Hemodialysis-related pruritus and associated cutaneous manifestations

BACKGROUND: Uremic pruritus is one of the most common disabling problems in patients with chronic renal failure. Few studies have evaluated itching and cutaneous manifestations in hemodialysis-dependent patients. OBJECTIVES: The aim of this prospective study was to identify the prevalence of pruritus and cutaneous changes affecting patients undergoing hemodialysis. METHODS: The degree of itching in 70 patients treated at the Haemek Medical Center Hemodialysis Unit, in northern Israel, was scored according to presence and severity. We examined the relationship between the quality of dialysis and the frequency of pruritus, and identified concurrent cutaneous disorders. RESULTS: Pruritus was a common problem in the study cohort and affected 74.3% of hemodialysis patients at some point. The main characteristics of pruritus were a general pattern in 65.7% and mild intensity in 78.3% of observed patients. Duration of hemodialysis varied between 3 months and 13 years. There was no correlation between occurrence of pruritus and demographic or medical parameters (sex, type of kidney disease, regular medications or duration of hemodialysis) of the patients. Higher dialysis efficacy, as expressed by dialyser clearance, volume distribution of area, dialysis duration (Kt/v), may reduce the prevalence of pruritus (P < 0.02). None of the blood and chemical values considered (hemoglobin, creatinine, urea, phosphorus, calcium, albumin, parathormone and alkaline phosphatase) revealed any statistically relevant differences between pruritus groups. The appearance of foot ulcers was different between diabetic and nondiabetic individuals undergoing hemodialysis (P < 0.001). CONCLUSIONS: Pruritus is still a common problem in hemodialysis-dependent patients. The prevalence of xerosis and excoriations was high in patients undergoing replacement therapy. Efficient replacement hemodialysis may provide a clinical benefit.     

Characteristics of Pruritus according to Morphological Phenotype of Psoriasis and Association with Neuropeptides and Interleukin-31

BackgroundPruritus is a common symptom in psoriasis. However, few studies have assessed the characteristics of pruritus according to morphological phenotypes of psoriasis.ObjectiveTo investigate the characteristics of pruritus according to morphological phenotypes of psoriasis and to assess the association with inflammatory mediators related to pruritus.MethodsPsoriasis patients were divided into 2 groups according to clinical phenotype: eruptive inflammatory (EI) and chronic stable (CS). Clinical data of pruritus were assessed by an itch questionnaire. Serum neuropeptides and cytokines including substance P, histamine, vasoactive intestinal peptide, neuropeptide Y, calcitonin gene-related peptide and interleukin-31 (IL-31) were quantitatively measured.ResultsIn total, 50 patients with psoriasis (30 male, 20 female; mean age, 45.7 years) were studied (EI, n=15 and CS, n=35). Pruritus was reported by 80% of EI and CS patients. There were no significant differences in prevalence of pruritus, pruritus intensity, severity of psoriasis, serum neuropeptides, or IL-31 between the 2 groups.ConclusionThe morphological phenotype does not seem to be an important factor affecting the prevalence and characteristics of pruritus in psoriasis.     

Computerized recording of itch in patients on maintenance hemodialysis

Itch was assessed both continuously using a computerized method, Pain-Track, and retrospectively using visual analogue scales (VAS) by 28 patients undergoing maintenance hemodialysis and suffering from uremic pruritus. Measurements were performed during 7 consecutive days including three dialysis sessions. Pain-Track recordings showed that itch intensity was greater during dialysis than on days following dialysis (p less than 0.05). Possible explanations are that pruritogenic substances might be released during treatment or that removal of such substances during dialysis leads to amelioration of symptoms after treatment. Alternatively, lowering of the sensory threshold due to general discomfort in association with dialysis may exacerbate the itch intensity. There was no consistent difference between daytime and bedtime itch scores over the week, except on the second day without treatment, when bedtime itch ratings significantly exceeded those during the day (p less than 0.05), suggesting that factors other than inactivity are essential for this peak in itch intensity. Thus, after 2 days without treatment, when patients become increasingly metabolically deranged, they reported maximal itch, implying that the accumulation of pruritogenic substances is of major importance in the pathogenesis of uremic pruritus. There was a positive correlation between Pain-Track and VAS data, although significant fluctuations in itching could be detected only with Pain-Track.     

Clinical characteristics of pruritus in chronic idiopathic urticaria

BACKGROUND: Although pruritus is a predominant symptom of chronic idiopathic urticaria (CIU) its clinical characteristics have not been explored. OBJECTIVES: To characterize the clinical pattern and sensory and affective dimensions of the itch experience, utilizing a comprehensive itch questionnaire. METHODS: A structured questionnaire based on the McGill pain questionnaire was used in 100 patients suffering from CIU randomly recruited from a tertiary referral centre. RESULTS: All 100 patients recruited with CIU completed the questionnaire. In 68 patients pruritus appeared on a daily basis. Most patients experienced their pruritus at night and in the evening (n = 83), and 62 reported difficulty in falling asleep. Pruritus involved all body areas, but mostly the arms (n = 86), back (n = 78) and legs (n = 75). Accompanying symptoms were a sensation of heat in 45 patients and sweating in 15. Most patients (n = 98) were prescribed antihistamines (mainly sedating), of whom 34 experienced long-term relief. The sensation of itch was reported to be stinging (n = 27), tickling (n = 25) and burning (n = 23). Seventy-six patients found their pruritus bothersome, 66 annoying and 14 complained of depression. The itch intensity at its peak was more than double that felt after a mosquito bite. The worst itch scores of those who felt depressed were significantly higher than of those who did not (P = 0.018). There was a positive correlation between the sensory and affective scores during worst itch (P < 0.001). CONCLUSIONS: This study describes the itch experienced in CIU, highlighting sensory and affective dimensions. The itch questionnaire was found to be a valuable tool for evaluating pruritus in CIU and its unique features.     

A randomized,placebo-controlled,double-blind trial of ondansetron in renal itch

BACKGROUND: Renal itch is a relatively common and distressing problem for patients with chronic renal failure. Ondansetron, a serotonin type 3 receptor antagonist was developed for relief of chemotherapy induced nausea. Recently, anecdotal reports describe relief of renal itch with ondansetron. OBJECTIVES: We performed a double-blind randomized placebo-controlled trial to objectively assess the effectiveness of ondansetron in renal itch. PATIENTS AND METHODS: With approval from the local ethical committee, 24 patients on haemodialysis were enrolled in the trial. On a random basis 14 patients were blindly allocated to the ondansetron-placebo sequence and 10 to the placebo-ondansetron sequence. Baseline values for itch were obtained for 7 days before the treatment period and there was a 7-day washout between the treatment periods. During the treatment patients received either 8 mg of ondansetron three times a day or a placebo tablet three times a day for 2 weeks. Patients were asked to record the severity of their pruritus on a visual analogue scale (VAS) twice a day. At the end of the study patients were asked blindly which treatment they had preferred. RESULTS: Seventeen patients completed the trial. Pruritus decreased by 16% (95% CI: 0.5-32%) during active treatment and by 25% (95% CI: 9-41%) during treatment with placebo. The change in VAS scores during treatment with ondansetron (P = 0.04) and placebo (P = 0.01) were both significant. Eleven patients expressed a preference, seven for placebo and four for ondansetron. CONCLUSIONS: Our results show that ondansetron is no better than placebo in controlling renal itch.     

Pruritus, personality traits and coping in long-term follow-up of burn-injured patients

Pruritus is a major problem after burn injury; however, prevalence and predictors of prolonged pruritus are not known. The aims were to assess frequency of pruritus and the role of personality traits and coping in prolonged pruritus. The participants were burn patients injured 1-18 years earlier (n=248). Pruritus was assessed with an item from the Abbreviated Burn Specific Health Scale, personality was assessed with the Swedish universities Scales of Personality, and coping with the Coping with Burns Questionnaire. In all, 60% of the participants had pruritus at follow-up, however as the time after injury increased, the number of patients with persistent itch decreased. In logistic regression, 39% of the likelihood of having persistent pruritus was explained by greater extent of burn, less time after injury, and psychological features (being less assertive, and using more instrumental but less emotional support). In summary, chronic burn-related pruritus is rather common and psychological factors such as anxiety-related traits and coping are significantly associated with its presence.     

Clinical characteristics of generalized idiopathic pruritus in patients from a tertiary referral center in Singapore

BACKGROUND: Generalized idiopathic pruritus is a rarely studied heterogeneous condition, where patients with non-inflamed, non-pathologic skin complain of widespread pruritus. METHODS: We had administered a detailed pruritus questionnaire, based on the short form of the McGill pain questionnaire, on 75 patients with this condition. RESULTS: All 75 patients recruited with generalized idiopathic pruritus completed the questionnaire. In 92% of the patients, pruritus appeared on a daily basis. Most patients experienced pruritus at night (56%) and in the evening (61%) and 69% had difficulty falling asleep. Pruritus mainly involved the legs (79%), arms (76%) and back (68%). Accompanying symptoms were heat sensation (17%) and pain (13%). 80% had been prescribed antihistamines, of whom 56% obtained short-term relief. The sensation of itch has been reported to be crawling (33%), tickling (20%), stinging (19%) and burning (19%). Patients also reported that the itch was unbearable (73%), bothersome (72%), annoying (67%) and worrisome (45%). The worst-state VAS scores were significantly higher in patients who reported agitation (P = 0.006), difficulty in concentration (P= 0.010) and anxiety (P= 0.033). CONCLUSION: This study describes the sensory and affective dimensions of generalized idiopathic pruritus, and this questionnaire has been found to be a useful tool for evaluating pruritus in this condition.     

Efficacy and tolerance of the cream containing structured physiological lipids with endocannabinoids in the treatment of uremic pruritus: a preliminary study

Uremic pruritus is still a common phenomenon in patients with end-stage renal failure, however, there is no effective treatment of choice for this condition. This study was undertaken to evaluate the efficacy and tolerance of the cream with structured physiological lipids (DMS, Derma Membrane Structure) and endogenous cannabinoids in controlling pruritus in patients on maintenance hemodialysis. Twenty-one subjects with uremic pruritus completed the trial. All patients applied the tested cream twice daily for a period of three weeks. Pruritus was evaluated using two pruritus scoring methods: standard visual analog scale (VAS) and a questionnaire method. Moreover, all patients had dry skin scored according to the 5-point scale. Global pruritus and xerosis were examined before the trial, on study visits at weekly intervals, and on follow-up visit performed two weeks of study discontinuation. After 3-week therapy pruritus was completely eliminated in 8 (38.1%) patients. Pruritus evaluation by both scales revealed significant reduction of pruritus scores (p<0.0001) during the tested product application. At the beginning of the trial there was no significant correlation between the intensity of dry skin and severity of pruritus. The 3-week treatment period resulted in complete reduction of xerosis in 17 (81%) patients, while xerosis scores were significantly reduced (p=0.0001) throughout the study period. The test product was very well tolerated by all patients. The test product appeared to be effective in reducing both pruritus and xerosis in hemodialysis patients. It is very probable that the observed decrease of pruritus with the test product therapy was not only the result of dry skin improvement but that the addition of endocannabinoids may have also played a role. These preliminary results are encouraging, however, additional controlled studies are needed to clarify the exact usefulness of this product in therapy of uremic pruritus.     

Peak Pruritus Numerical Rating Scale: psychometric validation and responder definition for assessing itch in moderate-to-severe atopic dermatitis

Atopic dermatitis (AD) is a chronic skin disease occurring in about 5 to 10% of adults worldwide. It can cause intense and persistent itch. For almost two-thirds of patients with moderate-to-severe AD, the itching lasts at least 12 hours a day, and is severe to unbearable. In clinical trials that are looking at how effective a treatment for AD is, itch intensity must be measured. Given itch is subjective, its intensity is most accurately reported by patients themselves. In this study, investigators from the U.S.A. and Europe developed a scale of itch called the Peak Pruritus Numerical Rating Scale (NRS). The scale measures the worst itch (peak pruritus) during the past 24 hours by asking patients “On a scale of 0 to 10, with 0 being ‘no itch’ and 10 being ‘worst itch imaginable’, how would you rate your itch at the worst moment during the previous 24 hours?”. To ensure the scale is reliable and valid (i.e., appropriate for assessing itch in AD patients), patients were interviewed about their opinions of the scale. The scale was then implemented in three large clinical trials of adults with moderate-to-severe AD. Interviewed patients said that the scale provided a relevant, clear, and comprehensive assessment of itch severity. As hypothesized, scores from the Peak Pruritus NRS showed moderate-to-strong correlation with other measures of itch, and weak-to-moderate correlation with measures of AD signs (clinical symptoms). The investigators concluded that the Peak Pruritus NRS is a well-defined, reliable, sensitive, and valid scale for evaluating worst itch intensity in adults with moderate-to-severe AD.     

The incidence of hydroxyethyl starch-associated pruritus

BACKGROUND: Pruritus due to hydroxyethyl starch (HES) is reported with a very variable frequency but appears to be relatively uncommon in the U.K. compared with other European countries. OBJECTIVES: To determine the frequency of HES-related pruritus in patients discharged from intensive care units (ICUs) in two U.K. hospitals. METHODS: A questionnaire survey was given to 253 patients after discharge from ICU. Questions were designed to exclude pre-existing skin disease and other causes of pruritus. RESULTS: One hundred and fifty-nine completed questionnaires were suitable for analysis. Seventeen of 135 (12.6%) subjects who had received HES reported itch, as did one of 24 who had not received HES. There was no apparent relationship between the occurrence of HES-related pruritus and either the surgical indication or the brand or volume of HES infused. CONCLUSIONS: HES-related pruritus is a problem that dermatologists need to recognize; however, its frequency in the U.K., when other causes of itch are excluded, appears to be lower than suggested in some previous reported studies.     

Pruritus as a leading symptom: clinical characteristics and quality of life in German and Ugandan patients

BACKGROUND: Pruritus is the most frequent and distressing symptom associated with dermatoses and various internal and neurological diseases. OBJECTIVES: To investigate two different populations of patients with pruritus, one in Germany and one in Uganda, with a particular focus on clinical characteristics, aetiology and quality of life. METHODS: We investigated by questionnaire 132 patients (59 men, 73 women, mean age 54.5 years) who were referred to the Department of Dermatology at the University Hospital of Magdeburg, Germany, with the diagnosis of pruritus as a leading symptom. The questionnaire was also applied in 84 patients who consulted the Dermatology Clinic at Mbarara, Uganda for pruritus. The questions referred to personal data and disease history of the individual, history and present occurrence of concomitant diseases, present and past therapy, quality, frequency and triggers of itching and scratching, other disorders and complaints, quality of life and impact on work and disability. RESULTS: Seventy-five (57%) of the German patients had pruritus due to dermatoses, 47 patients (36%) had pruritus due to a systemic disease and in 10 patients (8%) pruritus was of unknown origin. Most had a history of pruritus of several months up to years. Pruritus associated with dermatoses mostly affected the whole body and was permanent with an undulatory character. Affective reactions such as aggression and depression occurred more frequently in dermatological patients compared with those with systemic pruritus. The former group felt that pruritus had a greater impact on their lives. Almost all Ugandan patients had pruritus due to dermatoses except for three patients with pruritus of unknown origin. Eczema and prurigo were the most frequently observed dermatoses in both German and Ugandan patients. Patients with pruritus in both populations showed an impaired quality of life. There was no pronounced difference between the populations with regard to feelings of depression and suicidal thoughts. CONCLUSIONS: A great deal of helpful information in this complex group of patients can be obtained using this questionnaire. Pruritus has a major impact on quality of life and especially impairs those patients with pruritus associated with dermatoses and pruritus of unknown origin.     

Uremic pruritus: a clinical study of maintenance hemodialysis patients

Uremic pruritus is one of the most bothersome symptoms in patients with chronic renal failure. Its pathogenesis remains unclear. The aim of this study was to evaluate the frequency of uremic pruritus in hemodialysis patients and to correlate its presence and intensity with several clinical parameters. One hundred thirty patients on maintenance hemodialysis were included into the study. The intensity of pruritus was assessed by two methods: visual analog scale and specially adapted questionnaire scoring method. A significantly positive correlation (p < 0.00001) was demonstrated between the two methods for evaluating pruritus. Uremic pruritus was found in 40.8% of patients. An additional 36.1% of patients reported pruritus to have been present in the past during the renal disease period. Itching was generalized in 19% of patients; the remaining subjects suffered from scattered pruritus (50%) or pruritus in a single location (31%). A significant positive relationship (p < 0.02) was demonstrated between the total score of pruritus and duration of the hemodialysis period. Severity of pruritus and sleep disturbance caused by itching also significantly correlated (p < 0.05) with the duration of hemodialysis. Patients hemodialysed on polysulphone membranes more commonly suffered from pruritus than those on hemophane (p < 0.04) or cuprophane (p < 0.03) dialysis membranes. A marked relationship was demonstrated between the intensity of xerosis and prevalence of pruritus. Significantly more patients with very rough skin had pruritus compared to those with rough skin (p < 0.05) and those with slightly dry skin (p < 0.02). Itching was more common in female patients (p < 0.04), but patient age, underlying renal disease and erythropoietin intake did not correlate with the incidence or intensity of pruritus.     

Pruritus bei systemischen Erkrankungen

Chronic pruritus is a symptom of various internal disorders. In contrast to dermatological diseases, pruritus does not present with primary skin alterations in these patients. However, intense scratching may cause secondary skin changes such as abrasion, excoriation, prurigo nodularis, or in rare cases even scaring. The most common internal medicine causes for chronic pruritus are chronic kidney disease, hepatobiliary and hematological disorders as well as adverse drug reactions. Pruritus is less commonly seen in patients with endocrine or metabolic diseases, malabsorption syndromes, infectious diseases and solid tumors. The pathogenesis of pruritus in these disorders remains largely elusive, albeit preliminary insights have been gained for uremic and cholestatic pruritus. Antipruritic treatment is therefore symptomatic in most cases and may represent a clinical challenge. The calcium channel blockers gabapentin and pregabalin have the best proven efficacy in chronic kidney disease-associated pruritus. In Japan nalfurafine, a κ-opioid receptor agonist, has been licensed for this indication. UVB light may also attenuate uremic symptoms. In patients suffering from hepatobiliary disorders the sequestrant cholestyramine and the enzyme inducer rifampicin are effective. Furthermore, μ?opioid receptor antagonists and sertraline may be used to ameliorate cholestatic pruritus. So far, no randomized controlled trials have been performed for chronic itch in other internal medicine disorders. Antipruritic treatment is mainly based on effective therapy of the underlying disease.     

Renal itch

Renal itch is localized or generalized itch, affecting patients with chronic renal failure, where there is no primary skin disease and no systemic or psychological dysfunction that might cause pruritus. It does not result from raised serum urea levels. The prevalence of renal itch has increased with the growing population in chronic renal failure and is a considerable cause of morbidity. The prevalence of itch increases with deteriorating renal function but does not improve significantly with dialysis. The pruritus is independent of duration of dialysis or cause of renal failure. The aetiology of renal itch is unclear. There is little evidence of a major role for histamine and antihistamines are rarely beneficial. Hyperparathyroidism, abnormal cutaneous innervation and endogenous opioids have been postulated as contributory factors. Treatment of renal itch is difficult. Naltrexone, oral activated charcoal, UVB phototherapy and ondansetron have been shown to be effective. Topical capsaicin may be of benefit in patients with localized pruritus. The definitive treatment for renal itch remains renal transplantation.     

Neuropeptides and their receptors in psoriatic skin in relation to pruritus

BACKGROUND: Pruritus in patients with psoriasis has been reported to be more common than previously thought. OBJECTIVES: To determine the actual prevalence of pruritus in psoriasis according to severity of psoriasis and to verify the hypothesis of involvement of neuropeptides and their receptors in psoriatic pruritus. METHODS: We analysed questionnaire replies from 152 patients with chronic plaque-type psoriasis and we assayed the expression of neuropeptides and their receptors in lesional skin biopsies obtained from psoriatic patients with pruritus compared with those from psoriatic patients without pruritus, nonlesional skin of patients with pruritic psoriasis and normal controls by confocal laser scanning microscopy. RESULTS: Of the 152 patients with psoriasis, 112 (73.7%) had pruritus, and these patients had a higher mean Psoriasis Area and Severity Index (PASI) score than psoriatic patients without pruritus. There was positive correlation between the PASI score and the intensity of pruritus. Keratinocytes in the psoriatic plaques of patients with pruritus showed consistently increased expression of substance P receptor (SPR), high-affinity nerve growth factor receptor (TrkA) and calcitonin gene-related peptide receptor (CGRPR). CONCLUSIONS: Pruritus is a common feature in psoriasis. Considering the well-known roles of neuropeptides in pathogenesis of both psoriasis and pruritus, increased SPR, TrkA and CGRPR may be involved in the pathogenesis of pruritus in psoriasis and in the severity of psoriasis.     

Arterio-venous shunt dermatitis in chronic renal failure patients on maintenance haemodialysis

Seven (8%) of 88 patients in chronic renal failure on chronic haemodialysis had arterio-venous (A-V) shunt dermatitis. All were cumulative insult irritant contact dermatitis from soaps, disinfectants and alcohol used for skin cleansing during haemodialysis. None of the five patients with dermatitis who were patch tested had positive responses. The mean time on haemodialysis in those patients with A-V shunt dermatitis (4 years) was longer than in those patients without dermatitis (3 years). No patient with dermatitis had a history of atopy whereas its prevalence was 19% in patients without dermatitis. A-V shunt dermatitis was commoner in patients with pruritus, a common problem in patients in chronic renal failure requiring haemodialysis (29% in patients with pruritus vs. 17% in patients without pruritus). Four patients with A-V shunt dermatitis responded to treatment with mild topical steroids and substitution of normal saline for skin cleansing prior to haemodialysis.