[Efficacy of colchicine in the treatment of pruritus; hepatic pruritus and puritis in lymphosarcoma].
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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.
About, 22 cases with pruritus and 18 cases without pruritus of obstructive jaundice, serum bile acids were analysed quantitatively by high performance liquid chromatography (HPLC) before and after biliary decompression for the study on the relationship between pruritus and non-pruritus group. Analysis was also carried out on 11 cases with normal liver function as the control group. And 15 kinds of bile acids were as followed: unconjugates (ursodeoxycholic: UDCA, cholic: CA, chenodeoxycholic: CDCA, deoxycholic: DCA, lithocholic acid: LCA), glycine conjugates (Gly-UDCA, Gly-CA, Gly-CDCA, Gly-DCA, Gly-LCA) and taurine conjugates (Tau-UDCA, Tau-CA, Tau-CDCA, Tau-DCA, Tau-LCA). Data was analysed by t-test statistically. [I] Before biliary decompression (1) No significant difference was observed between the pruritus group and non-pruritus group about total bile acid level, total unconjugates level and CA/CDCA ratio. (2) On total glycine-conjugates level the pruritus group was significantly lower than the non-pruritus group, that level was about 3/5. Similarly on Gly-CA level was about 2/3, on Gly-CDCA level was about 1/2. (3) By contraries on total taurine-conjugates level the pruritus group was significantly high as compared with the non-pruritus group, that level was about two times. Similarly on Tau-CA and Tau-CDCA levels were about two times. (4) From there results on glycine/taurine ratio (G/T) of total bile acids pruritus group was significantly low as compared with the non-pruritus group, that level was about 1/3. Similarly on G/T ratio of CA level was about 2/5 and on G/T ratio of CDCA was about 1/3. (5) As for various unconjugates, UDCA level was significantly high in pruritus group as compared with non-pruritus group. [II] After biliary decompression No significant difference was shown in the composition of serum bile acids between the pruritus group and the non-pruritus group. These studies showed that the pruritus in the obstructive jaundice cases stood in a certain relation to the increase of taurine-conjugates, especially taurine-conjugated CA and taurine-conjugated CDCA, moreover increase of unconjugated UDCA.
Pruritus is a common, unpleasant symptom of uremic patients. Serotonin and histamine have been reported as possible mediators ofuremic pruritus, and ondansetron is a potent and selective inhibitor of 5-HT3 receptors. The aims of our study were (1) to evaluate the effect of ondansetron on uremic pruritus in continuous ambulatory peritoneal dialysis (CAPD) patients and its safety and (2) to investigate the role of histamine and serotonin in uremic pruritus. To study the prevalence and pathogenesis of uremic pruritus, CAPD and hemodialysis (HD) patients were asked to complete a pruritus questionnaire. The replies were scored based on numerical scales, and the results were evaluated by the same investigator who did not know the patients. Pruritus was graded, according to the total points for each patient, as mild, moderate, or severe. Of 54 patients on HD, 29 (53.7%) had pruritus, and of 43 patients on CAPD, pruritus was present in 21 (48.8%). In HD patients, pruritus was mild in 14 (48.3%), moderate in 12 (41.4%), and severe in 3 (10.3%) patients; the distribution in CAPD patients was 9 (42.9%), 10 (47.6%), and 2 (9.5%), respectively. There was no correlation between the presence and severity of pruritus and age, sex, primary renal disease, duration of dialysis, dialysis solutions used, and hematological and biochemical parameters except for serum histamine and serotonin levels and their product. Plasma histamine levels in CAPD patients were 13.1 +/- 1.1 ng/ml in pruritic and 11.0 +/- 3.9 ng/ml in nonpruritic patients (p = 0.06), serum serotonin levels were 115.6 +/- 43.3 ng/ml and 64 +/- 42.3 ng/ml (p < 0.05), respectively, and the histamine x serotonin product was 1,461 +/- 576 and 646 +/- 545 (p < 0.01), respectively. Eleven CAPD patients (6 males, 5 females) with a mean age of 66 (range 33-83) years and an average time on CAPD of 18 (range 3-31) months with moderate to severe pruritus were treated with ondansetron (4 mg twice daily p.o.) for a mean period of 3 (range 1-5) months. All patients responded to the treatment. There was a significant reduction of the severity of pruritus from the start of treatment, and on the 3rd day the pruritic score (mean value) was 10 (range 5-19) points, while at time 0 (before treatment) it was 26 (range 19-37) points (p < 0.0001). Pruritus disappeared in 7 patients at the end of the 1st week and in all patients at the end of the 2nd week of treatment. This effect was maintained during the study. Plasma histamine levels decreased significantly during the treatment from 12.9 +/- 1.2 to 6.7 +/- 5.9 ng/ml (p < 0.05). Also, serum serotonin levels were reduced from 125.1 +/- 47.8 to 59.3 +/- 27.5 ng/ml (p < 0.05) at the end of the 1st month of treatment, and the histamine x serotonin product showed a more significant reduction: from 1,544 +/- 656 to 454 +/- 436 (p < 0.01). Three patients reported an improvement in their nausea and vomiting during the treatment. Weekly clinical and laboratory examinations showed no side effects, adverse reactions, or other complications. Our data indicate that ondansetron is an effective, safe, and well-tolerated drug for the treatment of uremic pruritus in CAPD patients and that histamine and serotonin may have a crucial role in the appearance or perception of the uremic pruritus.
BACKGROUND: The pathophysiologic aspects of pruritus in patients with chronic renal insufficiency are poorly understood, and there is no universally effective treatment. The improvement of pruritus in several patients receiving erythropoietin therapy raised the possibility that erythropoietin affects uremic pruritus directly. METHODS: We undertook a 10-week placebo-controlled, double-blind, crossover study in a group of patients receiving hemodialysis who had severe pruritus, to investigate the effects of recombinant human erythropoietin on their pruritus and plasma histamine levels. Twenty patients with uremia, of whom 10 had severe pruritus and 10 did not, received erythropoietin (36 units per kilogram of body weight three times weekly) and placebo in random order, each for five weeks. The severity of pruritus was scored weekly, and plasma histamine levels were measured at the beginning and end of each five-week period. RESULTS: Eight of the 10 patients with pruritus had marked reductions in their pruritus scores during erythropoietin therapy. The mean (+/- SE) pruritus score decreased from 25 +/- 3 to 6 +/- 1 in these patients. The pruritus returned within one week after the discontinuation of therapy. The improvement was not related to the change in hemoglobin level. These eight patients were successfully treated again with low doses of erythropoietin (18 units per kilogram three times weekly), and the effect has persisted for six months. The patients with pruritus had elevated plasma histamine concentrations (20.7 +/- 2.7 nmol per liter), as compared with the patients without pruritus (4.2 +/- 0.6 nmol per liter; P less than 0.001) and normal subjects (2.1 +/- 0.2 nmol per liter; P less than 0.001). Therapy with erythropoietin induced a decrease in plasma histamine concentrations in both groups of patients with uremia, and recurrences of pruritus after the discontinuation of erythropoietin were accompanied by increases in plasma histamine concentrations. CONCLUSIONS: Erythropoietin therapy lowers plasma histamine concentrations in patients with uremia and can result in marked improvement of pruritus.
BACKGROUND: Although a close relationship between uraemic pruritus and serum calcium levels has been demonstrated for some time, the degree of pruritus was not always correlated with calcium concentrations. In the present study, we assessed calcium ion distribution in the skin of chronic haemodialysis patients with and without pruritus. METHODS: We excluded patients with concomitant psoriasis or atopic dermatitis or with a previous history of allergy, those who had an arteriovenous fistula created prior to induction of haemodialysis, and patients with only mild pruritus. From the enrolled 22 haemodialysis patients, we obtained forearm skin samples during arteriovenous fistula surgery. These patients were divided into two groups based their grade of pruritus. The pruritus group included patients with moderate to severe grades of pruritus (n = 11, age 64 +/-13 years) and the non-pruritus group consisted of patients without pruritus (n = 11, age 59 +/-13 years). We compared the distribution of calcium ions in the epidermis between the two groups using the ion-capture method (oxalate-pyroantimonate-osmium technique). In addition, we examined and compared the groups for thicknesses of the basal, spinous and granular layers, as well as of the stratum corneum using an electron microscope. RESULTS: The pruritus group had significantly higher calcium ion deposition in the extracellular fluid and cytoplasm of basal cells, and in the extracellular fluid, nuclei and cytoplasm of spinous cells compared with the non-pruritus group. In contrast, calcium ion depositions were similar between the two groups in the dermis/basal layer interface, the nucleus of basal cells, the nucleus and cytoplasm of granular cells, exterior of granular cells, the granular cells/stratum corneum interface, and in the interior and exterior of corneocytes. Although the stratum corneum was significantly thicker in the pruritus group than in the non-pruritus group, there were no differences in basal cell, spinal cell or granular cell layer thicknesses. CONCLUSION: In chronic haemodialysis patients with pruritus, the calcium ion concentration in the deepest layer of the epidermis was increased, which indicated a disrupted calcium ion gradient in the skin. These findings point to a role for increased skin calcium ion concentrations in the development and/or maintenance of uraemic pruritus. However, more extensive studies in larger patient cohorts will be necessary to confirm this hypothesis.
OBJECTIVES: Generalized pruritus is a common complication of cholestatic liver diseases, although its pathogenesis remains elusive. Current treatments are often inadequate and may be poorly tolerated, so the clinician is sometimes faced with a patient in misery and no good therapeutic options. Because, in our experience, several patients with primary biliary cirrhosis (PBC) claimed that sertraline had improved their pruritus, we sought to determine whether sertraline use was associated with changes in pruritus medications or self-reported severity of pruritus in a large cohort of patients with PBC. METHODS: The self-reported severity of pruritus was followed prospectively in 40 patients with PBC for a mean of 7.5 +/- 1.3 yr. These data were then retrospectively examined to determine the effect of sertraline on pruritus in all subjects who had received sertraline at some time during the study. RESULTS: For 28 of 32 patients with pruritus, itching was stable or fluctuated slightly over the follow-up period. No patient experienced rapid progression of pruritus, and four patients experienced a sustained resolution of their pruritus. Ten subjects started sertraline and continued it long enough (>6 months) to determine its lasting effect on pruritus. Three of these individuals did not have significant pruritus before or after sertraline. Of the seven patients with pruritus, six (86%) recorded a significant reduction or resolution of pruritus in their weekly diaries and also decreased or completely stopped other medications for pruritus. CONCLUSIONS: Sertraline use is associated with an improvement in cholestatic pruritus. This novel observation implies that serotonergic fibers are important in regulating the perception of itch.
BACKGROUND: Pruritus affects many haemodialysis (HD) patients. In this study, pruritus and its relationship to morbidity, mortality, quality of life (QoL), sleep quality and patient laboratory measures were analysed in >300 dialysis units in 12 countries. METHODS: Pruritus data were collected from 18 801 HD patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS) (1996-2004). Analyses were adjusted for age, gender, black race, Kt/V, haemoglobin, serum albumin, albumin-corrected serum calcium, serum phosphorus, 13 comorbidities, depression, years on dialysis, country and facility clustering effects. RESULTS: Moderate to extreme pruritus was experienced by 42% of prevalent HD patients in DOPPS during 2002/2003. Many patient characteristics were significantly associated with pruritus, but this did not explain the large differences in pruritus between countries (ranging from 36% in France to 50% in the UK) and between facilities (5-75%). Pruritus was slightly less common in patients starting HD than in patients on dialysis >3 months. Pruritus in new end-stage renal disease (ESRD) patients likely results from pre-existing conditions and not haemodialysis per se, indicating the need to understand development of pruritus before ESRD. Patients with moderate to extreme pruritus were more likely to feel drained [adjusted odds ratio (AOR) = 2.3-5.2, P < 0.0001] and to have poor sleep quality (AOR = 1.9-4.1, P < or = 0.0002), physician-diagnosed depression (AOR = 1.3-1.7, P < or = 0.004), and QoL mental and physical composite scores 3.1-8.6 points lower (P < 0.0001) than patients with no/mild pruritus. Pruritus in HD patients was associated with a 17% higher mortality risk (P < 0.0001), which was no longer significant after adjusting for sleep quality measures. CONCLUSIONS: The pruritus/mortality relationship may be substantially attributed to poor sleep quality. The many poor outcomes associated with pruritus underscore the need for better therapeutic agents to provide relief for the 40-50% of HD patients affected by pruritus.
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.