Effectiveness of a music intervention on pruritus: an open randomized prospective study.

BACKGROUND: Pruritus is a common symptom in many skin diseases. Music interventions have demonstrated their efficacy in different symptoms or diseases such as pain, depression and anxiety. OBJECTIVE: To evaluate the effects of a music intervention on pruritus. PATIENTS AND METHODS: A randomized controlled trial was conducted from November 2018 to April 2019. Fifty inpatients with pruritus intensity ≥3/10 in various chronic skin diseases were randomized in a music group or an emollient group. The primary endpoint was the evolution of pruritus as measured by the Numerical Rating Scale before and one hour after the procedure. The secondary judgement criteria were the effects on patient anxiety, the impact of pruritus on the quality of life and patient satisfaction (NCT03701971). RESULTS: Fifty patients with chronic pruritus were included, 62% were male, and the average age was 60.7 years. The most common diseases were psoriasis (N = 10), atopic dermatitis (N = 8) and contact eczema (N = 6). The average ItchyQol score was 64.8/110, showing a significant impact on quality of life. The intensity of pruritus decreased more significantly in the music intervention group than in the emollient group: 2.3 (SD 2.1) and 1.2 (SD 1.7), respectively (P < 0.05). There was a decrease in anxiety in both groups, with no statistical significant difference between groups. Among patients who received the music intervention, 64% reported feeling an improvement, 91% would recommend the music intervention, and 64% would like to continue this practice. DISCUSSION: Pruritus management is complex and requires first-line aetiological treatment. Aetiological or symptomatic treatments do not always provide enough relief; it is useful to find other therapeutic options. The music intervention has shown interest in our study. Its repeated use over the long term will be interesting to evaluate. As in pain, music may work by activating inhibitory neural circuits. The use of music is a simple method to manage chronic pruritus.

Importance of out-of-pocket costs for adult patients with atopic dermatitis in France.

BACKGROUND: Currently, few studies investigated the economic burden of atopic dermatitis (AD) in adult patients and specifically the estimation of out-of-pocket costs. Patients with skin disorders primarily use comfort care to ease dryness, itch or pain, and the costs of comfort care are not subject to any reimbursement from mandatory or complementary insurance. OBJECTIVE: The purpose of this study was to measure the medical and non-medical expenses paid by the patient. METHODS: Eczema Cohort Longitudinal Adults was a non-interventional study that aimed to assess the burden of AD in terms of quality of life and financial consequences. A self-assessment questionnaire was distributed to adult patients who were cared in four French hospitals. Patients were asked to list the resources consumed for the treatment of AD during the last 12 months and to estimate the corresponding amount of money they had to pay out of their own pockets. The severity of AD was subjected to a stratification based on the PO-SCORAD score. RESULTS: A total of 1024 patients answered the questionnaire: 31.9% with severe AD, 40.4% with moderate AD and 27.6% with mild AD. The mean annual out-of-pocket cost was €462.1 for severe AD and €247.4 for moderate AD. Emollients were the most commonly used product: 74.4% for an average out-of-pocket cost of €151.4. The out-of-pocket costs increased significantly with the severity: 27% of patients with severe AD declared having bought specially textured clothes, while 19% of patients with moderate AD reported the same. The corresponding mean out-of-pocket costs were €162 and €91, respectively. CONCLUSION: The amount of out-of-pocket costs for patients with AD for essential medical and non-medical expenses is relatively high, compared to the average out-of-pocket cost for French households. Integration of these essential resources into the list of reimbursed products and services appears necessary for a better coverage of AD.

Treatment of prurigo with methotrexate: a multicentre retrospective study of 39 cases.

BACKGROUND: Prurigo is a common primary pruritic condition. Treatment is challenging. Methotrexate (MTX) is effective for the treatment of pruriginous dermatoses, but its use in prurigo has been little studied. OBJECTIVES: To investigate the efficacy and safety of MTX in the treatment of difficult-to-treat prurigo. METHODS: Patients from six university dermatology departments treated with MTX between 2006 and 2016 for difficult-to-treat prurigo (i.e. with failure to conventional therapies) were included in this retrospective multicentre study. Patients with other pruritic dermatoses were excluded. Clinical efficacy was recorded after 3, 6 and 12 months of treatment: (i) subjective efficacy, that is, evaluation of the pruritus by the patient and (ii) objective efficacy, that is, assessment of cutaneous lesions by the physician: complete or almost complete remission (CR) (healing of lesions), partial remission (PR) (incomplete improvement of lesions) or failure (no improvement or worsening). The overall response rate (ORR) included CR and PR. RESULTS: Thirty-nine patients with previous failure of topical steroids, H1-antihistamine drugs or phototherapy were included. The median weekly dose of MTX was 15 mg (range 5-25 mg). The median follow-up was 16 months (2-108). The mean time between onset of MTX and objective efficacy was 2.4 ± 1.2 months and the mean duration of response was 19 ± 15 months. The ORR was 91% at 3 months [n = 36, CI 95% (81.2-100.8%), CR 44%], 94% at 6 months [n = 32, CI 95% (85.7-102.2%), CR 56%] and 89% at 12 months [n = 28, CI 95% (77.4-100.6%), CR 57%]. Seven patients stopped MTX because of failure, and five because of the discovery of hepatocarcinoma (n = 1), elevated transaminases (n = 1), infectious pneumonitis (n = 1) or gastrointestinal symptoms (n = 2). CONCLUSION: Methotrexate is a therapeutic option in difficult-to-treat prurigo.

Factors associated with the choice of the first biologic in psoriasis: real-life analysis from the Psobioteq cohort.

BACKGROUND: Decision-making is a complex process. The aim of our study was to assess factors associated with the choice of the first biological treatment in patients with moderate-to-severe psoriasis. METHODS: Data on all patients included in the French prospective, observational, cohort, Psobioteq and initiating a first biologic prescription between July 2012 and July 2016 were analysed. Demographic information and clinical features were collected during routine clinical assessments by the dermatology team at the recruiting centres using a standardized case report form. The primary outcome was the nature of the first biologic treatment. Four groups were identified as follows: adalimumab, etanercept, ustekinumab and infliximab groups. Factors associated with the choice of the first biological agent were determined by a multinomial logistic regression model adjusted on year of inclusion. RESULTS: The study population included the 830 biological-naïve patients who initiated a first biological agent. The mean age was 46.6 years (±SD 13.9), and 318 patients (38.3%) were female. The most commonly prescribed biologic was adalimumab: 355 (42.8%) patients, then etanercept (n = 247, 29.8%), ustekinumab (n = 194, 23.4%) and infliximab (n = 34, 4.0%). In the multinomial logistic regression analysis, patients were significantly more likely to receive adalimumab if they had a severe psoriasis as defined by baseline PASI or if they had psoriatic arthritis compared to etanercept (aOR, 0.42; 95% CI, 0.16-1.07) and ustekinumab (aOR, 0.15; 95% CI, 0.04-0.52). Patients were significantly more likely to receive ustekinumab (aOR, 2.39; 95% CI, 1.04-5.50) if they had a positive screening for latent tuberculosis compared to adalimumab. Younger patients were also more likely to receive ustekinumab. Patients with chronic obstructive pulmonary disease were more likely to be prescribed ustekinumab or etanercept compared to adalimumab. There was a trend in favour of etanercept prescription in patients with cardiovascular comorbidities, metabolic syndrome and in patients with a history of cancer. CONCLUSION: We identified patient- and disease-related factors that have important influence on the choice of the first biological agent in clinical practice. Clinicians appear to have a holistic approach to patient characteristics when choosing a biological agent in psoriasis.

Treatment for palmoplantar pustular psoriasis: systematic literature review, evidence-based recommendations and expert opinion.

BACKGROUND: Palmoplantar pustular psoriasis (PPPP) is a variant of psoriasis whose the association with psoriatic arthritis (PsA) has been recently described. There is limited evidence regarding how to best reduce palmoplantar pustular psoriasis severity and to maintain remission once achieved. OBJECTIVE: The aim of this study was to elaborate evidence-based recommendations for PPPP treatment supported by a systematic literature review. METHODS: A systematic literature search was carried out in Embase, Medline and Cochrane Library databases from 1980 to February 2013 searching for any trial in patients with PPPP assessing therapeutic interventions not including a systemic biotherapy. The selection of articles was limited to human subjects and English or French languages. RESULTS: Among the 675 articles identified, 29 including one Cochrane review were analysed. The Cochrane review summarised 23 randomised controlled trials (RCTs) in chronic PPPP until February 2003, including 724 patients. The authors concluded that oral retinoid therapy (acitretin), photochemotherapy or combination of both, low dose of ciclosporin or topical corticosteroids under occlusion appeared to be helpful in relieving symptoms of PPPP. Since the publication of this review, 9 open studies on PPPP treatment have been published. Three new studies evaluated the benefits of PUVA on PPPP. They all showed a better efficacy of PUVA compared to UVB therapy. One open study concluded that a retinoid treatment with an arotinoid ethylesther showed a good efficacy. Five prospective studies (level of evidence of 3) assessed Laser Excimer UVB-NB (Excimer 308 nm) in PPPP. The combined analysis of these studies showed that 64% of patients experienced an improvement of 70% at the end of treatment. CONCLUSION: Phototherapy, ciclosporin and topical corticosteroids seem to be able to control PPPP. However, the standard of care for PPPP remains an issue and there is a strong need for reliable RCTs to better define treatment strategies for PPPP.

Evidence-based recommendations on topical treatment and phototherapy of psoriasis: systematic review and expert opinion of a panel of dermatologists.

BACKGROUND: Although topical treatments and phototherapy are available for more than 40 years, there is a paucity of evidence-based recommendations regarding their use. OBJECTIVES: The aim of this work was to develop evidence-based recommendations on topical treatments and phototherapy in psoriasis for daily clinical use. METHODS: A scientific committee selected clinically relevant questions on efficacy and safety of topical agents and phototherapy in psoriasis. This selection was made using the Delphi method. A systematic literature search was performed in Medline, Embase and the Cochrane Library. The articles selected for analysis were reviewed and the level of evidence was appraised according to the Oxford Levels of Evidence. An Expert consensus meeting took place in June 2011, including 42 dermatologists. Recommendations for use of topical treatments and phototherapy were made during interactive workshops where the evidence was presented and discussed. Agreement among participants was assessed on a 10-point scale. The participants systematically assessed the impact of the recommendations on clinical practice. RESULTS: A total of 3555 references were identified, among which 312 articles were included in the systematic reviews. Three recommendations were issued on phototherapy including both PUVA and narrow-band UVB. The recommendations related to administration schedule, clearance rate and risk of side-effects. The mean agreement between participants was good varying from 8.5 to 9.5. Six recommendations were issued on topical treatments focusing on administration schedule, clearance rate, risk of side-effects, cost-effectiveness and measures to improve treatment adherence. The mean agreement between participants varied from 7.3 to 9.9. CONCLUSIONS: These recommendations for the use of topical agents and phototherapy in psoriasis are evidence-based and supported by a panel of dermatologists. The next step will be to disseminate these recommendations and assess the opinion of physicians who were not involved in generating the recommendations.

Efficacy of psoralen UV-A therapy vs. narrowband UV-B therapy in chronic plaque psoriasis: a systematic literature review.

BACKGROUND: Oral 8-methoxypsoralen-UV-A (PUVA) and Narrowband UV-B (NB-UVB or UVB TL-01) are well established treatments for chronic plaque psoriasis but there is limited evidence regarding their respective efficacy. OBJECTIVES: To prepare for evidence-based recommendations concerning the practical use of oral 8-methoxypsoralen-UV-A and Narrowband UV-B in psoriasis, a systematic review to assess respective response rates, remission duration and predictive factors of efficacy was performed. METHODS: A systematic search was carried out in PubMed, Cochrane and Embase databases, using the key words 'Psoriasis', 'UVB therapy', 'UVA therapy' for the period from 1980 to December 2010. RESULTS: The initial literature search identified 773 articles. The final selection included 29 randomized controlled trials: 18 were about the efficacy of PUVA, eight about the efficacy of NB-UVB and three directly compared PUVA vs. NB-UVB. The response rate defined by 75% or more improvement in PASI was 80% with PUVA vs. 70% with NB-UVB. The meta-analysis of the three comparative studies found a higher probability of remission at 6 months with PUVA than with NB-UVB [OR = 2.73 (95% CI 1.19-6.27), P = 0.02]. The choice of initial dose, according to skin type, the minimal erythemal dose or minimal phototoxic dose, incremental regimen and periodicity of the sessions did not appear to be predictive factors of efficacy for PUVA or NB-UVB. Despite methodological limitations in trials, the number of sessions needed for psoriasis clearance appeared to be lower with PUVA than with NB-UVB (approx. 17 vs. 25, respectively). CONCLUSION: PUVA and NB-UVB are both effective therapies in treatment of psoriasis. Our results suggest that compared with NB-UVB, PUVA tends to clear psoriasis more reliably, with fewer sessions, and provides with longer lasting clearance. However, the long-term safety of PUVA, especially its cutaneous carcinogenic risk, and the easier administration procedure often lead dermatologists to prefer NB-UVB as first line phototherapy treatment in plaque type psoriasis.

Carcinogenic risks of psoralen UV-A therapy and narrowband UV-B therapy in chronic plaque psoriasis: a systematic literature review.

BACKGROUND: Oral 8-methoxypsoralen-UV-A (PUVA) and narrowband UV-B (NB-UVB or UVB TL-01) are effective and widely used treatments for chronic plaque psoriasis. Although the role of PUVA therapy in skin carcinogenesis in humans with psoriasis has been clearly demonstrated, there is still controversy regarding the risk of skin cancer with NB-UVB. Furthermore, there is no clear evidence about the maximum cumulative number of sessions not to be exceeded in a lifetime. OBJECTIVES: To assess the respective cutaneous carcinogenic risks of PUVA or NB-UVB in psoriasis; to estimate the respective dose-relationship between skin cancers and PUVA or NB-UVB; to estimate a maximum number of sessions for PUVA or NB-UVB not to be exceeded in a lifetime. METHODS: A systematic literature search was carried out in Medline, Embase and Cochrane Library databases from1980 to December 2010 in English and French, with the keywords 'Psoriasis' AND 'UVB therapy' AND 'UVA therapy' AND 'cancer' AND 'skin' OR 'neoplasm' OR 'cutaneous carcinoma' OR 'melanoma'. RESULTS: Of 243 identified references, 49 published studies were included. Most of them (45/49) concerned PUVA therapy, with 41 assessing the risk of non-melanoma skin cancers (NMSC) following PUVA. All publications referring to the US prospective PUVA follow-up study revealed an increased risk of NMSC with the following characteristics: risk most pronounced for squamous cell carcinomas developing even with low exposures and increasing linearly with the number of sessions, tumors occurring also on non-exposed skin including invasive penile tumors, risk persisting after cessation of treatment. An increased risk of basal cell carcinomas was observed in patients receiving more than hundred PUVA sessions. The four prospective European studies selected in our review and most of the pre-1990 European and US retrospective studies failed to find a link between exposure to PUVA and skin cancer. Only the most recent cohorts, including three large long-term retrospective European studies comparing records with their respective national cancer registries reported on an independent increased risk of NMSC with PUVA, The risk was lower as compared to the US prospective PUVA follow-up study. Six studies assessed the risk of melanoma following PUVA therapy: two of the three US publications coming from the same PUVA prospective follow-up study revealed an increased risk with more than doubled incidence of both invasive and in situ melanoma among patients exposed to at least 200 PUVA treatments compared with patients exposed to lower doses, whereas the three retrospectives European studies, comparing the incidence of melanoma in PUVA users with national cancer registers, did not find any increased risk of melanoma. No increased risk of skin cancer was evidenced in the four studies specifically assessing the potential carcinogenic risk of NB-UVB. CONCLUSION: There is an increased risk of skin cancer following PUVA, shown by both US and European studies. The greater risk measured by the US studies may be at least partly explained by high UVA dose exposure and the lighter phototypes of the treated patients. The lack of prospective studies in psoriasis patients treated with NB-UVB constitutes a barrier to the robust assessment of carcinogenic risk of this phototherapy technique.

Methotrexate in psoriasis: a systematic review of treatment modalities, incidence, risk factors and monitoring of liver toxicity.

BACKGROUND/AIM: To define practical use and to specify the ideal method for monitoring the liver toxicity of MTX in the management of psoriasis. OBJECTIVE: To systematically review the literature regarding treatment modalities with methotrexate (MTX) in psoriasis, risk of MTX-mediated liver fibrosis and monitoring of hepatic toxicity. METHODS: A systematic literature search was carried out in Medline, Embase and Cochrane Library databases from 1980 to 2010 searching for randomized controlled trials and observational studies on methods of administering MTX in psoriasis and risk factors and assessment of liver toxicity. We limited the literature search to articles on human subjects over 19 years of age, articles in English or French on psoriasis and articles including psoriatic arthritis and original data. RESULTS: Among 949 references identified, 23 published studies were included. There were no studies focusing directly on the question of MTX treatment modalities. Treatment outcome appears to be dose dependent. A single study in rheumatoid arthritis showed the slightly superior efficacy of subcutaneous administration vs. oral dosing with a similar safety profile. Combination with folic acid may decrease the efficacy of MTX while improving tolerability. The extreme variability of the incidence of hepatic fibrosis in the literature does not allow the risk of hepatic fibrosis to be quantified. Type 2 diabetes and obesity, were associated with a significant increased risk of liver fibrosis. Hepatitis B and C and alcohol consumption were associated with a modest and non-significant increased risk of liver fibrosis. Procollagen III for detection of hepatic fibrosis dosing was the most extensively validated method to monitor liver fibrosis showing a sensitivity of 77.3% and a specificity of 91.5%. The Positive Predictive Value and Negative Predictive Value fluctuated depending on the prevalence of hepatic fibrosis. The sensitivities of the FibroTest and the fibroscan were of 83 and 50%, respectively, with specific features amounting to 61 and 88% respectively. CONCLUSIONS: Based on expert experience, the starting dose of MTX is between 5 and 10 mg/week for the first week. Fast dose escalation is recommended in order to obtain a therapeutic target dose of 15-25 mg/week. The maximum recommended dose is 25 mg/week. A folic acid supplement is necessary. The initiation of treatment by oral administration is preferred. In cases where inadequate response is obtained or in the event of poor gastrointestinal tolerance, subcutaneous dosing can be proposed at the same dose. Published data do not confirm the incidence of hepatic fibrosis. Type 2 diabetes and obesity appear to be significant risk factors in fibrosis. A combination of FibroTests and fibroscans together with measurement of the type III serum procollagen aminopeptide seem to be ideal method for monitoring liver toxicity.

Efficacy and safety of oral retinoids in different psoriasis subtypes: a systematic literature review.

BACKGROUND: There is limited evidence regarding the efficacy and safety of retinoids in different psoriasis subtypes. OBJECTIVE: To systematically review the available literature on: (i) modalities of administration and prescription of oral retinoids as single agent or combined therapy for the treatment of plaque-type psoriasis (PV), nail psoriasis and localized and generalized pustular psoriasis : initial and optimal dosage; (ii) skeletal toxicity of retinoid for the treatment of psoriasis. METHODS: A systematic literature search was carried out in MEDLINE, EMBASE, and Cochrane Library databases from 1975 to 2010 searching for randomized controlled trials and observational studies evaluating 1) various dosages of retinoid in psoriasis and 2) skeletal toxicity of retinoid in psoriasis. Articles were limited to human subjects and English/French languages. RESULTS: Efficacy of retinoids in psoriasis. Among 1348 identified references, 44 published studies were included. Starting daily dosages between 10 and 25 mg and stepwise escalation were associated with higher clinical efficacy and lower incidence of adverse events in comparison with higher doses and regimens rapidly reaching optimal dose. Retinoids as single agent therapy appeared to show limited efficacy in PV, while the good clinical efficacy reported in pustular forms should be cautiously considered, given the spontaneously remitting course of the disease. Combining retinoids with phototherapy appeared to be highly effective in patients with PV. Potential skeletal toxicity of retinoids. 15 published studies out of 105 identified references were included. There is no strong evidence of an increased risk of skeletal abnormalities in psoriasis patients treated with retinoids. CONCLUSION: Acitretin appears to provide better efficacy in pustular psoriasis than in PV as a single agent treatment. There is no evidence for skeletal toxicity of retinoids in the setting of psoriasis, and accordingly monitoring this risk through X-ray is not warranted.

How best to fight that nasty itch - from new insights into the neuroimmunological, neuroendocrine, and neurophysiological bases of pruritus to novel therapeutic approaches.

While the enormous clinical and psychosocial importance of pruritus in many areas of medicine and the detrimental effects of chronic 'itch' on the quality of life of an affected individual are widely appreciated, the complexity of this sensation is still often grossly underestimated. The current Controversies feature highlights this complexity by portraying pruritus as a truly interdisciplinary problem at the crossroads of neurophysiology, neuroimmunology, neuropharmacology, protease research, internal medicine, and dermatology, which is combated most successfully if one keeps the multilayered nature of 'itch' in mind and adopts a holistic treatment approach - beyond the customary, frequently frustrane monotherapy with histamine receptor antagonists. In view of the often unsatisfactory, unidimensional, and altogether rather crude standard instruments for pruritus management that we still tend to use in clinical practice today, an interdisciplinary team of pruritus experts here critically examines recent progress in pruritus research that future itch management must take into consideration. Focusing on new insights into the neuroimmunological, neuroendocrine, and neurophysiological bases of pruritus, and discussing available neuropharmacological tools, specific research avenues are highlighted, whose pursuit promises to lead to novel, and hopefully more effective, forms of pruritus management.