Validation of the German Pruritus Questionnaire for the systematic assessment of chronic pruritus.

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.

S2k guideline: Diagnosis and treatment of chronic pruritus.

Pruritus is a cross-disciplinary leading symptom of numerous diseases and represents an interdisciplinary diagnostic and therapeutic challenge. In contrast to acute pruritus, chronic pruritus (CP) is a symptom of various diseases that is usually difficult to treat. Scratching and the development of scratch-associated skin lesions can alter the original skin status. In the presence of an itch-scratch-cycle, even secondary diseases such as chronic prurigo can develop. Chronic pruritus leads to considerable subjective suffering of those affected, which can result in restrictions on the health-related quality of life such as sleep disturbances, anxiety, depressiveness, experience of stigmatization and/or social withdrawal up to clinically relevant psychic comorbidities. Medical care of patients should therefore include (a) interdisciplinary diagnosis and therapy of the triggering underlying disease, (b) therapy of the secondary symptoms of pruritus (dermatological therapy, sleep promotion, in the case of an accompanying or underlying psychological or psychosomatic disease an appropriate psychological-psychotherapeutic treatment) and (c) symptomatic antipruritic therapy. The aim of this interdisciplinary guideline is to define and standardize the therapeutic procedure as well as the interdisciplinary diagnosis of CP. This is the short version of the updated S2k-guideline for chronic pruritus. The long version can be found at www.awmf.org.

The role of personal attitudes of control and responsibility for the uptake of peritoneal dialysis- a national survey among dialysis patients.

BACKGROUND: Although most patients are suitable for both hemodialysis (HD) and peritoneal dialysis (PD), there seem to be differences in the outlook of patients who choose one modality over the other. There is currently limited literature about the impact of patients' personal attitudes on the decision for PD or HD. In this study, we tried to find out whether there were differences between patients who were on HD and PD in their desire for control and responsibility for their treatment. METHODS: The data were drawn from a nationwide postal survey of 630 HD and PD patients. Patients' desire for control was measured by scores on the internal locus of control (ILOC) scale. Patients were also asked how important taking responsibility for their dialysis had been for their treatment decision (ITR). Two multivariate logistic regression models, both adjusted for age, were applied to investigate whether there were differences between HD and PD patients in ILOC and ITR. Having one generic measure (ILOC) and one tailored to the dialysis context (ITR) gave the opportunity to investigate if it is a generic personality trait or rather a specific attitude that affects choice of dialysis modality. RESULTS: PD patients were younger and showed higher ILOC and ITR values. Multivariate logistic regression models adjusted for age confirmed the significant influence of ILOC and ITR on the uptake of PD. The odds ratios for being in the PD group were 1.53 for ILOC (p = 0.030; 95% CI 1.04-2.25), 1.49 for ITR (p = 0.019; 95% CI 1.07-2.07), and 0.95 (p = 0.000; 95% CI 0.94-0.97) for age in both models. CONCLUSIONS: Our analysis shows the impact of personal attitudes on the uptake of PD. Participants who generally want to keep control of their lives and take responsibility for their dialysis treatment tended to choose PD. As PD is a home dialysis treatment that requires patients to participate and contribute, it is beneficial if patients' personalities support the treatment procedure. Having two completely different treatment options that suit to different personalities gives us the opportunity to consider the relationship between personal attitudes and choice of dialysis modality. TRIAL REGISTRATION: The MAU-PD study is registered at the German Clinical Trials Register. DRKS-ID: DRKS00012555 . Date of Registration in DRKS: 2018/01/04.

Information about different treatment options and shared decision making in dialysis care - a retrospective survey among hemodialysis patients.

BACKGROUND: Hemodialysis (HD) and peritoneal dialysis (PD) are equivalent treatment alternatives for patients with end stage renal disease. In Germany, there is a legal obligation to inform every patient about all treatment alternatives and their possible harms and benefits. However, there is a low utilization of PD. Therefore, the question arises, whether HD patients perceive that they were informed about different dialysis options. We further investigate, if personal characteristics of informed and non-informed patients vary, and if both groups experienced the decision for their dialysis treatment as shared decision making (SDM). METHODS: The database was a nationwide postal survey of 590 HD patients from two statutory health insurers in Germany. Participants were asked whether they have been informed about both dialysis options. A logistic regression model examines impact factors on this information. We investigate differences in the German version of the 9-item SDM Questionnaire (SDM-Q-9) between informed and non-informed patients with a multivariate linear regression model. RESULTS: 56 % of the respondents reported they had been informed about different dialysis treatment options. Patients older than 65 had a 61 % lower chance than patients ≤ 65 for this information (p < 0.001). High educated patients had a 47 % higher chance for this information than patients with low education level (p = 0.030). Informed patients rated a higher SDM-Q-9 scores than non-informed patients (76.9 vs. 44.2; p < 0.001). Non-informed patients showed high values in those SDM-Q-9 items which had no regard to different treatment options. CONCLUSIONS: A great proportion of HD patients - mostly elderly patients and patients with a low education level - did not perceive that they were informed about different dialysis options before dialysis was initiated. The current obligation to provide information about all treatment alternatives in Germany is a first step to assure the unselected access to different treatment options. But it has not reached routine application in health care yet. Information about different treatment options can pave the way for SDM. While SDM is considered to be a valuable tool in clinical medicine, there is still room for improvement for its successful implementation when it comes to decision making on different dialysis treatment options. TRIAL REGISTRATION: The MAU-PD study (Multidimensional analysis of causes for the low prevalence of ambulatory peritoneal dialysis in Germany) is registered at the German Clinical Trials Register. DRKS-ID: DRKS00012555 Link: https://www.drks.de/drks_web/setLocale_EN.do . Date of Registration in DRKS: 2018/01/04.

Non-dermatological Challenges of Chronic Itch.

Chronic itch occurs in many skin diseases, but also in a variety of systemic, neurological, and psychogenic/psychosomatic disorders, or is caused by drug intake. When several diseases or causes co-exist, chronic itch is categorized as "mixed origin". These patients present with unaltered skin or with chronic scratch lesions including chronic prurigo. Precise diagnostics are necessary to evaluate the underlying aetiology, to enable identification of the best treatment available, and to improve patients' quality of life. This is of particular relevance in elderly people in whom chronic itch is often of systemic or mixed origin. Xerosis cutis is a frequent cofactor contributing to chronic itch of non-dermatological origin. Treatment is frequently multimodal, considering age, comorbidities, current drug intake, quality and intensity of itch. With regard to the demographic situation of the population, characterized by increasing life expectancy and polypharmacy, itch of non-dermatological origin will represent an increasing medical challenge in the future.

Prevalence of Pruritus in a Single Cohort of Long-term Kidney Transplant Recipients.

is missing (Short communication).

Mortality of Haemodialysis Patients With and Without Chronic Itch: A Follow-up Study of the German Epidemiological Hemodialysis Itch Study (GEHIS).

The GEHIS (German Epidemiological Hemodialysis Itch Study) is a representative cohort study started in 2013 with 860 haemodialysis (HD) patients in 25 German dialysis units. Chronic itch (CI) has been reported to be a poor prognostic marker for patients on HD; however, this has not been investigated in a representative patient cohort. In 2017, all HD patients were contacted again to investigate mortality in those with and without CI and to identify its determinants. Patients' characteristics, study instruments and CI were assessed, as in 2013. The response rate was 84.2% (n = 724). One-year mortality was 15.3%. Mortality was significantly higher in those with secondary scratch lesions compared with those with non-affected skin. This was also true after controlling for age and sex in a multivariate model. This study demonstrates a high mortality in HD patients; however, mortality depends on itch intensity, not on the occurrence of CI itself.

Strong Associations Between Inflammation, Pruritus and Mental Health in Dialysis Patients.

Pruritus, impaired mental health and inflammation contribute to morbidity in end-stage renal disease. There are no studies on all 3 conditions. We therefore obtained inflammatory parameter data (C-reactive protein and interleukin-6), pruritus data and psychological test data (36-Item Short-Form Health Survey, "Allgemeine Depressionsskala" and Toronto Alexithymia Scale-20) for 19 dialysis patients with pruritus, 20 dialysis patients without pruritus and 15 healthy controls. Non-parametric hierarchical clustering revealed 3 clusters of parameters: one mainly driven by pruritus scores (chronic kidney disease-associated pruritus cluster), one by mental health scores (mental health cluster) and one by inflammatory parameters (inflammatory cluster). Factor analysis showed strong associations (mental health cluster/chronic kidney disease-associated pruritus cluster, r=-0.49; mental health cluster/inflammatory cluster, r=-0.52; inflammatory cluster/chronic kidney disease-associated pruritus cluster, r=0.48). For the first time, complete correlations between inflammation, mental health and pruritus in dialysis patients have been established. As all 3 conditions are associated with mortality, knowledge about their interdependence helps to understand end-stage renal disease pathophysiology.

European S2k Guideline on Chronic Pruritus.

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).

S2k Guidelines for the diagnosis and treatment of chronic pruritus - update - short version.

Associated with a host of different diseases, pruritus is a cardinal symptom that poses an interdisciplinary diagnostic and therapeutic challenge. Over time, that symptom may progress independently of the initial cause, thus losing its function as a warning sign and turning into a clinically relevant disease of its own. In Germany, approximately 13.5 % of the general population are affected by chronic pruritus, with an incidence of 7 %. All forms of chronic pruritus require targeted treatment consisting of (a) diagnosis and management of the underlying disease, (b) dermatological treatment of primary or secondary (for example, dry skin, scratch lesions) symptoms, (c) symptomatic antipruritic treatment, and (d) psychological/psychotherapeutic treatment in case of an underlying or associated psychological or psychosomatic condition. Medical care of patients with chronic pruritus should therefore include an interdisciplinary approach, in particular with respect to diagnosis and therapy of the underlying disease as well as in terms of the management of treatment and adverse events. The objective of the present interdisciplinary guidelines is to define and standardize diagnostic and therapeutic procedures in patients with chronic pruritus. This is a short version of the current S2 guidelines on chronic pruritus. The long version may be found at www.awmf.org.

Health-related quality of life in haemodialysis patients suffering from chronic itch: results from GEHIS (German Epidemiology Haemodialysis Itch Study).

PURPOSE: Chronic itch (CI) is a common symptom in haemodialysis (HD) patients affecting about every 4th HD patient. Though it is known that health-related quality of life (HRQOL) is impaired in HD patients, data are lacking on how CI influences HRQOL in this group of patients, also regarding sex differences and the role of sleep and pain. METHODS: In order to investigate the itch prevalence and to investigate associated factors, GEHIS (German Epidemiology Haemodialysis Itch Study) was established as first cross-sectional study being representative for all dialysis units in Germany by considering their regional distribution and size of the located city according to population. HRQOL of 860 HD patients from a randomly selected cluster sample of 25 dialysis units was investigated using patient-reported outcomes as the Short-Form Health Survey (SF-12), the Hospital Anxiety and Depression Scale (HADS) as well as sleep and pain. Additionally, itch-specific QOL was assessed in HD patients affected by CI using the validated ItchyQoL. RESULTS: 42.8 % of HD patients were female. The mean age was 67.2 years (SD ± 13.5). Female patients showed significantly worse values in the mental component summary of the SF-12 as well as in the HADS subscale anxiety compared to male patients. Itch-specific HRQOL did not subject to sex. Patients with impairments in quality of sleep showed significantly worse values in both the SF-12 and the HADS subscales, however not in the ItchyQoL. The occurrence of pain was significantly associated with impaired SF-12, HADS and the ItchyQoL. Multivariate linear regression showed the itch-specific HRQOL to be significantly impaired with rising severity of CI. CONCLUSIONS: Impairments in HRQOL are a serious problem in HD patients. CI means an additional burden in affected patients, also impairing their HRQOL. GEHIS showed significant sex differences in HRQOL outcomes also in HD patients. CI and pain as well as sleep frequently occur combined and significantly impair HRQOL in HD patients. The care of HD patients should be complemented by psychosocial support and mental health services.

Uremic pruritus.

Uremic pruritus or chronic kidney disease-associated pruritus (CKD-aP) remains a frequent and compromising symptom in patients with advanced or end-stage renal disease, strongly reducing the patient's quality of life. More than 40% of patients undergoing hemodialysis suffer from chronic pruritus; half of them complain about generalized pruritus. The pathogenesis of CKD-aP remains obscure. Parathormone and histamine as well as calcium and magnesium salts have been suspected as pathogenetic factors. Newer hypotheses are focusing on opioid-receptor derangements and microinflammation as possible causes of CKD-aP, although until now this could not be proven. Pruritus may be extremely difficult to control, as therapeutic options are limited. The most consequential approaches to treatment are: topical treatment with or without anti-inflammatory compounds or systemic treatment with (a) gabapentin, (b) µ-opioid receptor antagonists and κ-agonists, (c) drugs with an anti-inflammatory action, (d) phototherapy, or (e) acupuncture. A stepwise approach is suggested starting with emollients and gabapentin or phototherapy as first-line treatments. In refractory cases, more experimental options as µ-opioid-receptor-antagonists (i.e., naltrexone) or κ-opioid-receptor agonist (nalfurafine) may be chosen. In desperate cases, patients suitable for transplantation might be set on 'high urgency'-status, as successful kidney transplantation will relieve patients from CKD-aP.

Paraneoplastic itch: an expert position statement from the Special Interest Group (SIG) of the International Forum on the Study of Itch (IFSI).

In clinical practice, the term "paraneoplastic itch" is used to describe itch in patients with cancer. Patients with hematological or solid tumor malignancies can be affected. In general, paraneoplastic itch is considered a rare disorder. However, paraneoplastic itch in hematological malignancies such as polycythemia vera and lymphoma are relatively frequent while other forms of paraneoplastic itch are in fact extremely rare. The true frequency of this symptom is unclear, epidemiological data in this field are limited. Itch in malignant disease may additionally impair patients' quality of life. A population-based cohort study showed that chronic itch without concomitant skin changes is a risk factor for having undiagnosed hematologic and bile duct malignancies. Paraneoplastic itch is rather resistant to treatment. In 2012, an interdisciplinary interest group of physicians and researchers was founded, aiming to generate a clear definition of paraneoplastic itch. In this paper we briefly review the current knowledge and aim to define what can be summarized under the term "paraneoplastic itch".

Prevalence of chronic itch and associated factors in haemodialysis patients: a representative cross-sectional study.

Chronic itch is a common symptom in haemodialysis (HD) patients, which is often underestimated. The aim of this cross-sectional study was to investigate the prevalence and factors associated with chronic itch in HD patients. A total of 860 HD patients from a randomly selected cluster-sample of patients attending dialysis units in Germany were included. The patients' mean?±?SD age was 67.2?±?13.5 years, 57.2% were male. The point prevalence of chronic itch was 25.2% (95% CI 22.4-28.1), 12-month prevalence was 27.2% (95% CI 24.1-30.3) and lifetime prevalence was 35.2% (95% CI 31.9-38.3). Chronic itch was significantly less prevalent in patients with secondary glomerulonephritis as primary renal disease. A history of dry skin, eczema, and age

Laboratory and dialysis characteristics in hemodialysis patients suffering from chronic itch--results from a representative cross-sectional study.

BACKGROUND: A representative cross-sectional study showed that chronic itch (lasting for a minimum of 6 weeks) affects 25.2 % (point prevalence) of hemodialysis (HD) patients. Pathophysiology and etiology of chronic itch (CI) in HD are still unclear. METHODS: We investigated 860 HD patients from a representative randomly selected cluster-sample considering the regional distributions of dialysis units in Germany. The current analyses report comorbidities, laboratory values and dialysis characteristics of HD patients in relation to CI. RESULTS: Diabetes was the only comorbidity that was associated with the occurrence of itch but interestingly with less CI. Except for creatinine, phosphorus, and parathormone, there were no significant associations between the occurrence and characteristics of CI and any laboratory value. Kt/V was not associated with the presence of CI. Patients dialyzed with polyarylethersulfone-membrane showed significantly more CI in all prevalence estimates and those dialyzed with polysulfone-membrane were significantly less affected by CI. CONCLUSIONS: Long-term follow-up studies will show if the type of dialysis membrane influences the development of CI in HD patients. It is most likely that several factors e.g. elevated parathormone, origin of end stage renal disease (ESRD), type of dialysis membrane, and a neuropathic component all contribute to the occurrence of CI in HD patients. Future research should consider a multifactorial origin of itch in HD.

Clinical management of pruritus.

The care of patients with chronic pruritus as a symptom of a wide variety of underlying diseases continues to confront dermatologists with diagnostic and therapeutic challenges. However, a structured history and a physical examination may already substantially help in narrowing down the number of potential differential diagnoses. Apart form reducing the intensity of pruritus, identification and appropriate treatment of the underlying disease are important needs of patients. If these goals doesn't lead to improvement of itch, current guidelines provide a number of topical and systemic therapies for symptomatic treatment. Various skin lesions (for example, xerosis caused by irritant substances, secondary scratch lesions) prompt patients to consult a dermatologist, but most cases require an interdisciplinary therapeutic approach to identify potential internal medicine, neurologic, or psychosomatic aspects. Although great strides have been made in basic research, specific therapies are still rare, and a precise knowledge of the legal framework for the implementation of guidelines (for example, off-label use) is essential. This CME article gives an overview of the causes of and treatment options for chronic pruritus and discusses both advances in basic research as well as progress in clinical knowledge.

Long-Term Efficacy and Tolerability of an Emollient Containing Glycerol and Paraffin for Moderate-to-Severe Uremic Xerosis: A Randomized Phase 3 Study.

INTRODUCTION: There is an unmet need for effective topical therapies for patients with uremic xerosis and chronic kidney disease-associated pruritus (CKD-aP). The long-term efficacy and tolerability of an emollient containing glycerol 15% and paraffin 10% (V0034CR) was evaluated in a phase 3 study. METHODS: In this randomized, double-blind, two-parallel group, vehicle-controlled study, patients with moderate-to-severe uremic xerosis were randomized to once-daily application of V0034CR or vehicle control for 28 days (period I). This was followed by a treatment-free period of ≤ 21 days (period II), then all patients received open-label treatment with V0034CR for ≥ 84 days (period III). Outcomes included treatment response at the end of period I (El Gammal's xerosis severity score), instrumental measures of scaling (D-Squame technique), time to relapse during period II, rate of recurrence during period III, pruritus severity over time, patient acceptability, and adverse events (AEs). RESULTS: The intent-to-treat population comprised 235 patients randomized to V0034CR (n = 118) or vehicle control (n = 117) during period I. Treatment response at the end of period I was achieved by 71 patients (60.2%) in the V0034CR group versus 48 (41.0%) with vehicle control (p = 0.0041). This coincided with greater reductions in the total surface area of squames (p = 0.001 vs vehicle control). Xerosis relapsed progressively without treatment in period II; however, remission was durable under maintenance therapy in period III. Improvements in pruritus severity were comparable between V0034CR and vehicle control, suggesting that the antipruritic effect of V0034CR was mainly exerted by its oil-in-water emulsion base. V0034CR had high patient acceptability and was well tolerated; the most common treatment-related AEs were irritation or erythema (2.1%), exacerbated pruritus (1.3%), and vesicles at the application site (0.9%). CONCLUSION: These data support the use of V0034CR, with its hydrating and occlusive properties, for the long-term management of patients with moderate-to-severe uremic xerosis and CKD-aP. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01084148; EudraCT number 2006-002201-31.

People on dialysis often experience dry and itchy skin that is hard to treat. This study tested the effectiveness of a new moisturizing cream (called V0034CR) in people with dry skin caused by dialysis (also known as uremic xerosis). In this study, 235 people with moderate or severe uremic xerosis were randomly split into two groups. One group (118 people) was given V0034CR cream, which contains glycerol and paraffin as its "active" ingredients. The other group (117 people) was given a "control" cream, which contains the same ingredients as V0034CR cream but without glycerol and paraffin. Both groups applied their assigned cream to their skin once a day for 4 weeks. If a person's dry skin had improved after 4 weeks, then they could stop using the cream for up to 3 weeks, and then switch to V0034CR cream from week 7 until the end of the study (19 weeks). If a person's dry skin had not improved after 4 weeks, or if their dry skin returned after stopping the cream, then they could start using V0034CR cream early and for the rest of the study. The study found that using V0034CR cream improved the signs and symptoms of dry skin more than the control cream. Most people in the study said that V0034CR cream was effective and easy to use, and no serious side effects were reported. The results of this study suggest that V0034CR cream is an effective treatment for people with dry skin caused by dialysis.

Serum autotaxin is increased in pruritus of cholestasis, but not of other origin, and responds to therapeutic interventions.

UNLABELLED: Pruritus is a seriously disabling symptom accompanying many cholestatic liver disorders. Recent experimental evidence implicated the lysophospholipase, autotaxin (ATX), and its product, lysophosphatidic acid (LPA), as potential mediators of cholestatic pruritus. In this study, we highlight that increased serum ATX levels are specific for pruritus of cholestasis, but not pruritus of uremia, Hodgkin's disease, or atopic dermatitis. Treatment of patients with cholestasis with the bile salt sequestrant, colesevelam, but not placebo, effectively reduced total serum bile salts and fibroblast growth factor 19 levels, but only marginally altered pruritus intensity and ATX activity. Rifampicin (RMP) significantly reduced itch intensity and ATX activity in patients with pruritus not responding to bile salt sequestrants. In vitro, RMP inhibited ATX expression in human HepG2 hepatoma cells and hepatoma cells overexpressing the pregnane X receptor (PXR), but not in hepatoma cells in which PXR was knocked down. Treatment of severe, refractory pruritus by the molecular adsorbents recirculation system or nasobiliary drainage improved itch intensity, which, again, correlated with the reduction of ATX levels. Upon reoccurrence of pruritus, ATX activity returned to pretreatment values. CONCLUSION: Serum ATX activity is specifically increased in patients with cholestatic, but not other forms of, systemic pruritus and closely correlates with the effectiveness of therapeutic interventions. The beneficial antipruritic action of RMP may be explained, at least partly, by the PXR-dependent transcriptional inhibition of ATX expression. Thus, ATX likely represents a novel therapeutic target for pruritus of cholestasis.