Search

Notalgia paresthetica (NP) is a sensory neuropathy characterized by chronic pruritus, skin pain, and other pathologic sensations affecting the mid-to-upper back. NP may be under-recognized and under-diagnosed, with limited data available on its symptom presentation and treatment patterns. NP-DERM was an internet-based survey of dermatologists (n = 650) from 8 different countries on their perspectives on NP symptoms and current treatment practices. Dermatologists typically treated a median of 12 patients with NP per month. Dermatologists reported that itch (pruritus) was the most common symptom for their patients with NP, followed by hyperpigmentation and sensitive skin. The most burdensome NP symptom was pruritus, followed by burning or hot sensation, and painful or raw skin. The most prescribed treatments included non-medicated skin care, topical corticosteroids, oral antihistamines, medicated topicals, and gabapentin or pregabalin. Physicians reported low satisfaction with available treatments. The most common reason for physicians to discontinue patients' therapy was lack of response.

Anhedonia, the reduced ability to experience pleasure, is a prevalent symptom in various psychiatric disorders, but has not been investigated in dermatological conditions, particularly those characterized by chronic itch. This study aimed to examine the prevalence and clinical correlates of anhedonia in patients with chronic itch. A cross-sectional study was conducted in 137 patients with chronic itch, classified according to the International Forum for the Study of Itch (IFSI) classification. Anhedonia was assessed using the Snaith-Hamilton Pleasure Scale (SHAPS) and Anticipatory and Consummatory Interpersonal Pleasure Scale (ACIPS). Itch severity, quality of life, and psychological distress were assessed using the Visual Analogue Scale (VAS), Verbal Rating Scale (VRS), ItchyQoL, and Hospital Anxiety and Depression Scale (HADS), respectively. The mean SHAPS score was 1.0 ± 1.7 points, and the mean ACIPS total score was 76.9 ± 16.2 points. In the study sample, 13.1% of patients were identified as anhedonic, with a higher prevalence observed in those with severe and very severe itch. Anhedonia was significantly correlated with itch severity (R = 0.2, p=0.02 for 24 h VASmean and SHAPS; R = 0.2, p = 0.01 for 24 h VASmax and SHAPS), anxiety symptoms (R = 0.3, p < 0.001 for SHAPS and HADS-anxiety), depression symptoms (R = 0.4, p < 0.001 for SHAPS and HADS-depression), and impairment in quality of life (R = 0.2, p = 0.014 for SHAPS and ItchyQoL). Anhedonia is a significant and prevalent aspect of psychological distress in patients with chronic itch. Addressing this symptom may not only improve patients' overall mental health but also enhance the effectiveness of treatments for chronic itch. Future research is needed to elucidate further the mechanisms underlying the relationship between anhedonia and chronic itch and to develop targeted interventions for this population.

The clinical manifestations of atopic dermatitis (AD) and chronic nodular prurigo (CNPG) include pruritus and eczema/lesions, posing significant challenges for patients. Th2 cells and ILC2, marked by cytokine production-particularly IL-4/13-are crucial therapeutic targets. Despite displaying a dose-dependent lack of pruritus induction post-injection, IL-13 acts through the IL-13Rα1 and IL-13Rα2 receptor system. Our study focused on investigating ex vivo skin biopsies in AD (n = 17), CNPG (n = 14) and healthy controls (HC; n = 10), examining the gene expression landscape of interleukins linked with pruritus (IL-13, IL-4, IL-31) and their corresponding receptors. Compared to HC, results revealed a significant upregulation of IL-4 , IL-13 , and IL-13RA1 in AD, whereas CNPG did not show increased IL13 expression. Notably, the decoy receptor IL-13RA2 displayed intriguing patterns, with AD showing a marked increase compared to both HC and CNPG. Positive correlations between receptor expression and itch intensity and hyperkinesis sensation underscore clinical relevance, potentially serving as biomarkers. The findings suggest a pivotal role of IL-4 and IL-13, along with IL-13RA1, in pruritus pathogenesis in both entities, while IL-13 upregulation in AD is countered by IL-13RA2. The comparable expression of IL-13RA2 to HC in CNPG suggests the absence of this regulatory mechanism, potentially worsening the disease and leading to prolonged scratching behavior. These insights illuminate the intricate interplay of interleukins and receptors in different pruritus phenotypes, laying the groundwork for understanding underlying mechanisms and offering avenues for therapeutic intervention.

Background: Lebrikizumab improved itch, interference of itch on sleep, and quality of life (QoL) in patients with moderate-to-severe atopic dermatitis (AD), in two Phase 3 trials at 16 weeks compared to placebo., Objectives: We assess improvements in itch and sleep interference due to itch and their impact on QoL measurements after treatment., Methods: Data were analyzed from ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967) in patients with moderate-to-severe AD. QoL was evaluated using Dermatology Life Quality Index (DLQI) at Week 16 in patients (>16 years of age) who were itch responders/non-responders (defined as ≥4-point improvement in Pruritus Numeric Rating Scale) or Sleep-Loss Scale responders/non-responders (defined as ≥2-point improvement in itch interference on sleep)., Results: In ADvocate1 and ADvocate2, significantly greater proportions of itch responders had a clinically meaningful improvement in measures related to QoL (DLQI scores (0/1), ≤5 DLQI total score and ≥4-point DLQI improvement) compared to itch non-responders. In both studies, a significantly greater proportion of Sleep-Loss Scale responders, reported a DLQI score of (0/1), DLQI total score of ≤5 and DLQI improvement of ≥4 points compared to Sleep-Loss Scale non-responders., Conclusions: Improvement in itch and sleep interference due to itch is associated with improvement in the QoL of patients after treatment with lebrikizumab for moderate-to-severe AD., ClinicalTrials.gov registration NCT04146363 (ADvocate1) and NCT04178967 (ADvocate2).

Background: Chronic pruritus is a clinically heterogeneous symptom that manifests itself with varying duration, intensity, or quality. To date, there is no validated German-language instrument that systematically assesses the relevant parameters. With the support of the Pruritus Research Working Group (Arbeitsgemeinschaft Pruritusforschung, AGP), a questionnaire for the assessment of chronic pruritus (AGP questionnaire) was developed in 2008. The subsequently revised instrument, now called the German Pruritus Questionnaire, records pruritus-specific parameters such as localization, course, intensity and quality, anamnestic data on the general state of health, sociodemographic data, quality of life, and coping methods. It is to be validated in the study presented here., Patients and Methods: The questionnaire was used in 366 patients with chronic pruritus of different etiologies from Germany (University Hospitals Heidelberg, Münster, Mainz, Erlangen, Giessen, private practice Bad Bentheim, TU Munich, Wiesbaden Kidney Center), Austria (Graz University Hospital) and Switzerland (Aarau Cantonal Hospital)., Results: The reliability for repeated completion (retest reliability) with regard to localization, first occurrence, and concomitant diseases showed high values for Cohen's kappa (> 0.8). The data on the retest reliability of the pruritus characteristics showed lower values (< 0.7). With regard to the measurability of practically relevant changes (change sensitivity), medium to strong effect sizes were found (0.09-0.19). A statistically significant differentiation of the pruritus etiologies based on the recorded parameters was not possible., Conclusions: The German Pruritus Questionnaire allows a comprehensive and structured recording of patient- and clinician-reported, relevant dimensions of chronic pruritus of different etiologies. Further adaptation and development are planned., (© 2024 The Author(s). Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Background: Poor sleep quality is associated with higher mortality and lower quality of life in patients with chronic kidney disease-associated pruritus (CKD-aP). Difelikefalin reduces itch in patients with CKD-aP undergoing haemodialysis (HD). This post hoc analysis of the Phase 3 difelikefalin studies (Study 3105 and the pooled dataset from KALM-1 and KALM-2) evaluated whether itch reduction in individuals with CKD-aP improved sleep quality., Methods: Itch intensity was assessed in patients undergoing HD who had moderate-to-severe CKD-aP treated with intravenous difelikefalin (0.5 µg/kg, three times weekly) (N = 222, Study 3105; N = 426, KALM-1 and -2) or placebo (N = 425, KALM-1 and -2) for 12 weeks, using the Worst Itch Intensity Numerical Rating Scale (WI-NRS). Sleep quality was assessed using the sleep disability question of the 5-D Itch Scale (5-D SDQ) in all studies and, in Study 3105, with the Sleep Quality Numeric Rating Scale (SQ-NRS)., Results: Greater improvements in sleep quality were observed in patients with ≥3-point versus <3-point WI-NRS improvement using SQ-NRS in Study 3105 [mean (95% confidence interval) -5.2 (-5.6, -4.8) vs -1.5 (-2.0, -1.0)] and 5-D SDQ in KALM-1 and -2 [-1.8 (-2.1, -1.6) vs -0.8 (-1.1, -0.4)]. SQ-NRS and WI-NRS scores were highly correlated at both baseline and Week 12 in Study 3105 (Spearman correlation coefficient: 0.77 and 0.84, respectively). Correlations were also observed between 5-D SDQ and WI-NRS scores in Study 3105 and KALM-1 and -2., Conclusions: In patients undergoing HD with moderate-to-severe CKD-aP, itch reduction with intravenous difelikefalin was associated with improved sleep quality. As disturbed sleep may contribute to mortality and morbidity in CKD-aP, difelikefalin may help to address a major clinical burden by improving sleep quality, secondary to itch relief., Trial Registration: KALM-1 (NCT03422653), KALM-2 (NCT03636269), Study 3105 (NCT03998163)., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Chronic pruritus is a prevalent interdisciplinary symptom with a strong influence on health-related quality of life. Patients need extensive diagnostics and long-term treatment. This retrospective and prospective cohort study compared routine and university-based specialized care in terms of cost-effectiveness and patient benefit. Direct medical and non-medical costs and patient-reported outcomes (PRO; pruritus intensity, quality of life, treatment needs and benefits) were assessed. Data analyses were conducted using descriptive methods and non-parametric statistical tests. A total of 300 adult patients (54.3% female) participated in the study. Six months after the treatment start in a specialized German pruritus care unit, the total costs were significantly reduced (mean total costs 686 € vs 433 € per patient per half year (total cohort); p <  0.001; mean out-of-pocket costs 198 € vs 124 € per half year (total cohort), p <  0.001). Pruritus intensity (numerical rating  scale 5.3 vs 3.7, p < 0.001), quality of life (Dermatology Life Quality Index 8.9 vs 5.7, p < 0.001) and patient benefit (Patient Benefit Index Pruritus 1.2 vs 2.1, p < 0.001) improved significantly (total  cohort). The results of this study show, that treatment of chronic pruritus patients in a specialized itch centre leads to an improvement in patient  benefit and reduces the economic burden at the same time.

This article presents the case of a patient with massive pruritus sine materia. Naloxone was proven as quick and effective therapy which led to a complete reduction of itching., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: The underlying mechanisms of pruritus and chronic pruritus (CP) in particular, remain poorly understood; however, current research has revealed promising new concepts in which the importance of the interaction of neuronal cells of different classes, immune cells and keratinocytes is becoming increasingly clearer., Research Question: In this review article the current concepts in pruritus research are presented and summarized., Material and Method: This is a review article based on the current literature., Results: Different classes of sensory afferents, such as mechano-insensitive C‑fibers (histaminergic pruritus) and non-histaminergic pruriceptive C‑fibers and Aδ-fibers are involved in CP. The central sensitization in CP manifests as hyperknesis and alloknesis, the latter triggered by Aβ-fibers and Merkel cells. In recent years, the importance of inflammatory cells, such as Th1 and Th2 cells but also basophilic, eosinophilic granulocytes and mast cells has become clear. In CP there appears to be close communication between neuronal cells, immune cells and keratinocytes. Recent studies have focused on proinflammatory interleukins, such as IL-31, IL‑4 and IL-13 and their receptors. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway also plays an important role in the triggered signaling cascades that ultimately lead to pruritus perception. Therefore, in current treatment studies not only the interleukins and their receptors but also the JAK/STAT signaling pathway are directly targeted., Conclusion: The discovery of new mechanisms and interactions in CP highlights the complexity of this disease. Even if this and the treatment options derived from this are already very promising, a much better understanding of the mechanisms of CP is urgently needed in order to enable further options for an optimized treatment., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Neuropathic pruritus conditions arise from structural and/or functional damage of the peripheral or central nervous system. Novel findings of pruritus specific mediators and pathways strengthen the specificity theory of pruritus transmission, however electrophysiological studies suggest that focal activation of nociceptors and distinct discharge patterns of primary afferents also contribute to the development of the sensation of pruritus. A complex interplay between excitatory and inhibitory interneurons at spinal level, non-neuronal cells and descending modulation from upper centers contributes to neuronal sensitization and clinically to the chronicity of pruritus, as well as accompanying phenomena such as alloknesis and hyperknesis. Several topical, systemic and non-pharmacological therapeutic approaches directed at distinct targets are currently available., Competing Interests: Conflict of interest statement Nothing declared., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The underlying mechanisms of chronic pruritus (CP), which is often very debilitating for patients, are still not well understood. Over the past few years, peripheral and central mechanisms involving different classes of pruriceptive and nociceptive neuron (e.g., C- and Aδ-fibers), immune cells (e.g., eosinophils, basophils, Th1, Th2, and mast cells) and epithelial cells (e.g., keratinocytes) have been investigated. Based on these, numerous promising target-specific therapies are under development. In this review, we highlight the cells, key mediators, and receptors involved in itch perception and CP, and conclude by summarizing the therapies developed for these conditions., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Itch is a common symptom, but there is limited evidence on the prevalence of itch in children. The aim of this study was to assess the prevalence of itch in schoolchildren. A questionnaire was developed by experts in the field and based on a literature search. The questionnaire was applied in a pilot study of 25 consecutively selected paediatric patients and their parents. It confirmed the high content validity of the questionnaire, and the questionnaire was comparable to hospital records regarding chronic itch (n = 19, mean consistency 89.47%). The questionnaire was distributed among German schoolchildren in 9/12 randomly selected primary schools in Kiel, Germany. Of 1,722 invited students, 443 schoolchildren aged 6-10 years participated, and 26.2% (n = 116) reported itch. The prevalence of acute itch was 20.0% (n = 87), and 14.7% (n = 65) reported chronic itch. Reduced sleep and mood were often related to chronic itch. This study demonstrated that itch is a common symptom in German schoolchildren.

This systematic review aims to provide an update on measurement properties of patient-reported outcome measures for pruritus. A Medline literature search was conducted to update the systematic review published in this journal in 2017 and to identify new validation studies published between October 2015 and July 2019. The methodological quality of validation studies was assessed on the basis of the COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) checklist, and the measurement properties of patient-reported outcome measures were evaluated. A total of 19 new studies were included and added to the 22 studies identified in the previously published review. Evidence from all the 41 studies evaluating 38 different measures was summarized. Outcome measures were mapped to one of three constructs where possible: pruritus intensity, pruritus severity, pruritus-specific health-related QOL. COSMIN rating revealed mixed results, with deficiencies in the methodological quality of many studies across all constructs. The most appropriate pruritus severity measure was the Itch Severity Scale. ItchyQoL and the disease-specific Uremic Pruritus in Dialysis Scale achieved the most promising results considering the construct pruritus-specific health-related QOL. For pruritus intensity, nine measures performed similarly well., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Human hands are complex structures essential for a variety of functions in everyday life. This study prospectively investigated the clinical features of hand pruritus and the resulting functional impairment and disease-related burden in 395 patients with chronic pruritus (210 females, median age 59 years). Moderate to very severe hand pruritus was reported by 91.2% of patients, while 79% perceived additional sensory symptoms, such as burning, pain or tingling. A long duration of pruritus occurred in most cases (>6 months: 71.4%). A considerable proportion of patients showed moderate to severe impairment in the use of their hands (40.2%), performance of daily activities (65.0%) and quality of life (45.2%). Disease severity and burden is particularly high when both the palms and the backs of the hands are affected, and when pain is present simultaneously. Pruritus located on the hands is impairing and burdensome due to the functional relevance of the hands in everyday life.

Chronic pruritus of unknown origin is established when no underlying origin for pruritus can be determined. This retrospective cohort study aimed to determine the clinical profile and disease-related burden of chronic pruritus of unknown origin. A total of 263 patients (female/male: 154/109, median age 55 years) were included. Moderate to severe itch intensities were recorded (median average itch: 5.5/10, n = 200; median worst itch: 7.5/10, n = 199). In most cases pruritus lasted longer than 1 year (77.6%), occurred daily (68.2%), occurred in attacks (72.8%), and was often accompanied by dysaesthesias, such as burning, tingling and stinging. Quality of life was moderately impaired, while 22.2% and 12.4% of patients showed pathological anxiety and depression scores. Scratch lesions were associated with higher intensities of itch and greater impairment of quality of life, while women were more burdened by the disease than men. Chronic pruritus of unknown origin may occur at any age and the majority of patients endure severe itch with substantial disease-related burden.

Background: Atopic dermatitis imparts a substantial patient burden, including itch, sleep disturbance, and decreased health-related quality of life., Objective: This analysis evaluated changes in patient-reported outcomes of disease-specific signs/symptoms and health-related quality of life in adult and adolescent patients with moderate-to-severe atopic dermatitis treated with once-daily oral abrocitinib 200-mg or 100-mg monotherapy., Methods: Pooled data from one phase IIb (NCT02780167) and two phase III (NCT03349060, JADE MONO-1; NCT03575871, JADE MONO-2) monotherapy trials in adult and adolescent patients with moderate-to-severe atopic dermatitis were analyzed. Patient-reported outcome assessments included: global severity, itch, and multi-item measures that assess other signs and symptoms of atopic dermatitis. Additional patient-reported outcome assessments measured depression, anxiety, fatigue, disease-specific and general health-related quality of life, and work and general productivity among employed patients., Results: Overall, 942 patients were included in this analysis. Improvements were observed from the first post-baseline assessment to week 12 across all patient-reported outcomes, including Patient Global Assessment (PtGA) score of 0/1 (35.5%, 19.8%, and 5.9% for 200 mg, 100 mg, and placebo, respectively), ≥ 4-point improvement in Night Time Itch Scale (NTIS; 57.0%, 42.7%, and 12.7%), change from baseline in Patient-Oriented Eczema Measure (POEM) score (- 11.4, - 8.2, and - 3.4), 1-point improvement in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD; 75.2%, 65.1%, and 33.5%), Hospital Anxiety and Depression Scales (HADS) anxiety (- 2.0, - 1.7, and - 1.0) and depression (- 1.7, - 1.3, and - 0.1)., Conclusions: Abrocitinib monotherapy improved disease-specific signs/symptoms and health-related quality of life across multiple domains as reported by adult and adolescent patients with moderate-to-severe atopic dermatitis, complementing clinician-reported efficacy and safety outcomes., Clinical Trial Registration: NCT02780167 (registered 23 May, 2016), NCT03349060 (registered 21 November, 2017), NCT03575871 (registered 3 July, 2018).

In the past 10 years specific pathways for pruritus have been characterized on a cellular and molecular level but their exact role in the pathophysiology of neuropathic pruritus remains unclear. This also applies to the question which of the competing theories for pruritus, e.g. specificity, temporal/spatial pattern or intensity, would best apply. While experimental trials on mice have mostly confirmed the theory of specificity, the results on humans indicate a role of spatial and temporal patterns. The skin innervation is greatly reduced by the neuropathy and could provide a "spatial contrast pattern" and the axotomy could induce a de novo expression of gastrin-releasing peptide (GRP) in primarily afferent nociceptors and thus modulate spinal pruritus processing. In addition, the overlap of pruritus and pain in neuropathy patients complicates the direct translation from animal experiments and requires collaboration at the clinical level between pain medicine and dermatology.

Importance: There is an unmet need for psychometrically sound instruments to measure pruritus associated with prurigo nodularis (PN)., Objective: To evaluate the psychometric properties of the itch numeric rating scale (itch NRS), both the Worst Itch Numeric Rating Scale (WI-NRS) and the Average Itch Numeric Rating Scale (AI-NRS)., Design, Setting, and Participants: This secondary analysis is based on a secondary end point of a phase 2 randomized clinical trial of serlopitant for treatment of pruritus associated with PN. This randomized, double-blind, placebo-controlled study was conducted at 15 sites in Germany. Eligible patients were aged 18 to 80 years and had generalized PN for more than 6 weeks that was refractory to previous antipruritic therapies. Patients were required to have a visual analog scale itch score of 7 or higher at screening. Data were collected from July 2014 to June 2016 and analyzed from June 2016 to January 2017., Main Outcomes and Measures: The itch NRS (AI-NRS and WI-NRS) was correlated together with the following measures: the electronic verbal rating scale (eVRS) for itch self-categorization, average itch visual analog scale (AI-VAS), worst itch visual analog scale (WI-VAS), the pruritus-specific quality-of-life rating instrument ItchyQoL, Dermatology Life Quality Index (DLQI), and Prurigo Activity and Severity Score (items 7b and 7a: percentage healed prurigo lesions and percentage of prurigo lesions with excoriations)., Results: There were 123 participants in this study; the mean (SD) age of participants was 57.3 (11.58) years, and 58 (47.2%) were male. Strong associations (r ≥ 0.5) were observed between itch NRS items (WI-NRS and AI-NRS) and AI-VAS (24 hours) at weeks 2, 4, and 8 (r = 0.72-0.90; P < .001). Similar strong associations were also observed between itch NRS items and WI-VAS (24 hours) and eVRS for itch severity across weeks 2, 4, and 8 (r = 0.65-0.92; all P < .001). Strong correlations were seen between change scores for WI-NRS and WI-VAS and AI-VAS (r = 0.76 and 0.70, respectively; both P < .001). Similar findings were seen for AI-NRS, where correlations between change scores for WI-VAS and AI-VAS were 0.71 and 0.72, respectively (both P < .001). Analyses for the itch NRS items also showed that test-retest reliability was acceptable and provided evidence of acceptable convergent validity based on the eVRS and visit verbal rating score for itch self-categorization, ItchyQoL, and DLQI., Conclusions and Relevance: Results from this secondary analysis show that the itch NRS items WI-NRS and AI-NRS have good psychometric properties for pruritus associated with PN and should be considered acceptable tools for assessing pruritus in future clinical trials of PN., Trial Registration: ClinicalTrials.gov Identifier: NCT02196324.

Skin pain is increasingly recognized as an impactful symptom in atopic dermatitis (AD) because of its association with patient discomfort, disease burden, and reduced quality of life. Although the nature of skin pain in AD has not been systematically studied and is therefore not well understood, patients report soreness, discomfort, and tenderness that may reflect peripheral and central pain sensitization. The high prevalence of skin pain suggests that it is not adequately addressed by current therapies for AD and may be undertreated compared with other symptoms. This review discusses the clinical relevance of skin pain with respect to its experience, pathophysiology, relationship with itch, and treatment implications. Recent studies suggest that skin pain presents as a neuropathic symptom independent from itch and the &ldquo;itch-scratch cycle&rdquo;, and poses a unique burden to patients. Recognition of the significant consequences of skin pain and discomfort should reinforce the need to assess and treat this symptom in patients with moderate-to-severe AD. J Drugs Dermatol. 2020;19(10)921-926. doi:10.36849/JDD.2020.5498.

Chronic pruritus (CP) is a highly prevalent, difficult-to-treat, and burdensome condition. Today, multiple topical and systemic therapy concepts are available for the treatment of CP. Current guidelines recommend, besides topical treatments, the use of a vast array of mostly off-label systemic drugs with different mechanisms, including antihistamines, gabapentinoids, antidepressants, immunosuppressive drugs, and μ‑opioid receptor antagonists. The choice of the right agent depends on the indication, the safety profile of the drug, and patient-specific features, such as comorbidities and comedication. Thanks to a deeper understanding of the pathophysiology of CP, novel drugs have been developed and have already shown antipruritic efficacy in clinical studies and case reports. Of note, phosphodiesterase‑4 inhibitors as topical agents and monoclonal antibodies, neurokinin‑1 receptor antagonists, Janus kinase inhibitors, and opioid receptor modulators as systemic agents are in the frontline of innovative CP treatment. Other promising targets include structures of the peripheral and central nervous system which are involved in itch signaling. This article provides an overview of currently available topical and systemic therapies for CP and their indications and discusses novel innovative agents and promising new targets in CP.

While psychological factors are relevant in many patients with chronic pruritus, not all patients can be offered psychologic, psychosomatic or psychiatric consultation. The aim of this exploratory study was to identify criteria suggestive of psychological factors relevant for the etiology of chronic pruritus and of somatoform pruritus. Routine data from the database of the Center for Chronic Pruritus of the University Hospital Münster were used, including the Neuroderm Questionnaire, Dermatology Life Quality Index and Hospital Anxiety and Depression Scale. Chronic pruritus patients (n = 3,391) without a psychiatric diagnosis in their medical history were compared to the 331 chronic pruritus patients with diagnoses of "psychological factors associated with etiology and course of chronic pruritus" (ICD-10:F54) or "somatoform pruritus" (F45.8) confirmed by an expert. The latter reported more pruritus triggers, especially "strain" and "emotional tension" and used more emotional adjectives to describe their pruritus. They reported more often scratching leading to excoriations, higher levels of pruritus, impairment of quality of life, anxiety and depression. These aspects suggest the presence of psychological factors in the etiology of chronic pruritus and somatoform pruritus. Prospective validation, however, needs to be carried out.

Objective: To evaluate the efficacy of orvepitant (10 or 30 mg given once daily, orally for 4 weeks), a neurokinin-1 receptor antagonist, compared with placebo in reducing the intensity of epidermal growth factor receptor inhibitor (EGFRI)-induced intense pruritus., Design: Randomised, double-blind, placebo-controlled clinical trial., Setting: 15 hospitals in Italy and five hospitals in the UK., Participants: 44 patients aged ≥18 years receiving an EGFRI for a histologically confirmed malignant solid tumour and experiencing moderate or intense pruritus after EGFRI treatment., Intervention: 30 or 10 mg orvepitant or placebo tablets once daily for 4 weeks (randomised 1:1:1)., Primary and Secondary Outcome Measures: The primary endpoint was change from baseline in mean patient-recorded numerical rating scale (NRS) score (over the last three recordings) at week 4. Secondary outcome measures were NRS score, verbal rating scale score, Skindex-16 and Leeds Sleep Evaluation Questionnaire at each study visit (baseline, weeks 1, 4, 8); rescue medication use; EGFRI dose reduction; and study withdrawal because of intense uncontrolled pruritus., Results: The trial was terminated early because of recruitment challenges; only 44 of the planned 90 patients were randomised. All patients were analysed for efficacy and safety. Mean NRS score change from baseline to week 4 was -2.78 (SD: 2.64) points in the 30 mg group, -3.04 (SD: 3.06) points in the 10 mg group and -3.21 (SD: 1.77) points in the placebo group; the difference between orvepitant and placebo was not statistically significant. No safety signal was detected. Adverse events related to orvepitant (asthenia, dizziness, dry mouth, hyperhidrosis) were all of mild or moderate severity., Conclusions: Orvepitant was safe and well tolerated. No difference in NRS score between the orvepitant and placebo groups was observed at the week 4 primary endpoint. A number of explanations for this outcome are possible., Trial Registration Number: EudraCT2013-002763-25., Competing Interests: Competing interests: MT is a current employee and ER is a past employee of NeRRe Therapeutics, and both are inventors on a granted patent on novel uses of orvepitant. BV and PG received payment from NeRRe as investigators in this study. AD received payment from NeRRe for service as the chief medical officer for this study. DJ is an employee of Cromsource, who received payment from NeRRe for statistical analysis of this study. PH has received payment from NeRRe as a consultant. MEL reports receiving personal fees from Legacy Healthcare Services, AdgeroBio Pharmaceuticals, Amryt Pharma, Celldex Therapeutics, Debiopharm, Galderma Research and Development, Johnson & Johnson, Novocure, Lindi Skin, Merck Sharp and Dohme, Helsinn Healthcare, Janssen Research & Development, Menlo Therapeutics, Novartis Pharmaceuticals, F Hoffmann-La Roche, AbbVie, Boehringer Ingelheim Pharma, Allergan, Amgen, ER Squibb & Sons, EMD Serono, AstraZeneca Pharmaceuticals, Genentech, Leo Pharma, Seattle Genetics, Bayer, Männer SAS, Lutris Pharma, Pierre Fabre, Paxman Cooler, Adjucare, Dignitana, Biotechspert, Teva Pharmaceuticals Mexico, Parexel, OnQuality Pharmaceuticals, Novartis, Our Brain Bank, Millennium Pharmaceuticals, and research funding from Berg Health, Bristol-Myers Squibb, Lutris Pharma, Novocure, Paxman, Biotest and Veloce BioPharma. GT reports no conflicts of interest. AW reports receiving payment from NeRRe as chair of the advisory board and from Advent Life Sciences for consultancy, Canbex Therapeutics as a non-executive director (past position), Calcico Therapeutics as chairman (past position) and a non-executive director (past position), and the Wellcome Trust as a member of grant committees. SS reports receiving payment from NeRRe as a member of the advisory board and from Almirall, Astellas Pharma, Beiersdorf, Celgene, Chugai Pharma, Creabilis, Daiichi Sankyo, Galderma, Helsinn, Kiniska Pharmaceuticals, Kneipp, Maruho, Merz Pharma, Novartis, Pierre Fabre Laboratories, Sienna Biopharmaceuticals and Ziarco as a member of their advisory boards and from Menlo Therapeutics as an investigator and participation as an investigator in trials sponsored by Dermascence, Trevi Therapeutics and Vanda Pharmaceuticals., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Chronic pruritus is a frequent global condition. The pathophysiology, underlying aetiology, clinical manifestation, associated burden and response to therapy of chronic pruritus varies from patient to patient, making clinical research and management of this condition challenging. There are still several unmet needs, such as the need to standardize translational research protocols, diagnostic and therapeutic procedures and to enhance the knowledge of the humanistic and economic burden associated with chronic pruritus. Basic and clinical research is of the utmost importance to target these matters. Clinical research has the potential to identify new relevant mechanisms in affected patients, which may lead to identification of novel therapy targets. This article discusses in depth current shortcomings in the daily care of patients with chronic pruritus and the challenges clinical researchers and physicians treating chronic pruritus face in addressing these matters.

Neurophysiological mechanisms leading to chronicity of pruritus are not yet fully understood and it is not known whether these mechanisms diverge between different underlying diseases of chronic pruritus (CP). This study aimed to detect such mechanisms in CP of various origins. A total of 120 patients with CP of inflammatory origin (atopic dermatitis), neuropathic origin (brachioradial pruritus), and chronic prurigo of nodular type, the latter as a model for chronic scratching, as well as 40 matched healthy controls participated in this study. Stimulation with cowhage induced a more intensive itch sensation compared with stimulation with other substances in all patient groups but not in healthy controls, arguing for sensitization of cutaneous mechano- and heat-sensitive C-fibers in CP. All patient groups showed a decreased intraepidermal nerve fiber density compared with controls. A decreased condition pain modulation effect was observed in all patient groups compared with controls, suggesting a reduced descending inhibitory system in CP. In sum, CP of different etiologies showed a mixed peripheral and central pattern of neuronal alterations, which might contribute to the chronicity of pruritus with no differences between pruritus entities. Our findings may contribute to the development of future treatment strategies targeting these pathomechanisms., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

There is a paucity of studies regarding pruritus in patients with chronic leg ulcers. Data were collected using newly developed questionnaires for patients and physicians to evaluate pruritus in individuals with chronic leg ulcers. The results show that a total of 50 patients with chronic leg ulcers were included in this prospective study. Frequent pruritus was observed in 32.0% of the participants, while 36.0% reported occasional pruritus. The average pruritus intensity was 3.5 points (0-10 numeric rating scale [NRS]) and was found to increase with age. Patients experiencing pruritus achieved a higher Wound-quality of life (QoL) score (32.1) as that of patients without pruritus (25.8). Additional dermatological findings around the wounds included xerosis (26.0%), eczema (4.0%), and excoriations (2.0%). Pruritus was reported by all subjects with eczema and 84.6% of those with xerosis. The pruritus lasted significantly longer in women (average 98.4 months) vs men (average 37.5 months). Interestingly, men reported more intense pruritus than women (4.4 vs 2.8). Females reported more frequent use of skin care products than males. In conclusion, the current data show that two-thirds of patients with chronic leg ulcers suffer from moderate intense pruritus. Therefore, pruritus is a frequent and often neglected problem that should be regularly evaluated in all patients with chronic leg ulcers and considered in future therapy concepts., (© 2019 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Barrier damage, dry skin and itch are intricately linked and form the basis of many common skin diseases. Damage from environmental insults, or genetic or inflammatory causes, can impair the skin barrier, resulting in an increase in transepidermal water loss and activation of itch-associated nerve fibres. The itch-scratch cycle can perpetuate skin barrier damage and itch. Topical therapeutic strategies are utilised to overcome dry skin and itch, primarily in the form of emollients. Recent advances in our understanding of the mechanisms underlying itch have enabled the development of new topical therapies, which may be incorporated into existing treatment regimes. Ultimately, treatment of dry skin and itch must be highly tailored to the individual according to their needs.

Chronic pruritus (CP) is defined by itching lasting 6 weeks or more and is known to be both a highly prevalent and burdensome symptom of many pruritogenic diseases. Its status as a symptom has many implications mainly that the symptom should evolve and subside with the disease. However, according to the clinical experience, CP often does not parallel the disease course and requires an own management. It is speculated that neuronal sensitization processes take place, which lead to disconnection of the symptom from the underlying disease and establishment of an own course of pruritus. It is thus discussed that pruritus can be both a symptom of diseases and an entity by itself. Further studies are needed to learn more and improve our understanding of this condition. This article compares its role in pruritogenic diseases, encourages discussion on the topic and provides an overview of the proper questions to ask., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Chronic pruritus is a bothersome symptom in psoriasis vulgaris and can profoundly reduce quality of life (QoL). In this exploratory analysis of the PSORITUS study, the impact of pruritus on QoL in 130 subjects with moderate-to-severe psoriasis was assessed using the ItchyQoL questionnaire. The majority of patients (n = 127) had to scratch their itchy skin regularly, which led to painful skin and frustration (mean ± standard deviation; SD ItchyQoL scores; 4.50 ± 0.56; 3.80 ± 1.09 and 4.20 ± 0.87, respectively). Changes in either temperature or season led to a worsening of itching in most of the patients (n = 126; mean ± SD ItchyQoL score; 3.80 ± 1.02). Many patients felt ashamed (n = 125) or embarrassed (n = 127) due to their itchy skin (mean ± SD ItchyQoL scores; 3.90 ± 1.26 and 3.40 ± 1.19, respectively). The results demonstrated the ItchyQoL questionnaire as a validated tool responsive to treatment for detailed insights into chronic pruritus in patients with psoriasis.

Central sensitization induces pain augmentation in chronic pain states. An analogous mechanism is speculated for chronic pruritus. This study compared patients with chronic pruritus (n = 79) of different origins (atopic dermatitis, chronic pruritus on non-lesional skin, chronic prurigo) and healthy controls (HC, n = 54) with regard to itch intensity and qualities of sensory symptoms after selective peripheral nerve fibre activation by electrical stimulation at 5 Hz (surrogate for C-fibre function) and 2,000 Hz (surrogate for Aβ-fibre function) using a Neurometer®. Electrically-induced itch was more intense in patients with chronic pruritus than in HC, but patients with chronic pruritus did not report "itch" more often than HC at 5 Hz. Stimulation at 2,000 Hz induced more pricking and tingling, but less throbbing in patients with chronic pruritus compared with HC. Treatment with cooling compound reduced clinical and experimental itch, but did not alter the distribution of sensory symptoms. These data show hyperknesis in chronic pruritus of various origins, arguing for common central sensitization mechanisms.

Introduction : Pruritus is a common symptom associated with several potential underlying causes, including both dermatologic and systemic diseases; it can also occur without an identifiable cause. Current treatment options are limited and most patients experience impaired quality of life. Serlopitant is a neurokinin 1 (NK 1 ) receptor antagonist under development for the treatment of pruritus associated with various dermatologic conditions and chronic pruritus of unknown origin. Areas covered : This review describes the epidemiology and unmet needs of patients with chronic pruritus, focusing specifically on patients with prurigo nodularis, psoriatic itch, and chronic pruritus of unknown origin; the rationale for targeting the NK 1 receptor for treatment of chronic pruritus; and the clinical development of serlopitant, including efficacy and safety data from completed phase II studies. Expert opinion : There is an unmet need for novel, safe, and effective therapies to treat chronic pruritus. Serlopitant has shown promising efficacy, safety, and tolerability across different patient populations, including adolescents and elderly patients. In contrast to less convenient administration options, serlopitant is a once-daily oral tablet, which is expected to facilitate compliance.

Background: The burden of pruritus is high, especially among patients with dermatologic diseases. Identifying trends in pruritus burden and people's medical needs is challenging, since not all affected people consult a physician., Objective: The purpose of this study was to investigate pruritus search behavior trends in Germany and identify associations with weather factors., Methods: Google AdWords Keyword Planner was used to quantify pruritus-related search queries in 16 German cities from August 2014 to July 2018. All identified keywords were qualitatively categorized and pruritus-related terms were descriptively analyzed. The number of search queries per 100,000 inhabitants of each city was compared to environmental factors such as temperature, humidity, particulate matter 10 micrometers or less in diameter (PM10), and sunshine duration to investigate potential correlations., Results: We included 1150 pruritus-related keywords, which resulted in 2,851,290 queries. "Pruritus" (n=115,680) and "anal pruritus" (n=102,390) were the most-searched-for keywords. Nearly half of all queries were related to the category localization, with Berlin and Munich having a comparatively high proportion of people that searched for pruritus in the genital and anal areas. People searched more frequently for information on chronic compared to acute pruritus. The most populated cities had the lowest number of queries per 100,000 inhabitants (Berlin, n=13,641; Hamburg, n=18,303; and Munich, n=21,363), while smaller cities (Kiel, n=35,027; and Freiburg, n=39,501) had the highest. Temperature had a greater effect on search query number (beta -7.94, 95% CI -10.74 to -5.15) than did PM10 (beta -5.13, 95% CI -7.04 to -3.22), humidity (beta 4.73, 95% CI 2.70 to 6.75), or sunshine duration (beta 0.66, 95% CI 0.36 to 0.97). The highest relative number of search queries occurred during the winter (ie, December to February)., Conclusions: By taking into account the study results, Google data analysis helps to examine people's search frequency, behavior, and interest across cities and regions. The results indicated a general increase in search queries during the winter as well as differences across cities located in the same region; for example, there was a decline in search volume in Saarbrucken, while there were increases in Cologne, Frankfurt, and Dortmund. In addition, the detected correlation between search volume and weather data seems to be valuable in predicting an increase in pruritus burden, since a significant association with rising humidity and sunshine duration, as well as declining temperature and PM10, was found. Accordingly, this is an unconventional and inexpensive method to identify search behavior trends and respective inhabitants' needs., (©Linda Tizek, Maximilian Schielein, Melvin Rüth, Sonja Ständer, Manuel Pedro Pereira, Bernadette Eberlein, Tilo Biedermann, Alexander Zink. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 12.07.2019.)

Objective of this open, noninterventional, noncontrolled study was to investigate the tolerability and performance of a woad extract containing cream in subjects with dry, pruritic skin after twice daily application over 2 weeks. Assessments included sensorial characteristics, skin condition, pruritus (numeric rating scale [NRS], dynamic pruritus score [DPS]), skin dryness (itch-controlled days [ItchCD], overall dry skin [ODS]), transepidermal water loss (TEWL), skin hydration and quality of life (5PLQ, DLQI). All sensorial characteristics were well perceived (>4), with tolerability (4.77 ± 0.47) and no negative skin feelings (4.73 ± 0.74) achieving the highest scores (0-5 scale). Dry skin and symptoms improved significantly (p < .001) for all variables: NRS (from 4.8 ± 1.74 to 1.83 ± 2.18), ItchCD (from 8.23 ± 4.40 to 4.81 ± 4.07), ODS (from 1.80 ± 0.85 to 0.65 ± 0.65), hydration (23.33 ± 1.33 to 40.70 ± 1.86), and quality of life (5PLQ: from 7.12 ± 4.25 to 4.24 ± 3.67; DLQI: from 5.29 ± 4.79 to 3.00 ± 3.98). The DPS revealed a moderate antipruritic effect. The TEWL decreased slightly (p = .511). No side effects were reported. The study suggests that, the cream is effective, and well tolerated in treating dry, irritated, and pruritic skin., (© 2019 Wiley Periodicals, Inc.)

Crisaborole ointment is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild to moderate atopic dermatitis. Using pooled data from two phase 3 studies (NCT02118766/NCT02118792), mediation modeling determined the interrelationship among pruritus, quality of life (QoL), and treatment. Patients aged ≥ 2 years received crisaborole ointment 2% or vehicle twice daily for 28 days. QoL measures were Dermatology Life Quality Index (DLQI) (≥ 16 years) and Children's Dermatology Life Quality Index (CDLQI) (2-15 years). Pruritus was assessed by the Severity of Pruritus Scale (4-point scale from 0 to 3). The indirect effect of crisaborole on QoL mediated through its effect on pruritus was 51% (DLQI model, p < 0.05) and 72% (CDLQI model, p < 0.05). Direct effect (other effects) on QoL was 49% (DLQI model, p < 0.05) and 28% (CDLQI model, p > 0.05). Mediation modeling shows that crisaborole affects QoL mostly indirectly through pruritus severity reduction.

Pruritus in autoimmune and inflammatory dermatoses is a common symptom that can be severe and affect the quality of life of patients. In some diseases, pruritus is related to disorders activity and severity or may occur independent of the disease. Despite the high prevalence, the symptom is still underrated and there are only a few trials investigating the efficacy of drugs for disease-specific pruritus. In this review, the characteristics and possible pathomechanisms of pruritus in various dermatoses like autoimmune bullous diseases, connective tissue diseases as well as autoimmune-associated dermatoses (atopic dermatitis, psoriasis vulgaris) is illustrated. Additionally, studies analyzing the antipruritic treatment are discussed. Summarizing, the prevalence of pruritus in these diseases demonstrates the importance for symptom recognition and the need for an efficient antipruritic therapy.

Chronic pruritus (CP) is often accompanied by paresthetic sensations like warmth, burning and stinging. The aim of this study was to analyze, whether divergent sensations are linked to structural and functional skin alterations in clinically diagnosed CP patients. Clinical responses to capsaicin, histamine, and to thermal and mechanical stimulation, intraepidermal nerve fiber density, and epidermal expression of transient receptor potential (TRP)-channels were investigated in healthy controls, and in CP patients, reporting either warmth (CP-W) or neuropathic sensations (CP-N). In CP-W, pinprick hyperalgesia and increased sensitivity to capsaicin were aligned with increased epidermal TRPV1 expression, while smaller histamine axon reflex erythema matched with significantly reduced intraepidermal nerve fiber density. CP-N showed earlier onset of sensations after capsaicin stimulation, significantly increased warmth detection threshold, and higher epidermal expression of TRPV4 compared to healthy controls. The present study contributes to the neurobiological understanding of the divergence of sensory sensations in CP, indicating new treatment targets.

Chronic pruritus is a highly prevalent, debilitating disease, which is often refractory to conventional therapies. A step-wise, guideline-driven approach should be adopted in the management of these patients. Emollients as well as topical corticosteroids if appropriate should be initiated whilst looking for the cause underlying the pruritus. If these measures fail, and the origin of the pruritus remains unknown, cannot be treated or does not respond to therapy, systemic therapies as for example gabapentinoids, antidepressants, mu-opioid-receptor antagonists or, in case of inflammatory conditions, immunosuppressive drugs should be recommended. Novel agents, especially systemic monoclonal antibodies, neurokinin-1 receptor antagonists and opioid receptor modulators, are promising in providing relief in refractory cases., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Few studies have validated standard measurement instruments for evaluation of chronic pruritus. The Chronic Pruritus Tools Questionnaire PRURITOOLS assembles a set of instruments for the assessment of pruritus, such as the visual analogue scale (horizontal 100-mm line), numerical rating scale (0-10), verbal rating scale, and information on pruritus quality and improvement during therapy. This study, with 40 subjects, analysed PRURITOOLS regarding convergent validity and test-retest reliability (60 min), followed by a feasibility questionnaire. Test-retest reliability for PRURITOOLS items was excellent (intraclass correlation coefficient 0.84-1). Strong to very strong correlations between the pruritus intensity scales indicated convergent validity. The feasibility questionnaire showed an overall acceptance of PRURITOOLS, and the majority of subjects (82.5%) considered it an appropriate questionnaire to measure pruritus. In conclusion, PRURITOOLS offers validated tools for rapid pruritus assessment in routine care or endpoints of clinical trials.

Background: Anecdotal evidence suggests that neurokinin 1 receptor antagonism reduces pruritus intensity in chronic pruritic conditions such as prurigo nodularis (PN)., Objective: This study assessed safety and efficacy of the neurokinin 1 receptor antagonist serlopitant for treatment of pruritus in PN., Methods: In this randomized, double-blind, placebo-controlled study, 128 patients with chronic, treatment-refractory PN for more than 6 weeks received serlopitant, 5 mg, or placebo orally once daily for 8 weeks. The primary end point was change in average itch visual analog scale score at weeks 4 and 8., Results: Average itch visual analog scale scores significantly improved with serlopitant versus with placebo at weeks 4 and 8: the least squares mean difference (serlopitant minus placebo) was -1.0 at week 4 (P = .02) and -1.7 at week 8 (P < .001). The least squares mean difference between serlopitant and placebo reached statistical significance at week 2 (-0.9 [P = .011]). The most frequently reported treatment-emergent adverse events in the serlopitant group were nasopharyngitis, diarrhea, and fatigue., Limitations: The 8-week duration may be insufficient to assess clinically relevant resolution of PN lesions., Conclusions: Serlopitant reduced pruritus in patients with treatment-refractory PN and was well tolerated., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Neuropathic itch is clinically important but has received much less attention as compared to neuropathic pain. In the past decade, itch-specific pathways have been characterized on a cellular and molecular level, but their exact role in the pathophysiology of neuropathic itch is still unclear. Traditionally, mutually exclusive theories for itch such as labeled line, temporal/spatial pattern, or intensity theory have been proposed, and experimental studies in mice mainly favor the specificity theory of itch. By contrast, results in humans also suggest a role for spatial and temporal patterns in neuropathic itch. Rarefication of skin innervation in neuropathy could provide a "spatial contrast" discharge pattern, and axotomy could induce de novo expression of the itch-specific spinal neuropeptide, gastrin-releasing peptide, in primary afferent nociceptors, thereby modulating itch processing in the dorsal horn. Thus, clinical neuropathy may generate itch by changes in the spatial and temporal discharge patterns of nociceptors, hijacking the labeled line processing of itch and abandoning the canonical scheme of mutual exclusive itch theories. Moreover, the overlap between itch and pain symptoms in neuropathy patients complicates direct translation from animal experiments and, on a clinical level, necessitates collaboration between medical specialities, such as dermatologists, anesthesiologists, and neurologists.

Background: Pruritus has been associated with cancer. However, limited data are available on the types of underlying malignancies associated with pruritus., Objective: We sought to characterize the association between pruritus and different cancer types, as well as variations by racial group., Methods: Cross-sectional study of patients ≥18 years of age seen at the Johns Hopkins Health System during 2013-2017. Patients with pruritus were compared with patients without pruritus. Analyses were stratified by race., Results: Patients with pruritus were more likely to have concomitant malignancy than those without pruritus (odds ratio 5.76, 95% confidence interval 5.53-6.00). Most strongly associated were cancers of the liver, gallbladder and biliary tract, hematopoietic system, and skin. Compared with white patients, black patients more frequently had soft tissue, dermatologic, and hematologic malignancies and less frequently had liver, respiratory, gastrointestinal, and gynecologic malignancies., Limitations: The cross-sectional design precludes analysis of the temporal association between pruritus and malignancy. The study is limited to a single tertiary care center., Conclusion: Pruritus is most strongly associated with cancers of the liver, skin, and hematopoietic system. Black patients with pruritus have a higher likelihood of skin, soft tissue, and hematologic malignancies than white patients, while whites have higher likelihoods of liver, respiratory, gastrointestinal, and gynecologic malignancies., (Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Pruritus is a frequent symptom in medicine. Population-based studies show that every 5th person in the general population has suffered from chronic pruritus at least once in the lifetime with a 12-month incidence of 7%. In patient populations its frequency is much higher depending on the underlying cause, ranging from around 25% in haemodialysis patients to 100% in skin diseases such as urticaria and atopic dermatitis (AD). Pruritus may be the result of a dermatological or non-dermatological disease. Especially in non-diseased skin it may be caused by systemic, neurological or psychiatric diseases, as well as being a side effect of medications. In a number of cases chronic pruritus may be of multifactorial origin. Pruritus needs a precise diagnostic work-up. Management of chronic pruritus comprises treatment of the underlying disease and topical treatment modalities, including symptomatic antipruritic treatment, ultraviolet phototherapy and systemic treatment. Treating chronic pruritus needs to be targeted, multimodal and performed in a step-wise procedure requiring an interdisciplinary approach. We present the updated and consensus based (S2k) European guideline on chronic pruritus by a team of European pruritus experts from different disciplines. This version is an updated version of the guideline that was published in 2012 and updated in 2014 (www.euroderm.org).

Chronic pruritus can be a diagnostic sign of an underlying disease. In the intracutaneous histamine test, histamine (one of the best-known inducers of pruritus) may cause different reaction patterns depending on the underlying disease. The aim of this study was to determine if an intracutaneous injection of histamine can differentiate between the causes of chronic pruritus and thus be used as a diagnostic test in chronic pruritus of unknown aetiology. A total of 140 subjects with chronic pruritus with various dermatological, systemic or neurological diseases were included. The intracutaneous histamine test was performed once on each subject. Erythema, wheal and pruritus intensity were measured and analysed. Significantly greater wheal size was observed in patients with systemic or multifactorial causes. In general, there was a significant correlation between age and wheal size. Also, noticeable differences were found between males and females regarding pruritus and wheal size. In summary, the exact type of chronic pruritus could not be clearly determined based on the results of the intracutaneous histamine test. However, the results provide valuable insights into specific reaction patterns to experimental histamine-induced itch, e.g. sex-specific differences in the neurophysiology of pruritus, which should be considered in future studies.

Introduction: Chronic pruritus (CP) is a multidimensional condition severely affecting the quality of life of those affected. Although a multitude of topical and systemic agents are recommended for CP of different origins, the condition often remains refractory to treatment. However, a deeper understanding of the pathophysiology of CP is leading to the development of novel antipruritic drugs., Areas Covered: This paper reviews antipruritic therapies in development by gathering data from recently published articles and clinical trials databases. Interleukin-31 antibodies and other biologics, neurokinin-1 receptor antagonists, opioid-receptor agonists/antagonists, TrkA-antagonists, and ileal bile acid transporter inhibitors are discussed., Expert Opinion: Clinical trials have rendered promising data on the antipruritic efficacy and safety of novel drugs, but further studies are necessary to enhance our understanding of the different conditions associated with CP. High-quality clinical trial data is necessary for these agents to be approved for the treatment. Basic research should be intensified to identify pathways relevant for CP and to further the development of new specific antipruritic drugs.

Chronic pruritus (CP) is a bothersome symptom of many different diseases and is often associated with psychosomatic and psychiatric comorbidity. This review gives an overview of psychologic factors that influence the perception and modulation of pruritus based on the well-known biopsychosocial model. Not only psychic comorbidities, such as anxiety and depression, play an important role in the etiology and perception of pruritus, but also internal factors, including personality, mentalization, suggestibility, and external factors, as well as stress. Expectations concerning the intensity of pruritus can also play a role in itch perception that can be modulated by cognitions and behavior of the patient. Obsessive rituals of scratching and skin manipulation with instruments present challenges in the treatment of CP. Initial studies on the efficacy of psychotherapeutic approaches to different problems, such as scratching, comorbidity, or stress-associated itch, show that these might be very useful additions to the multidisciplinary treatment of pruritus., (Copyright © 2018 Elsevier Inc. All rights reserved.)