An epidemiology study of patients with uremic pruritus

BACKGROUND: Pruritus is a common problem in continuous ambulatory peritoneal dialysis (CAPD) and haemodialysis patients. There are few studies on the clinical characteristics of uremic itch, the cause of which is still unknown. OBJECTIVES: The aim of this study was to define the prevalence and clinical characteristics of pruritus in CAPD and haemodialysis patients. METHODS: A questionnaire was used to evaluate pruritus in 52 CAPD and 289 haemodialysis patients in two dialysis units. The relationship of various factors and medical parameters to itch was examined. RESULTS: Of the 341 patients, 177 (51.9%) had pruritus at the time of examination, 97 (28.4%) had pruritus in the past. Pruritus was present in 145 (50.2%) of the haemodialysis patients and 32 (61.5%) of the CAPD patients. Men, patients with liver disease, and patients with pruritus before starting dialysis treatment were more likely to have uremic pruritus. CONCLUSIONS: This study showed us that uremic pruritus was observed more in men than women. The high prevalence of uremic pruritus in our study does not support the decrease of pruritus due to an improvement in the management of dialysis patients.     

A comparative study on the effects of naltrexone and loratadine on uremic pruritus

BACKGROUND: Two recent studies have provided opposite results on the efficacy of naltrexone on uremic pruritus. We have performed a third study. OBJECTIVE: To compare the efficacy and tolerance of naltrexone and loratadine in uremic pruritus. PATIENTS/METHODS: Among 296 hemodialyzed patients, 65 suffered from uremic pruritus. Fifty-two patients participated in the study. The patients were treated for 2 weeks with naltrexone (50 mg/day; 26 patients) or loratadine (10 mg/day; 26 patients), after a washout of 48 h. Pruritus intensity was scored by a visual analogue scale (VAS). Adverse events were carefully searched for. The two groups were statistically equivalent. RESULTS: There was no significant difference in the mean VAS scores after treatment, but naltrexone allowed a dramatic decrease in VAS scores (Delta >3/10) in 7 patients. Adverse events (mainly nausea and sleep disturbances) were observed in 10/26 patients. CONCLUSIONS: Naltrexone is effective only in a subset of patients. Adverse events are very frequent. The differences of efficacy and tolerance between patients might be due to metabolism. Naltrexone might be considered as a second-line treatment.     

尿毒症患者皮肤屏障功能改变及含青刺果油保湿霜治疗尿毒症瘙痒疗效观察

目的:探讨尿毒症瘙痒患者皮肤屏障功能改变及研究含青刺果油保湿霜对治疗尿毒症瘙痒的有效性及安全性。方法:分别测量60例尿毒症瘙痒患者(UP+组)、60例尿毒症无瘙痒的患者(UP-组)及30名健康人(HV组)胸前V形区、季肋区、前臂屈侧及小腿伸侧皮肤角质层含水量(SCH)、经皮失水率(TEWL)及酸碱度(p H)并分别进行问卷调查、干燥评分(XS)及尿毒症瘙痒评分(UIS)。随机将UP+组分为试验组及对照组,试验组予含青刺果油保湿霜治疗28d,对照组不给予干预。于D0、D28进行皮肤病生活质量评分(DLQI)。于D0、D7、D14及D28对受试者进行XS、UIS及SCH、TEWL及皮肤p H值测量。结果:UP+组及UP-组测SCH均显著低于健康人群(P<0.01)。UP+组胸前V形区、季肋区、小腿伸侧TEWL较健康人群显著升高(P<0.05)。UP+组胸前V形区及小腿伸侧皮肤p H值高于HV组(P<0.05)。尿毒症患者发生UP与TEWL呈正相关(P<0.001)。皮肤瘙痒程度与干燥程度呈正相关(P<0.001),糖尿病加重瘙痒程度(P=0.011)。试验组受...     

Some aspects of the experimental induction and measurement of itch

Two different rating scales--a visual analogue scale (VAS) connected to a chart-recorder, and Pain-Track, a micro-computerized system with a 7-step-graded, fixed-point, non-verbal scale (FPNVS)--were evaluated for their capacity to assess experimental, histamine-induced itch continuously in 38 healthy subjects. The consequences for itch perception of using different injection sequences of various histamine concentrations were also investigated. A linear dose-response relationship was shown with random injection order for all subjective variables studied (itch latency and duration, maximal itch intensity, 'total itch index') with the VAS, but only for itch duration and 'total itch index' with the FPNVS. Using the VAS and injecting histamine solutions with increasing concentration, a significant dose-response curve was obtained for maximal itch intensity and 'total itch index', but when the same histamine stimuli were presented in the reverse (i.e. decreasing) order, there was no dose-response relationship. This indicates that central nervous system interaction may be unequally activated, depending on the order of different injected histamine stimuli. The objective variable flare was unaffected by the injection sequence. It is concluded that random injection order should be used in the assessment of itch sensation, in order to avoid systematic errors. The fact that the FPNVS did not discriminate as well as the VAS could indicate that our experimental stimuli were too weak to be properly discriminated with a 7-step-graded scale.     

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.     

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.     

Doxepin affects acetylcholine induced cutaneous reactions in atopic eczema

BACKGROUND: Atopic eczema (AE) is a chronic inflammatory skin disease with strong itching as the prominent symptom. The pathology of itch is still in discussion, but acetylcholine (ACH) seems to be a relevant pruritogenic mediator in AE. Since efficient benefit on pruritus and excoriations has been demonstrated with tricyclic agents, we investigated how the topical treatment with doxepin (5%, Boehringer Standard, Mannheim, Germany), a tricyclic compound with anticholinergic properties, may influence ACH induced itch and cutaneous sensations (erythema, wheal, axonreflex flare). METHODS: Eleven patients with AE were included in this double blind study. For 3 days we applied doxepin cream to a defined area on the volar forearm and basic ointment to the other side 4 times daily. On day 4, ACH and sodium chloride were i.c. injected into the pretreated arms. Vasoreactions and cutaneous sensations were measured similar to studies described in previous publications from our group. RESULTS: Doxepin treatment over 3 days reduced ACH provoked flare size more than 53% (P<0.005) and wheal size about 48% (P<0.005) whereas the maximal antipruritic effect was similiar to the basic therapy. The itch intensity, which is expressed as the mean AUC value, was rated at 6.12 arbitrary units after the neutral cream application and 5.9 arbitrary units after doxepin. CONCLUSIONS: The clinical and experimental effectiveness of doxepin as an antipruritic drug has been known for years. However, studies focusing on ACH as a pruritogenic mediator have not been performed. The duration of the doxepin application in our study seems to be appropriate since flare and wheal development were diminished. The reason why doxepin did not develop more antipruritic action compared to the vehicle cream may be due to the fact that the doxepin free cream already possessed an antipruritic action in this experimental study design. This is probably caused by rehydrating and moisturizing effects.     

The sensitivity of uremic and normal human skin to histamine

Cutaneous reactions induced by intradermal histamine injection were studied in uremic patients with and without pruritus who were undergoing maintenance hemodialysis and also in healthy subjects. Flare reactions were significantly smaller in both groups of patients than in controls. However, the itch responses following histamine injection were greater in patients with pruritus than in non-pruritic patients and healthy subjects, indicating an augmented sensitivity to pruritogens in these patients. The development of histamine tachyphylaxis was demonstrated in healthy human skin. After repeated histamine injections at intervals of 90 min, both itch and flare responses decreased rapidly. A similar decline in histamine reactivity occurred when the interval between injections was extended to 24 h. The phenomenon of histamine tolerance was confirmed in 2 uremic patients.     

Cholestatischer Pruritus

Pruritus is a common symptom of hepatobiliary disorders and may considerably diminish quality of life. Cholestatic pruritus exerts a circadian rhythm and is typically most severe in the evening hours and early at night. Itching is reported often to be most intense at the palms and the soles, but may also be generalized. The pathophysiological mechanisms of cholestatic pruritus have not been completely clarified. In the past, bile salts, histamine, progesterone metabolites and opioids have been discussed as potential causal substances; a correlation with itch intensity could never be proven. The enzyme autotaxin, which releases lysophosphatidic acid, has recently been identified as potential cholestatic pruritogen. Treatment aims to bind pruritogens in the gut lumen by resins such as cholestyramine, to modulate pruritogen metabolism by rifampicin and to influence central itch signaling by μ-opioid antagonists and selective serotonin re-uptake inhibitors. In cases of refractory pruritus experimental treatment options such as UV-therapy, extracorporeal albumin dialysis and nasobiliary drainage may be considered.     

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.     

Elevated Plasma Histamine in Chronic Uremia Effects of Ketotifen on Pruritus

A role for histamine in the pathogenesis of uremic pruritus was investigated in maintenance hemodialysis patients. Venous plasma histamine levels, as determined by radioenzymatic assay, were significantly higher (p less than 0.05) in hemodialysis patients with pruritus (368 +/- 103 pg/ml [mean +/- SEM], n = 6) than in those without pruritus (146 +/- 22 pg/ml, n = 5) and in normal controls (142 +/- 16, n = 5). Arteriovenous fistula histamine levels (202 +/- 52 pg/ml, n = 6) were significantly lower (p less than 0.05) than simultaneously drawn venous samples. Markedly elevated histamine-degrading enzyme (histaminase) activities were found in both hemodialysis patients with (2.95 +/- 0.18 pg histamine degraded/minute) and without (2.44 +/- 0.28) pruritus, but was undetectable in normal controls. Histaminase activities did not significantly differ in simultaneously drawn venous and fistula samples. With hemodialysis, histaminase activities fell significantly (p less than 0.01), whereas plasma histamine did not change. We further examined the effects of ketotifen, a putative mast cell stabilizer, on severe uremic pruritus. Five of five patients had significant (p less than 0.01) reductions in pruritus, as judged on a six-point pruritus index, after 8 weeks of drug (x = 2.3), as compared to conventional therapy (x = 5.9). Despite these improvements, no significant differences were noted in pre- versus post-drug plasma histamine levels, histaminase activities, or the histamine content per gram of skin biopsy specimen. These data support prior hypotheses that mast cell activation contributes to the pruritus of uremia.     

Density of mast cells and intensity of pruritus in psoriasis vulgaris: a cross sectional study

Background:Psoriasis is a chronic and prevalent disease, and the associated pruritus is a common, difficult-to-control symptom. The mediators involved in psoriatic pruritus have not been fully established.Objective:To evaluate associations between the number of mast cells in psoriatic lesions and the intensity of pruritus.Methods:29 patients with plaque psoriasis were recruited. In all participants, Psoriasis Area and Severity Index and Body Surface Area were assessed. A questionnaire was administered to obtain clinical information and the Dermatology Life Quality Index. Pruritus was assessed using a visual analog scale and skin biopsies were performed for staining with Giemsa and Immunohistochemistry with C-Kit.Results:Pruritus was observed in 91.3% of our patients. Median VAS was 6 (p25-75: 2-8). The immunohistochemical method revealed a mean of 11.32 mast cells/field and Giemsa staining revealed a mean of 6.72 mast cells/field. There was no correlation between the intensity of pruritus and mast cell count, neither in Immunohistochemistry (p = 0.15; rho = -0.27) nor in Giemsa (p = 0.16; rho = -0.27). Pruritus did not impact on the Dermatology Life Quality Index (p = 0.51; rho = -0.13).Study limitations:The small sample size may be considered the main limitation of our study.Conclusions:Although mast cells are mediators of pruritus in many cutaneous diseases, our findings support that psoriatic pruritus is a complex disorder with multifactorial, complex pathophysiology, involving pruritogenic mediators others than mast cells.     

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.     

Anti pruritic effects of topical crotamiton, capsaicin, and a corticosteroid on pruritogen-induced scratching behavior

Itch accompanies various skin diseases. As a number of mediators other than histamine can be involved in the itch sensation, H1 receptor antagonists are not necessarily effective in treating itch. External application of antipruritic drugs is occasionally used as an alternative therapy for pruritic skin conditions, such as pruritus on primary non-diseased, non-inflamed skin. Even so, the actual effects of these drugs on the itch sensation have yet to be studied in detail. To verify the antipruritic effects of crotamiton, capsaicin, and a corticosteroid on the itch sensation, we examined the inhibitory effects of these drugs on various pruritogen-induced scratching behaviors in mice. Topical application of 10% crotamiton moderately inhibited histamine-, serotonin-, and PAR-2 agonist-induced scratching behaviors. Topical capsaicin (0.025%) also exerted a moderate suppressive effect on histamine-, substance P-, and PAR-2 agonist-induced itch responses. Notably, topical corticosteroid (0.05% clobetasol propionate) remarkably inhibited the scratching behaviors induced by all of the pruritogenic agents tested. Therapeutic effects of capsaicin on substance P-induced pruritus did not seem to be mediated by desensitization of the TRPV1 (+) C fibers and/or by altered responsiveness of the mast cells. In addition, the antipruritic effects of crotamiton and corticosteroid appear to be, at least partly, associated with a TRPV1-independent pathway. This study examined the itch responses to pruritogens and demonstrated the mode of action of the externally applied antipruritic drugs.     

The antipruritic effect of a sedative and a non-sedative antihistamine in atopic dermatitis

A double-blind, randomized, cross-over study was carried out on the effect of a sedative and a non-sedative antihistamine on 25 adults with atopic dermatitis. Intensity of itch was recorded using a computerized method for self-assessment (Pain-Track) and using conventional visual analogue scales. The antipruritic effect of 3 days of treatment with the non-sedative H1 antagonist terfenadine (60 mg b.i.d.) and with the sedative antihistamine, clemastine (2 mg b.i.d.) did not differ from that found with the placebo. Our findings support the view that histamine is not of importance in the pathogenesis of itch in atopic dermatitis.     

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.     

Assessment of pruritus intensity: prospective study on validity and reliability of the visual analogue scale, numerical rating scale and verbal rating scale in 471 patients with chronic pruritus

The most commonly used tool for self-report of pruritus intensity is the visual analogue scale (VAS). Similar tools are the numerical rating scale (NRS) and verbal rating scale (VRS). In the present study, initiated by the International Forum for the Study of Itch assessing reliability of these tools, 471 randomly selected patients with chronic itch (200 males, 271 females, mean age 58.44 years) recorded their pruritus intensity on VAS (100-mm line), NRS (0-10) and VRS (four-point) scales. Re-test reliability was analysed in a subgroup of 250 patients after one hour. Statistical analysis showed a high reliability and concurrent validity (r>0.8; p<0.01) for all tools. Mean values of all scales showed a high correlation. In conclusion, high reliability and concurrent validity was found for VAS, NRS and VRS. On re-test, higher correlation and less missing values were observed. A training session before starting a clinical trial is recommended.     

曲安奈德联合点阵CO2激光治疗增生性瘢痕的疗效观察

目的探讨曲安奈德(TA)联合点阵CO₂激光治疗增生性瘢痕(HS)的临床疗效。方法选取2015年7月-2018年8月收治的80例HS患者,随机数字表法分为TA组(瘢痕内注射TA治疗)和联合组(瘢痕内注射TA联合点阵CO₂激光治疗)。对比两组治疗前后温哥华瘢痕量表(VSS)、视觉模拟疼痛量表(VAS)、瘙痒评分;对比两组临床疗效,采用列联表分析瘢痕面积与临床疗效的相关性;对比两组治疗前后血清VEGF、TGF-β1水平及不良反应发生率、满意度、复发率。结果治疗前两组VSS、VAS和瘙痒评分比较,差异无统计学意义(P>0.05);与治疗前比较,治疗后两组VSS、VAS和瘙痒评分降低,且联合组低于TA组(P<0.05);联合组临床有效率(97.50%)高于TA组(82.50%)(P<0.05),瘢痕面积与临床疗效有相关性(P<0.05);联合组不良反应发生率(10.00%)低于TA组(25.00%),满意度(92.50%)高于TA组(77.50%)(P<0.05);两组复发率比较,差异无统计学意义(P>0.05)。结论TA联合点阵CO₂激光可有效抑制瘢痕增生,疗效确切,不良反应少,患者满意度高。