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PubMed2006

Effect of oral naltrexone on pruritus in cholestatic patients.

AIM: To determine the efficacy and potential complications of oral naltrexone used in the treatment of pruritus in cholestatic patients and to compare them with other studies. METHODS: Thirty-four enrolled cholestatic patients complaining of pruritus were studied. In the initial phase, pruritus scores during day and night were evaluated. Subsequently, patients were given a placebo for one week followed by naltrexone for one week. In each therapeutic course (placebo or naltrexone) day and night pruritus scores were distinguished by a visual analogue scale (VAS) system and recorded in patients' questionnaires. RESULTS: Both naltrexone and placebo decreased VAS scores significantly. Naltrexone was more effective than placebo in decreasing VAS scores. Both day and night scores of pruritus decreased by half of the value prior to therapy in thirteen patients (38%). Daytime pruritus improved completely in two patients (5.9%), but no improvement in the nighttime values was observed in any patient. Sixteen patients (47%) suffered from naltrexone complications, eleven (32%) of them were related to its withdrawal. Complications were often mild. In the case of withdrawal, the complication was transient (within the first 24-28 h of therapy) and self-limited. We had to cease the drug in two cases (5.9%) because of severe withdrawal symptoms. CONCLUSION: Naltrexone can be used in the treatment of pruritus in cholestatic patients and is a safe drug showing few, mild and self-limited complications.

Administration, Oral↗
PubMed1995

Effects of naloxone infusions in patients with the pruritus of cholestasis. A double-blind, randomized, controlled trial.

OBJECTIVE: To determine whether endogenous opioids contribute to the pruritus of cholestasis by studying the effect of the opiate antagonist naloxone on the perception of pruritus and on scratching activity in patients with this form of pruritus. DESIGN: Double-blind, placebo-controlled, crossover trial with four periods. SETTING: Clinical research referral center. PATIENTS: 29 pruritic patients with liver diseases of various causes. INTERVENTION: Each patient received as many as two naloxone and two placebo solution infusions consecutively in random order. Each infusion lasted 24 hours. MEASUREMENTS: During the infusions, visual analog scores of pruritus were recorded every 4 hours while patients were awake; scratching activity independent of limb movements was recorded continuously. RESULTS: One patient had a mild reaction consistent with a naloxone-precipitated syndrome similar to opiate withdrawal. A significant 24-hour rhythm of scratching activity was seen in 7 of 11 patients for whom complete 96-hour data were collected. The mean of a visual analog score of the perception of pruritus (maximum, 10.0) recorded during naloxone infusions was 0.582 lower than that recorded during placebo infusions (95% CI, 0.176 to 0.988; P < 0.01). Furthermore, the ratio of the geometric mean hourly scratching activity during naloxone infusions to that during placebo infusions was 0.727 (CI, 0.612 to 0.842; P < 0.001) and was greater than 1.0 in only five patients. CONCLUSIONS: Naloxone administration is associated with amelioration of the perception of pruritus and reduction of scratching activity in cholestatic patients. Because of the opioid receptor specificity of the action of naloxone, these findings support the hypothesis that a mechanism underlying the pruritus of cholestasis is modulated by endogenous opioids and suggest that opiate antagonists may have a role in the management of this complication of cholestasis.

Adult↗
PubMed2006

Clinical characteristics of uremic pruritus in patients undergoing haemodialysis.

OBJECTIVE: To document various characteristics of uremic pruritus in patients undergoing haemodialysis. DESIGN: Case series. PLACE AND DURATION OF STUDY: This study was carried out at Sindh Institute of Urology, Karachi, and Departments of Dermatology and Medicine, PNS Shifa, Karachi, over a period of 3 months. PATIENTS AND METHODS: One hundred patients of end stage renal disease undergoing haemodialysis were studied. Characteristics of pruritus like occurrence, duration, appearance, intensity, distribution, areas of maximum intensity, relationship to HCV status, effect on mood and sleep were documented. Effect of rest, dry skin, heat, sweat, clothing, cold, tiredness, dialysis, medications, application of lubricants and association of pruritus with different laboratory parameters was also noted. A comprehensive proforma was used to collect the data. RESULTS: Pruritus appeared within 2-3 months of start of dialysis in 75%. It occurred daily in 83%, weekly in 11% and monthly in 6%. It was intermittent in 45%, all day in 32%, and exacerbated at night in 23%. It was mild in 48%, moderate in 17%, severe in 27% and intractable in 8%. Areas of maximum intensity were legs (60%) and back (30%), 55% had sleep problems, 21% became agitated, while 11% became depressed. Dry skin and cold environment exacerbated while rest and hot environment ameliorated pruritus. Patients with pruritus did not differ from those without it with regard to laboratory parameters or use of medication. CONCLUSION: This study gives us a comprehensive characterization of uremic pruritus which may be a useful guideline for the treating physician.

Female↗
PubMed2006

Pregnancy outcome in women with pruritus gravidarum.

OBJECTIVE: To investigate obstetric risk factors and pregnancy outcome in women with pruritus gravidarum who delivered during a 15-year period. METHODS: A population-based study comparing all pregnancies in women with and without pruritus gravidarum delivered between 1988 and 2002 was conducted. A multivariable logistic regression model was constructed in order to find independent risk factors associated with pruritus gravidarum. RESULTS: During the study period there were 159,197 deliveries, of which 376 (0.2%) occurred in patients with pruritus gravidarum. Using a multivariable analysis, the following conditions were found to be significantly associated with pruritus gravidarum: twin pregnancies, fertility treatments, diabetes mellitus and nulliparity. No significant differences were noted between the groups regarding perinatal outcomes, such as birth weight, low Apgar scores or perinatal mortality. Pruritus gravidarum was associated with higher rates of labor induction, and accordingly those fetuses were more likely to be delivered by cesarean delivery. CONCLUSION: Pruritus gravidarum, associated with multiple gestations, fertility treatments, diabetes mellitus and nulliparity, is not associated with adverse perinatal outcomes. However, there are higher rates of labor induction and cesarean delivery.

Adult↗
PubMed1990

Study on pruritus in hemodialysis patients and the antipruritic effect of neurotropin: plasma levels of substance P, somatostatin, IgE, PTH and histamine.

It has been reported that Neurotropin can markedly improve pruritus in patients undergoing hemodialysis (HD). In order to elucidate the probable causes of pruritus and the antipruritic effect of Neurotropin, various biochemical parameters in the plasma of patients before and during HD were investigated. Forty-three patients undergoing HD were divided into three groups. Eighteen patients had suffered no episode of pruritus (group A), 17 patients had on-going pruritus (group B) and the remaining 8 patients had experienced improvement of pruritus following Neurotropin treatment (group C). The mean concentration of substance P was in only B group significantly increased with HD only in B group, indicating that substance P could be one of the causes of pruritus in patients undergoing HD. Neurotropin appears to exert its antipruritic effect by lowering the level of substance P. The change in parathyroid hormone (PTH) level during HD was not significant in any of the groups, but the mean concentration of PTH in group B was higher than that of group A, indicating that PTH may also be one of the causes of pruritus.

Adjuvants, Immunologic↗
PubMed2006

Intravenous nalbuphine 50 microg x kg(-1) is ineffective for opioid-induced pruritus in pediatrics.

PURPOSE: This investigation evaluated the efficacy of nalbuphine in treating postoperative opioid-induced pruritus (Pr) in pediatric patients. METHODS: After Ethics Board approval, the dual site, tertiary care teaching centre study recruited 212 subjects, age > or = seven years, who received opioid analgesia postoperatively. A modified, self-report colour analogue scale (CAS) scored pruritus intensity (PrI). Subjects who reported PrI score > or = 5/10 were randomized to treatment with nalbuphine 50 microg x kg(-1) iv (max 5 mg) or saline placebo. A pruritus intensity difference (PrID) > or = 50% was considered a positive outcome. RESULTS: Of 260 subjects approached, 212 consented and 184 received opioids. Median age was 13 yr (range 7-19) and median weight was 51 kg (range 19.6-134.8 kg). Pruritus intensity > or = 5/10 occurred in 37 (20.1%) subjects. Intravenous morphine [patient-controlled analgesia (PCA)/continuous infusion] was associated with Pr in 68% of subjects over a wide dose range (9.4-63.2 mug.kg(-1).hr(-1)). Pruritus occurred in 36% of patients in the PCA group compared to continuous opioid infusion (27%) and epidural administration (27%). Pruritus intensity difference > or = 50% was achieved in 55.6% of nalbuphine and 57.9% of saline-treated subjects. CONCLUSION: This preliminary report suggests that nalbuphine 50 microg x kg(-1) iv is not effective in treating postoperative opioid-induced pruritus in pediatric patients. The modified CAS score and PrID warrant further investigation.

Adolescent↗
PubMed1994

[Pruritus associated with liver disease: propofol, a new therapeutic approach?].

Pruritus is a severe and troublesome symptom in patients with cholestasis and is often difficult to treat. Propofol was recently shown to be efficient in the treatment of pruritus secondary to spinal morphine administration. In a prospective, randomized, double-blind, cross-over and placebo controlled study, 20 patients received 1 dose of propofol (15 mg) and 1 dose of Intralipid (1.5 mg) during a 2-day study period. Pruritus was assessed by a visual analogue scale from 0 (no pruritus) to 10 (most severe pruritus imaginable). Treatment success was defined as a decrease in pruritus of at least 4 points on the scale in 80% of the patients receiving propofol and in 15% of those receiving intralipid (p < 0.05). Discomfort on injection was observed in 15% under propofol treatment. In conclusion this study shows that subhypnotic doses of propofol are effective for the short-term symptomatic relief of pruritus associated with liver disease. At the dose administered, side effects were rare and minor.

Adult↗
PubMed2003

Successful use of the Molecular Adsorbent Recirculating System (MARS) in a patient with primary biliary cirrhosis (PBC) and treatment refractory pruritus.

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease often associated with severe pruritus. Despite maximal medical management pruritus often persists and has a detrimental effect on quality of life. For patients that are refractory to all medical treatments, more invasive approaches have been tried. Recently, a new extracorporeal hemodiafiltration method, Molecular Adsorbent Recirculating System (MARS), has been described. Based on the hypothesis that hydrophobic, protein-bound metabolites play a major role in the development of liver failure, this device uses an albumin enriched dialysate to facilitate the removal of albumin bound toxins. AIM: To assess the safety and efficacy of a single MARS treatment on the pruritus score in a patient with PBC and treatment refractory pruritus. DESIGN/PATIENTS: A 61-year-old female patient with biopsy proven PBC, who had been accepted on our liver transplantation waiting list because of treatment refractory pruritus, was subjected to a single MARS treatment. RESULTS: At the end of a single 8 h MARS treatment session pruritus completely disappeared. Not unexpectedly, however, this effect was only short lived. Except for a slight hypercalcemia no adverse events were observed. CONCLUSION: A single MARS treatment very effectively improved pruritus. Long-term repetitive treatment, however, might be necessary to sustain its effectiveness.

Journal Article↗
PubMed1965

PRURITUS AND JAUNDICE.

The records of 147 patients who had pruritus and jaundice (11% of a series of 1262 patients with jaundice) were reviewed in an effort to delineate more clearly the etiology of jaundice associated with pruritus.Fifty-two had obstructive jaundice caused by neoplasm, 51 had obstructive jaundice not caused by neoplasm, 42 had pruritus associated with hepatogenous jaundice, and two had jaundice and pruritus associated with a lymphoma.Pruritus occurred in 17% of all patients with non-neoplastic obstructive jaundice and in 45% of patients with neoplastic obstructive jaundice. Hepatogenous jaundice was the cause of pruritus in almost one-third of the patients in this series-occurring in 20% of patients with infectious hepatitis and in 7% of patients with cirrhosis.This large series confirms the clinical impression that pruritus occurs most often in association with extrahepatic biliary obstruction, and as well re-emphasizes the common association of pruritus with hepatogenous jaundice.

Bile Duct Neoplasms↗
PubMed1983

Severe pruritus should be a B-symptom in Hodgkin's disease.

Pruritus was evaluated with respect to frequency, intensity, and prognostic significance in 360 patients with Hodgkin's disease. In order to discriminate severe from mild pruritus, the following criteria was used: (1) multiple excoriations; (2) ineffectiveness of local and systemic antipruritics; and (3) improvement with either radiotherapy or chemotherapy. Ninety of 360 patients had mild itching on admission and showed the same survival as the 249 nonitching cases; 21 patients presented with severe pruritus, which was also generalized, and showed a statistically shorter survival than that of mild and non-itching cases. This comparison was carried out between patients homologous with respect to sex, age, stage, A or B category, and histotype. Analysis of the data pointed out that the third requirement, i.e., improvement with antineoplastic therapy, is not substantial; moreover, for staging purposes, it is preferably replaced by the requisite of generalized pruritus. The intrinsically poor prognosis related to severe pruritus may be important for treatment, when this symptom occurs in early stages or without other systemic symptoms. The inclusion of severe pruritus among the Ann Arbor criteria for definition of the B-clinical category is proposed.

Adolescent↗
PubMed1994

Pruritus ani. Causes and concerns.

PURPOSE: The aim of this study was to determine how frequently pruritus ani (PA) is a symptom secondary to benign or malignant colon and anorectal pathology. METHODS: One hundred nine patients with PA as the only presenting symptom were prospectively evaluated over a two-year period. All patients underwent anoscopy, rigid proctoscopy, and colonoscopy and were treated for PA. Patient data were entered into a computer data base and analyzed. RESULTS: The mean age was 52.1 years; males outnumbered females 2:1. The mean duration of symptoms was 6.1 weeks. Mean coffee intake was four cups per day. Forty-five percent of patients smoked and 45 percent drank alcohol daily. Thirty-five percent had an abnormal proctosigmoidoscopy or colonoscopy. Twenty-seven (25 percent) patients had primary pruritus and 82 (75 percent) patients had coexisting colon or anorectal pathology. The PA-associated neoplasia included rectal cancer (11 percent), anal cancer (6 percent), adenomatous polyps (4 percent), and colon cancer (2 percent). Hemorrhoids (20 percent) and anal fissures (12 percent) were the most common pruritus-related anorectal diseases. Among the 23 percent of patients with PA and neoplasia, pruritic symptoms were present longer compared with those with PA and anorectal disease < 0.001 and primary pruritus (P < 0.0001). All patients with primary PA were initially treated with dietary fibers, steroid cream, and drying agents. The recurrence rate for primary pruritus was twice that for anorectal disease (P < 0.0001). CONCLUSIONS: PA responds to treatment in 89 percent of patients, while 11 percent are refractory to treatment. Symptoms suggestive of pruritus ani, especially those of long duration, should alert the surgeon to the potential for proximal colon and anorectal neoplasia.

Adenomatous Polyps↗
PubMed2006

[Rational symptomatic therapy for chronic pruritus].

Chronic pruritus is a difficult-to-treat problem which accompanies many dermatologic and systemic diseases. Frequently, therapy is ineffective and prolongs the pruritus. Thus significant costs arise for the health system, which are clearly lowered by a rational therapy concept. Extensive knowledge about both topical and systemic therapy of pruritus has been acquired in recent years. Currently, new therapeutic approaches are available, which intervene in different pruritogenic mechanisms. Substances can block the cutaneous pruritus induction (e.g. antihistamines, leukotriene antagonists, cannabinoid agonists) or mediate central effects such as the inhibition of pruritus transmission via the spinal cord (e.g. naltrexone, gabapentin) or the suppression of the cerebral itch perception (e.g. antidepressants, neuroleptics). Usually combining several therapeutic principles is necessary in order to suppress chronic pruritus with lasting effect. The most effective approach is to gradually combine therapies, always considering both the medical and financial impacts.

Aged↗
PubMed1988

Treatment of pruritus in primary biliary cirrhosis with rifampin. Results of a double-blind, crossover, randomized trial.

The cause of pruritus of cholestasis is unknown. We have hypothesized that pruritus may be caused by an indirect effect of high hepatic concentrations of toxic bile acids. To test this hypothesis, we have conducted a double-blind, controlled, crossover clinical trial of rifampin, an agent that inhibits hepatic bile acid uptake and may detoxify hepatic bile acids by stimulation of mixed-function oxidases. Nine patients with primary biliary cirrhosis received 300-450 mg/day of rifampin and placebo sequentially, in random order. Each treatment was administered for 14 days, with a 14-day washout between treatments. Endpoints included patient preference, changes in a daily visual analogue scale pruritus score, and amount of cholestyramine ingested. Antipyrine elimination rates and serum bile acids were tested at the end of each treatment period. All 9 patients completed the trial and 8 of them preferred rifampin to placebo (p = 0.03). There were no adverse reactions. Visual analogue scale pruritus scores showed no significant placebo response or any effect from the order of treatment, but did show a highly significant reduction in pruritus in response to rifampin (p less than 0.002). This effect was evident within the first week of rifampin treatment. Rifampin produced a 33% reduction in antipyrine plasma half-life, but no change in fasting total serum bile acids. Cholestyramine usage did not change significantly. We conclude that rifampin is useful for short-term relief of pruritus in primary biliary cirrhosis; however, the mechanism of this effect is unknown. Longer trials are needed, as are trials in other cholestatic disorders.

Antipyrine↗
PubMed1995

Optimal dialysis improves uremic pruritus.

The authors analyzed data on 59 hemodialyzed patients who did not have significant disorders of calcium and phosphate metabolism and found that more than 60% suffered from disabling pruritus possibly related to chronic uremia. Both biochemical correlates of the prevalence of pruritus and dialysis efficacy calculated by urea kinetics were investigated. Significantly higher values of blood urea nitrogen and plasma beta 2-microglobulin just before the dialysis session were observed in pruritic patients with lower dialysis efficacy estimated by Kt/V urea and normalized protein catabolic rate (nPCR). After 3 months without changing the dialysis prescriptions, 16 patients with a mean Kt/V urea and a normalized protein catabolic rate (nPCR) of 1.28 and 1.22 g/kg/d, respectively, experienced significant reductions in the degree of pruritus estimated by the pruritic score, from 12.6 +/- 5.1 to 6.3 +/- 3.2. Twenty-two patients with a mean Kt/V urea and an nPCR of 1.09 and 1.01, respectively, continued to have severe pruritus (score: 12.3 +/- 4.7 to 12.7 +/- 6.4). In 9 of 22 patients with prolonged severe pruritus, dialysis efficacy was heightened with an increase in dialyzer membrane area of more than 0.3 m2. Seven of nine patients with increased dialysis prescriptions had significant reductions of the mean pruritic score, from 12.6 +/- 4.8 to 6.3 +/- 2.4, which inversely related to the significant increase of Kt/V urea from 1.05 +/- 0.25 to 1.24 +/- 0.33; among patients whose dialysis prescriptions were not changed, only one had a significant reduction in score. The authors concluded that higher dialysis efficacy with good nutritional state reduces the prevalence and degree of pruritus in hemodialyzed patients.

Blood Urea Nitrogen↗
PubMed1996

Transnasal butorphanol for the treatment of opioid-induced pruritus unresponsive to antihistamines.

Pruritus is a common opioid side effect and can be so severe that opioid therapy must be modified or abandoned. Antihistamines, opioid antagonists, and propofol have been proposed as treatment options, but none is universally effective. The use of intranasal butorphanol, an opioid agonist-antagonist, for pruritus has not been described previously. Six patients complaining of severe opioid-induced pruritus unresponsive to diphenhydramine received 2 mg intranasal butorphanol every 4-6 hr. Scores for pruritus, pain, and sedation were recorded on separate visual analogue scales (VAS). All patients reported significant relief from pruritus 60 min after butorphanol administration (P < 0.001); five patients noted an improvement within 15 min (P < 0.08). Sedation and pain VAS scores were not significantly different from baseline at all time points. These preliminary data demonstrate a substantial effect of intranasal butorphanol on opioid-induced pruritus that has not responded to antihistamines. Prospective controlled studies are needed to validate these findings.

Administration, Intranasal↗
PubMed2004

Intrathecal fentanyl-induced pruritus during labour: the effect of prophylactic ondansetron.

Fentanyl is commonly used for spinal analgesia during labour but it is associated with a high incidence of pruritus. This randomised, double-blind, placebo-controlled study was performed to evaluate the effect of prophylactic ondansetron on the incidence and severity of pruritus among parturients receiving intrathecal fentanyl as part of combined spinal-epidural analgesia. Seventy-three women were randomised to receive either saline placebo (group P, n = 25), ondansetron 4 mg (group O4, n = 23) or ondansetron 8 mg (group O8, n = 25) intravenously before intrathecal fentanyl 25 micrograms and bupivacaine 2 mg. The incidence and severity of pruritus were measured using a verbal rating and a visual analogue scale, and by the requirement for rescue anti-pruritic medication (naloxone). The overall incidence of pruritus was 95% (group P 100%, group O4 95%, group O8 90%). There were no significant differences between groups for severity of pruritus or requirement for treatment (naloxone given to 45%, 28% and 35% of groups P, O4 and O8 respectively). Secondary outcomes such as the incidence of headache, pain and nausea were not significantly different between groups. We conclude that prophylactic ondansetron 4 or 8 mg intravenously was ineffective in reducing the incidence or severity of intrathecal fentanyl-induced pruritus during labour.

Adult↗
PubMed2006

Relief of intractable pruritus in Alagille syndrome by partial external biliary diversion.

BACKGROUND: Patients with Alagille syndrome (AGS) may develop pruritus, skin hypertrophy, and xanthomas because of chronic cholestasis and hypercholesterolemia. Partial external biliary diversion (PEBD) has been used successfully to treat chronic cholestasis in patients with progressive familial intrahepatic cholestasis (PFIC) and is a potentially useful treatment for patients with severe and intractable pruritus because of AGS. METHODS: Four children with chronic cholestasis and intractable pruritus were treated with PEBD, 1 by surgical cholecystostomy and 3 by cholecystojejunostomy. RESULTS: Three patients had a known diagnosis of AGS. The fourth was an 11-month-old infant boy with PFIC. The first patient, a 15-month-old boy with AGS, underwent surgical cholecystostomy, which has required frequent tube changes to maintain patency. Three patients underwent PEBD using a segment of jejunum as a conduit between the gallbladder and the skin, where bile is collected in a standard ostomy appliance. Mean follow-up is 15.5 months (range, 9-26 months). All patients experienced rapid and enduring relief of pruritus. Two adolescents with AGS had significant improvement of the hypertrophic skin of their hands. There was one significant complication: the infant with PFIC required reoperation for bleeding from the jejunal anastomosis 1 week after PEBD; he has subsequently done well. One adolescent girl with AGS initially had difficulty with her ostomy because of poor site placement and partial retraction, but nevertheless has managed quite well. The patient treated by cholecystostomy has had excellent relief of his pruritus and is being considered for conversion to cholecystojejunostomy. CONCLUSIONS: Chronic cholestasis caused by AGS can cause debilitating symptoms that are resistant to medical therapy. Partial external biliary diversion is a safe and technically straightforward operation that may be effective for the relief of intractable pruritus and other symptoms in patients with AGS.

Adolescent↗
PubMed2005

Therapy of intractable pruritus with MARS.

INTRODUCTION: Pruritus is the most disabling symptom in patients with cholestatic liver diseases. Many drug therapies have been used for the treatment of these diseases, with different outcomes. The molecular adsorbent recirculating system (MARS) has been used in the treatment of intractable pruritus in cholestatic syndromes. We report our experience with MARS in 3 patients with intractable pruritus on the waiting list: 2 liver transplant recipients and a patient with primary biliary cirrhosis. PATIENTS AND RESULTS: Two middle-aged women and 1 middle-aged man, who were recipients of an orthotopic liver transplant for primary biliary cirrhosis, underwent three (n = 2) and two (n = 1) 6-hour sessions of MARS due to medically uncontrollable pruritus. All noted marked improvement of pruritus, with decreased bilirubin levels, but this improvement lasted only a few days in all cases. We observed no changes in transaminase or albumin levels, or prothrombin time. Complications included an episode of angina due to anemia caused by jugular catheter bleeding, and thrombocytopenia in all patients. CONCLUSIONS: MARS is an effective treatment for intractable pruritus in cholestatic liver diseases, although its beneficial effect is short. This extracorporeal liver device is safe, because most related adverse events are mild.

Adult↗