Computerized recording of itch in patients on maintenance hemodialysis

Itch was assessed both continuously using a computerized method, Pain-Track, and retrospectively using visual analogue scales (VAS) by 28 patients undergoing maintenance hemodialysis and suffering from uremic pruritus. Measurements were performed during 7 consecutive days including three dialysis sessions. Pain-Track recordings showed that itch intensity was greater during dialysis than on days following dialysis (p less than 0.05). Possible explanations are that pruritogenic substances might be released during treatment or that removal of such substances during dialysis leads to amelioration of symptoms after treatment. Alternatively, lowering of the sensory threshold due to general discomfort in association with dialysis may exacerbate the itch intensity. There was no consistent difference between daytime and bedtime itch scores over the week, except on the second day without treatment, when bedtime itch ratings significantly exceeded those during the day (p less than 0.05), suggesting that factors other than inactivity are essential for this peak in itch intensity. Thus, after 2 days without treatment, when patients become increasingly metabolically deranged, they reported maximal itch, implying that the accumulation of pruritogenic substances is of major importance in the pathogenesis of uremic pruritus. There was a positive correlation between Pain-Track and VAS data, although significant fluctuations in itching could be detected only with Pain-Track.     

A randomized, double-blind, placebo-controlled study of the efficacy of tetracaine gel (Ametop) for pain relief during topical photodynamic therapy

BACKGROUND: Many patients find topical 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) painful. Local anaesthetics are not routinely used and their effect on PDT pain has not been examined. OBJECTIVES: To evaluate the efficacy of tetracaine gel (Ametop) for pain relief during and after PDT. METHODS: A prospective, double-blind, placebo-controlled study of 42 patients with lesions (< or =2 cm diameter) of superficial nonmelanoma skin cancer or dysplasia. Patients were randomized to either tetracaine (4% w/w) (n=22) or vehicle (n=20) gel under occlusion for 1 h pre-irradiation. Pain was assessed during and after irradiation using a visual analogue scale (VAS) and faces pain scale. RESULTS: Patients who received tetracaine gel experienced only slightly less pain during PDT (median VAS 4) compared with those who received placebo (median VAS 4.5) (95% confidence interval for difference 0-3, P=0.08). No significant difference in pain was experienced between the treatment groups immediately after irradiation or later. CONCLUSIONS: When compared with placebo, tetracaine gel did not significantly reduce pain during or after PDT for small lesions of superficial basal cell carcinoma, Bowen's disease or actinic keratosis.     

Renal itch

Renal itch is localized or generalized itch, affecting patients with chronic renal failure, where there is no primary skin disease and no systemic or psychological dysfunction that might cause pruritus. It does not result from raised serum urea levels. The prevalence of renal itch has increased with the growing population in chronic renal failure and is a considerable cause of morbidity. The prevalence of itch increases with deteriorating renal function but does not improve significantly with dialysis. The pruritus is independent of duration of dialysis or cause of renal failure. The aetiology of renal itch is unclear. There is little evidence of a major role for histamine and antihistamines are rarely beneficial. Hyperparathyroidism, abnormal cutaneous innervation and endogenous opioids have been postulated as contributory factors. Treatment of renal itch is difficult. Naltrexone, oral activated charcoal, UVB phototherapy and ondansetron have been shown to be effective. Topical capsaicin may be of benefit in patients with localized pruritus. The definitive treatment for renal itch remains renal transplantation.     

Transepidermal water loss, serum IgE and beta-endorphin as important and independent biological markers for development of itch intensity in atopic dermatitis

BACKGROUND: Although itch is the predominant symptom of atopic dermatitis (AD), it is poorly characterized and subjective. The objective assessment of itch intensity is important for treatment and follow-up in patients with AD. OBJECTIVES: To determine what objective clinical parameter(s) could be used as biomarker(s) for itch intensity in patients with AD. METHODS: This is a retrospective and cross-sectional study. Seventy-five patients, aged 7 months-49 years with equal sex ratio, were enrolled in 2000 according to criteria proposed by Hanifin and Rajka. Thirty-five age- and sex-matched subjects who visited the dermatological clinic but were otherwise healthy served as controls. Subjective itch intensity was divided into four grades of severity. Disease severity was measured by SCORAD index, which also includes itch intensity as part of the measurement. Transepidermal water loss (TEWL) and skin surface pH were measured by noninvasive methods in clinically normal skin on the forearm. Serum beta-endorphin and vasoactive intestinal peptide (VIP) were determined by radioimmunoassay. Ordinal logistic regression was used to assess the trend of the subjective itch intensity and SCORAD index by serum IgE, beta-endorphin, VIP, TEWL and skin pH. RESULTS: There were significant trends for itch intensity with IgE, beta-endorphin and TEWL. After adjustment for sex, age and other variables, the odds ratio (OR) for itch intensity by log IgE, beta-endorphin and TEWL was 2.103 [95% confidence interval (CI) 1.222-3.618], 1.100 (95% CI 1.005-1.203) and 1.081 (95% CI 1.009-1.158), respectively. The OR for disease severity by log IgE, beta-endorphin and TEWL was 2.250 (95% CI 1.149-4.407), 1.156 (95% CI 1.086-1.231) and 1.071 (95% CI 0.971-1.182), respectively. In contrast, there was no association between serum VIP concentration and itch intensity. CONCLUSIONS: Beta-endorphin and IgE are both useful biomarkers for itch and disease severity in patients with AD, while TEWL is a good biomarker for itch intensity. These biomarkers provide a way to assess the itch intensity in patients with AD.     

The addition of topical doxepin to corticosteroid therapy: an improved treatment regimen for atopic dermatitis

Three hundred and forty-nine (349) patients with pruritic atopic dermatitis who provided written informed consent participated in this study. To enter, patients had to have experienced moderate to severe pruritis accompanying their eczematous lesions daily for at least 1 week prior to enrollment, a family history of atopy and/or a personal history of atopic dermatitis, 25% or less body surface area affected by atopic dermatitis, and good general health. After enrollment, patients were required to discontinue systemic corticosteroids at least 4 weeks prior to study entry as well as antipruritic and central nervous system-active medications at least 1 week before entry. In addition, no topical medications were permitted to be applied to treatment sites for at least 2 days before entry. Patients who had infected treatment sites, other concurrent cutaneous conditions, or who were pregnant or lactating were excluded from the study. This was an 8-day multicenter double-blind parallel-design study assessing the effects of adding topical doxepin to topical corticosteroid treatment vs. the topical corticosteroid treatment itself. All test products were incorporated in an identical cream base to that for doxepin hydrochloride cream. Using a computer-generated randomization schedule, patients were assigned to treatment groups receiving creams containing: (1) 2.5% hydrocortisone; (2) 0.1% triamcinolone acetonide; (3) 2.5% hydrocortisone and 5% doxepin hydrochloride; (4) 0.1% severity acetonide and 5% doxepin hydrochloride. Patients were instructed to apply the study cream four times daily for 8 days of treatment. The physician initially rated the patients’ pruritis as mild, moderate, or severe, and their atopic dermatitis as mild, moderate, marked, or severe. A baseline visual analog scale (VAS) for pruritis severity, consisting of a 100-mm horizontal line labeled “no itch” and “worst itch imaginable” at opposite ends, was completed by the patients to quantify the intensity of pruritis experienced during the week before study entry and daily during the study. Additionally, daily during the study, each patient completed a VAS for pruritis relief by marking a 100-mm vertical line labeled “no relief from itching” and “complete relief from itching” at opposite ends. After the baseline evaluation, subsequent visits were scheduled for days 2, 3, 4, and 8. At each visit, the physician reviewed the patient’s daily VASs to record a global evaluation of pruritis relief and rated the overall change in dermatitis on a five-point scale ranging from much worse to much better. Any reports of adverse effects were also recorded. Analysis of covariance was used to assess the VAS for pruritis severity. With the use of the row mean score with ridit assigned scores, Cochran–Mantel–Haenszel (CMH) analysis for ordered response categories was performed in the analysis of the physicians’ global evaluations (pruritis and dermatitis). Intent-to-treat analysis was used for all efficacy variables. Statistical significance was defined as p < 0.05 (two-tailed).     

Azathioprine in severe adult atopic dermatitis: a double-blind,placebo-controlled,crossover trial

BACKGROUND: There is a limited range of treatments for severe atopic dermatitis (AD). Azathioprine has often been used but there has been no randomized controlled trial of this drug to confirm its efficacy in AD. OBJECTIVES: To establish or refute the efficacy of azathioprine in severe AD. To investigate the safety and tolerability of azathioprine in this patient population. METHODS: We performed a double-blind, randomized, placebo-controlled, crossover trial of azathioprine in adult patients with severe AD. Each treatment period was of 3 months' duration. Treatments were azathioprine 2.5 mg kg(-1) day(-1) and matched placebo. Disease activity was monitored using the SASSAD sign score. In addition, severity of pruritus, sleep disturbance and disruption of work/daytime activity were monitored using visual analogue scales. Adverse events were recorded and haematological and biochemical monitoring was performed. RESULTS: Thirty-seven subjects were enrolled, mean age 38 years (range 17-73). Sixteen were withdrawn, 12 during azathioprine treatment and four during placebo treatment. The SASSAD score fell by 26% during treatment with azathioprine vs. 3% on placebo (P < 0.01). Pruritus, sleep disturbance and disruption of work/daytime activity all improved significantly on active treatment but not on placebo. The difference in mean improvement between azathioprine and placebo was significant for disruption of work/daytime activity (P < 0.02) but not for pruritus or sleep disturbance. Gastrointestinal disturbances were reported by 14 patients during azathioprine treatment and four were withdrawn as a result of severe nausea and vomiting. Leukopenia was observed in two patients and deranged liver enzymes in eight during treatment with azathioprine. CONCLUSIONS: Azathioprine is an effective and useful drug in severe AD although it is not always well-tolerated. Monitoring of the full blood count and liver enzymes is advisable during treatment.     

Prospective randomized non-blinded clinical trial on the use of dapsone plus antihistamine vs. antihistamine in patients with chronic idiopathic urticaria

Background Treatment of chronic idiopathic urticaria (CIU) is difficult. Objective The purpose of this study was to evaluate the efficacy and safety of dapsone in CIU. Methods The response to dapsone was evaluated in 65 CIU patients with a randomized, two armed study: 3‐month dapsone + desloratadin and 3‐month desloratadin. All were followed for up to 3 months and 3 months after; all took desloratadine 10 mg daily throughout the study. The primary measure of efficacy was a daily urticaria activity score (UAS) of weal numbers and itch (maximum score, 42 per week). Results Sixty‐five patients completed the randomized 3‐month trial medication. Mean reduction in UAS from baseline at 3 months was 7 [95% confidence interval (95% CI), 6.92–7.08] for active group and 5.77 (95% CI, 5.47–6.08) for control subjects (P < 0.001). The reduction in visual analogue score (VAS) at 3 months for active group (mean, 2.58; 95% CI, 2.33–2.83) and control subjects (mean, 2.55; 95% CI, 2.38–2.73) was also significant (P < 0.001). The reduction of UAS and VAS at 3 months compared between active group and control subjects showed no significant difference. Mean reduction in UAS from the end of the study at 3 months after was 1.16 and –4.8 for active and control subjects, respectively. These results were compared with each other, and it was statistically significant (P ≤ 0.05). Limitations No placebo was used. The study was not blinded. Lack of blinding may have led to bias. The follow‐up period was short. Conclusion This study shows that dapsone leads to a persistent decrease in VAS and UAS and is associated with complete remission in some patients.     

The effect of topically applied aspirin on localized circumscribed neurodermatitis

BACKGROUND: Lichen simplex chronicus is a troublesome intractable itchy dermatosis, which may persist despite intensive topical treatments. Recently it has been demonstrated that topical aspirin solution with dichloromethane has a significant antipruritic effect in an experimentally induced itch. OBJECTIVE: The aim of this double-blind, crossover placebo trial was to evaluate the efficacy of this solution in the treatment of lichen simplex chronicus. METHODS: Twenty-nine patients with lichen simplex chronicus of at least 3 months' duration that did not respond to topical corticosteroids were randomized in a double-blind fashion to receive aspirin/dichloromethane solution in treatment period 1 for 2 weeks followed by placebo in treatment period 2 or placebo followed by aspirin in period 2 with a crossover design after a 2-week washout. The patients rated the pruritus intensity before and during therapy with a visual analog scale; a blinded investigator performed photographic assessment. RESULTS: A significant therapeutic response was achieved in 11 (46%) of the patients who completed the study compared with 3 patients (12%) receiving placebo. Overall, aspirin-treated patients experienced an average decrease in the visual analog scale of 2.18 +/- 2.86 versus 0.69 +/- 2.31 of those receiving placebo. The difference between the 2 treatments for week 2 was significant (P =.03). CONCLUSION: The study suggests that topical aspirin/dichloromethane might be a practical treatment for lichen simplex chronicus.     

Efficacy of short-course oral prednisolone in polymorphic light eruption: a randomized controlled trial

BACKGROUND: Polymorphic light eruption (PLE) is the most common so-called idiopathic photosensitivity disorder and affects up to 15% of the population in the U.K.; brief courses of systemic steroids have been tried and anecdotally have apparently been dramatically effective in the treatment of acute attacks. OBJECTIVES: To assess the efficacy and safety of a short course of moderate-dose oral prednisolone used from the earliest onset of the eruption in the treatment of PLE. METHODS: The study was double-blind placebo-controlled, all patients being given both prednisolone and placebo, but randomized to take either one or the other from the earliest sign of onset of rash; if within 48 h there was no improvement, they transferred to the other medication. Each participant also applied a broad-spectrum, highly protective sunscreen 2-hourly during sun exposure, continued his or her usual degree of exposure after any development of PLE, and kept a diary noting details of the eruption, amount of exposure, weather conditions and any adverse events. Statistical analysis was performed by means of the non-parametric log rank test based on Kaplan-Meier plots and bootstrapped confidence intervals (CIs) for the means, using the time in days for the itch and rash to clear as the end-points. RESULTS: Twenty-one patients entered the study but only 10 required medication. Eight who took prednisolone first and remained on it or transferred to it from placebo all improved, with the itch settling fully within a mean 2.8 days of starting the prednisolone and the rash clearing by 4.2. In the two who took placebo first and remained on it, the itch took a mean 5.4 days to settle and the rash a mean 7.8. No patient who started with prednisolone changed to placebo. Thus, the prednisolone as randomized was better than placebo at settling both the itch (mean 2. 6 days less, CI 0.7-4.0, P = 0.015) and rash (mean 3.6 days less, CI 0.6-6.1, P = 0.036); only one patient experienced mild adverse effects of transient gastrointestinal upset and depressed mood. CONCLUSIONS: The acute eruption of PLE is likely to respond rapidly to short courses of prednisolone therapy given from the earliest onset of the condition, and the treatment is safe.     

Randomized double-blind study of cyclosporin in chronic 'idiopathic' urticaria

BACKGROUND: Histamine-releasing activity (HRA) is detectable in up to 50% of patients with chronic ordinary urticaria. OBJECTIVES: To determine the effect of cyclosporin on clinical features and HRA in patients with chronic urticaria. METHODS: Thirty patients with severe unremitting disease, responding poorly to antihistamines and showing a positive autologous serum skin test (ASST) as a marker of HRA, were randomized to 4 mg kg-1 daily of cyclosporin (Sandimmun, n = 20) or placebo (n = 10) for 4 weeks. Non-responders were offered open-label cyclosporin for 4 weeks. All were followed for up to 20 weeks or until clinical relapse; all took cetirizine 20 mg daily throughout the study. The primary measure of efficacy was a daily urticaria activity score (UAS) of weal numbers and itch (maximum score 42 per week). A positive response was defined as a reduction to < 25% of baseline weekly UAS and relapse as a return to > 75%. The effect of cyclosporin on serum HRA was assessed by in vitro basophil histamine release assays and ASSTs before and after treatment. RESULTS: Twenty-nine patients (19 active, 10 controls) completed the randomized trial medication. Eight of 19 on active treatment but none on placebo had responded at 4 weeks (P < 0.05). Three others on active drug met the criterion for response at 2 weeks but not at 4 weeks. Mean reduction in UAS between weeks 0 and 4 was 12.7 (95% confidence interval, CI 6.6-18.8) for active and 2.3 (95% CI - 3.3-7.9) for placebo (P = 0.005). Seventeen non-responders (seven randomized to active and 10 to placebo) chose open-label cyclosporin and 11 responded after 4 weeks. Six of the eight randomized active drug responders relapsed within 6 weeks. Of the 19 responders to randomized and open-label cyclosporin, five (26%) had not relapsed by the study end-point. Mean in vitro serum HRA fell from 36% (95% CI 22-49%) to 5% (95% CI 1-8%) after cyclosporin treatment (n = 11, P < 0.0001). The ASST response to post-treatment serum was also reduced (P < 0.05). CONCLUSIONS: This study shows that cyclosporin is effective for chronic urticaria and provides further evidence for a role of histamine-releasing autoantibodies in the pathogenesis of this chronic 'idiopathic' disease.     

Antipruritic and thermal sensation effects of hydrocortisone creams in human skin

Few studies evaluate the effect of topical corticosteroids on thermal sensation and in alleviation of itch produced by intradermal injection of histamine. We evaluated the antipruritic effect of hydrocortisone (1% and 2.5%) on histamine-induced itch and sensory effects by measuring itch magnitude, itch duration and thermal thresholds using a computerized thermal sensory analyzer (TSA). This was a double-blind, random, comparative, controlled, single-dose and single-center study. Itch was experimentally induced in both forearms by intracutaneous injection of histamine in 18 subjects. Hydrocortisone 1%, 2.5% and placebo were applied to test sites on both forearms. The thermal threshold for warmth sensation, cold sensation, cold and heat pain was measured with the TSA. Itch magnitude was measured each minute after histamine injection for 10 min with a visual analogue scale (VAS). Itch duration was also recorded. In comparison to placebo, 2.5% hydrocortisone significantly (p = 0.03) reduced itch duration from 12.6 +/- 11.0 min (mean +/- SD) to 8.6 +/- 8.2 min (the reducing rate was 32%) as well as itch magnitude (at minutes 3, 6, 7 and overall). Placebo, 1% and 2.5% hydrocortisone significantly altered (p <0.05) the cold sensation threshold. No treatment altered cold or heat pain thresholds. These data suggest that topical application of 2.5% hydrocortisone may be significantly beneficial for the treatment of histamine-induced itch. The correlation between thermal measurements and antipruritic effects warrants further study.     

Transcutaneous nerve stimulation and itching.

The response to transcutaneous nerve stimulation (TNS)--a method used for treatment of chronic pain--was studied in 41 patients with itching of diverse etiology. At a first trial, 63% of the patients found that TNS ameliorated their itching, 20% reported complete relief. As a rule the effect lasted for many hours, although TNS was given only for 5-30 min. In 15 of the patients, having suffered from extensive pruritus for more than one year, TNS was given several times a day for 5-47 days. During this time the effect declined. Twelve patients were relieved initially, either partially or completely, but ultimately only 6 had a partial relief and in none had the itching disappeared completely. Only one patient wanted to continue the TNS therapy. The decreasing efficacy is discussed; probably there was an initial placebo effect which declined during the course of treatment. The results indicate that TNS is of limited value for treating chronic itching.     

A randomized two‐sided placebo‐controlled study on the efficacy and safety of atmospheric non‐thermal argon plasma for pruritus

Background To look into new potential indications for physical plasma and because some reports suggest plasma having antipruritic effects, we investigated the treatment of pruritus that often represents a therapeutic challenge. Objectives To assess the efficacy and safety of cold atmospheric argon plasma as add‐on‐therapy in pruritic diseases. Methods We treated 46 patients with various pruritic diseases with cold plasma for 2 min daily in addition to standard treatment. All patients served as their own control, when their pruritic disease was treated with argon gas (placebo). The outcome measure was a long‐term and short‐term reduction in itching measured by means of a visual analogue score (VAS). Results The VAS scores at baseline were comparable (plasma 4.57, SD 2.38, argon 4.34, SD 2.35). We did not find any significant differences in VAS reduction between plasma and argon: long‐term VAS difference of 1.97 (SD 1.33) for plasma and 1.74 (SD 2.37) for argon [P = 0.224, 95% CI: (?0.15; 0.60)], short‐term VAS difference of 1.92 (SD 1.33) for plasma and 1.97 (SD 1.29) for argon [P = 0.544, 95% CI: (?0.21; 0.11)]. In both groups, patients experienced a significant reduction of pruritus at the end of therapy compared to baseline [plasma 1.97 (P < 0.0001), placebo 1.74 [P < 0.0001)]. No relevant side effects occurred, and treatment was well tolerated. Conclusions Treatment with cold plasma did not result in higher pruritus reduction than treatment with placebo. A significant reduction of pruritus compared to no effect was found at the end of therapy in both groups. Both treatment options had similar safety profiles.     

Are subjective accounts of itch to be relied on? The lack of relation between visual analogue itch scores and actigraphic measures of scratch

There is a widespread belief that subjective accounts of disease are key components of measures of disease severity and quality of life. In the present study we have set out to test this hypothesis using visual analogue scales (VAS) for itch, as a subjective measure, and actigraphy as an objective measure. One-hundred and seventeen itchy children and adults (and 25 controls) were studied for clusters of nights (total number 1,654) and actigraphy scores and VAS itch taken daily. Fifty-six percent of the night-to-night variation in actigraphy scores occurred between different individuals, while 44% was intra-subject. Neither age nor sex (children's or adults') predicted actigraphy scores, and the only significant predictor of actigraphy score was disease type (p?=?0.001, r2?=?0.51). In a multivariate model VAS itch score was not a significant determinant of actigraphy scores for either children or adults (p?=?0.26). In order to see if there was a relation between VAS itch and actigraphy within the same patients (rather than between patients), 20 eczema patients wore the actigraph and scored VAS itch nightly for 42 nights. Little relationship was found between the actigraphy score and the VAS itch. Empirical autocorrelation analysis of VAS itch and actigraphy score reveal a clear autocorrelation for subjective VAS scores that was not found for the objective actigraphy score. Our data suggest a dissociation between scratch and perceived or recalled itch. One explanation is that VAS itch scores suffer from considerable anchoring, and context bias, and that their use in measures of disease severity is problematic.     

Assessment of the impact of sex in intensity,skin flares and central processing of histaminergic itch—A pilot study

Itch is the commonest skin‐related symptom, and sex differences are increasingly recognised as important determinants in stratified medicine, but only little is known about sex differences in itch. Questionnaire‐based studies indicated that women perceive itch as more intensive and bothersome in comparison with men. However, data of studies using standardised itch models to objectify sex differences are scarce and inconsistent. To determine sex differences in intensity, skin flares and central processing of histaminergic itch, we compared 15 female and 15 male healthy subjects in a double‐blinded, within‐subject, placebo‐controlled study using a histamine skin prick itch model (histamine 1% applied onto the volar forearm) and functional MRI. We found trends in higher mean itch intensity (0.58 VAS, CI 95% 0.004‐1.19, P = .056) and maximum itch intensity (men 3.93 VAS ± 0.39 SD at 3 minutes, women 4.73 VAS ± 0.31 SD at 4 minutes, P = .073) in women paralleled by a trend in a stronger positive correlation between itch intensity and blood oxygen level–dependent (BOLD) activity in brain structures identified during itch in comparison with men (r_s in women: .46, P = .08, r_s in men: .07, P = .79). The erythema and wheal following histamine skin pricking were (non‐significantly) larger in men, indicating that higher mean itch intensities on the right volar forearm in women may not be explained by more intense flares. The comparison of the activation patterns between the sexes revealed increased activity in men compared to women in the left middle temporal gyrus (temporooccipital part)/lateral occipital cortex. Thus, our findings indicate that histaminergic itch perception and central itch processing differ between the sexes under standardised conditions.     

Topical capsaicin for treatment of hemodialysis-related pruritus.

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.     

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

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

Brodalumab and ixekizumab,anti‐interleukin‐17‐receptor antibodies for psoriasis: a critical appraisal

Aim Papp et al. (N Engl J Med 2012; 366: 1181–9) and Leonardi et al. (N Engl J Med 2012; 366: 1190–9) respectively assessed the efficacy and safety of brodalumab (AMG 827), a human monoclonal antibody directed against interleukin (IL)‐17RA, the receptor of IL‐17A and ixekizumab (LY2439821), a humanized anti‐IL‐17 monoclonal antibody for the treatment of moderate‐to‐severe plaque psoriasis. Setting and design In these phase II, multicentre, randomized, double‐blind, placebo‐controlled, dose‐ranging studies, 198 patients with severe chronic plaque‐type psoriasis [Psoriasis Area and Severity Index (PASI) ≥ 12, body surface area (BSA) ≥ 10] were enrolled in Papp et al. between December 2009 and April 2010 and 142 patients in Leonardi et al. between April 2010 and March 2011. Study exposure In Papp et al., patients with chronic plaque‐type psoriasis were randomly assigned to receive placebo or brodalumab at a dose of 70, 140 or 210 mg, administered subcutaneously on day 1 and at weeks 1, 2, 4, 6, 8 and 10, or at a dose of 280 mg administered subcutaneously on day 1 and at weeks 4 and 8. In Leonardi et al., patients were randomly assigned to receive subcutaneous injections of placebo or 10, 25, 75 or 150 mg of ixekizumab at 0, 2, 4, 8, 12 and 16 weeks, followed by a 4‐week follow‐up period. Outcomes In both studies the PASI, static Physician’s Global Assessment (sPGA), Dermatology Life Quality Index (DLQI), adverse events, and routine haematological and laboratory values were analysed. Additionally in Papp et al. the BSA and Medical Outcomes Study 36‐item short‐form health survey, and in Leonardi et al. the joint pain visual analogue scale (VAS), itch severity VAS, Nail Psoriasis Severity Index (NAPSI) and the Psoriasis Scalp Severity Index (PSSI) were also measured. Primary outcome measures At week 12, in Papp et al. and Leonardi et al.: (A) The percentage improvement in PASI. In Leonardi et al. (and in Papp et al. as one of the secondary outcomes): (B) The percentage of patients who achieved a reduction in the PASI by at least 75% (PASI 75) over baseline. Results Primary endpoints: (A) At week 12 in Papp et al., the mean improvements in PASI were significantly greater in the 140, 210 and 280 mg brodalumab groups than in the 70 mg brodalumab group (85·9%, 86·3% and 76·0%, respectively, vs. 45·0%; P < 0·001); in addition, the mean improvement in PASI was significantly greater in each brodalumab group than in the placebo group (16·0%; P < 0·001). (At week 16 lower but still significant percentages compared with placebo were seen). In Leonardi et al., the mean improvements in PASI of the 10, 25, 75 and 150 mg ixekizumab groups are not reported. Significant differences between the two highest dose groups and the placebo group were seen as early as 1 week in PASI. (B) At week 12 in Papp et al., the percentages of patients with PASI 75 were 33% in the 70 mg, 77% in the 140 mg, 82% in the 210 mg and 67% in the 280 mg brodalumab group. The percentages of patients with a 50%, 75%, 90% or 100% improvement in PASI at week 12 were significantly higher among patients who received brodalumab (taking into account all doses) than among patients who received placebo. The authors do not give an explanation for the lower improvements at week 16. In Leonardi et al., the PASI 75 occurred in significantly more patients in the 25 mg (76·7%), 75 mg (82·8%) and 150 mg (82·1%) ixekizumab groups vs. placebo (7·7%; P < 0·001). No significant difference was seen for the 10 mg group. Significant differences between the 150 mg group and the placebo group were seen as early as 2 weeks in PASI 75. Differences were sustained through 20 weeks for all clinical measures in the ixekizumab study. Secondary endpoints: At week 12, in Papp et al., significant decreases of BSA, sPGA and DLQI were also seen. In Leonardi et al., significantly higher percentages of patients in the three highest ixekizumab dose groups had an sPGA score of 0 (clear of disease) or of 0 or 1 (minimal disease) for each dose and score group vs. placebo (P < 0·05). Significant reductions in the mean ± SD DLQI scores were detected at 8 weeks in the 150 mg ixekizumab group (?7·8 ± 5·7), the 75 mg ixekizumab group (?8·5 ± 5·1) and the 25 mg ixekizumab group (?7·1 ± 6·5) as compared with placebo (?2·4 ± 4·4) for all comparisons (P < 0·001). In addition, at 16 weeks, significantly more patients had a DLQI score of 0 in the 150, 75 and 25 mg ixekizumab groups (39·3%, 37·9% and 31·0%, respectively) as compared with placebo (0%) for all comparisons (P < 0·05). In Leonardi et al., significant reductions were seen in the PSSI, in the NAPSI and in the itch severity (VAS scores). Significant reductions from baseline of the joint pain VAS were also observed in the 150 mg ixekizumab group at 12 weeks, and this reduction was sustained through 20 weeks. At week 16: with respect to the other secondary efficacy endpoints and patient‐reported outcomes, significant improvements in scores were seen compared with placebo, but some of these differences were lower than observed at week 12. Safety Papp et al. summarized that during the first 12 weeks of the trial, 68% of the patients in the 70 mg brodalumab group, 69% (140 mg), 82% (210 mg), 73% (280 mg) and 62% in the placebo group had at least one adverse event. Although the authors mentioned only three serious adverse events, four were reported during the study: renal colic (70 mg brodalumab group), two patients with grade 3 asymptomatic neutropenia (210 mg brodalumab group; Papp et al. clarified that only one of these episodes was a serious adverse event) and an ectopic pregnancy in one patient in the placebo group. Leonardi et al. reported that there were no serious adverse events in any group. The frequency of adverse events was similar between the combined ixekizumab groups and the placebo group. A few patients were withdrawn from the trial due to adverse events including hypertriglyceridaemia (placebo group), peripheral oedema (10 mg ixekizumab), hypersensitivity (10 mg ixekizumab) and urticaria (25 mg ixekizumab). Conclusions Papp et al. and Leonardi et al. concluded that brodalumab and ixekizumab, respectively, significantly improved plaque psoriasis in 12‐week, phase II studies. For difficult‐to‐treat areas such as the scalp and nails, significant differences from placebo were observed with ixekizumab treatment. These trials were not large enough or of long enough duration to ascertain uncommon adverse events or to assess the risk of infection or cardiovascular events.