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Uremic pruritus: skin divalent ion content and response to ultraviolet phototherapy.

Pruritus is a frequent and troublesome consequence of end-stage renal disease. We have surveyed 155 chronic dialysis patients and found pruritus to be a significant problem in approximately 70%. Seventeen patients reporting severe pruritus were treated thrice weekly with total body exposure to either UVA or UVB light. UVB light resulted in resolution of pruritus in all cases. UVA light was without significant effect. Skin biopsies obtained before and after UV phototherapy revealed elevated contents of calcium, magnesium, and phosphorus in all pruritic patients. The resolution of pruritus following UVB treatment was associated with a reduction of skin phosphorus to values comparable with nonpruritic uremics or healthy volunteers. Uremic pruritus may be due to increased skin divalent ion content resulting in microprecipitation of calcium or magnesium phosphate.

Biopsy↗

Continuous epidural, not intravenous, droperidol inhibits pruritus, nausea, and vomiting during epidural morphine analgesia.

PURPOSE: To investigate whether continuous epidural droperidol and intravenous (IV) intraoperative droperidol inhibit pruritus and postoperative nausea and vomiting (PONV) during epidural morphine analgesia. DESIGN: Randomized, double-blinded, controlled study. SETTING: Metropolitan cancer center. PATIENTS: 120 ASA physical status I and II patients undergoing thoracic or abdominal surgery with general anesthesia combined with epidural anesthesia. INTERVENTIONS: Patients received an intraoperative epidural injection of 2 mg morphine hydrochloride, followed postoperatively by a continuous epidural infusion of morphine hydrochloride 4 mg/day for 4 days. Patients were randomly allocated to four groups: Group A = control group, Group B = intraoperative single IV injection of droperidol (2.5 mg), Group C = postoperative continuous epidural droperidol infusion (2.5 mg/day), and Group D = intraoperative IV injection of droperidol (2.5 mg) and postoperative continuous epidural droperidol infusion (2.5 mg/day). MEASUREMENTS AND MAIN RESULTS: The frequency and severity of pruritus and PONV in each group were evaluated during the postoperative period. Continuous epidural infusion of droperidol significantly reduced the frequency and severity of pruritus and PONV induced by epidural morphine without causing significant side effects. Intraoperative single IV injection of droperidol was effective for PONV (p < 0.05) but not for pruritus. CONCLUSION: Postoperative epidural droperidol infusion significantly decreased both the frequency and severity of pruritus and PONV during postoperative continuous epidural morphine analgesia. IV intraoperative droperidol significantly reduced the frequency and the severity of PONV but not pruritus.

Abdomen↗

A study on pruritus after parathyroidectomy for secondary hyperparathyroidism.

BACKGROUND: The effective therapy for uremic pruritus remains a clinical challenge, and the factors affecting the pruritus before and after parathyroidectomy have not been defined. STUDY DESIGN: Thirty-seven patients were operated on for secondary hyperparathyroidism. Their ages ranged from 14 to 73 years, and the duration of dialysis from 12 to as long as 168 months. Indications for surgery were skin itch in 22 patients and other reasons in 15 patients. Serum levels of calcium, phosphorus, intact PTH (i-PTH), and alkaline phosphatase were checked at two different intervals-before surgery and 1 week after operation. Immunohistochemical stain of mast cells, antihuman macrophage (CD68), antihuman dendritic reticulum cell (CD35), and i-PTH (IHPTH) were performed on skin specimens. Skin samples were prepared into tissue homogenates and analyzed for concentrations of interleukin-2 (II-2) and tumor necrosis factor-alpha (TNF-alpha). II-2 and TNF-alpha were measured by sandwich enzyme-linked immunosorbent assay. The extent of pruritus was evaluated on a visual analog scale (VAS) ranging from 0 to 10 and a behavior rating scale (BRS) ranging from 0 to 5, at a preoperative stage and 1 week after operation. RESULTS: Serum levels of calcium, phosphorus, the product of calcium and phosphorous (Ca x P), alkaline phosphatase, and i-PTH changed significantly after parathyroidectomy. The VAS decreased from 5.4 +/- 3.2 to 1.8 +/- 1.5 (p < 0.001). Significant improvement of BRS was achieved 1 week after surgery (p < 0.001), and in the followup period. Before surgery, there was no correlation between serum levels of calcium, phosphorus, Ca x P, alkaline phosphatase, i-PTH, number of mast cells, CD68, CD35, and IHPTH, and the scale of itch estimated with either VAS or BRS. The tissue levels of Il-2 and TNF-alpha were not detectable in any of them. We noted that high levels of phosphorus and Ca x P affected the postoperative extent of pruritus. But a linear regression test showed Ca x P was the only factor affecting postoperative itch. CONCLUSIONS: Pruritus in patients with secondary hyperparathyroidism can be reduced by parathyroidectomy. Apparently, high-level Ca x P is the only factor that seems to affect the postoperative extent of pruritus.

Adult↗

Intractable pruritus in HIV infection: immunologic characterization.

BACKGROUND: Severe, intractable pruritus, often associated with erythematopapular skin lesions and hypereosinophilia, is a condition observed in some nonatopic, HIV-infected patients. We performed immunovirologic analyses of this condition. METHODS: Immunologic (mitogen-stimulated production of cytokines, tumor necrosis factor-alpha [TNF-alpha], and soluble CD23; serum levels of soluble CD23, ICAM-1, TNF-alpha, IgG, IgE, and IgA) and virologic (HIV viral load) parameters were analyzed in six patients with therapy-resistant pruritus. Hypereosinophilia was present in all these patients. Results were compared to those of seven HIV-seropositive individuals similar to the first one in terms of CD4 counts and clinical staging, but without pruritus. RESULTS: Hypereosinophilia; hyper-IgE and hyper-IgA; augmented interleukin (IL)-4, IL-5, and sCD23; and reduced interferon-gamma production by mitogen-stimulated peripheral blood mononuclear cells (PBMC) were detected when patients with pruritus were compared to HIV controls. HIV viral load was also augmented in patients in whom pruritus was present. CONCLUSIONS: The results suggest that therapy-resistant, intractable pruritus accompanied by hypereosinophilia may be used to define a subset of HIV-seropositive individuals showing prototypic hyperactivation of humoral immunity, and in whom augmented HIV viral load is present.

Adult↗

Review article: pruritus in cholestatic and other liver diseases.

Pruritus is often the most troublesome symptom in patients with chronic liver disease, particularly when cholestasis is a prominent feature. The exact pathogenesis is unknown, but empirical treatment, such as cholestyramine, based on a liver-based origin of pruritus, has been used for many years. Recently, evidence for a central mechanism for pruritus has been obtained and opioid antagonists have been tried clinically with some benefit, but their use is not widespread. In addition, the pruritus associated with intrahepatic cholestasis of pregnancy can now be alleviated in many cases by ursodeoxycholic acid. As it also improves foetal outcome, this should become first-line therapy. We review the pathogenesis and therapy of pruritus, highlighting practical aspects to help with patients with seemingly intractable pruritus.

Anion Exchange Resins↗

Mast cell mediators other than histamine induce pruritus in atopic dermatitis patients: a dermal microdialysis study.

While histamine is the crucial mediator of pruritus in type 1 allergic reactions, its role in atopic dermatitis (AD) is unclear. In this study, the role of mast cell mediators in protein extravasation and pruritus was evaluated using intradermal microdialysis. The microdialysis capillaries were used to apply the mast cell degranulating substance compound 48/80 (C48/80; 0.05%) or histamine (0.01%) and also to deliver H1-blockers (cetirizine, 200 microg mL-1) in nine AD patients and nine controls. Large pore size membranes (3000 kDa) enabled simultaneous analysis of protein extravasation. Itch sensation was measured psychophysically and weal and flare reaction were evaluated planimetrically. Protein extravasation induced by histamine and C48/80 was significantly reduced in AD patients. Blockade of H1-receptors by cetirizine significantly reduced C48/80-induced protein extravasation in AD patients and controls to an identical level. C48/80-induced pruritus was abolished by cetirizine in controls, whereas pruritus in AD patients was unchanged after H1 blockade. We conclude that mast cell mediators others than histamine are involved in C48/80-induced pruritus in AD patients. Whether the reduced capacity of AD patients to induce protein extravasation is of pathophysiological relevance for pruritus remains to be established.

Adult↗

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.

Activities of Daily Living↗

Pruritus in polycythaemia vera: prevalence, laboratory correlates and management.

In a retrospective cohort, 192 (48%) out of 397 patients with polycythaemia vera had a documented history of pruritus. At diagnosis, the presence of pruritus was significantly associated with a lower mean corpuscular volume and a higher leucocyte count. Among 66 patients with documentation of treatment for pruritus, 389 'patient visits' were reviewed, revealing a significant correlation between active pruritus and low mean corpuscular volume, but not platelet, leucocyte or basophil count. Paroxetine and hydroxyzine were rated by patients to be the most effective drugs in controlling pruritus. These observations suggest a pathogenetic role for both iron deficiency and biogenic amines in polycythaemia vera-associated pruritus.

Acute Disease↗

Pruritus in cancer patients.

Pruritus is an uncommon symptom in cancer patients but can often be difficult to treat. The pathogenesis is complex and is not fully understood although there is evidence of involvement of a number of mediators from which treatment options are developing. In cancer patients pruritus may be directly related to the cancer, indirectly related (e.g. cholestasis) or associated with treatment. It is not always possible to treat the underlying cause of the pruritus in these patients, or desirable to stop treatments that may contribute and in these cases we must address the pruritus itself. The treatment of pruritus is a developing area, and helpful research is slowly emerging. The evidence base is not extensive but some high quality studies exist. This short paper briefly discusses the pathogenesis, causes, effects and treatment options for pruritus in cancer patients.

Humans↗

Partial external biliary diversion for intractable pruritus and xanthomas in Alagille syndrome.

Alagille syndrome (AGS) causes intractable pruritus and disfiguring xanthomas because of retained bile acids and cholesterol. This study was performed to determine whether partial external biliary diversion (PEBD) is effective for relief of pruritus and xanthomas in AGS patients who fail conventional medical therapy. Between the years 1985 and 2001, 9 AGS patients underwent PEBD. Complete follow-up data were available for all patients. The average age at PEBD was 4.8 (range 1.4-10) years. The average duration of follow-up was 7.5 (range 0.5-16.0) years. All 9 patients had severe, mutilating pruritus (grade 4) prior to diversion. At 1 year post-PEBD, the average pruritus score was 1.1; 8 patients had only mild scratching when undistracted. Three patients with extensive xanthomas prior to PEBD had complete resolution within 1 year. Mean serum bile salt levels (n = 5) decreased from 136.5 to 37.1 micromol/L and mean cholesterol (n = 7) from 724 to 367 mg/dL 1 year after PEBD. A single 21-year-old patient with PEBD for 14 years experienced an increase in pruritus from grade 1 to grade 4 within 2 months of elective reversal of PEBD. In conclusion, PEBD is effective for treating severe pruritus and hypercholesterolemia in AGS patients without cirrhosis who did not respond to medical therapy. PEBD should be considered as a therapeutic option for these patients before referral for liver transplantation because of morbid complications.

Alagille Syndrome↗

Intrathecal fentanyl-induced pruritus is more severe in combination with procaine than with lidocaine or bupivacaine.

BACKGROUND AND OBJECTIVES: Fentanyl is used as an additive to prolong intrathecal anesthesia with both lidocaine and low-dose bupivacaine in the outpatient setting to minimize voiding or discharge delays. Pruritus is the most common side effect. When using procaine as a substitute for lidocaine, we perceived an increased frequency and severity of pruritus. We compared prospectively the frequency and severity of itching with combinations of fentanyl with lidocaine, bupivacaine, and procaine. METHODS: After institutional review board approval, 135 patients requesting neuraxial anesthesia were asked to evaluate the presence and severity (using a 100 point verbal pruritus score [VPS]) of itching 30 minutes after injection of their spinal anesthetic, on arrival to the postanesthesia care unit (PACU), and at the time of resolution of their block. Choice of anesthetic drug and dose and the use of intravenous sedation was left to the discretion of the attending and resident anesthesiologist. RESULTS: Thirty-three patients received lidocaine and fentanyl, 47 received bupivacaine and fentanyl, and 55 received procaine and fentanyl. In the lidocaine group, 21% of patients experienced pruritus compared with 55% of the bupivacaine group and 55% of the procaine group (P =.003). The average VPS at 30 minutes postblock was 18.4 in the procaine group compared with 0 and 5.5 in the lidocaine and bupivacaine groups (P =.06). On admission to the PACU, it was 37 compared with 16 and 20 for lidocaine and bupivacaine, respectively (P =.006). CONCLUSION: Procaine produces a higher frequency of pruritus than that seen with lidocaine-fentanyl combinations and a greater severity of pruritus than seen with lidocaine-fentanyl and bupivacaine-fentanyl spinal anesthesia. Reg Anesth Pain Med 2001;26:252-256.

Adjuvants, Anesthesia↗

Pruritus of unknown origin: a retrospective study.

BACKGROUND: Pruritus of unknown origin is a common complaint, and systemic causes must be considered. However, there is little data on how frequently systemic causes are responsible or whether any patient characteristics make a systemic cause more likely. OBJECTIVE: We attempted to determine how frequently pruritus of unknown origin had a systemic etiology in an outpatient population seen in a university dermatology department and whether any patient characteristics made a systemic explanation more likely. METHODS: This is a retrospective study using chart reviews and telephone interviews to collect data. RESULTS: Of 50 patients, 11 had a systemic cause of pruritus. Pruritus was the initial symptom of systemic disease in 7 of these patients. No patient characteristics were statistically associated with systemic causes of pruritus. CONCLUSION: Pruritus of unknown origin was the initial symptom of a systemic disease in 7 of 50 patients presenting to a dermatology clinic with this complaint. The underlying diseases included hypothyroidism, gastric adenocarcinoma, hepatitis C, HIV, laryngeal carcinoma, graft-versus-host disease, and chronic lymphocytic leukemia.

Adenocarcinoma↗

A questionnaire for the assessment of pruritus: validation in uremic patients.

A questionnaire was constructed for the evaluation and measurement of pruritus. The questionnaire, based on the short form of the McGill Pain Questionnaire, was tested in 145 patients suffering from uremic pruritus and currently undergoing hemodialysis treatment in 3 centers. The newly developed questionnaire proved to be reliable and provided valid data on the sensory, affective and overall intensity of uremic pruritus. The data suggest that uremic pruritus tends to be prolonged, frequently intense and a major source of distress to the patient. Dialysis was not found to influence the pruritus. The questionnaire may also be useful in pruritus secondary to other causes.

Adult↗

Comparative clinical characteristics and responses to oral 4-aminoquinoline therapy of malarious children who did and did not develop 4-aminoquinoline-induced pruritus.

The clinical characteristics and the responses to oral 4-aminoquinoline therapy of 150 malarious children presenting consecutively were investigated in an endemic area. At presentation, the 75 children who subsequently developed pruritus were significantly older and had significantly higher body temperatures than the 75 children who did not develop pruritus. There were no other significant differences in clinical presentation between the two groups. In children with pruritus, there was no correlation between age, weight, presenting body temperature, duration of illness or presenting peripheral parasite density and duration of pruritus. Responses to oral antimalarial drugs were similar in both groups. There was no correlation between indices of therapeutic response and the duration of pruritus. Analysis of the disposition kinetics of parasitaemia and of the hepatomegaly associated with malaria, using a non-compartmental model similar to that used in characterizing drug disposition, showed that the two groups had similar half-lives of parasitaemia (t(1/2 pd)), volumes of blood completely cleared of parasites per unit time (CL(Bpd)) and ratios of parasite-clearance time to t(1/2 pd), and similar values for the corresponding parameters derived from hepatomegaly resolution. There was no apparent relationship between the indices of parasite- or hepatomegaly-disposition kinetics and the duration of pruritus.

Acute Disease↗

Uremic pruritus.

Uremic pruritus and its treatment are reviewed. Pruritus affects 50-90% of patients undergoing peritoneal dialysis or hemodialysis; symptoms usually begin about six months after the start of dialysis and range from localized and mild to generalized and severe. The mechanism underlying uremic pruritus is poorly understood; possibilities include secondary hyperparathyroidism and divalent-ion abnormalities; histamine, allergic sensitization, and proliferation of skin mast cells; hypervitaminosis A; iron-deficiency anemia; neuropathy and neurologic changes; or some combination of these. The cornerstone of therapy for uremic pruritus is regular, intensive, efficient dialysis. Other nonpharmacologic measures consist of the use of non-complement-activating dialysis membranes, compliance with dietary restrictions, electric-needle (acupuncture) therapy, and ultraviolet light therapy. Pharmacologic treatments that have been used include activated charcoal, antihistamines, capsaicin, cholestyramine, emollients and topical corticosteroids, epoetin, pizotyline, ketotifen, and nicergoline. Treatment results have been highly variable, and many of the clinical trials have been flawed. Phosphate-binding agents appear to be the most effective. Although enough is known to determine a reasonable set of steps in approaching a patient's uremic pruritus, more research is needed to understand the pathophysiology of this condition and to establish more reliable treatments. Pruritus is a common and sometimes severe complication of chronic renal failure. Efficient dialysis, dietary restrictions, phosphate-binding therapy, and phototherapy are the most effective treatments currently available.

Humans↗

Pruritus and skin hydration during dialysis.

BACKGROUND: Dry skin is frequently observed in uraemic patients and a link with the common complaint of pruritus has been suggested. Objective data on skin dryness in haemodialysed patients is sparse and equivocal. No such information exists for the many patients now receiving peritoneal dialysis. We assessed the prevalence and severity of both pruritus and skin dryness in a uraemic population receiving maintenance dialysis. METHODS: Forty-eight haemodialysis and 24 peritoneal dialysis patients were examined and skin dryness assessed by clinical grading and measurement of stratum corneum hydration using a corneometer. Forty age- and sex-matched controls were also assessed. Several biochemical parameters with possible relevance to pruritus were measured. Regular emollient therapy was prescribed to pruritic dialysis patients and efficacy assessed. RESULTS: Dialysis patients overall had clinically drier skin than controls, especially the peritoneal dialysis group. Stratum corneum hydration levels were significantly reduced in the peritoneal dialysis (P < 0.004), but not the haemodialysis, population. Twenty-seven per cent of haemodialysed and 54% of peritoneal dialysis patients complained of pruritus. Pruritic patients in each dialysis group had significantly lower hydration than non-pruritic patients (P < 0.05). Regular emollient use in pruritic patients produced a marked reduction in severity of pruritus, abolishing the symptom in nine of 21 patients treated. CONCLUSION: Reduced stratum corneum hydration correlates with pruritus in patients on maintenance haemodialysis and peritoneal dialysis, and may be alleviated by simple emollient therapy.

Adolescent↗

Cholestatic pruritus - the role of cutaneous mast cells and nerves.

BACKGROUND: The pathogenesis of pruritus in cholestatic liver disease is poorly understood. Cutaneous mast cells and nerves are thought to contribute to pruritus in several dermatological diseases. AIM: To determine if cutaneous mast cell density, neural density and mast cell-neural interaction are increased in patients with pruritus and cholestatic liver disease. METHODS: Skin biopsy specimens from (i). patients with pruritus due to cholestatic liver disease (CLDP+; n = 6), (ii). patients with chronic liver disease without pruritus (CLDP-; n = 5), and (iii). healthy controls (n = 6) were studied. Biopsies were dual stained immunohistochemically for mast cells and nerves. RESULTS: Mast cell density in the control group was not significantly different from that in CLDP+ group or from that in the CLDP- group. Similarly neural density was not significantly different between groups when assessed either in terms of total nerve area, or in terms of the number of neural elements seen. The frequency of mast cell-nerve contact was not significantly different between groups. CONCLUSIONS: These findings suggest that mast cells, nerves or interaction between the two may not contribute to cholestatic pruritus. Therefore, therapies targeted at cutaneous mast cells or nerves are unlikely to be of benefit.

Adult↗

Familial brachioradial pruritus.

BACKGROUND: The cause of brachioradial pruritus (a localized itching on the arms or shoulders) is controversial. A hereditary form of this condition has not been reported. OBJECTIVES: To describe the occurrence of brachioradial pruritus in several members of one family. PATIENTS AND METHODS: The pedigree of the three generations and the history of brachioradial pruritus was outlined. Four sisters were investigated by radiography of the cervical spine. RESULTS: Five sisters and one brother, together with five of their daughters suffered from recurring brachioradial pruritus. The sisters had had occupations requiring heavy lifting, spent much time outdoors and exposed themselves extensively to the sun. Several complained of neck pain and cervical radiographs of four of them indicated arthrosis. CONCLUSIONS: Spinal disease alone cannot explain the symptoms of brachioradial pruritus, which in our patients was characterized by symptom-free periods broken off by relapse late in the summer each year. The pedigree suggests this hereditary form of brachioradial pruritus to be dominant and possibly X-linked.

Adolescent↗