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

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.

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 patient-relevant 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.

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.

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.

Chronic nodular prurigo is characterized by recalcitrant itch. Patient perspectives on therapeutic goals, satisfaction with therapy and efficacy of therapeutic regimens for this condition are unknown. This questionnaire study examined these issues in 406 patients with chronic nodular prurigo from 15 European dermatological centres. Improvements in itch, skin lesions and sleep were the most important goals. Emollients, topical corticosteroids and antihistamines were the most frequently used treatments, while a minority of patients were prescribed potent medications, such as systemic immunosuppressants and gabapentinoids. Most patients were not satisfied with their previous therapy (56.8%), while 9.8% did not receive any therapy despite having active disease. A substantial number of respondents (28.7%) considered none of the therapeutic options effective. Although chronic nodular prurigo is a severe disease, most patients were not treated with potent systemic drugs, which may contribute to the high levels of dissatisfaction and disbelief in available therapies. Specific guidelines for chronic nodular prurigo and the development of novel therapies are necessary to improve care.

Chronic prurigo is a pruritic disease characterized by the development of pruriginous lesions due to scratching. The number of lesions is representative of the stage of the disease, while the presence of excoriations reflects the scratching activity. Aim of this study was to validate a new developed tool for the objective assessment of chronic prurigo. Investigator's Global Assessment scales for stage and activity were completed for 187 patients with chronic prurigo, who also reported patient-reported outcomes for itch intensity and quality of life. To assess the reliability and objectivity of the Investigator's Global Assessment, 5 independent raters completed the Investigator's Global Assessment scales for 8 patients twice. The scores increased with increased intensity of pruritus. The Investigator's Global Assessment stage scales correlated strongly with each other (Kendall's-tau-b 0.62) and moderately with the Investigator's Global Assessment activity scale (Kendall's-tau-b 0.47). Intra-rater test-retest reliability was excellent for all items, while the congruence among raters was very good for Investigator's Global Assessment - chronic prurigo activity (Kendall's W 0.84) and good for Investigator's Global Assessment stage scales (Kendall's W 0.747). Investigator's Global Assessment - chronic prurigo stage and activity are thus the best Investigator's Global Assessment instruments for use in assessing chronic prurigo.

Prurigo nodularis is an itchy skin disease with unknown epidemiology. This study aimed to describe the epidemiology of prurigo nodularis compared with that of psoriasis. The German sickness fund claims database, with 2,783,175 continuously insured patients, included 1,720 patients diagnosed with prurigo nodularis and 51,390 with psoriasis. Patients with prurigo nodularis were averagely 8 years older than psoriasis patients and more often were women (p < 0.001). Annual incidence was a constant 0.02% in prurigo nodularis, and decreased steadily from 0.53 to 0.42% in psoriasis; cumulative incidence was 0.1% for prurigo nodularis and 1.9% for psoriasis. Prevalence was 0.1% for prurigo nodularis and 4.7% for psoriasis, with a 1-year mortality of 5.4% for prurigo nodularis and 1.2% for psoriasis (p < 0.001). The most frequent pre-existing comorbidities in patients with prurigo nodularis were inflammatory dermatoses and depression. This epidemiological study found a low prevalence of prurigo nodularis, manifesting different demographics and comorbidities compared with psoriasis.

Chronic nodular prurigo presents with multiple pruriginous nodules and severe pruritus. This study aims to explore the treatment course and regimens in patients with chronic nodular prurigo and to analyse predictive factors contributing to therapeutic success. A total of 325 patients with chronic nodular prurigo (male 37.5%) were analysed concerning demographic data, pruritus intensity, medical history, psychological impairment, quality of life, treatment duration, regimens and outcome. These parameters were compared with 325 sex- and age-matched patients with chronic pruritus on non-lesional skin. Treatment success was dependent on duration and regime of treatment and independent of age, sex and initial itch intensity. Non-responders displayed a higher percentage of inflamed nodules, a higher portion of excoriated nodules and a higher impairment of quality of life and mood factors before initiation of treatment. Gabapentinoids and immunosuppressants proved to be the most successful therapeutic agents. Compared with patients with chronic pruritus, those with chronic nodular prurigo needed longer duration of therapy.

Isatis tinctoria L. (woad) has been used in medicine for centuries and has demonstrated anti-inflammatory effects. However, to date, no well-defined extracts with precise analysis of active substances have been developed. The aim of this study was to develop novel extracts of Isatis tinctoria L., and to characterize their active ingredients and anti-inflammatory properties. Various extracts of Isatis tinctoria L. were analysed for their active ingredients, and screened for anti-inflammatory effects using cyclooxygenase-2 activity assays. A petroleum ether extract was found to have the best effects, and was tested in a mouse model of acute allergic contact dermatitis. In the mouse model the petroleum ether extract resulted in significantly reduced ear swelling, oedema and inflammatory cell density. In mouse skin and human keratinocyte cultures, petroleum ether extract inhibited pro-inflammatory cytokine expression. Furthermore, human mast cell degranulation was significantly inhibited in LAD2 cell cultures. In conclusion, novel woad extracts were developed and shown to have anti-inflammatory properties in a contact hypersensitivity animal model and human keratinocytes. The production of such extracts and further characterization of their specific properties will enable determination of their potential dermatological effects in the treatment of inflamed and irritated skin.

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.

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.

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 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.

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.

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.

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.

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 crossed-over 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. (DRKS00005594; EudraCT Number: 2013-001601-85).

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.

Impaired sleep due to nocturnal pruritus is a common symptom in patients with chronic pruritus. However, 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.

Tofacitinib is an oral Janus kinase inhibitor. This post-hoc analysis aimed to investigate the psychometric properties of the Itch Severity Item (ISI), a numeric rating scale from 0 (no itching) to 10 (worst possible itching) for pruritus in psoriasis, and review the effect of tofacitinib on pruritus in patients with psoriasis participating in Phase 3 studies (N = 3,641). The ISI showed high test-retest reliability (intra-class correlation coefficient: 0.84). The clinically important difference was defined as a 1.48-point change, using Patient Global Assessment as an anchor. Mean changes from baseline in ISI scores with tofacitinib were significantly greater than placebo by Day 2 and exceeded the clinically important difference by Week 4 and Week 2 for tofacitinib 5 and 10 mg twice daily, respectively. The sound psychometric properties of the ISI as an assessment tool for pruritus in psoriasis were confirmed. Tofacitinib provided clinically meaningful improvements in psoriatic pruritus versus placebo.

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.

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 r c for metric variables and weighted kappa κ w for categorical variables. 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.

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.

The central processing of itch is not completely understood. This is the first study to use functional magnetic resonance imaging (fMRI) to examine the central modulation by distraction of experimentally induced itch. A total of 33 healthy volunteers were examined with fMRI. Periods of itch induction without distraction and itch with distraction by a Stroop task (psychological test, where the participants have to decide if the colour of the writing corresponds to the written word, for example if "red" is written in red or not) were counterbalanced during the scanning to examine task-specific changes in blood oxygenation level dependent-signal. The intensity of the subjects' itch sensation, desire to scratch and pain sensation were evaluated. Distraction by a Stroop task did not reduce itch intensity or urge to scratch. However, the Stroop task led to significantly higher activation of the left brainstem when it followed the "pure" itch sensation. Itch and pain seem to have similar inhibition pathways, particularly concerning brainstem activation during distraction. But as itch sensation, in contrast to pain, could not be sufficiently reduced by distraction, both entities might have different modulation systems.

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.

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.

Patients with chronic pruritus may develop scratch-induced lesions with elevated borders and central necrosis. This so-called umbilicated type of prurigo (UP) is rare and is assumed to develop preferentially in the context of metabolic diseases. The aim of this study was to characterize UP in its clinical and histological dimension. Demographic and clinical data were collected from 23 patients with UP. Intensive light microscopical analysis of biopsied lesions was performed. Statistical comparison with previous results for prurigo nodularis (PN) showed that UP is clearly a subtype of PN. In addition, clinical and microscopic features of epidermal perforation identical to those in acquired reactive perforating dermatosis (ARDP) were observed. Hence, we suggest that ARDP is identical to UP and is therefore a subtype of PN. We assume that reduced wound healing capacities due to underlying systemic disorders, particularly diabetes mellitus and uraemia, underlie the pathomechanism of development of umbilicated skin lesions with a perforating aspect.

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.

Sensitive skin is a frequent complaint in the general population, in patients, and among subjects suffering from itch. The International Forum for the Study of Itch (IFSI) decided to initiate a special interest group (SIG) on sensitive skin. Using the Delphi method, sensitive skin was defined as "A syndrome defined by the occurrence of unpleasant sensations (stinging, burning, pain, pruritus, and tingling sensations) in response to stimuli that normally should not provoke such sensations. These unpleasant sensations cannot be explained by lesions attributable to any skin disease. The skin can appear normal or be accompanied by erythema. Sensitive skin can affect all body locations, especially the face". This paper summarizes the background, unresolved aspects of sensitive skin and the process of developing this definition.

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. Trial registration ClinicalTrials.gov #NCT01792713.

This study investigated sex-specific differences in itch perception and skin reactions, as modulated by verbal suggestions, and the role of the investigator's sex. Healthy volunteers (50 males, 50 females), divided into 4 groups, were tested by male and female investigators. Itch was induced via prick testing with sodium chloride and histamine in 4 runs; 2 control conditions (with no exaggerated verbal comments about expected itch) and 2 experimental conditions (with exaggerated verbal comments). After 5 min, wheal and flare reactions were measured and itch intensity was rated by subjects on a numerical rating scale. Exaggerated verbal suggestions resulted in higher itch intensity ratings in the sodium chloride and histamine condition, and higher unpleasantness ratings and a wheal of greater extent in the sodium chloride condition, as well as a flare of greater extent in the histamine condition. The magnitude of the differences between the exaggerated verbal suggestion conditions and respective control conditions was only significantly different between male and female investigators concerning flare size in the histamine condition. There were no differences between male and female participants. Therefore, sex differences may play only a minor role in nocebo-induced itch perception.

Pruritus is a frequent sensation in dermatoses, but its prevalence in patients in dermatological practices has not been fully studied. The aim of this cross-sectional study is to investigate its prevalence and characteristics in all patients attending a dermatology practice in Germany over a period of one week (n = 334; 52.7% female; median age 45.0 years). The point prevalence of pruritus in this study population was 36.2% (87.6% of whom had chronic pruritus). It inhibited the everyday life of 73.6% of all patients, with 77.7% reporting a frequently to permanently experienced moderate intensity. (5.2 ± 2.3 on the numerical rating scale). Of the patients, 52.1% had previously consulted their general practitioner, and 62% had visited the dermatologist due to pruritus. This study shows that pruritus is a highly prevalent, clinically and economically relevant symptom in dermatological practices. The majority of patients suffering from chronic pruritus are severely burdened and medically underserved. Dermatologists should be aware that pruritus also occurs frequently in patients who do not primarily present due to their symptoms.

The objective of this study was to examine the subgroup of patients with chronic pruritus with dysesthetic subqualities for the presence of psychiatric comorbidities and to evaluate whether anxiety and depression make a difference in perception of somatosensory stimuli in quantitative sensory testing (QST). Forty-nine patients underwent routine diagnostics, a standardised QST testing battery, a psychosomatic evaluation for psychic comorbidities and filled out 2 questionnaires: the Patient Health Questionnaire for the assessment of depressive mood and the State Trait Anxiety Inventory. Twenty-seven (55.1%) of the sample had at least one psychiatric comorbid diagnosis. QST parameters were not correlated to anxiety and depression levels. We conclude that psychosomatic evaluation should become part of routine diagnostics of these patients in order to detect and treat psychiatric comorbidity. However, research on somatosensory aspects in these patients seems not to be affected by the levels of anxiety and depression.

The complex nature and difficult-to-establish aetiology of chronic pruritus (CP) makes it challenging to provide medical care for patients with CP. This challenge can only be met with a multidisciplinary approach. The first multidisciplinary Itch Centre in Germany was established at the University of Münster in 2002 to meet the needs of this patient population. More than 2,500 outpatients and 400 inpatients are diagnosed and receive treatment each year. To ensure evidence-based medical care, an electronic system for medical documentation and patient-reported outcomes was established. Automated data transfer to a research database enables comprehensive data analysis. Our translational research has characterized peripheral and central itch mechanisms, provided novel clustering of CP patients, and identified novel target-specific therapies (e.g. neurokinin 1 receptor-antagonist). The multidisciplinary approach, combined with basic, clinical and translational research, enables comprehensive medical care of patients as well as implementation of high-quality experimental and clinical studies.

Severe persistent pruritus is a common, but incompletely characterized, complication of hydroxyethyl starch (HES) infusion. This retrospective study aimed to assess HES-induced pruritus by electron microscopic findings, pruritus characteristics, and response to stimuli, and to determine the impact of HES dosage, molecular weight and substitution. Seventy patients with electron micro-scopy-proven HES-induced pruritus were included. HES-laden vacuoles were observed in skin macrophages of all patients. The median latency between HES exposure and pruritus onset was 3 weeks, and the median duration of pruritus was 6 months. Pruritus was severe, or very severe, in 80% of patients. Mechanical stimuli triggered pruritus in 74% of patients. Although the median cumulative dose of HES was 300 g, 15% of patients developed pruritus after only 30 g. There were no significant differences between HES 130/0.4 and HES 200/0.5 in pruritus latency, duration or severity. HES-induced pruritus thus may occur at any dose, molecular weight or substitution.

Chronic pruritus is a common symptom and there is an urgent need to test new anti-pruritic substances in high-quality clinical trials. However, no widely accepted standardized and validated method for objectively measuring pruritus is yet available. A special interest group of the International Forum for the Study of Itch has been established to assess scoring methods and questionnaires for use in clinical trials. This paper presents our current recommendations. The set of measures we recommend includes pruritus intensity scales, instruments for assessment of scratch lesions, chronic pruritus course, quality of life and patient benefits.