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.     

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.     

Baseline serum levels of mast cell tryptase are raised in hemodialysis patients and associated with severity of pruritus

Background: The pathogenesis of pruritus in renal disease is not yet understood. Evidence suggests that mast cells play a role; for example, the number of dermal mast cells is increased in patients on hemodialysis. Patients and methods: To investigate a possible role of mast cell tryptase in pruritus of patients undergoing chronic hemodialysis, serum mast cell tryptase concentrations were measured in blood samples taken from 93 such patients, 53 of whom also recorded the severity of their pruritus on a visual analogue scale. Results: Serum mast cell tryptase levels were above 11.4 µg/l (95^th percentile) in 84 of 93 hemodialysis patients (90.3 %). The intensity of pruritus correlated significantly (p = 0.014) with the tryptase levels, an associated not yet shown for other mast cell‐related parameters. Conclusions: Mast cells or even tryptase itself may be involved in the pathogenesis of pruritus of hemodialysis patients.     

Gabapentin for uremic pruritus: a systematic review of randomized controlled trials

Uremic pruritus is one of the most prevalent and bothersome dermatologic symptoms in patients with end-stage renal disease. Some studies suggest a possible neuropathic cause of uremic pruritus. Gabapentin, an anticonvulsant, may control pruritus with neuropathic origin. The objectives of this study were to assess the efficacy of gabapentin in reducing pruritus scores of patients with uremic pruritus and evaluate its safety among dialysis patients. Meta-analysis of randomized controlled trials, using gabapentin as treatment for uremic pruritus among hemodialysis patients was included and analyzed using Review Manager Version 5.1.4 software. Seven out of 17 screened articles were included, with a total of 315 participants. Meta-analysis of the incidence of improved pruritus scores after treatment from four studies (n = 171) showed that treatment with gabapentin decreased the severity of uremic pruritus as compared to the placebo (risk ratio = 0.18; 95% confidence interval: 0.09, 0.33; I² = 4%: P =< 0.00001). Six studies (n = 290) presented with incidence of adverse drug events such as dizziness, drowsiness, and somnolence. In the pooled analysis, treatment with gabapentin was associated with a higher incidence of adverse drug events compared to the comparator drugs, but the results were not significant (risk ratio = 1.3, 95% confidence interval: 0.81, 2.11; P = 0.28, I² = 37%). The results of this systematic review suggest that gabapentin is efficacious and safe in improving uremic pruritus among dialysis patients.     

Itching in patients suffering from psoriasis

Some psoriatic patients suffer from intensive itching, however, literature data on its prevalence and especially on clinical manifestation are very limited. This study was undertaken to evaluate the frequency and clinical characteristics of itching in patients with psoriasis and to correlate the presence and intensity of pruritus with clinical severity of psoriasis. One hundred psoriatic individuals (psoriasis vulgaris in 77% and arthropatic psoriasis in 23%) were included in the study. The severity of psoriasis was assessed according to PASI score. Itching was evaluated using two methods: visual analog scale (VAS) and a specially designed questionnaire method. Itching was found in 80% of psoriatic patients. The severity of psoriasis in pruritic patients was significantly (p<0.004) higher as compared to non-pruritic subjects. Significant correlations were found between PASI scores and intensity of itching, as assessed by both scales: VAS and the questionnaire method (r=0.29, p<0.01 for both analyses). The presence and intensity of itching did not depend on age and gender of patients, type of psoriasis, duration of disease, and last outbreak of psoriasis. Generalized itching was reported by 28.7% of pruritic patients. The most common sites of itching were lower limbs (50%), trunk (48.7%), upper limbs (48.7%) and scalp (35%). Face appeared to be the least commonly affected skin area by itching (only 1.2%). We conclude that itching is a common symptom in patients with psoriasis, and its intensity correlates with clinical severity of the disease.     

Relationship between itch and psychological status of patients with atopic dermatitis

Background Itching is a cardinal symptom of atopic dermatitis (AD). Objective The study aim was to evaluate the relationships between pruritus and stress, health‐related quality of life (HRQoL) and depression in adult patients with AD. Methods Eight‐nine patients (30 men and 59 women) with AD were included. Demographic and clinical data were collected. The intensity of pruritus was assessed according to the 10‐point Visual Analogue Scale (VAS) and the 4‐Item Itch Questionnaire, HRQoL according to Dermatology Life Quality Index, and depression symptoms with Beck’s Depression Inventory (BDI). Stress experienced by patients was evaluated with Social Readjustment Rating Scale and Stress Self‐assessment Scale. Results The mean intensity of pruritus according to VAS was 7.9 ± 2.2 points, and according to 4‐Item Itch Questionnaire 14.0 ± 4.4 points. The intensity of pruritus was related to the stress experienced by the patients prior to disease exacerbation (ρ = 0.37, P < 0.001). A significant correlation between pruritus and HRQoL was also found (VAS: ρ = 0.5, P < 0.001, 4‐Item Itch Questionnaire: ρ = 0.5, P < 0.001) as well as between pruritus and BDI (VAS: ρ = 0.44, P < 0.001, 4‐Item Itch Questionnaire: ρ = 0.51, P < 0.001). Patients with symptoms suggesting depression had more intense pruritus compared with the rest of patients (VAS: 9.1 ± 1.6 vs. 7.6 ± 2.2 points, P = 0.004; 4‐Item Itch Questionnaire: 17.3 ± 2.5 vs. 13.1 ± 4.4 points, P < 0.001). Conclusions Itching intensity in AD plays an important role in determining patients’ psychosocial well‐being. Patients with atopic dermatitis require an effective, long‐term antipruritic therapy to improve their QoL and reduce the potential risk of depression.     

Skin changes in long-term dialysis patients. clinical study

Fifty-one regular hemodialysis patients underwent clinicodermatologic examination. Twenty-three of them were on regular hemodialysis for 2-3 years (group I), 28 patients for more than 8 years (group II). Both groups were matched in regard to primary kidney disease, age, and sex. A characteristic feature found was a marked premature aging of the skin, mainly imposing as actinic elastosis. The incidence was related to the duration of hemodialysis (56.5% of patients of the first group and 100% of patients of the second group). There was also a correlation between time on hemodialysis and an increase of skin pigmentation. Other phenomena like xeroderma, decrease of sebaceous and sweat gland secretion, and Raynaud syndrome were also seen more frequently in the second group, but the extent of these alterations was equal in both groups. Seventy-eight percent of the patients of the first group and 43% of the second group suffered from generalized pruritus. Two different froms of pruritus could be observed, one possibly atopic, only occurring during regular hemodialysis, the other occurring independent of hemodialysis. accumulation of rare phenomena like carpal-tunnel syndrome and Dupuytren's contractures in group II together with the frequent occurrence of actinic elastosis implies systemic disturbance of collagen metabolism in long-term regular hemodialysis patients.     

Quality of life in patients with uraemic xerosis and pruritus

A total of 334 end-stage renal disease patients with moderate-to-severe uraemic xerosis were surveyed for quality of life assessment, using the generic Short-Form (SF-12) scale and the Dermatology Life Quality Index (DLQI). In parallel, the intensity of xerosis at four sites (the two lower legs, chest, forearm without arterio-venous shunt) was assessed, using a five-point lesional intensity score. Pruritus was auto-assessed by the patients, using a 100-mm visual analogue scale. Uraemic xerosis patients had a marked deterioration in the Physical Component Summary of SF-12 (mean?±?SD: 34.92 ± 9.98) and DLQI (5.06?±?4.73). Younger age (r?=?-0.20), xerosis intensity (r?=?0.14), and the presence of pruritus (p?相似文献   

Gabapentin versus dexchlorpheniramine as treatment for uremic pruritus: a randomised controlled trial

Background

Uremic pruritus is acommonsymptom in chronic renal failure patients with undefined pathophysiology. Initial treatment involves topical therapy mainly in the form of moisturizers, however, in many cases, this is not sufficient to relieve itching. Systemic adjuvant therapy is therefore necessary, which commonly includes oral antihistamines, with limited success. Positive effects have been reported for gabapentin.

Objectives

To evaluate the efficacy and safety of gabapentin vs. dexchlorpheniramine in reducing uremic pruritus.

Materials & Methods

A randomized, controlled, double-blinded clinical trial for haemodialysis patients with persistent pruritus was performed. Pre-randomisation, cold cream was used for 15 days by 71 participants. Those with pruritus who remained in the study (60 patients) were randomised to receive gabapentin (30 patients; GABA group) or dexchlorpheniramine (30 patients;DEXgroup) for 21 days. The primary outcomewas the decrease in pruritus score and improvement in quality of life.

Results

After cold cream use, the participants demonstrated a 37.5% median reduction in Visual Analogue Scale (p<0.01) and a 50% reduction in Quality of Life in Dermatology (DLQI) score (p<0.01). There was an additional reduction of pruritus in both groups (p<0.01), with no difference between the two (p>0.7). The median DLQI was reduced from 2 to 1 in the GABA group and from 2 to 0 in the DEX group. Nineteen patients (32%) reported mild/moderate side effects without differences between the groups.

Conclusions

Uremic pruritus was reduced upon treatment with gabapentin or dexchlorpheniramine with good safety profiles; no difference was observed between the two treatments.

     

Stratum corneum hydration in patients undergoing maintenance hemodialysis

Dry-looking skin of unknown etiology develops in a majority of patients with chronic renal failure. The hydration of the stratum corneum influences the appearance of the skin and lack of water is considered to induce roughness, e.g. in atopic dermatitis. The aim of the present study was to compare the water content in uremic and healthy skin and to evaluate the possible relationship between skin hydration and pruritus in uremic patients. Thirty-one patients, 19 with pruritus, undergoing chronic hemodialysis participated. Twelve healthy age-matched subjects served as controls. The skin of the uremic patients appeared generally xerotic, whereas the controls had normal-looking skin. The water content of the stratum corneum was recorded with the Corneometer, a capacitance-measuring device, on three different sites: the neck, the chest and the lower leg. There was a significant difference in water content between locations in all groups, the water content being highest in the neck and lowest in the leg (p less than 0.01). There was a tendency that patients with pruritus had a lower water content than patients without pruritus, but there was no significant difference between uremic patients and controls. Hence, insufficient hydration does not seem to explain the difference in skin texture between uremic patients and healthy subjects.     

Vulvar lichen sclerosus: A single‐center retrospective study in China

Vulvar lichen sclerosus (VLS) is an uncommon, chronic inflammatory skin disease lacking clinical data of large sample size in China. This study was intended to provide missing data on this condition through investigating the clinical characteristics of Chinese VLS patients. The medical records of 129 VLS patients from our vulvar outpatient clinic were analyzed with SPSS version 18.0 software. The age of onset followed a normal distribution, with the peak at 25–30 years. Of all cases, the incidence rate during the postmenopausal period was 14.0% with an average duration of 9.22 years. The most frequently involved site was the bilateral labia minora (71.3%). Itching was the principal symptom (94.6%); meanwhile, patients with severe itching more commonly experienced longer duration, flaring at night, hyperkeratotic lesions or rashes on the posterior commissure than those with mild to moderate itching (P < 0.05). Furthermore, 60% of the enrolled patients suffered from sexual dysfunction. The major sign was pallor (92.2%), followed by hyperkeratosis (55.0%) and atrophy (40.3%). The patients with atrophy had a significantly longer duration of the disease, and the older patients presented more frequently with edema in the area of lesions (both P < 0.05). Of our patients, 9.3% suffered concomitantly from autoimmune diseases, mostly thyroid with one case being complicated by vulvar squamous cell carcinoma (SCC). In our study, the severity of pruritus was partly related to clinical manifestations. Moreover, Chinese patients could have developed VLS mostly in the reproductive period, with less complications of autoimmune diseases or SCC.     

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.     

Polymorphic light eruption sine eruptione

Seven patients, four female and three male, who develop intense pruritus without visible skin changes in light-exposed areas after sun exposure are reviewed. Onset in all cases has been in childhood or adolescence and the condition has persisted indefinitely except in one patient who has been in remission-for I year and one who was in remission for 5 years before relapse. Itching occurs on sun-exposed areas within 45 min to 24 h and lasts for 1–5 days. No patient has taken photosensitizing medications or suffered from any significant systemic illness. There is a positive family history of polymorphic light eruption (PLE) in one, and of sunlight-induced pruritus in another.
Porphyrin studies and antinuclear factor titres are normal. Cutaneous phototesting of the back by monochromator is normal in the UV-B, UV-A and visible light ranges. Irradiation from a xenon arc solar simulator in one patient induced intense pruritus with no visible skin changes on the tested sites of the anterior forearm and back in a time course mimicking that of sun-induced symptoms.
Treatment by sun avoidance, topical sunscreens and antihistamines has been only partially effective.
Two patients have subsequently developed occasional typical PLE upon sun exposure, but sun-induced pruritus alone occurs most frequently. This suggests that polymorphic light eruption sine eruptione is a variant of PLE and, to our knowledge, is the first report of this condition.     

Skin mast cells in polycythaemia vera relationship to the pathogenesis and treatment of pruritus

We have measured skin mast cell numbers, circulating basophils and whole blood histamine in 13 patients with polycythaemia vera. Itching was present in nine cases and correlated well with the numbers of skin mast cells but not with circulating basophils or whole blood histamine. Immediate relief of pruritus was achieved with aspirin, and myelosuppressive therapy was useful for long-term control of symptoms. Neither histamine (H1 or H2) antagonists nor iron replacement therapy were effective forms of treatment. The findings suggest that mast cell prostaglandins are an important factor in the pathogenesis of pruritus and that local vascular responses may trigger mast cell degranulation.     

Cutaneous manifestations in patients with chronic renal failure on hemodialysis

BACKGROUND: Chronic renal failure (CRF) presents with an array of cutaneous manifestations. Newer changes are being described since the advent of hemodialysis, which prolongs the life expectancy, giving time for these changes to manifest. AIM: The aim of this study was to evaluate the prevalence of dermatologic problems among patients with chronic renal failure (CRF) undergoing hemodialysis. METHODS: One hundred patients with CRF on hemodialysis were examined for cutaneous changes. RESULTS: Eighty-two per cent patients complained of some skin problem. However, on examination, all patients had at least one skin lesion attributable to CRF. The most prevalent finding was xerosis (79%), followed by pallor (60%), pruritus (53%) and cutaneous pigmentation (43%). Other cutaneous manifestations included Kyrle's disease (21%); fungal (30%), bacterial (13%) and viral (12%) infections; uremic frost (3%); purpura (9%); gynecomastia (1%); and dermatitis (2%). The nail changes included half and half nail (21%), koilonychia (18%), onychomycosis (19%), subungual hyperkeratosis (12%), onycholysis (10%), splinter hemorrhages (5%), Mees' lines (7%), Muehrcke's lines (5%) and Beau's lines (2%). Hair changes included sparse body hair (30%), sparse scalp hair (11%) and brittle and lusterless hair (16%). Oral changes included macroglossia with teeth markings (35%), xerostomia (31%), ulcerative stomatitis (29%), angular cheilitis (12%) and uremic breath (8%). Some rare manifestations of CRF like uremic frost, gynecomastia and pseudo-Kaposi's sarcoma were also observed. CONCLUSIONS: CRF is associated with a complex array of cutaneous manifestations caused either by the disease or by treatment. The commonest are xerosis and pruritus and the early recognition of cutaneous signs can relieve suffering and decrease morbidity.     

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.     

Behandlung von Pruritus als Symptom von Hauterkrankungen mit dem Serotonin‐Rezeptorantagonisten Ondansetron

Background: Pruritus is often a stressing symptom and a therapeutic challenge. We report our experience with the serotonin receptor antagonist ondansetron in the symptomatic treatment of pruritus accompanying various skin diseases. Patients and Methods: The influence of ondansetron (8 – 12 mg orally per day) on pruritus was assessed in twelve patients with various skin disorders. The intensity of pruritus was quantitated daily by a visual analogue scale over the time period of one week before, during, and one week after treatment. Results: Ondansetron decreased pruritus intensity in prurigo simplex (four patients), asteatotic eczema (two patients), parapsoriasis en plaques, and pruritus of unknown origin (one patient each). One of two patients with atopic dermatitis experienced relief, whereas no benefit was observed in urticaria factitia and notalgia paraesthetica (one patient each). Conclusions: Ondansetron may ameliorate the concomitant pruritus of some dermatologic diseases.     

维持性血液透析终末期肾病患者皮肤病变调查分析

目的　调查进行维持性血液透析（maintenance hemodialysis, MHD）的终末期肾脏病患者皮肤病变的发病情况和病变特点，探讨其危险因素。方法　对181例MHD的终末期肾病患者进行皮肤体检；收集其临床和生化资料，分析皮肤病变的患病率，病变类型及其危险因素。结果　 ①181例患者中161例（88.95％）存在不同种类的皮肤病变，其中38例（23.60％）存在1种皮肤病变，52例（32.30％）有2种，40例（24.84％）有3种、26例（16.15％）有4种、5例（3.11％）有5种。②最常见是皮肤干燥（128/181， 77.72％），其次是瘙痒（101/181，55.80％）、脱屑（73/181，40.33％）和色素沉着（70/181，38.67％）。其他有皮肤苍白（6/181，3.31％）、瘀斑（4/181，2.21％）、指（趾）干性坏疽（3/181，1.66％）、足部溃疡（2/181，1.10％）、甲纵裂（1/181，0.55％）。③皮肤病变组患者的透析龄、超滤量、血磷、钙磷乘积、甲状旁腺激素、超敏C-反应蛋白（Hs-CRP）水平，乙肝、丙肝病毒标志物阳性率明显高于无皮肤病变组；而血红蛋白、血清尿素清除指数（Kt/V）明显低于无皮肤病变组。④Logistic回归分析结果显示，透析龄、KT/V、血钙磷乘积、血甲状旁腺激素、高敏C反应蛋白（Hs-CRP）和丙肝病毒标志物阳性是MHD患者发生皮肤病变的独立危险因素。结论MHD的终末期肾病患者皮肤病变的患病率高，以皮肤干燥症和皮肤瘙痒最常见。透析龄、KT/V、血钙磷乘积、血甲状旁腺激素、Hs-CRP和丙肝病毒标志物阳性是MHD终末期肾病患者发生皮肤病变的独立危险因素。