Sertraline as a first-line treatment for cholestatic pruritus. Topical capsaicin for treatment of hemodialysis-related pruritus. Kappa-opioid system in uremic pruritus: multicenter, randomized, double-blind, placebo-controlled clinical studies. A pramoxine-based anti-itch lotion is more effective than a control lotion for the treatment of uremic pruritus in adult hemodialysis patients. Oral naltrexone treatment for cholestatic pruritus: a double-blind, placebo-controlled study. House-dust mite sublingual-swallow immunotherapy in perennial conjunctivitis: a double-blind, placebo-controlled study. Paroxetine in the treatment of severe non-dermatological pruritus: a randomized, controlled trial. A clinical trial of hydrocortisone/potassium hydroxyquinoline sulphate ('Quinocort') in the treatment of infected eczema and impetigo in general practice. A controlled trial of ondansetron in the pruritus of cholestasis. Pruritus in HIV-1 disease: therapy with drugs which may modulate the pattern of immune dysregulation. Comparison of the efficacy of subcutaneous and sublingual immunotherapy in mite-sensitive patients with rhinitis and asthma--a placebo controlled study. Allergic rhinitis due to house dust mites: evaluation of the efficacy of specific sublingual immunotherapy. Hemodialysis-related pruritus: a double-blind, placebo-controlled, crossover study of capsaicin 0.025% cream. Treatment of common warts with an intralesional mixture of 5-fluorouracil, lidocaine, and epinephrine: a prospective placebo-controlled, double-blind randomized trial. Ondansetron therapy for uremic pruritus in hemodialysis patients. Uremic pruritus: roles of parathyroid hormone and substance P. House-dust-mite sublingual-swallow immunotherapy (SLIT) in perennial rhinitis: a double-blind, placebo-controlled study. Quality control in chronic wound management: the role of local povidone-iodine (Betadine) therapy. Photodynamic therapy (PDT) and waterfiltered infrared A (wIRA) in patients with recalcitrant common hand and foot warts. Topical capsaicin therapy for uremic pruritus in patients on hemodialysis. Monotherapy with a broad-spectrum beta-lactam is as effective as its combination with an aminoglycoside in treatment of severe generalized peritonitis: a multicenter randomized controlled trial. The Severe Generalized Peritonitis Study Group. Prophylaxis with GM-CSF mouthwashes does not reduce frequency and duration of severe oral mucositis in patients with solid tumors undergoing high-dose chemotherapy with autologous peripheral blood stem cell transplantation rescue: a double blind, randomized, placebo-controlled study. Phase III controlled evaluation of sucralfate to alleviate stomatitis in patients receiving fluorouracil-based chemotherapy. Topical treatment with 5-aminosalicylic in distal ulcerative colitis by using a new suppository preparation. A double-blind placebo controlled trial. 1% pimecrolimus, 0.005% calcipotriol, and 0.1% betamethasone in the treatment of intertriginous psoriasis: a double-blind, randomized controlled study. Efficacy and safety of retapamulin ointment as treatment of impetigo: randomized double-blind multicentre placebo-controlled trial. Effect of a novel kappa-receptor agonist, nalfurafine hydrochloride, on severe itch in 337 haemodialysis patients: a Phase III, randomized, double-blind, placebo-controlled study. Treatment of post-transplant premalignant skin disease: a randomized intrapatient comparative study of 5-fluorouracil cream and topical photodynamic therapy. Intralesional 5-fluorouracil, lidocaine and epinephrine mixture for the treatment of verrucae: a prospective placebo-controlled, single-blind randomized study. A randomized, placebo-controlled, double-blind trial of ondansetron in renal itch. Pentoxifylline therapy: a new adjunct in the treatment of oral submucous fibrosis. [Diluted injectable quinine in the intramuscular and intrarectal route: comparative efficacity and tolerance in malaria treatment for children ]. Comparison between the efficacy of photodynamic therapy and topical paromomycin in the treatment of Old World cutaneous leishmaniasis: a placebo-controlled, randomized clinical trial. Lack of efficacy of tacrolimus ointment 0.1% for treatment of hemodialysis-related pruritus: a randomized, double-blind, vehicle-controlled study. Three-year follow-up of clinical and inflammation parameters in children monosensitized to mites undergoing sub-lingual immunotherapy. Specific immunotherapy with Dermatophagoides pteronyssinus and D. farinae results in decreased bronchial hyperreactivity.
Pruritus is frequently the most debilitating symptom of cholestatic liver diseases. Moreover, existing therapies are often ineffective. Recent small, retrospective case series reports suggest that serotonin reuptake inhibitors can improve pruritus. This study was undertaken to establish the dose of sertraline and to evaluate its efficacy for cholestatic pruritus. Twenty one subjects with chronic pruritus due to liver disease (including primary biliary cirrhosis, primary sclerosing cholangitis, chronic hepatitis C, and postnecrotic cirrhosis) initially underwent an open-label, dose escalation to determine the dose with optimal efficacy and tolerability. After a washout period, 12 of the subjects entered a randomized, double-blind, placebo-controlled trial. Participants quantified their pruritus using a 0-10 visual analog scale, and pruritus was assessed for distribution, timing, degree of disability, and physical evidence of scratching. The optimum sertraline dose (75-100 mg/day) was well tolerated. In the controlled portion of the study, itch scores improved in patients taking sertraline, but worsened in patients taking placebo (P=0.009). Changes in itch distribution, duration, direction, and physical evidence of scratching paralleled changes in the visual analog pruritus score.
                Sertraline seems to be an effective, well-tolerated treatment for pruritus due to chronic liver disease. These results suggest that serotonergic pathways are important in the perception of itch. Pruritus is a significant problem for many patients undergoing long-term hemodialysis. Topical capsaicin depletes and prevents the reaccumulation of substance P in peripheral sensory neurons. Substance P functions in the transmission of pain and probably itch sensations. An open-label, uncontrolled trial and a double-blind, vehicle-controlled trial were conducted to evaluate the efficacy and safety of capsaicin 0.025% cream in the treatment of localized areas of pruritus in patients undergoing long-term hemodialysis. Eight of nine evaluable patients in the open-label trial reported marked relief or complete resolution of itching during the study period, and two of five evaluable patients in the double-blind trial reported complete resolution of itching in the capsaicin-treated arm with no or minimal improvement in the vehicle-treated arm. Twelve patients in the open-label trial and two in the double-blind trial were unevaluable. No serious treatment-related adverse reactions occurred. Uremic pruritus is a very common and frustrating condition for both patients and clinicians because no treatment has been demonstrated to be effective in relieving the itch. In this report, nalfurafine, a new kappa-opioid receptor agonist, was used to treat uremic pruritus in patients who were undergoing routine hemodialysis. Two multicenter, randomized, double-blind, placebo-controlled studies enrolled 144 patients with uremic pruritus to postdialysis intravenous treatment with either nalfurafine or placebo for 2 to 4 wk. A meta-analysis approach was used to assess the efficacy of nalfurafine. Statistically significant reductions in worst itching (P = 0.0212), itching intensity (P = 0.0410), and sleep disturbances (P = 0.0003) were noted in the nalfurafine group as compared with placebo. Improvements in itching (P = 0.0025) and excoriations (P = 0.0060) were noted for the nalfurafine-treated patients. Nalfurafine showed similar types and incidences of drug-related adverse events as did placebo. Nalfurafine was shown to be an effective and safe compound for use in this severely ill patient population. The objective of this study was to evaluate the efficacy of a commercially available anti-itch lotion containing 1% pramoxine hydrochloride versus control lotion in the treatment of uremic pruritus in adult hemodialysis patients.
                This was a randomized, double-blind, controlled comparative trial set in a community hemodialysis center. The study population comprised 28 individuals (mean age 53.5) with moderate to severe uremic pruritus who had been receiving hemodialysis for at least 3 months. All participants were recruited from one community hemodialysis center. Topical anti-itch lotion containing 1% pramoxine was applied twice daily to all affected areas of pruritus for 4 weeks. The main outcome measure was a reduction in itch intensity. Secondary outcomes included increases in the investigator's global assessment and improvement in skin hydration.
                There was a 61% decrease in itch intensity in the treatment group, whereas a 12% reduction in itch intensity was observed in the control group. The rate of decline in itching was also greater in the treatment arm versus the control arm. No significant differences were displayed in other studied disease-related variables.
                Our study shows that individuals using pramoxine 1% lotion experienced a reduction in pruritus to a greater degree than those using the control lotion. This safe, convenient and effective topical lotion may potentially benefit the large number of patients affected by pruritus associated with end-stage renal disease. The efficacy of currently available therapeutic agents for cholestatic pruritus is often disappointing. The aim of this study was to assess the antipruritic effect of naltrexone, an oral opiate receptor antagonist.
                Sixteen patients with pruritus of chronic cholestasis were randomized to receive naltrexone (4-week course of 50 mg naltrexone daily) or placebo. Pruritus, quality of sleep, fatigue (using visual analogue scales), side effects, and liver function were assessed every 2 weeks. Serum naltrexone and 6 beta-naltrexol concentrations in all patients and 5 healthy controls were measured during the first day of naltrexone treatment.
                Mean changes with respect to baseline were significantly different, in favor of the naltrexone group, for daytime itching (-54% vs. 8%; P < 0.001) and nighttime itching (-44% vs. 7%, P = 0.003). In 4 naltrexone-treated patients, side effects (transient in 3 cases) consistent with an opiate withdrawal syndrome were noted. No deterioration of the underlying disease was observed. Naltrexone and 6 beta-naltrexol levels did not differ between patients and controls, and there was no significant association with treatment response.
                For patients with cholestatic liver disease and itching, refractory to regular antipruritic therapy, oral naltrexone may be an effective and well-tolerated alternative. The safety and the efficacy of sublingual-swallow immunotherapy (SLIT) in perennial conjunctivitis caused by house dust mite were evaluated in a double-blind, placebo-controlled study including 60 patients for 24 months.
                Patients received either placebo or SLIT with standardized Dermatophagoides pteronyssinus (D.pt.) and D. farinae (D.f.) 50/50 extract. The evaluation of the efficacy of the SLIT was obtained by using standardized D. pteronyssinus (D.pt.) extracts on the antigen-specific conjunctival provocation test (CPT). Specific CPT, skin sensitivity and serum-specific IgE were performed before starting treatment and 6, 12, 18 and 24 months.
                Of the 60 patients included, only 45 completed the study (26 in the active group and 19 in the placebo group, P < 0.05). Two out of 30 (6.6%) patients dropped out because of insufficient efficacy in the active group compared to eight out of 30 (26.6%) in the placebo group (P < 0.05). There was a significant increase in the antigen threshold required to obtain a positive CPT from 8.2 IR [95% confidence interval (CI) 5.9-11.4] at baseline to 21.7 IR (95% CI 15.4-30.4) at 2 years (M24) in the active group, compared to 8.1 IR (95% CI 5.4-12.1) at baseline to 8.1 IR (95% CI 5.1-12.4) at M24 in the placebo group (P < 0.04 for overall treatment difference, P < 10-7 for the time-treatment interaction; repeated measures ANOVA). Differences between groups at individual time points were significant from 18 months on. Despite increased antigen concentrations, CPT scores were lower overall in the active than in the placebo group (P < 0.001). No serious adverse effects were reported.
                SLIT effectively increased the antigenic threshold required to obtain a positive CPT to house-dust mite antigen. Tolerance to and innocuity of SLIT were comparable to previous studies. This could justify recommending SLIT for the preventive treatment of perennial conjunctivitis caused by house dust mites. Severe pruritus may be an idiopathic phenomenon or associated with advanced systemic disease. It is one of the most distressing and difficult to treat symptoms. Uncontrolled studies have suggested that, in patients experiencing severe pruritus, paroxetine appeared to have a rapid anti-pruritic effect. This study was a prospective double-blind, randomized within patient comparison of paroxetine and placebo. The intensity of pruritus was measured subjectively with a numerical analogue scale. The primary endpoint of the trial was the mean pruritus score, measured for seven days after randomization and after cross-over. The secondary endpoint was individual global response to the treatment. Response was defined as at least 50% reduction of intensity of pruritus in the last three days of the treatment period vs. baseline. Adverse effects and patient satisfaction and preferences were also recorded. Twenty-six patients were included in the study; 17 of them had solid tumors, 4 had hematological malignancies and 5 had various nonmalignant or idiopathic conditions. Eight patients had drug-induced pruritus (none opioid-induced), 7 patients had paraneoplastic pruritus and 3 had cholestatic pruritus. After a run-in period, patients were randomly assigned to treatment with 20 mg paroxetine or placebo. The crossover took place after 7 days. Two patients discontinued treatment because of adverse effects of paroxetine. Twenty-four patients treated with paroxetine had lower pruritus intensity scores over the 7 treatment periods (mean+/-SE=5.2+/-0.32) as compared to placebo (mean+/-SE=6.0+/-0.32). Mean difference between placebo and paroxetine was 0.78 (95% CI=0.37-1.19). Nine of twenty-four patients (37.5%) fulfilled criteria of response. The onset of anti-pruritic action was observed usually after 2-3 days, irrespective of the order of treatment. The outcome of this study indicates that paroxetine is effective in the treatment of severe pruritus of non-dermatological origin. A double-blind, multi-centre study was carried out in general practice in 76 patients with infected eczema and 43 with impetigo to assess the effectiveness and acceptability of treatment with 1% hydrocortisone plus 0.5% potassium hydroxyquinoline sulphate cream compared with that of 1% hydrocortisone plus 2% miconazole nitrate cream. Patients were allocated at random to receive treatment with one or other preparation, applied twice daily, over a period of 2 weeks. Assessments were made of total symptom severity scores on entry and at the end of each week, as also were bacteriological investigations. The results showed that both combinations produced marked clinical and bacteriological improvement or cure in approximately 90% of patients with infected eczema and the success rate was similar with each preparation. In the case of patients with impetigo, hydrocortisone/potassium hydroxyquinoline sulphate proved significantly more effective than the other combination, the success rates being 92% and 74%, respectively. Patient assessment of the two topical preparations in terms of greasiness, odour and staining showed that, whilst both were considered acceptable by most, there was a trend in favour of the hydrocortisone/potassium hydroxyquinoline sulphate cream. No systemic or local side-effects were reported. In patients with pruritus of cholestasis, response to conventional drug treatment may be unsatisfactory. Activation of 5-hydroxytryptamine receptors on dermal sensory nerve-endings plays a role in the perception of pruritus. The 5-hydroxytryptamine(3) receptor antagonist, ondansetron, has been used in the treatment of pruritus of cholestasis, but there are few controlled data.
                To determine whether ondansetron is effective in treating the pruritus of cholestasis.
                A total of 19 patients with resistant pruritus were randomized, double blind, to receive either ondansetron 8 mg or placebo as a single intravenous bolus, followed by oral ondansetron 8 mg or placebo twice daily for 5 days. Patients' perception of pruritus was recorded hourly using a visual analogue scale, and scratching activity measured by means of a piezo-electric crystal attached to the fingernail.
                Mean pruritus score using visual analogue scale and scratching activity were reduced on the first treatment day compared with baseline in both the ondansetron and placebo groups (P < 0.05), but there were no significant differences in mean pruritus perception or scratching activity between the two groups.
                Ondansetron was of no benefit in this group of pruritic patients during short-term treatment. Pruritus in HIV-1+ patients is common and increases with disease progression. The causes of pruritus are numerous including xerosis, drug and photoeruptions, follicular and papular eruptions as well as infestations and infections by a wide range of organisms. One other possible factor contributing to pruritus is the pattern of immune dysregulation. With advancing HIV-1 disease there is Th1 to Th2 cytokine switching.
                After some positive results with prostaglandin inhibitors, we undertook a study in which we randomly placed patients on four different forms of therapy for their pruritus. The therapies included hydroxyzine with or without doxepin at night, pentoxifylline, indomethacin and topical moisturization with medium-strength topical steroids. All patients were evaluated for both subjective relief as well as side effects.
                Patients placed on indomethacin obtained relief more consistently and more completely. Patients on pentoxifylline had the fewest side effects of all oral therapies. Patients on antihistamines with or without doxepin had the highest incidence of side effects, although more of these patients reported a greater degree of relief than patients on pentoxifylline. All patients on oral therapy overall had greater relief than patients using topical steroids.
                The systemic therapies which may modulate the pattern of immune dysregulation seen in HIV-1 disease may be beneficial in the pruritus seen in late-stage patients. The efficacy of therapy with sublingual allergen extracts is unproven.
                To evaluate the clinical and immunologic outcome of sublingual immunotherapy and to compare the results with subcutaneous immunotherapy and placebo in 36 patients with rhinitis and asthma due to mite allergy.
                Thirty-six patients with rhinitis and asthma due to mite allergy were randomly divided into three groups in order to receive subcutaneous injections with allergenic extracts, sublingual drops with solutions of purified standardized allergen preparations, or sublingual placebo for a period of 1 year. Assessment of clinical and immunologic efficacy included symptom and medication scores, methacholine provocation tests, skin prick tests, and specific IgE and IgG4 antibody concentrations.
                Subcutaneous immunotherapy for both rhinitis and asthma was clinically effective. Patients treated with sublingual immunotherapy had decreased rhinitis symptoms (P < .01) but no change in asthma scores. Medication scores significantly decreased in both actively treated groups (P < .01) at the first year compared with baseline. When skin prick tests were evaluated, the subcutaneously treated group had a significant decrease in the wheal diameter of D. pteronyssinus (P < .01), D. farinae (P < .05), and histamine (P < .05) while other two groups showed no difference. There was no significant change in methacholine PC20 values in all groups at the end of the first year when compared with baseline. No change in D. pteronyssinus and D. farinae specific IgE levels were observed; however, specific IgG4 concentrations were significantly higher than baseline both in sublingual and subcutaneous immunotherapy groups (P < .05) after 1 year immunotherapy. No significant difference was obtained in any of these parameters in the placebo group.
                Sublingual immunotherapy may be effective in patients with allergic rhinitis. Further, we believe it is a potential therapy for allergic asthmatic patients. The clinical usefulness of this form of immunotherapy (when administered to larger study groups for a longer time) and the mechanisms underlying its immunologic effect deserve additional studies. The efficacy and safety of sublingual immunotherapy (SLIT) in patients with chronic rhinitis related to sensitization to house dust mites are still controversial.
                After application of an anti-mite mattress cover, patients were only included in the study when the cumulative symptom score over a fortnight was greater than 70 out of a possible total of 168. Thirty-two of the 120 patients selected were randomized to receive SLIT for 2 years: 17 received placebo and 15 received the Dermatophagoides pteronyssinus and D. farinae 50/50 allergen extract.
                Significant between-group differences were observed after 1 year and persisted at the end of the second year for the rhinitis total score (P < 0.02), blocked nose score (P < 0.01) and nasal itching score (P < 0.01). Skin reactivity to house dust mites was significantly reduced in the group receiving house dust mite extract (P < 0.03). No statistical difference was observed between the two groups for medication scores, but a low medication consumption was observed in all patients. No serious and no systemic adverse reactions were reported.
                This study indicates the superiority of active treatment vs. placebo, evaluated on efficacy criteria (rhinitis score) or objective criteria (skin reactivity). The availability of a solid form (tablet) could represent a progress in terms of patient acceptability. Pruritus is a significant symptom among patients receiving hemodialysis. However, its underlying mechanisms remain obscure. Substance P, a neuropeptide, has been implicated in the mediation of pain and some itch sensations. Local application of capsaicin depletes the peripheral neurons of substance P and may block the conduction of pain or pruritus. This study aims to assess the efficacy and safety of capsaicin 0.025% cream in the treatment of hemodialysis-related pruritus and to further explore the underlying pathomechanism. Nineteen hemodialysis patients with idiopathic, moderate (n = 5) to severe (n = 14) pruritus were examined in a double-blind, placebo-controlled, crossover study and 17 of them completed the study. Topical agent of capsaicin or placebo base cream was applied to localized areas of pruritus 4 times a day. The severity of pruritus and treatment-related side effects (cutaneous burning/stinging sensations, dryness, or erythema) were evaluated weekly. The results showed (1) that 14 of 17 patients reported marked relief and 5 of these 14 patients had complete remission of pruritus during capsaicin treatment (Wilcoxon signed-ranks test, 2p < 0.001); (2) capsaicin was significantly more effective than placebo (Mann-Whitney rank sum test, 2p < 0.001) and a prolonged antipruritic effect was observed 8 weeks posttreatment; (3) no serious side effects were noted during the study and (4) there were no significant changes in serum concentrations of albumin, calcium, phosphorus, alkaline phosphatase, or intact parathyroid hormone during the treatment with either capsaicin or placebo. In summary, the present study indicates indirectly that idiopathic pruritus in some patients on maintenance hemodialysis may be transmitted by substance P from the peripheral sensory neurons to the central nervous system. Topical capsaicin with the unique pharmacological effect is demonstrated to markedly improve the pruritus of these patients. 5-Fluorouracil is an antimetabolite that has been known to be effective for the treatment of common warts.
                The objective was to evaluate the efficacy of a combination of 5-fluorouracil, lidocaine, and epinephrine (5-FU+LE) for the treatment of common warts.
                Of the 40 patients initially enrolled, 34 patients with at least 68 verruca vulgaris (one pair for each subject) completed the study. The selected warts were randomized into two treatment groups, with one wart on each patient receiving intralesional 5-FU+LE (4 mL of 50 mg/mL 5-fluorouracil and 1 mL of a mixture of 20 mg/mL [2%] lidocaine and 0.0125 mg/mL epinephrine) and the other receiving intralesional normal saline placebo using a Mantoux needle. Patients received up to four injections at weekly intervals and were followed at 1 and 6 months after the initial injection.
                Complete response was observed in 64.7% of the warts treated with 5-FU+LE compared to 35.3% in the warts treated with placebo (p<.05). Systemic reaction or treatment-related adverse medical events and recurrence rate did not differ significantly between two groups.
                The results show that intralesional 5-FU+LE is a safe and effective approach for common warts with high success rate. Pruritus is a distressing symptom affecting up to 90% of dialysis patients. Conventional treatment with antihistamines is often ineffective and may have unacceptable side effects. Serotonin (5-hydroxytryptamine type 3 [5-HT(3)]) is known to enhance pain perception and pruritic symptoms through receptors on sensory nerve endings. Antagonism of 5-HT(3) receptors may be of use in treating uremic pruritus. We randomly assigned 16 hemodialysis patients with persistent pruritus to treatment with the 5-HT(3)-receptor antagonist, ondansetron (8 mg), or placebo three times daily for 2 weeks each in a prospective, placebo-controlled, double-blind crossover study. Patients scored their intensity of pruritus daily on a 0-to-10 visual analogue scale (0 = no pruritus, 10 = maximal pruritus), and daily use of antihistamines as escape medication was recorded. The median daily pruritus score did not change significantly during active or placebo treatment (preondansetron, 5. 3; interquartile range [IQR], 3.4 to 6.3; during ondansetron, 3.9; IQR, 2.7 to 5.0; P = not significant; preplacebo, 3.7; IQR, 3.0 to 4. 6; during placebo, 3.6; IQR, 2.4 to 4.8; P = not significant). The median daily percentage of escape medication use decreased from 21% (IQR, 9 to 61) to 9% (IQR, 0 to 33) with ondansetron (P = not significant) and from 53% (IQR, 0 to 88) to 5% (IQR, 0 to 31) with placebo (P = not significant). There was no difference in predialysis biochemistry test results or dialysis efficacy during treatment phases. Ondansetron does not improve pruritus in hemodialysis patients. Use of antihistamines decreased with both ondansetron and placebo. Most patients receiving maintenance hemodialysis have pruritus, but its underlying mechanism remains unknown. Secondary hyperparathyroidism is another common problem in these patients, but its role in uremic pruritus is controversial. Capsaicin can deplete substance P from the peripheral neurons and is known to be effective in the treatment of pain and itching.
                Our purpose was to evaluate the role of parathyroid hormone (PTH) and substance P in uremic pruritus and to elucidate the underlying mechanisms.
                The study contained two phases. In phase I, we analyzed the correlation between the intensity of itching and serum levels of intact PTH. In phase II, patients with moderate to severe pruritus were placed into two groups: one with high PTH levels and one with low levels. A double-blind, placebo-controlled study of capsaicin 0.025% cream was conducted in phase II.
                Serum levels of intact PTH did not correlate with the intensity of pruritus and did not significantly change during treatment with capsaicin or placebo. Capsaicin was significantly more effective in alleviating uremic pruritus than the placebo, and no serious side effects were noted.
                Uremic pruritus is not related to PTH. Substance P may act as a neurotransmitter in uremic pruritus and topical capsaicin can be used in the treatment of localized pruritus. The safety and efficacy of sublingual-swallow immunotherapy (SLIT) in rhinitis caused by house-dust mite were evaluated in a double-blind, placebo-controlled study including 75 patients for 24 months.
                Patients received either placebo or SLIT with a standardized Dermatophagoides pteronyssinus (D.pt.) - D. farinae (D.f) 50/50 extract. The mean cumulative dose was 90,000 IR, equivalent to 2.2 mg of Der p 1 and 1.7 mg of Der f I. Symptom and medication scores were assessed throughout the study. Exposure to house-dust mite, skin sensitivity, and serum specific IgE and IgG4 were assessed before starting treatment and after 12 and 24 months.
                Seventy-two patients (36 active-36 placebo) were eligible for intent-to-treat analysis. Thirty-six patients dropped out of the study. The number of patients who dropped out due to lack of efficacy was eight out of 37 (21.6%) in the active treatment group compared to 15 out of 38 (39.5%) in the placebo group (chi-square=2.81, P=0.09). Total symptom and medication scores decreased significantly after 12 and 24 months (P<0.05) of treatment in both groups, but no significant difference was observed between the active and placebo groups. After 24 months, the number of patients with high levels of indoor allergenic load decreased significantly in both groups compared to baseline data (P=0.01). Specific IgE (D.pt. and D.f.) increased significantly in the active treatment group after 12 and 24 months, while no change was observed in the placebo group. Specific IgG4 levels were not significantly modified in either group. Two patients in each group reported mild adverse effects. No severe adverse effects were reported.
                We conclude that SLIT in rhinitis caused by house-dust mite was safe, but there was a lack of consistent clinical benefit compared to placebo, probably due to the impact of the allergen avoidance measures that lowered the allergen burden. The treatment of venous leg ulcers is often inadequate, because of incorrect diagnosis, overuse of systemic antibiotics and inadequate use of compression therapy. Stasis dermatitis related to chronic venous insufficiency accompanied by infected superficial ulcers must be differentiated from erysipelas, cellulitis and contact eczema.
                To assess the effectiveness of (1) topical povidone-iodine with and (2) without compression bandages, (3) to compare the efficacy of systemic antibiotics and topical antimicrobial agents to prevent the progression of superficial skin ulcers.
                63 patients presenting ulcerated stasis dermatitis due to deep venous refluxes were included in the study. The clinical stage of all patients was homogeneous determined by clinical, aetiological, anatomical and pathological classification. They were examined by taking a bacteriological swab from their ulcer area. Compression bandages were used in a total of 42 patients. Twenty-one patients with superficial infected (Staphylococcus aureus) ulcers were treated locally with povidone-iodine (Betadine), and 21 patients were treated with systemic antibiotics (amoxicillin). Twenty-one patients were treated locally with Betadine but did not use compression. The end point was the time of ulcus healing. The healing process of the ulcers was related to the impact of bacterial colonization and clinical signs of infection.
                Compression increases the ulcer healing rate compared with no compression. Using the same local povidone-iodine (Betadine) treatment with compression bandages is more effective (82%) for ulcus healing than without compression therapy (62%). The healing rate of ulcers treated with systemic antibiotics was not significantly better (85%) than that of the Betadine group. Using systemic antibiotics, the relapse rate of superficial bacterial infections (impetigo, folliculitis) was significantly higher (32%) than in patients with local disinfection (11%).
                Compression is essential in the mobilization of the interstitial lymphatic fluid from the region of stasis dermatitis. Topical disinfection and appropriate wound dressings are important to prevent wound infection. Systemic antibiotics are necessary only in systemic infections (fever, lymphangitis, lymphadenopathy, erysipelas). Common warts (verrucae vulgares) are human papilloma virus (HPV) infections with a high incidence and prevalence, most often affecting hands and feet, being able to impair quality of life. About 30 different therapeutic regimens described in literature reveal a lack of a single striking strategy. Recent publications showed positive results of photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) in the treatment of HPV-induced skin diseases, especially warts, using visible light (VIS) to stimulate an absorption band of endogenously formed protoporphyrin IX. Additional experiences adding waterfiltered infrared A (wIRA) during 5-ALA-PDT revealed positive effects.
                First prospective randomised controlled blind study including PDT and wIRA in the treatment of recalcitrant common hand and foot warts. Comparison of "5-ALA cream (ALA) vs. placebo cream (PLC)" and "irradiation with visible light and wIRA (VIS+wIRA) vs. irradiation with visible light alone (VIS)".
                Pre-treatment with keratolysis (salicylic acid) and curettage. PDT treatment: topical application of 5-ALA (Medac) in "unguentum emulsificans aquosum" vs. placebo; irradiation: combination of VIS and a large amount of wIRA (Hydrosun) radiator type 501, 4 mm water cuvette, waterfiltered spectrum 590-1400 nm, contact-free, typically painless) vs. VIS alone. Post-treatment with retinoic acid ointment. One to three therapy cycles every 3 weeks. Main variable of interest: "Percent change of total wart area of each patient over the time" (18 weeks). Global judgement by patient and by physician and subjective rating of feeling/pain (visual analogue scales). 80 patients with therapy-resistant common hand and foot warts were assigned randomly into one of the four therapy groups with comparable numbers of warts at comparable sites in all groups.
                The individual total wart area decreased during 18 weeks in group 1 (ALA+VIS+wIRA) and in group 2 (PLC+VIS+wIRA) significantly more than in both groups without wIRA (group 3 (ALA+VIS) and 4 (PLC+VIS)): medians and interquartile ranges: -94% (-100%/-84%) vs. -99% (-100%/-71%) vs. -47% (-75%/0%) vs. -73% (-92%/-27%). After 18 weeks the two groups with wIRA differed remarkably from the two groups without wIRA: 42% vs. 7% completely cured patients; 72% vs. 34% vanished warts. Global judgement by patient and by physician and subjective rating of feeling was much better in the two groups with wIRA than in the two groups without wIRA.
                The above described complete treatment scheme of hand and foot warts (keratolysis, curettage, PDT treatment, irradiation with VIS+wIRA, retinoic acid ointment; three therapy cycles every 3 weeks) proved to be effective. Within this treatment scheme wIRA as non-invasive and painless treatment modality revealed to be an important, effective factor, while photodynamic therapy with 5-ALA in the described form did not contribute recognisably - neither alone (without wIRA) nor in combination with wIRA - to a clinical improvement. For future treatment of warts an even improved scheme is proposed: one treatment cycle (keratolysis, curettage, wIRA, without PDT) once a week for six to nine weeks. Pruritus is one of the common problems in patients on hemodialysis. There are several causes for pruritus, and different treatment modalities are applied to control it. The aim of this study was to evaluate the therapeutic effect of capsaicin on pruritus, compared with placebo, in patients on hemodialysis.
                This randomized double-blinded cross-over clinical trial was performed on 34 patients on hemodialysis with uremic pruritus. The patients were divided into 2 groups, one group received capsaicin 0.03% and the other, placebo, for 4 weeks. Treatment was stopped for 2 weeks as washout period and continued as a cross-over technique. Pruritus scores were analyzed and compared.
                Thirty-four patients on long-term hemodialysis, 14 men and 20 women with a mean age of 57.0 +/- 18.6 years were studied. The mean of pruritus score before capsaicin treatment was 15.9 +/- 6.3, which was reduced to 6.4 +/- 3.9, 4.7 +/- 3.1, 3.2 +/- 2.9, and 2.5 +/- 2.5 on weeks 1 to 4, respectively (P < .001). In the placebo group, pruritus score before treatment was 15.0 +/- 6.0 on average, and it was 11.7 +/- 5.8, 9.4 +/- 5.9, 7.9 +/- 5.5, and 7.2 +/- 5.5, respectively, on weeks 1 to 4 (P < .001). There was no significant difference in pruritus scores before the treatment between the two groups, but after each week, the difference was significant (P < .001). Repeated measurement test showed that decreasing in pruritus severity in the capsaicin group was more than that in the placebo group during treatment period (P < .001).
                Capsaicin is a new safe and effective topical treatment for hemodialysis-induced pruritus in patients with end-stage renal disease. In a randomized trial conducted in 35 centers, we compared the clinical efficacy and safety of piperacillin plus tazobactam (TAZ) alone (monotherapy [MT]) versus those of TAZ combined with amikacin (AMK) (combined therapy [CT]) for the treatment of severe generalized peritonitis (SGP). Primary analysis consisted of blind assessment by an independent committee of the failure rate 30 days after the end of treatment in the modified intent-to-treat (ITT) analysis (mITT) population. Of the 241 patients with suspected SGP randomized into the study, 227 were eligible for ITT analysis, including 204 (99 in the MT group and 105 in the CT group) with confirmed SGP (mITT population). A total of 159 patients were eligible for per-protocol (PP) analysis. The clinical failure rates were equivalent in the mITT and PP populations (MT versus CT): 56 versus 52%, (odds ratio [OR] 0.87, 90% confidence interval [CI] = 0. 6 to 1.27) for mITT and 49 versus 49% (OR = 1.03, 90% CI = 0.67 to 1. 59) for PP analysis. Mortality rates (ITT population, 19%; PP population, 21%) and overall adverse event rates (ITT population, 55%; PP population, 54%) were also similar. Six patients (three in MT group and three in the CT group) developed acute renal failure. In conclusion, the addition of AMK to TAZ does not seem to be necessary for the treatment of SGP, even after adjustment for the simplified acute physiology score (SAPS II) and type of SGP. The aim of this study was to evaluate the effectiveness of granulocyte-macrophage colony-stimulating factor (GM-CSF) mouthwashes in the prevention of severe mucositis induced by high doses of chemotherapy.
                Ninety consecutive patients affected by solid tumors and undergoing high-dose chemotherapy with autologous peripheral blood stem cell transplantation rescue were randomized to receive placebo versus GM-CSF mouthwash 150 micro g/day. Patients were stratified on the basis of the conditioning treatment and the consequent different risk of severe oral mucositis. Treatment was administered from the day after the end of chemotherapy until the resolution of stomatitis and/or neutrophil recovery.
                The statistical analyses were intention-to-treat and involved all patients who entered the study. The severity of stomatitis was evaluated daily by the physicians according to National Cancer Institute Common Toxicity Criteria. Both study and control groups were compared with respect to the frequency [30% versus 36%, chi(2) exact test, not significant (NS)] and mean duration (4.8 +/- 4.7 versus 4.4 +/- 2.7 days, t-test, NS) of severe stomatitis (grade > or =3). Oral pain was evaluated daily by patients themselves by means of a 10 cm analog visual scale: the mean (+/- standard error of the mean) maximum mucositis scores were 4.8 +/- 3.5 versus 4.2 +/- 3.5 cm (t-test, NS). Furthermore, 15/46 patients in the study group (33%) and 19/44 patients in the control group experienced pain requiring opioids (chi(2) exact test, NS).
                We did not find any evidence to indicate that prophylaxis with GM-CSF mouthwash can help to reduce the severity of mucositis in the setting of the patients we studied. Stomatitis is a major dose-limiting toxicity of bolus fluorouracil (5FU)-based chemotherapy regimens, despite the use of oral cryotherapy. Pursuant to preliminary data that suggested a sucralfate oral solution could alleviate chemotherapy-induced oral mucositis, we developed a prospective trial to test this contention.
                A phase III, double-blind, placebo-controlled clinical trial was designed. Patients were entered onto the study at the time of the first cycle of 5FU-based chemotherapy. All patients received oral cryotherapy for 30 minutes with each dose of 5FU. In addition, each patient was randomized to receive either a sucralfate solution or a placebo solution to be used if they developed mouth tenderness or mouth sores. The study solution was to be used four times daily for 7 days starting on the first day of mouth tenderness or mouth sores. Stomatitis scores were determined by health care providers and by patients themselves.
                There was a total of 131 assessable patients entered onto this trial, 50 of whom developed mucositis and used the study medication (27 sucralfate and 23 placebo). There was no suggestion of any difference in stomatitis severity or duration on either protocol arm.
                The resultant data from this clinical trial did not support the prestudy hypothesis that sucralfate would be beneficial for the treatment of 5FU-induced stomatitis. Sixty-two patients with ulcerative colitis localised to the distal sigmoid colon and rectum (less than 20 cm) entered the trial. Thirty-two were treated with 5-ASA 500 mg suppositories (Asacol) 3 times a day for 1 month while 30 received a placebo given in the same regime. Clinical, sigmoidoscopic and histological assessment was carried out before, after 15 days and after 1 month of treatment. At the end of the study 5-ASA suppositories showed significantly better results in all the parameters recorded than placebo (p less than 0.01). There were no unwanted effects related to the use of suppositories. This treatment should therefore be offered as a first choice for patients with distal rectosigmoiditis. During the last decades, management of intertriginous psoriasis (IP) has been unsatisfactory because of the adverse effects associated with long-term corticosteroid application and the lack of alternatives. Recently, both pimecrolimus and tacrolimus have been investigated for this indication and shown to be safe and effective. So far, to our knowledge, a comparison of one of these drugs with standard regimens for IP has not been performed.
                A single-center, 4-week, double-blind, randomized, vehicle-controlled comparison study to assess the safety and efficacy of 1% pimecrolimus, 0.005% calcipotriol, and 0.1% betamethasone valerate in the treatment of IP.
                Dermatologic hospital at Ruhr University of Bochum.
                Eighty adults with IP.
                Treatment of IP with 1% pimecrolimus, 0.005% calcipotriol, 0.1% betamethasone, or the vehicle once daily for 28 days.
                Mean reduction of the Modified Psoriasis Area and Severity Index (M-PASI) score after 28 days of treatment was considered the primary outcome measure, which was analyzed on an intention-to-treat basis. The secondary outcome was a visual analog scale score for itching.
                After 4 weeks of treatment, the 3 active compounds and the vehicle resulted in a significant decrease in mean M-PASI score (86.4% for 0.1% betamethasone, 62.4% for 0.005% calcipotriol, 39.7% for 1% pimecrolimus, and 21.1% for vehicle). The 0.1% betamethasone was significantly more effective than 1% pimecrolimus during the study period (P<.05). No significant difference was found between 0.005% calcipotriol and 0.1% betamethasone and between 0.005% calcipotriol and 1% pimecrolimus. The visual analog scale score for pruritus decreased by 78% for 0.1% betamethasone, 57% for 0.005% calcipotriol, 35% for 1% pimecrolimus, and 43% for the vehicle, again demonstrating a clear advantage for the corticosteroid (P<.05).
                The 1% pimecrolimus was shown to be less potent than 0.1% betamethasone in the treatment of IP. Considering the adverse-effect profile of long-term application of corticosteroids, occasional or intermittent rescue therapy with short-term topical corticosteroids and maintenance with a less potent agent, such as 1% pimecrolimus or 0.005% calcipotriol, might be appropriate for patients with IP in general practice. Impetigo is a common skin infection, primarily caused by Staphylococcus aureus and mainly occurring in children. It is usually treated topically with antibiotics to achieve a quick cure and prevent spread of the infection. Worldwide, resistance rates of S. aureus against commonly used antibiotics are rising. Retapamulin belongs to a newly developed class of antibiotics for the treatment of uncomplicated skin infections.
                Our aim was to compare the efficacy and safety of topical application of retapamulin ointment with topical placebo ointment in the treatment of primary impetigo.
                In a randomized, double-blind, multicentre study, patients received either topical retapamulin ointment 1% twice daily for 5 days or topical placebo. Patients were enrolled into the study for 14 days and attended the clinic for three visits during which clinical and laboratory evaluations were performed.
                Two hundred and thirteen patients were randomized, with 139 evaluable patients in the retapamulin group and 71 in the placebo group. Based on the primary efficacy endpoint of clinical response after 7 days (intention to treat), retapamulin ointment was superior to placebo (success rate 85.6% vs. 52.1%; P<0.0001). Similar results were found in the per protocol analysis and in the subgroup of patients who had a pathogen isolated at baseline. The most common adverse effect, pruritus at the application site, was reported by 6% and 1% of patients in the retapamulin and placebo groups, respectively.
                This study shows that topical retapamulin is effective and safe in the treatment of primary impetigo, offering a new treatment option. Pruritus in haemodialysis patients is an intractable disease and substantially impairs their quality of life. Based on the results of our earlier clinical study, we hypothesized that the micro-(mu) opioid system is itch-inducible, whereas the kappa (kappa) system is itch-suppressive.
                The efficacy and safety of nalfurafine hydrochloride (a novel kappa-receptor agonist) were prospectively investigated by randomly (1:1:1) administering 5 or 2.5 microg of the drug or a placebo orally for 14 days using a double-blind design in 337 haemodialysis patients with itch that was resistant to currently available treatments, such as antihistamines.
                The mean decrease in the visual analogue scale (VAS) from baseline, the study's primary endpoint, was significantly larger in the 5-microg nalfurafine hydrochloride group (n = 114) than in the placebo group (n = 111, P = 0.0002, one-sided test at 2.5% significance level). The decrease in the VAS in the 2.5-microg group (n = 112) was also significantly larger than that in the placebo group (P = 0.0001). The incidence of adverse drug reactions (ADRs) was 35.1% in the 5-microg group, 25.0% in the 2.5-microg group and 16.2% in the placebo group. Moderate to severe ADRs were observed in 10 of the 226 patients. The most common ADR was insomnia (sleep disturbance), seen in 24 of the 226 nalfurafine patients.
                This Phase III, randomized, double-blind, placebo-controlled, parallel-group, prospective study based on VAS evaluations clearly showed that orally taken nalfurafine hydrochloride effectively reduced itches that were otherwise refractory to currently available treatments in maintenance haemodialysis patients, with few significant ADRs. This novel drug was officially approved for clinical use in January 2009 by the Ministry of Health, Labour and Welfare of Japan. Organ transplant recipients (OTR) are at high risk of developing nonmelanoma skin cancer and premalignant epidermal dysplasia (carcinoma in situ/ Bowen's disease and actinic keratoses). Epidermal dysplasia is often widespread and there are few comparative studies of available treatments.
                To compare topical methylaminolaevulinate (MAL) photodynamic therapy (PDT) with topical 5% fluorouracil (5-FU) cream in the treatment of post-transplant epidermal dysplasia.
                Eight OTRs with epidermal dysplasia were recruited to an open-label, single-centre, randomized, intrapatient comparative study. Treatment with two cycles of topical MAL PDT 1 week apart was randomly assigned to one area of epidermal dysplasia, and 5-FU cream was applied twice daily for 3 weeks to a clinically and histologically comparable area. Patients were reviewed at 1, 3 and 6 months after treatment. The main outcome measures were complete resolution rate (CRR), overall reduction in lesional area, treatment-associated pain and erythema, cosmetic outcome and global patient preference.
                At all time points evaluated after completion of treatment, PDT was more effective than 5-FU in achieving complete resolution: eight of nine lesional areas cleared with PDT (CRR 89%, 95% CI: 0.52-0.99), compared with one of nine lesional areas treated with 5-FU (CRR 11%, 95% CI: 0.003-0.48) (P = 0.02). The mean lesional area reduction was also proportionately greater with PDT than with 5-FU (100% vs. 79% respectively). Cosmetic outcome and patient preference were also superior in the PDT-treated group.
                Compared with topical 5-FU, MAL PDT was a more effective and cosmetically acceptable treatment for epidermal dysplasia in OTRs and was preferred by patients. Further studies are now required to confirm these results and to examine the effect of treating epidermal dysplasia with PDT on subsequent development of squamous cell carcinoma in this high risk population. The treatment of viral warts remains challenging. A variety of treatment modalities have been used with a range of success. Fluorouracil has been shown to be effective in treating warts but the method of its delivery directly onto the affected tissue has been of little efficacy. We evaluated the safety and efficacy of intralesional 5-fluorouracil in the treatment of verrucae.
                Seventy-six patients with a total 315 verrucae were randomized to receive either a 5-fluorouracil, lidocaine and epinephrine (5-FU + LE) mixture or serum saline injection into the paired verrucae in the same patient. The mixture of 5-FU (4 cm(3), 50 mg/mL), lidocaine (1 cm(3), 20 mg/mL) and epinephrine (0.0125 mg/mL) was injected into the base of the wart using a mantoux needle. Each lesion was infiltrated with either of the solutions once a week for up to a maximum of 4 weeks, and the patients were followed up for 6 months.
                Complete response was noted in an average of 70% of the verrucae treated with the 5-FU + LE mixture and in 29% of those in the placebo group (P < 0.001). No clinically significant systemic and local adverse effects occurred. Pain and burning were noted as an immediate injection pain. Recurrence rates were evaluated and no statistically significant difference between the two groups was found.
                The results demonstrate that treatment of verrucae with 5-FU + LE mixture is safe and effective. Renal itch is a relatively common and distressing problem for patients with chronic renal failure. Ondansetron, a serotonin type 3 receptor antagonist was developed for relief of chemotherapy induced nausea. Recently, anecdotal reports describe relief of renal itch with ondansetron.
                We performed a double-blind randomized placebo-controlled trial to objectively assess the effectiveness of ondansetron in renal itch.
                With approval from the local ethical committee, 24 patients on haemodialysis were enrolled in the trial. On a random basis 14 patients were blindly allocated to the ondansetron-placebo sequence and 10 to the placebo-ondansetron sequence. Baseline values for itch were obtained for 7 days before the treatment period and there was a 7-day washout between the treatment periods. During the treatment patients received either 8 mg of ondansetron three times a day or a placebo tablet three times a day for 2 weeks. Patients were asked to record the severity of their pruritus on a visual analogue scale (VAS) twice a day. At the end of the study patients were asked blindly which treatment they had preferred.
                Seventeen patients completed the trial. Pruritus decreased by 16% (95% CI: 0.5-32%) during active treatment and by 25% (95% CI: 9-41%) during treatment with placebo. The change in VAS scores during treatment with ondansetron (P = 0.04) and placebo (P = 0.01) were both significant. Eleven patients expressed a preference, seven for placebo and four for ondansetron.
                Our results show that ondansetron is no better than placebo in controlling renal itch. This study was designed to determine the effect of pentoxifylline (Trental) on the clinical and pathologic course of oral submucous fibrosis. This drug is a methylxanthine derivative that has vasodilating properties and was envisaged to increase mucosal vascularity.
                This investigation was conducted as a randomized clinical trial incorporating a control group (Standard drug group SDG, multivitamin, and local heat therapy) in comparison to pentoxifylline test cases (Experimental drug group EDG, 400mg 3 times daily, as coated, sustained release tablets). The stipulated treatment period was 7 months and a total of 29 cases of advanced fibrosis (14 test subjects and 15 age and sex matched diseased controls) were included in this study and 100% compliance was reported at the end ofthe test period.
                Mild gastric irritation that could be managed by diet protocols was the only untoward symptom reported during this trial. Review of the patients and controls was done at an interval of 30 days and subjective and objective measurements were recorded. The follow up data at each visit with respect to each other and to base-line values was calibrated using a nonparametric test of Mann-Whitney (Kruskal-Wallis test). Significant comparisons with regard to improvement were recorded as objective criteria of mouth opening (t=11.285, p= 0.000), tongue protrusion (t= 3.898, p = 0.002), and relief from perioral fibrotic bands (p = 0.0001554). Subjective symptoms of intolerance to spices (p = 0.0063218), burning sensation of mouth (p = 0.0005797), tinnitus (p=0.000042), difficulty in swallowing (p=0.0000714). and difficulty in speech (p=0.0000020) were also recorded significant improvement at the end of the trial period.
                This pilot investigation points to the effectiveness of pentoxifylline as an adjunct therapy in the routine management of oral submucous fibrosis. The intramuscular (i.m.) route is generally used for treatment of childhood falciparum malaria in outlying health care units in Togo. The purpose of this randomized therapeutic trial was to compare the efficacy and tolerance of diluted injectable quinine administered by the i.m. versus intrarectal (IR) route. A total of 64 children ranging in age from 8 months to 15 years were treated, i.e. 32 for each administration route. All children presented uncomplicated falciparum malaria in association with vomiting in 30 cases, a single unrecurring seizure with postictal coma lasting less than 30 minutes in 25 patients, or prostration without neurological manifestations in 9. Injectable quinimax (an association of cinchona alkaloids) was diluted to a concentration of 60 mg base/ml for i.m. injection into the thigh and 30 mg base/ml for use by the IR route. Administration was performed every 12 hours for 72 hours at a dose of 12.5 mg/kg for patients in the i.m. group or at a dose of 15 mg/kg in the IR group. The anus and lower rectal mucosa were examined using an anal valve before and after treatment using the IR route. Analysis of mean temperature curves demonstrated no significant difference between the clinical effectiveness of quinimax administered by the i.m. versus IR route (p > 0.05). Similar effect were also observed on parasitemia which disappeared completely in all patients by the end of the 72-hour treatment. The main problems were insufficient product retention requiring re-administration in 25% of patients in IR group and residual pain at the injection site in 12.5% of patients in the i.m. group. Endoscopic examination revealed no evidence of ulceration or necrosis of the anorectal mucosa. These findings indicate that administration of diluted injectable quinine by IR route is an effective, well-tolerated alternative for treatment of childhood falciparum malaria. It should be used preferentially in outlying health care units in patients presenting severe malaria pending transfer to an hospital, or signs of "intermediate severity" such as hyperpyrexia, hyperparasitemia, unrepeated seizure, or intensive vomiting. The optimal treatment for cutaneous leishmaniasis (CL) is not known. Topical paromomycin is one of the many drugs that have been suggested for the treatment of CL caused by Leishmania major. Recently, topical photodynamic therapy (PDT) has been reported to be effective in the treatment of CL.
                To compare the parasitological and clinical efficacy of PDT vs. topical paromomycin in patients with Old World CL caused by L. major in Iran.
                In this trial, 60 patients with the clinical and parasitological diagnosis of CL were recruited and were randomly divided into three treatment groups of 20 subjects each. Group 1 was treated with weekly topical PDT, and groups 2 and 3 received twice-daily topical paromomycin and placebo, respectively. The duration of treatment was 4 weeks for all groups. These groups were followed for 2 months after the end of treatment.
                In total, 57 patients with 95 lesions completed the study. At the end of the study, complete improvement was seen in 29 of 31 (93.5%), 14 of 34 (41.2%) and 4 of 30 lesions (13.3%) in groups 1, 2 and 3, respectively (P<0.001). At the same time point, 100%, 64.7% and 20% of the lesions had parasitological cure in group 1, 2 and 3, respectively (P<0.001).
                Topical PDT can be used safely as a rapid and highly effective alternative treatment choice for Old World CL in selected patients. Pruritus is a common and disabling symptom for patients undergoing hemodialysis. Many topical and systemic treatments have been used for uremic pruritus, mostly in anecdotal reports. A recent case series demonstrated that topical tacrolimus ointment 0.03% had a significant antipruritic effect for patients with uremia. In an attempt to confirm these findings, we conducted a randomized, double-blind, vehicle-controlled study to assess the efficacy of tacrolimus ointment 0.1% for the treatment of hemodialysis-related pruritus. The results of this study do not demonstrate that tacrolimus ointment 0.1% is more effective than vehicle in relieving uremic pruritus. Parallel follow-up of clinical and inflammatory markers during sub-lingual immunotherapy (SLIT) is highly beneficial. Twenty-four children (age 4-16) monosensitized to house dust mite were randomized to receive either active or placebo SLIT for 1 yr in a double-blind placebo controlled design (Marcucci et al., Allergy 2003: 58: 657-62). Thereafter, for 2 yr they all received active treatment. Symptom scores for rhinitis, asthma, and drug usage were daily recorded. Eosinophil cationic protein (ECP) and tryptase in sputum and nasal secretions, serum and nasal mite-specific immunoglobulin E (IgE) were recorded before treatment and at 10-12 months intervals. Nasal ECP and nasal tryptase after specific nasal provocation tests were significantly reduced as compared to baseline values (p = 0.0043 and 0.0195, respectively) in the third year of active treatment. None of the other inflammatory parameters was increased. In placebo treated patients all these parameters tended to decrease only after switching to active treatment. Clinical scores did not improve in treated vs. placebo patients in the double-blind placebo-controlled phase of the study. In both cohorts a clinical benefit was observed as intra-group score reduction as compared to baseline. A significant difference was reached in patients treated for 2 yr for rhinitis and asthma (p = 0.0009 and 0.0019, respectively) but not for drug usage and in patients treated for 3 yr for rhinitis, asthma, and drug usage (p = 0.0105, 0.0048, and 0.02, respectively). SLIT in children monosensitized to mites reverted the spontaneous increase in nasal IgE and in local parameters of allergic inflammation. These outcomes were followed by a consolidated clinical improvement in the second and third year of treatment. To evaluate the tolerability and efficacy of specific immunotherapy with mite extracts, we performed a double-blind, placebo-controlled immunotherapy study in 30 patients with proven allergy to mite allergens. The specific immunotherapy with standardized extracts of Dermatophagoides pteronyssinus and D. farinae by a clustered rush protocol was well tolerated. After 1 year of treatment, the actively treated group showed a significant improvement compared to their starting value as well as to the placebo-treated patients with regard to skin prick test, conjunctival provocation test, and subjective rhinitis score. The subjective asthma score and bronchial hyperreactivity, measured by the methacholine provocation test, was improved in comparison to the starting value, but not to the placebo group, after 12 months. However, a further, open comparison of the placebo- and verum-treated groups at 18 months revealed a significant reduction. The drug intake was not increased in the verum-treated group. Exposure to mite levels was constant throughout this time period, as revealed by antigen measurement. We conclude that specific immunotherapy in perennial, mite-allergen-induced asthma may reduce not only immediate, IgE-mediated symptoms but, after a rather long time period of 12-18 months, also the inflammatory component of bronchial asthma, thus leading to a reduction of unspecific hyperreactivity.
The findings of this review indicate that the number of systemic and topical drugs used for the different subforms of pruritus is increasing. Different interventions have been shown to be effective in the treatment of pruritus of different origins. Nevertheless, an optimal therapy for pruritus is constrained due to the limited understanding of crucial itch mediators and receptors in the various subforms of itch. Ideal antipruritic therapies are still lacking, especially for palliative care patients.
This systematic review also indicates that there is insufficient evidence to give any concrete recommendations regarding treatment of pruritus in palliative care patients. Due to the very small sample sizes and poor methodological quality of the majority of studies that were included, the results of this review need to be interpreted with caution. Furthermore, the generalizability is questionable. Additional studies, and particularly carefully designed treatment trials, are needed to provide valid evidence for adequate treatment of pruritus in palliative care patients.