnaires to determine the impact of ichthyosis and associated pruritus on quality of life (QoL). RESULTS: We recruited 144 patients with ichthyosis (median age: 23; 53.5% female) from the Department of Dermatology in Muenster (Germany) and the German patient support group including common, rare and syndromic subtypes. Eighty-seven percent reported applying topical therapeutics at least once per day, 66.4% several times with an overall median duration of 15 min. Highest single expenditure of time was due to balneotherapy (n = 115; median bathing time: 40 min). In 81.9%, the health insurance did not completely cover the costs for topical treatment causing additional financial burden to the patient with a median of 71 € per quarter, herein creams being the largest cost factor (50 €). Patients with Netherton syndrome showed the highest median expenditure (170 €). The QoL impairment under treatment was moderate (median DLQI: 8.5 points). Pruritus was prevalent in 79.9% and showed a distinct impact on QoL (median 5PLQ: 7.5 points) without any significant difference between the subtypes (p = 0.37). CONCLUSION: Patients suffering from ichthyoses have a large and lifelong overall burden in mild and severe subtypes. Since continuous topical treatment is required, financial and psychosocial support needs to be considered beyond dermatological care.

Estimating meaningful change thresholds for Skin Pain-Numeric Rating Scale, Sleep-Numeric Rating Scale and Dermatology Life Quality Index in patients with prurigo nodularis.

BACKGROUND: Prurigo nodularis (PN) is characterized by intensely itchy nodules/lesions and skin pain, which can have a substantial impact on health-related quality of life (HRQoL). Treatment benefits on such symptoms and impacts are best assessed in trials using patient-reported outcome (PROs) instruments such as Skin Pain Numerical Rating Scale (NRS), Sleep-NRS and Dermatology Life Quality Index (DLQI). However, no guidance exists for interpreting meaningful changes in scores using these PROs in patients with PN. OBJECTIVES: The main objective was to derive within-patient (responder definition) and between-group improvement thresholds for interpreting Skin Pain-NRS, Sleep-NRS and DLQI total scores in patients with PN. The measurement properties of the three PROs were also evaluated. METHODS: Intention-to-treat (ITT), blinded and pooled data were used from the Phase 3 PRIME (NCT04183335) and PRIME2 (NCT04202679) studies evaluating the efficacy of dupilumab in adult patients with PN. Anchor- and distribution-based methods were applied to derive responder definition and between-group thresholds for Skin Pain-NRS, Sleep-NRS and DLQI. Data were additionally used to examine the instrument measurement properties, including reliability, validity and responsiveness. RESULTS: A total of 311 patients (mean age 49.5 years, 65.3% female) were included in the pooled ITT population. The within-patient improvement threshold for Skin Pain-NRS was estimated as 4.0 points, 2.0 points for Sleep-NRS and 9.0 points for DLQI total score. A 1.5-point improvement in Skin Pain-NRS scores, 1.0-point in Sleep-NRS and 4.0-point in DLQI indicated a between-group meaningful change. Adequate to good psychometric properties were demonstrated for all three instruments. CONCLUSIONS: The results of this study can aid interpretation of Skin Pain-NRS, Sleep-NRS and DLQI scores in patients with PN in both clinical trials and clinical practice to better understand and treat PN-related skin pain and the impact of PN on sleep quality and HRQoL.

[Management of pruritus in the elderly]. / Praktischer Umgang mit Pruritus im Alter.

BACKGROUND: Chronic pruritus (CP), a frequent (20.3%) symptom in the elderly, increases with age. It has a significant impact on the quality of life, ranking among the 50 most burdensome diseases worldwide (Global Burden of Disease Study). OBJECTIVES: The aim is to provide an overview of the symptom CP in the elderly and to improve differentiation of underlying conditions and management of this entity. MATERIALS AND METHODS: A literature search in PubMed was performed, using the terms 'pruritus', 'elderly' and 'gerontodermatology'. RESULTS: The main causes of CP in the elderly are the physiologic aging process (xerosis cutis, immunosenescence, neuropathy), the increase in potentially pruritic diseases with increasing age (diabetes mellitus, chronic renal failure), and polypharmacy. Therapeutic options relate to causes, severity of pruritus, and individual patient factors (multimorbidity, impaired organ function). The recently updated S2k guideline 'Diagnosis and therapy of chronic pruritus' is helpful. CONCLUSION: CP in the elderly is challenging for both patients and physicians. Not only the difficulty of identifying the underlying cause, but the complexity of treatment and its tolerability and practicability determines these patients' further burden.

[Current dermatology guidelines in Germany-selected recommendations from 2021 and 2022]. / Aktuelle dermatologische Leitlinien in Deutschland ­ Ausgewählte Empfehlungen aus den Jahren 2021 und 2022.

Guidelines are systematically developed decision-making aids to ensure appropriate clinical care for specific medical conditions. In Germany, dermatological guidelines are developed under the aegis of the German Dermatological Society (DDG) and the Professional Association of German Dermatologists (BVDD), while European and international guidelines are published by organisations such as the European Centre for Guidelines Development (EuroGuiDerm), founded by the European Dermatology Forum (EDF) in cooperation with the Division of Evidence-Based Medicine at Charité-Universitätsmedizin Berlin. In 2021 and 2022, the German guidelines were revised or developed on topics such as the management of anticoagulation during dermatological procedures, chronic pruritus, contact dermatitis, laser therapy of the skin, psoriasis vulgaris, rosacea, extracorporeal photopheresis, onychomycosis, mucous membrane pemphigoid and prevention of skin cancer. A selection of the most important recommendations and innovations in the guidelines is summarized here.

Altered resting-state functional connectivity of default mode network in brachioradial pruritus.

BACKGROUND: Patients with chronic pruritus (CP) have a low quality of life, thus it is important to gain a better understanding of the underlying processes. Previous functional magnetic resonance imaging studies at rest (rsfMRI) have shown that mainly areas associated with the default mode network (DMN), sensorimotor (SMN), frontoparietal (FPN) and salience networks (SN) are involved in the processing of itch in patients with chronic pruritus (CP), as well as the cortico-striatal circuit, which is involved in the motoric preparation of scratching. rsfMRI studies on functional connectivity (FC) patterns of resting-state networks (RSNs) in patients with inflammatory atopic dermatitis (AD) or with neuropathic brachioradial pruritus (BRP) compared with healthy controls (HC) are lacking. OBJECTIVES: The main goals of this study were to investigate whether functional connectivity within networks and areas associated with itch detection and processing are altered in patients with AD and BRP compared with matched healthy controls by rsfMRI, respectively. METHODS: Patients with AD (n = 28) and with BRP (n = 28) were compared with corresponding matched healthy controls by rsfMRI. Group-specific RSNs were identified by independent component analysis (ICA) and between-group differences in the RSNs were analysed by dual regression technique. Seed-based functional connectivity was analysed in several itch-related brain regions belonging to the DMN, SN and FPN, respectively. RESULTS: ICA and seed-based analyses revealed decreased functional connectivity in BRP compared with HC specially within the DMN including the precuneus and cingulate cortex. For AD patients in comparison with HC, as well as when BRP and AD patients were compared directly, no significant FC differences at rest were seen. CONCLUSIONS: Our findings point towards decreased FC particularly in the DMN at rest in patients with BRP. These results seem to indicate that central connectivity patterns at rest differentially encode itch in BRP and AD.

Nemolizumab efficacy in prurigo nodularis: onset of action on itch and sleep disturbances.

BACKGROUND: Patients with prurigo nodularis (PN) have multiple itchy nodules, impaired quality of life and sleep deprivation. Prurigo nodularis patients have a high burden of disease, primarily due to the intensity of the itch. It is reasonable to expect that rapid relief of itch - and associated improvement of sleep - are highly valued clinical outcomes for patients. Nemolizumab is an IL-31A-receptor inhibitor that modulates the neuroimmune response with reported positive efficacy and safety data in a phase 2 study of PN. OBJECTIVES: To evaluate the onset of action of nemolizumab on itch and sleep disturbances. METHODS: Post hoc analysis of a phase 2 trial of nemolizumab 0.5 mg/kg SC vs. placebo in patients (n = 70) with moderate-to-severe PN (≥20 nodules) and severe pruritus (NRS ≥ 7). Time to significant reduction was assessed for peak pruritus (PP) and sleep disturbance (SD) using numerical rating scales (NRS), also assessed was scratching time during sleep. RESULTS: Nemolizumab significantly reduced itch vs. placebo within 48 h (PP NRS -19.5% vs. -5.8%, respectively, P = 0.014). Significant difference between nemolizumab and placebo in reducing itch by ≥4 on PP NRS was achieved at Day 3 (23.5% vs. 0%, P < 0.001). A significant difference in SD NRS was reported by Day 4 (-24.0% vs. -4.3% placebo, P = 0.012). In addition, there was a separation between groups in SD responders (decrease of ≥4 points) in favour of nemolizumab by Day 2 (8.8% vs. 0%, P = 0.037). Sleep continued improving through Week 4, when there was a -56.0% reduction in SD NRS vs. -22.9% placebo (P < 0.001). Actigraphy data showed improvement in scratch/sleep duration for nemolizumab vs. placebo, respectively, by Week 1 (-32.15 vs. +28.15 min/h, P = 0.001). CONCLUSION: Nemolizumab has a rapid and robust onset of action in PN with itch reduction and improvement of sleep within 48 h.

High threshold efficacy responses in moderate-to-severe atopic dermatitis are associated with additional quality of life benefits: pooled analyses of abrocitinib monotherapy studies in adults and adolescents.

BACKGROUND: Once-daily abrocitinib treatment provided meaningful improvements in signs and symptoms of moderate-to-severe atopic dermatitis (AD) in randomized controlled studies. OBJECTIVE: To evaluate proportions of patients with responses meeting higher threshold efficacy responses than commonly used efficacy end points and to determine if these responses were associated with quality-of-life (QoL) benefits. METHODS: Data from a phase 2b (NCT02780167) and two phase 3 studies (NCT03349060/JADE MONO-1; NCT03575871/JADE MONO-2) in adult and adolescent patients (N = 942) with moderate-to-severe AD receiving once-daily abrocitinib 200 mg, abrocitinib 100 mg or placebo were pooled. Commonly used (Eczema Area and Severity Index [EASI]-75 and ≥4-point improvement in Pruritus Numerical Rating Scale [PP-NRS4]) and higher threshold efficacy end points (EASI-90 to

Worst itch numerical rating scale for prurigo nodularis: a psychometric evaluation.

BACKGROUND: Study TR03 evaluated the safety and efficacy of nalbuphine ER for prurigo nodularis (PN; NCT02174419). OBJECTIVE: We conducted supplementary analyses to assess the psychometric properties of the Worst Itch Numeric Rating Scale (WI-NRS), the TR03 primary endpoint. METHODS: Study TR03 was a double-blind, placebo-controlled, phase 2 trial in PN patients with documented scores ≥5 on the WI-NRS (0 [no itch]-10 [worst itch imaginable]) on ≥5 of 7 days before baseline. Using TR03 data, the WI-NRS's psychometric properties, including reliability, validity and ability to detect change, were evaluated. A responder threshold was estimated to facilitate interpretation of WI-NRS score changes. RESULTS: Amongst 62 treated patients, improvements in mean [SD] (median) WI-NRS scores were observed between baseline (8.2 [1.21] (8.1)) and week 10 (5.8 [2.43] (6.0)). The WI-NRS had an intraclass correlation coefficient of 0.96 (95% confidence interval, 0.93-0.98) in 42 patients who had stable Itch verbal rating scale (VRS) scores from week 9-10, supporting strong test-retest reliability. Construct validity was supported, with strong correlations at week 10 with Average Itch NRS (r = 0.87) and Itch VRS single-day/weekly mean scores (r = 0.81/0.89) and moderate correlations with ItchyQoL™ total/domain scores (r = 0.41-0.43). The WI-NRS discriminated between predefined severity subgroups based on the Itch VRS and detected changes in itching severity (effect-size estimate: -2.05; standardized response mean: -1.21). An anchor-based threshold based on a two-category improvement in the single-day Itch VRS suggests a responder threshold of ≥3.8 points (~40% improvement). CONCLUSIONS: The WI-NRS demonstrates good measurement properties, supporting its use in evaluating treatment change in PN.

Efficacy and safety of oral nalbuphine extended release in prurigo nodularis: results of a phase 2 randomized controlled trial with an open-label extension phase.

BACKGROUND: Treatment of prurigo nodularis (PN) is challenging and new treatment options are needed. OBJECTIVE: To evaluate the efficacy and safety of two oral doses of the kappa opioid agonist and mu opioid antagonist nalbuphine extended release (NAL-ER) tablets in a phase 2, multicentre, randomized, double-blind, placebo-controlled trial with an open-label, 50-week extension phase. METHODS: Subjects with moderate-to-severe PN were randomized to NAL-ER 81 mg (NAL-ER81) or 162 mg (NAL-ER162) tablets twice-daily or placebo for 8 weeks of stable dosing following a 2-week titration period. Subjects completing Week 10 with a Worst Itch Numerical Rating Scale (WI-NRS) score ≥5 at the time of rollover (or during the observation period) were eligible for open-label treatment. RESULTS: Of 63 randomized subjects, 62 were treated and comprised the modified intent-to-treat population (MITT), 50 completed 10 weeks of treatment. In the MITT analysis, 8 subjects (44.4%) treated with NAL-ER162 (P = 0.32) and 6 (27.3%) treated with NAL-ER81 (P = 0.78) achieved ≥30% reduction from baseline in 7-day WI-NRS at Week 10 (primary efficacy endpoint) vs. 8 (36.4%) in the placebo group. Itch reduction was significant among 8/12 (66.7%) subjects completing Week 10 treated with NAL-ER162 vs. placebo (8/20, 40.0%; P = 0.03). Additionally, 6 subjects (33.3%) treated with NAL-ER162 and 3 (13.6%) treated with NAL-ER81 achieved ≥50% reduction from baseline in 7-day WI-NRS at Week 10 (coprimary endpoint). Extended open-label treatment was associated with further improvements in itch reduction and favourable changes in PN lesion activity as assessed by Prurigo Activity Score. Adverse events occurred predominantly during dose titration and were of mild-to-moderate severity. The safety profile did not change with extended open-label treatment. CONCLUSION: In adult subjects with PN, oral treatment with NAL-ER 162 mg twice daily provided measurable anti-pruritic efficacy in subjects completing ≥10 weeks of treatment and was well tolerated (ClinicalTrials.gov: NCT02174419).