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). CONCLUSION: 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.

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.

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.

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.

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.

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.

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).

Refinement and validation of the ItchyQoL using classical test theory and item response theory resulted in a reduction of the response categories from a 5-point to a 3-point scale.

BACKGROUND: The ItchyQoL is an itch-specific patient-reported outcome measure used to assess quality of life in patients with chronic pruritus (CP). OBJECTIVES: We aimed to assess and extend the psychometric properties of the ItchyQoL using classical test theory (CTT) and item response theory (IRT). METHODS: Item characteristic curves were analysed to investigate whether the response categories were functioning optimally. Confirmatory factor analyses were carried out on the ItchyQoL prior to and after rescoring of the response categories. We conducted a Rasch analysis for the ItchyQoL with revised response options and assessed the mean fit residuals in addition to the assumptions of unidimensionality and local independence. RESULTS: In total, 551 patients with CP from nine European countries completed the 22 items of the ItchyQoL. IRT analysis supported the revision of response options from five points to three. This revision was supported by excellent structural validity using CTT. The overall fit to the Rasch model was adequate. Unidimensionality was supported by the ItchyQoL overall scale and by the single subscales; however, local independence was violated in eight cases. CONCLUSIONS: We suggest a revision of the response categories of the ItchyQoL from a 5-point to a 3-point scale. When this revision was applied, the ItchyQoL showed excellent structural validity according to CTT and IRT/Rasch. The calculation of an overall ItchyQoL sum score is allowed.

Prevalence, incidence and presence of comorbidities in patients with prurigo and pruritus in Germany: A population-based claims data analysis.

BACKGROUND: There are currently no published population-based data on prurigo and pruritus epidemiology in Germany. OBJECTIVES: We present the prevalence, incidence and comorbidity frequency of prurigo and pruritus in Germany. METHODS: This was a retrospective healthcare research study based on anonymized routine data from the German health insurance company DAK-Gesundheit. Evaluations were carried out for 2 006 003 adults who were insured as of 31 December 2010. Prurigo and pruritus diagnoses were based on International Classification of Diseases, Tenth Revision, German Modification (ICD-10-GM) codes. RESULTS: Prevalence was determined to be 0.21% (adjusted for sex and age 0.19%) for prurigo and 2.21% (adjusted 2.14%) for pruritus in 2010. The adjusted rates extrapolated to the total German population in 2010 show that 130 685 adults would have received a prurigo diagnosis and 1 461 024 a diagnosis of pruritus. In 2011, incidence of new prurigo and pruritus cases was 0.13% (adjusted 0.12%, extrapolated 77 263 cases) and 1.51% (adjusted 1.46%, extrapolated 978 885), respectively. Adults with prurigo suffered most frequently from hypertension (35.16%), hyperlipidaemia (24.95%) and depression (21.97%); all were reported more frequently in patients with prurigo compared with the general population (P < 0.001). Similarly, adults with pruritus suffered most frequently from hypertension (31.28%), hyperlipidaemia (23.52%) and depression (18.91%) compared with patients without pruritus (P < 0.001). CONCLUSIONS: Our data show that prurigo is a relatively rare but significant disease and that pruritus is frequent and very variable in appearance, and both have a high comorbidity burden.

Patients with bullous pemphigoid and comorbid psoriasis present with less blisters and lower serum levels of anti-BP180 autoantibodies.

BACKGROUND: Although the association of bullous pemphigoid (BP) and psoriasis is well-established, the clinical and immunological features of patients with coexisting BP and psoriasis are yet to be investigated. OBJECTIVE: We aimed to estimate the prevalence of psoriasis amongst patients with BP and to elucidate the clinical and immunological characteristics of BP patients with comorbid psoriasis. METHODS: A retrospective cohort study including all consecutive patients diagnosed with BP throughout the years 2009-2019 in a tertiary referral centre. RESULTS: The study encompassed 273 patients with BP, of whom 11 (4.0%; 95% CI, 2.3-7.1%) had comorbid psoriasis. The onset of psoriasis preceded that of BP in 81.8% of patients by a median (range) latency of 26.5 (5.0-34.0) years. Compared to BP patients without psoriasis, those with BP and comorbid psoriasis were significantly younger at the onset of BP [71.8 (9.3) vs. 79.4 (9.8) years; P = 0.023], had a milder erosive phenotype [erosion/blister BPDAI mean (SD)score; 5 (4.1) vs. 22.3 (15.2); P = 0.025], lower levels of anti-BP180 NC16A serum autoantibodies [236.6 (266.3) vs. 556.2 (1323.6) U/mL; P = 0.008] and a higher prevalence of isolated linear C3 deposits (36.4% vs. 14.1%; P = 0.043) and a lower prevalence of linear immunoglobulin G deposits (36.4% vs. 68.7%; P = 0.025) along the dermal-epidermal junction by direct immunofluorescence microscopy. CONCLUSIONS: Patients with BP and comorbid psoriasis present at a younger age with milder erosive phenotype and lower levels of pathogenic autoantibodies.

The burden in chronic prurigo: patients with chronic prurigo suffer more than patients with chronic pruritus on non-lesional skin: A comparative, retrospective, explorative statistical analysis of 4,484 patients in a real-world cohort.

BACKGROUND: Chronic prurigo (CPG) is known as a high burdensome disease characterized by severe pruritus and multiple pruriginous lesions. Interestingly, the disease-specific burden is not well established and there are no data which compare the impact of CPG with chronic pruritus (CP) on non-lesional skin (CP-NL). OBJECTIVES: To address this issue, we analysed datasets from 4484 patients with either CPG or CP-NL. METHODS: Demographic medical data and additional information collected by validated patient reported outcome tools were analysed. The visual analogue scale and numerical rating scale (NRS) were used for assessing the pruritus intensity, the ItchyQoL for patients' quality of life, the Hospital Anxiety and Depression Scale and the Patient Needs Questionnaire' as a part of Patient Benefit Index for Pruritus for measuring the importance of 27 patient needs in terms of treatment goals. The Neuroderm questionnaire was used to assess the history of pruritus characteristics and the impact on sleep. RESULTS: Patients with CPG suffered longer and with a higher intensity from pruritus [NRS worst the last 24 h, CPG 6.0 (4.0;8.0) vs. CP-NL 3.0 (5.0;7.0), P < 0.001]. In them, pruritus occurred more often and the whole day and night which led to more loss in sleeping hours [CPG 3.0 h (2.0;4.0) vs. CP-NL 2.0 h (1.0;4.0), P < 0.001]. Patients with CPG showed higher scores for depression [HADS-D, CPG 6.0 (3.0;10.0) vs. CP-NL 5.0 (2.0;8.0), P < 0.001], more impaired quality of life [ItchyQol; CPG: 72.6 (61.6;83.6) vs. CP-NL 59.4 (48.4;70.4), P < 0.001] and higher weighted needs in the predefined treatment goals. DISCUSSION: Not only the presence of severe pruritus and pruriginous lesions but also sleep disorders and other mental symptoms may contribute to a higher burden in patients with CPG when compared with patients with CP-NL.

The impact of lesional inflammatory cellular infiltrate on the phenotype of bullous pemphigoid.

BACKGROUND: The influence of cutaneous cellular infiltration on the phenotype of bullous pemphigoid (BP) remains to be established. OBJECTIVES: To evaluate the main histopathological characteristics of patients with BP and to assess the association between the composition of lesional inflammatory infiltrate and the various clinical, immunological and immunopathological aspects of the disease. METHODS: Retrospective study encompassing patients diagnosed with BP throughout the years 2009-2020 in a specialized tertiary referral centre. RESULTS: The study encompassed 136 patients with BP, of whom 27 (19.9%) demonstrated a cell-poor inflammatory infiltrate in lesional skin specimens. Overall, 78 (57.4%), 71 (52.2%) and 5 (3.7%) specimens were found to include eosinophil-predominant, lymphocyte-predominant and neutrophil-predominant inflammatory infiltrates, respectively. Relative to the remaining patients with BP, those with an eosinophil-predominant inflammatory infiltrate had higher (90.8% vs. 77.2%; P = 0.030) whilst those with a cell-poor inflammatory infiltrate lower (70.3% vs. 88.7%; P = 0.017) seropositivity of anti-BP180 NC16A IgG. The latter subgroup presented with higher prevalence of mucosal involvement (25.9% vs. 8.3%; P = 0.011) and a non-inflammatory clinical phenotype (50.0% vs. 17.1%; P = 0.041). Patients with lymphocyte-predominant inflammatory infiltrate manifested with higher severity BPDAI scores and a lower frequency of the non-inflammatory subtype (11.1% vs. 36.4%; P = 0.035), whilst those with a neutrophilic infiltrate presented with lower mean (SD) levels of anti-BP180 NC16A IgG [269.3 (227.6) vs. 722.7 (1499.6) U/mL; P = 0.003]. CONCLUSIONS: Eosinophil-predominance and high cellularity in the lesional inflammatory infiltrate of BP skin are associated with increased seropositivity of anti-BP180 NC16A IgG. Lymphocyte-predominant infiltrates predict a more severe phenotype, pointing towards a pathogenic role of autoreactive lymphocytes.

Significance of chronic pruritus for intrapersonal burden and interpersonal experiences of stigmatization and sexuality in patients with psoriasis.

BACKGROUND: 60-90% of patients with psoriasis suffer from pruritus and 65% report itching as one of the most burdensome symptoms, raising significant quality of life (QoL) impairments. However, pruritus is not only an intrapersonal symptom but also a psychosocial interactive phenomenon and little is known about the effects of itching on interpersonal experiences. OBJECTIVES: This study aimed to compare the disease burden and patient needs between patients with none/mild vs. moderate/severe pruritus, and to examine the impact of disease parameters and intrapersonal burden on perceived stigmatization and sexual relationships. METHODS: This cross-sectional study included German patients aged ≥ 18 years with psoriasis vulgaris. Disease severity was assessed with Psoriasis Area and Severity Index; patients reported on intensity of pruritus, skin-generic and pruritus-specific QoL, patient needs and benefits, anxiety and depression symptoms, dysmorphic concerns, perceived stigmatization and sexual dysfunction. RESULTS: A total of 107 patients with psoriasis participated (mean age = 46.3 ± 14.6 years; 52.3% male): 64 with none/mild pruritus (NRS ≤ 3) and 43 with moderate/severe pruritus (NRS ≥ 4). Patients with moderate/severe pruritus reported more QoL impairments, depression and anxiety symptoms and dysmorphic concerns, but less treatment benefits, than those with none/mild pruritus. The patient needs most frequently rated as 'very/quite important' were 'be healed of all skin defects' (88.8%), and 'be free of itching' (87.0%), with no differences between the groups. Younger age, disease severity, frequency of scratching behaviours, dysmorphic concerns and treatment benefits were positively associated with stigmatization experiences; disease severity, sleeping problems and skin-generic QoL impairments were positively associated with sexual dysfunction. CONCLUSIONS: Pruritus induces significant burden in patients with psoriasis. Along with disease severity, intrapersonal burden has a great impact on social and dyadic relationships. Treatment choices that are effective in reducing pruritus should be prioritized in patient-centred healthcare.

Coexistence of bullous pemphigoid with neuropsychiatric comorbidities is associated with anti-BP230 seropositivity.

BACKGROUND: While clustering of bullous pemphigoid (BP) with neuropsychiatric diseases is well-established, the clinical and immunological profile of BP patients with this comorbidity remains to be decisively determined. OBJECTIVES: To evaluate the burden of neurological and psychiatric comorbidities among patients with BP and to elucidate the clinical, immunological and immunopathological features of patients with BP and comorbid neuropsychiatric conditions. METHODS: We performed a retrospective study encompassing patients diagnosed with BP throughout the years 2009-2020 in a specialized tertiary referral centre. Multivariate logistic regression model was used to identify predictors of neuropsychiatric conditions among patients with BP. RESULTS: The study included 273 patients with BP, of whom 123 (45.1%) presented with comorbid neuropsychiatric disease. Compared to the remaining patients with BP (n = 150), those with pre-existing neuropsychiatric diseases demonstrated older mean [standard deviation (SD)] age [81.7 (9.1) vs. 76.9 (10.1); P < 0.001], female preponderance (65.0% vs. 49.3%; P = 0.009), higher seropositivity rate of anti-BP230 (67.7% vs. 36.5%; P = 0.006) and higher levels of anti-BP180 NC16A IgG [651.3 (1279.6) vs. 370.4 (818.6) U/mL; P = 0.039]. In multivariate analysis, anti-BP230 seropositivity was independently associated with coexistence of BP with neuropsychiatric conditions [adjusted odds ratio (OR), 3.43; 95% CI, 1.24-9.52; P = 0.018]. In a sensitivity analysis confined to patients with neurological diseases (n = 103), older age [82.1 (8.4) vs. 77.2 (10.3); P < 0.001] and increased anti-BP230 seropositivity (68.0% vs. 39.7%; P = 0.018) were identified. CONCLUSIONS: The coexistence of BP with neuropsychiatric diseases is independently associated with the generation of anti-BP230 antibodies.

Pruritus Intensity Scales across Europe: a prospective validation study.

BACKGROUND: Chronic pruritus (CP) is a subjective symptom, and it is necessary to assess its intensity with validated patient-reported outcome tools in order to allow determination of the treatment course. OBJECTIVES: So far, the itch intensity scales were validated in small cohorts and in single languages. Here, we report the validation of the numerical rating scale, the verbal rating scale and the visual analogue scale for the worst and average pruritus intensity in the last 24h in several languages across Europe and across different pruritic dermatoses. METHODS: After professional translation, the intensity scales were digitized for use as a tablet computer application. Validation was performed in clinics for Dermatology in Austria, France, Germany, Italy, Poland, Russia, Spain, Switzerland and Turkey. RESULTS: A total of 547 patients with contact dermatitis, chronic nodular prurigo, psoriasis vulgaris, lichen planus or cutaneous T-cell lymphoma were included. The intensity scales showed a high level of reproducibility and inter-correlations with each other. The correlation with the Dermatology Life Quality Index was weak to strong in nearly all countries and dermatoses with the exception of France and patients with chronic nodular prurigo, for which no statistically significant correlations were found. CONCLUSIONS: The numerical rating scale, the verbal rating scale und the visual analogue scales are valid instruments with good reproducibility and internal consistency in German (Germany, Austria, Switzerland), French, Italian, Polish, Russian, Spanish and Turkish for different pruritic dermatoses. VAS worst was the best reproducible and consistent measuring instrument in all countries.

Google search trends for itch in Europe: a retrospective longitudinal study.

BACKGROUND: Itch is a common symptom in the general population. Affected individuals often do not seek medical consultation and rely on Internet searches to obtain information regarding their itch. OBJECTIVES: The aim of this study was to attain insights into common concerns of the general population regarding itch can by analysing itch-related Internet search behaviour. METHODS: Google AdWords Keyword Planner was used to assess search volumes for itch-related terms in 15 European countries between September 2014 and August 2018. All identified keywords were qualitatively categorized. Itch-related terms were descriptively analysed and are shown as number of searches/100 000 inhabitants. RESULTS: The search volume for the keyword 'itch' per 100 000 inhabitants was highest in Northern Europe, followed by Eastern, Central and Southern Europe. In 4/15 countries, itch was searched for more often in the autumn/winter months compared to in the spring/summer months. Most itch-related terms were related to dermatological conditions such as inflammatory skin diseases (e.g. psoriasis, atopic dermatitis), allergic or immunologic conditions (e.g. urticaria), and infectious diseases or infestations (e.g. scabies). In terms of body location, genitoanal itch dominated the searches. Symptoms and signs related to itch, possible non-dermatological aetiologies, and treatment options were also among the most searched terms. CONCLUSIONS: These analyses provided for the first time insights into the search behaviour patterns related to itch across Europe. People from Northern and Eastern Europe are more likely to seek online information regarding itch. Causes for the itch, especially dermatological conditions, and genitoanal itch are the most important concerns for Internet users. This unconventional and inexpensive method identifies medical needs of people beyond the medical setting, including people who do not seek medical consultation. Accordingly, the data could be used to guide public health interventions and manage respective inhabitants' medical needs.

[Quality of care for patients with atopic dermatitis in Germany-no improvements in indicators after ten years]. / Qualität der dermatologischen Versorgung von Neurodermitis in Deutschland ­ keine Verbesserung der Indikatoren nach 10 Jahren.

BACKGROUND: With AtopicHealth1, the first national care study on atopic dermatitis (AD) was conducted in 2010. At that time, about one third of the patients undergoing treatment by dermatologists showed severe limitations in quality of life, which indicated an insufficient quality of care. The aim of the present study was to characterise the current care of patients with AD undergoing dermatological treatment in comparison between different severity grades, as well as in comparison to 2010 and to psoriasis. METHODS: The Germany-wide multicentre cross-sectional study "AtopicHealth2" recorded clinical data, quality of life (DLQI), therapies, preventive behaviour and patient-defined treatment benefit (PBI). Patients with an indication for systemic therapy were considered moderately to severely affected for subgroup analyses, the others mildly affected. RESULTS: Between 2017 and 2019, 1291 patients (median age 41 years, 56.5% female) were enrolled by 111 centres. Compared with 2010, there were no improvements in quality of life (DLQI 8.5 in both studies), severity (SCORAD 45.4 vs. 42.3 in 2010) or treatment benefit (PBI 2.2 vs. 2.4 in 2010). Moderately to severely affected patients were more likely to show impaired quality of life (45.4% vs. 23.6%) and less likely to have relevant treatment benefits (PBI < 1: 21.3% vs. 13.2%) than mildly affected patients. In contrast to psoriasis, patients with AD revealed higher quality of life limitations (DLQI 8.5 vs. 6.1) and lower treatment benefit (PBI 2.2 vs. 2.8). DISCUSSION: Compared to 2010, there is no improvement in the quality of care for AD in Germany. Compared to psoriasis, patients with AD show higher burden and lower treatment benefit, which underlines the need for therapeutic innovations.