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Background Objectives Methods Results Conclusions Prurigo nodularis (PN) also known as chronic prurigo, is a chronic inflammatory skin disease characterized by intensely itchy nodules/lesions which occur due to intensive scratching. PN management is, in part, based on clinician evaluations of PN lesions, which can be supported by clinician‐reported outcomes (ClinRO) such as the Prurigo Activity and Severity (PAS) instrument. A 5‐item version of PAS was included in recent phase‐3 dupilumab PN trials (PRIME [NCT04183335]/PRIME2 [NCT04202679]). The PAS score was derived using the unweighted sum of 3‐items of the 5‐item PAS (range, 0–11; higher score indicates worse activity and severity): Item 2 (number of lesions), Item 5a (percentage of lesions with excoriations/crusts) and Item 5b (percentage of healed lesions) for use in clinical practice and for communication of treatment benefit to physicians.To evaluate the measurement properties of PAS score and derive within‐patient (responder definition) and between‐group improvement thresholds for interpreting changes in PAS score in patients with PN.The data source was the pooled treatment group, intention‐to‐treat (ITT) data from the phase‐3 PRIME (NCT04183335) and PRIME2 (NCT04202679) studies evaluating the efficacy of dupilumab in adult patients with PN with ≥20 nodules and severe itch uncontrolled with topical therapies. PAS score reliability, validity and sensitivity to change were evaluated, and anchor‐ and distribution‐based methods were applied to derive meaningful change thresholds.The pooled ITT population included 311 patients (mean age 49.5 years, 65.3% female). Adequate to good psychometric properties were demonstrated for PAS score. The within‐patient meaningful improvement threshold was estimated as 3.0 points (absolute change) and 37% (per cent change). A 1.7‐point (absolute change) and 20% (per cent change) improvement were estimated to reflect a between‐group meaningful change in PAS score.PAS score is a simple, clinically relevant indicator of PN lesion activity and severity supported by suitable psychometric performance. [ABSTRACT FROM AUTHOR]

Chronic prurigo (CPG) is a neuroinflammatory, fibrotic dermatosis that is defined by the presence of chronic pruritus (itch lasting longer than 6 weeks), scratch-associated pruriginous skin lesions and history of repeated scratching. Patients with CPG experience a significant psychological burden and a notable impairment in their quality of life. Chronic prurigo of nodular type (CNPG; synonym: prurigo nodularis) represents the most common subtype of CPG. As CNPG is representative for all CPG subtypes, we refer in this review to both CNPG and CPG. We provide an overview of the clinical characteristics and assessment of CPG, the burden of disease and the underlying pathophysiology including associated therapeutic targets. The information provided results from a PubMed search for the latest publications and a database search for current clinical trials (ClinicalTrials.gov, EU Clinical Trials Register [European Medicines Agency]; using the following terms or combinations of terms: 'chronic prurigo', 'prurigo', 'prurigo nodularis', 'pathophysiology', 'therapy', 'biologics', 'treatment'). Dupilumab is the first authorized systemic therapy by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for CNPG to date. Topical and systemic agents that are currently under investigation in clinical randomized, placebo-controlled phase II and III trials such as biologics (e.g., nemolizumab, vixarelimab/KPL-716, barzolvolimab/CDX-0159), small molecules (ruxolitinib cream, povorcitinib/INCB054707, abrocitinib) and the opioid modulator nalbuphine are highlighted. In the last past 15 years, several milestones have been reached regarding the disease understanding of CPG such as first transcriptomic analysis, first terminology, first guideline, and first therapy approval in 2022, which contributed to improved medical care of affected patients. The broad range of identified targets, current case observations and initiated trials offers the possibility of more drug approvals in the near future. [ABSTRACT FROM AUTHOR]

Dear Editor, Brachioradial pruritus (BRP) is typically located at the dorsolateral part of the forearms, mostly at the dermatomes C5/C6 but it may also involve other dermatomes at the arm and neck. Prior to treatment with naloxone, pruritus intensity was severe in all patients (worst pruritus intensity on the numerical rating scale [WI-NRS]: 8-10/10). [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

Chronic prurigo is an extremely severe pruritic skin disease which presents with multiple, hyperkeratotic and erosive papules, nodules and/or plaques. Patients with this high-burden disease require effective therapies, but effective treatments with regulatory agency approval are currently lacking. Deeper understanding of the pathophysiology suggests that hypersensitive nerves play an important role in the development of chronic prurigo. Accordingly, a treatment with neuroactive substances which modulate hypersensitivity seems promising. Here, we review antipruritic therapies with a neuromodulative effect. Current treatment options, such as topical capsaicin or opioid-receptor modulators, and also novel and future treatment regimens, such as, for example, interleukin-31 antibodies and neurokinin-1 receptor antagonists, are discussed. [ABSTRACT FROM AUTHOR]

The aim of this multicentre, randomized, double-blind, placebo-controlled, cross-over, phase-II study was to determine the antipruritic effect of aprepitant vs. placebo in 58 patients with anti-histamine-refractory chronic pruritus in chronic nodular prurigo. Patients were randomized to receive either first oral aprepitant 80 mg/day or placebo for 4 weeks. Following a 2-week wash-out phase, the patients were crossedover to receive the other treatment for 4 weeks. Primary efficacy criterion was the intra-individual difference between mean itch intensity (visual analogue scale) at baseline compared with the end of treatment period. Prurigo lesions, pruritus course, quality of life, patient benefits, and safety were secondary parameters. No significant differences were found between aprepitant treatment and placebo for any of the parameters investigated. Under the experimental conditions of the study, aprepitant, 80 mg daily for 4 weeks, did not have an antipruritic effect in patients with chronic prurigo. [ABSTRACT FROM AUTHOR]

Impaired sleep due to nocturnal pruritus is a common symptom in patients with chronic pruritus. How ever, there is no standardized, simplified instrument for assessing sleep-related problems in patients with chronic pruritus. After a literature search, we conducted 50 interviews with patients with chronic pruritus and tested 12 items most frequently used in routine sleep questionnaires. Afterwards, 2 sleep assessment questionnaires (Pittsburgh Sleep Quality Index; Regensburg Insomnia Scale) were selected for use in 88 patients with chronic pruritus with sleep impairment due to pruritus. They were completed twice; once before optimizing their individual pruritus therapy and once again after 4 weeks. During the latter survey, 21 patients reported that pruritus no longer negatively affected their sleep. These patients also achieved a significant improvement in their sleeping behaviour in the Regensburg Insomnia Scale. Therefore, the Regensburg Insomnia Scale appears to be well-suited to assessing sleep impairment in patients with chronic pruritus. [ABSTRACT FROM AUTHOR]

Prurigo nodularis (PN) is a subtype of chronic prurigo presenting single to multiple symmetrically distributed, hyperkeratotic and intensively itching papules and nodules. PN evolves along with chronic pruritus in the context of diverse dermatological, systemic, neurological or psychiatric conditions. Permanent scratching is possibly a major trigger of PN, although its exact pathophysiology remains unclear. Current state-of-the-art therapy for PN consists of topical steroids, capsaicin, calcineurin inhibitors, ultraviolet (UV) therapy, systemic administration of gabapentinoids, µ-opioid receptor antagonists, antidepressants or immunosuppressants. Novel treatment concepts, such as inhibitors of neurokinin-1, opioid and interleukin-31 receptors, have been developed and are currently being clinically tested. [ABSTRACT FROM AUTHOR]

In order to improve diagnosis and treatment, physicians require information about the social context and quality of life of their patients. The Center for Chronic Pruritus at the University Hospital Münster achieves this goal using the electronic patient-reported outcome system "Mobile Patient Survey", which assesses pruritus and quality of life measures. The aim of this study is to evaluate the consistency and reliability of such measures. A total of 42 patients, age range 19-82 years, participated in the study and were asked to assess the measures at baseline via a paper questionnaire, and to use the "Mobile Patient Survey" at baseline and after 1 h in order to test reliability. Statistical analysis was performed using coefficient rc for metric variables and weighted kappa κw for categorical vari- ables. The internal consistency of all measures was unaffected. It was shown that 6 out of 7 measures can be assessed without loss of reliability. It is recommended that questionnaires for electronic usage are assessed for validity and reliability. [ABSTRACT FROM AUTHOR]

The article discusses research concerning the major role of nerve fibres in prurigo nodularis (PN). It examines the intraepidermal nerve fibre density (IENFD) of PN at various stages which is reduced in lesional and inter-lesional prurigo nodularis. Also investigated is the skin biopsies from representative lesional and non-lesional areas and healed skin in patients with PN.

Pruritus in pregnancy is a common and burdensome symptom that may be a first sign of a pregnancy-specific pruritic disease (atopic eruption of pregnancy, polymorphic eruption of pregnancy, pemphigoid gestationis, and intrahepatic cholestasis in pregnancy) or a dermatosis coinciding with pregnancy by chance. Despite its high prevalence, pruritus is often underrated by physicians, and data regarding the safety profiles of drugs for pruritus are very limited. In this review, we illustrate the epidemiology, possible pathophysiology, clinical characteristics, and diagnostic workup of various pregnancy-related diseases and discuss antipruritic treatments. The prevalence of pruritus in pregnancy demonstrates the importance of symptom recognition and the need for an holistic approach, taking into account both the potential benefits for the patient and the potential risks to the fetus. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Performing a reliable assessment of chronic pruritus remains a challenge. Electronic diaries are often used, but many of the scales have not been validated. ItchApp© was developed for Android smartphones in order to address this lack. A total of 40 subjects with chronic pruritus completed questionnaires both on paper and with ItchApp© (verbal rating scale, numerical rating scale, dynamic pruritus score) in order to validate the software application. Strong correlations were found for test–retest reliability (intraclass correlation coefficient: 0.865-0.977) and convergent validity (Spearman's r: 0.442-0.924). A feasibility questionnaire for ItchApp© revealed a high level of user friendliness and compliance. This was confirmed in a randomized controlled trial with 68 subjects, for which the clinically important difference in the numerical rating scale values for ItchApp© was calculated (2.61 points). In summary, ItchApp© is a recently developed eDiary that can provide experts with a reliable evaluation of patients with chronic pruritus. It will be made available for future clinical trials. [ABSTRACT FROM AUTHOR]

In brachioradial pruritus and notalgia paraesthetica, the 8% capsaicin patch is a novel and effective, but cost-intense, therapy. Routine data for 44 patients were collected 6 months retrospectively and prospectively to first patch application. The cost to health insurance and the patient, and patient-reported outcomes were analysed (visual analogue scale, numerical rating scale, verbal rating scale for pruritus symptoms, Dermatological Life Quality Index, and Patient Benefit Index). Mean inpatient treatment costs were reduced by €212.31, and mean outpatient treatment and medication costs by €100.74 per patient (p.p.). However, these reductions did not offset the high cost of the patch itself (€767.02 p.p.); thus the total cost to health insurance increased by €453.97 p.p. (p ≤ 0.01). The additional costs of therapy to the patient decreased by €441.06, thus the overall cost p.p. remained approximately the same (€3,306.03 vs. €3,318.94). Capsaicin patch therapy resulted in reduced pruritus, improved quality of life and greater patient benefit, thus long-term cost-efficiency analyses are necessary. [ABSTRACT FROM AUTHOR]

Chronic pruritus is a common symptom, associated with several severe medical conditions, great psychological burden, and reduced quality of life. It also poses socio-economic challenges concerning patients' work loss and healthcare costs. In Germany, medical rehabilitation programmes represent an integral part of the medical care of patients with chronic inflammatory skin diseases. However, such programmes play only a rudimentary role in the treatment of other dermatological diseases, such as dermatological oncology, genetic skin diseases, and chronic pruritus. Therefore, a specific antipruritic dermatological rehabilitation programme was developed in cooperation between the Department of Dermatology of the Medical Rehabilitation Center Bad Bentheim and the Center for Chronic Pruritus of the University Hospital of Muenster, Germany. This prospective study compared short-term patient-reported outcomes (n = 121) at the beginning and end of the rehabilitation programme. The majority of subjects had chronic pruritus on primary diseased, inflamed skin. Significant improvements in pruritus intensity (p ≤ 0.001), quality of life (p ≤ 0.001), anxiety symptoms (p ≤ 0.001) and depression (p ≤ 0.001), as well as an overall patientrelevant benefit (Patient Benefit Index 2.6 ± 1.06) and treatment-related patients' satisfaction, were shown. This suggests that implementation of this standardized rehabilitation programme for treatment of patients with chronic pruritus was successful. [ABSTRACT FROM AUTHOR]

The article presents a study for tailoring the cut-off values of the visual analogue scale and numeric rating scale in itch assessment. Topics include challenges in routine daily practice and clinical trials while examining itch severity; questionnaires on pruritus intensity and quality of life for itching assessment; and using statistical analysis for finding cut-offs among patients.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article reports the minimal clinically important difference (MCID) difference in chronic pruritus appearing to be dependent on baseline itch severity. Topics include how MCID depends on the method of calculation, response to an instrument and anchor measure reliability; and investigating the overall MCID in chronic pruritus using a visual analogue scale (VAS) and numeric rating scale (NRS).

Brachioradial pruritus (BRP) and notalgia paraesthetica (NP) represent 2 of the most common neuropathic itch syndromes. A total of 58 consecutive patients presenting at the Center for Chronic Pruritus, University Hospital Münster, were analysed with regard to clinical presentation, anatomical and morphological pathologies, impairment in quality of life, and response to treatment with topical capsaicin. Patients with BRP reported stinging and burning more often than those with NP. In the BRP group structural magnetic resonance imaging abnormalities more frequently correlated with localization of the symptoms compared with in patients with NP. In addition, intraepidermal nerve fibre density was decreased in lesional skin in patients with BRP, but not in those with NP, confirming the neuropathic origin in BRP. Topical capsaicin resulted in a significantly higher alleviation of itch and pain intensity and improvement in quality of life in patients with BRP compared with those with NP, which may reflect clinical and aetiological differences between the conditions. [ABSTRACT FROM AUTHOR]

Currently valid itch intensity scales, such as the visual analogue scale (VAS), are indispensable, but they can be influenced by the patient's overall health status. The aim of this study was to evaluate the reliability and validity of the Dynamic Pruritus Score (DPS), a new instrument comparing reduction in current pruritus with a defined earlier time-point. Eighty-one randomly selected adults (50 females, mean age 53.9 years) recorded their pruritus at visit 1 and repeatedly at visit 2 on the DPS, VAS, numerical rating scale, and on health status questionnaires (EuroQol; EQ-5D), skin-related quality of life (Dermatology Life Quality Index; DLQI), anxiety and depression (Hospital Anxiety and Depression Scale; HADS) and patient benefit (Patient Benefit Index; PBI). Intraclass correlation showed high reliability for both DPS and VAS (r > 0.9, p < 0.001), while the DPS has shown higher concurrent validity (rDPS to PBI = 0.570; p < 0.001). The DPS can then be considered an alternative instrument to the VAS for assessment of pruritus in adults. Further research is needed to confirm these results with a more representative sample size. [ABSTRACT FROM AUTHOR]

This study was a prospective, parallel-group, randomized, double-blind, vehicle-controlled, multi-centre clinical trial to compare the efficacy of topical sertaconazole 2% cream with vehicle in reducing chronic pruritus in subjects with atopic dermatitis, and to assess its safety and local tolerability. A total of 70 subjects applied either of the 2 treatments twice daily for a period of 4 weeks on affected, itchy skin areas. Treatment efficacy was evaluated primarily considering the item itch intensity on a 5-point verbal rating scale. Insomnia, state of atopic dermatitis (Scoring Atopic Dermatitis; SCORAD), quality of life and therapy benefit were also assessed. No significant difference between active treatment and vehicle was found at any of the time-points for any of the investigated parameters. Under the experimental conditions of the study, sertaconazole 2% cream did not exert anti-pruritic effects that were better than vehicle in subjects with atopic dermatitis who had chronic pruritus. [ABSTRACT FROM AUTHOR]

A quiz concerning the diagnosis for itchy nodules and papules on the body surface of a 54-year-old male is presented.