Adeline Gallini

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.

BACKGROUND: Treatment adherence has been recognized as an important issue in the management of chronic diseases such as psoriasis. OBJECTIVE: The aim of this work was to analyse data about topical treatment adherence in psoriasis. METHODS: Systematic literature review (62 references) between 1980 and 2011 (database: PubMed, Embase and Cochrane; Mesh keywords: Patient Compliance [Mesh] OR Medication Adherence [Mesh] AND Psoriasis [Mesh]; limits: date of publication >1980, humans subjects, written in French or English, aged ≥ 19 years). Two parameters were evaluated: (i) the ratio of number of product applications performed vs. number of applications expected according to physician recommendations, (ii) the ratio of amount of product used vs. amount of product prescribed. RESULTS: A total of 22 studies were selected. Nine studies reported on the frequency of topical treatment application in a real world setting. Five studies showed a frequency of applications varying between 50% and 60% of those expected. Because of the high variability in medication adherence assessment methods, the data could not be combined. Twelve articles reported on the frequency of topical treatment application in randomized controlled trials with adherence varying between 55% and 100%. Concerning the amount of product use, four studies showed patients applied between 35% and 72% of the recommended dose during a treatment period of 14 days to 8 weeks. The most frequently mentioned reasons for non-adherence to topical treatment were low efficacy, time consumption and poor cosmetic characteristics of topical agents. Patients experiencing adherence issues were significant younger, were men, had younger age at onset of psoriasis and had a higher self-assessed severity. To improve adherence, the following strategies were suggested: to give patients information about psoriasis, to recognize social impact, to give written instructions for use such as a care plan, to explain side effects of topical therapies, to choose treatment and its cosmetic properties in agreement with the patient. CONCLUSIONS: Literature data about topical treatment adherence are heterogeneous and scarce. They confirm the limited topical treatment adherence in psoriasis in real life, much lower than what is reported in randomized controlled trials. Therapeutic education and clear instructions on the use of topical agents are necessary to improve adherence. Studies are needed to identify predictors of limited adherence and to identify interventions improving adherence to topical medications in psoriasis.

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.

BACKGROUND: Although cyclosporin (CyA) has been in use in psoriasis for more than 20 years, there is still controversy regarding treatment strategy, monitoring of kidney function and utility in non-plaque psoriasis. OBJECTIVES: To prepare for evidence-based recommendations concerning the practical use of CyA in psoriasis, we performed a systematic review to better define treatment strategy, risk of kidney toxicity and evidence for use in non-plaque psoriasis. METHODS: A systematic search was performed on PubMed, Cochrane and Embase databases, using the key-words 'psoriasis', 'CyA', 'nephrotoxicity' during the period from 1980 to June 2010. RESULTS: The initial literature search identified 428 articles. The final selection included 16 randomized controlled trials (RCT) for treatment strategy, 25 articles (histological studies and RCT) for risk of kidney toxicity and 10 articles (RCT, prospective studies and case series) for use in non-plaque psoriasis. Higher doses of CyA of 5 mg/kg produced Psoriasis Area Severity Index (PASI) 75 response in between 50 and 97% of patients, whereas lower doses of 2.5 mg/kg yielded PASI 75 in between 28 and 85%. CyA could maintain remission at doses of at least 3 mg/kg/day. Low calory diet in obese patients was shown to improve CyA efficacy. More than 50% of the patients treated with CyA may have an increase in serum creatinin value over 30% of baseline if treatment is prolonged for 2 years. CyA at a dose of 2.5 mg/kg/day was effective for 89% of patients with palmoplantar pustulosis. More than 50% of the patients with erythrodermic psoriasis obtained a significant improvement at doses between 3 and 5 mg/kg/day at 2-4 months. CyA was more effective than etretinate on nail psoriasis. CONCLUSION: Oral CyA is indicated for patients with plaque psoriasis, pustular psoriasis or erythrodermic psoriasis. The starting dose of 5 mg/kg is associated with a higher degree of clearance. The benefit-risk appears to be better for patients without risk factors for nephrotoxicity: non-obese patients without hypertension and aged below 60. Although CyA is ideally suited for crisis intervention, continuous maintenance treatment with CyA may be envisaged in some patients provided serum creatinin is regularly monitored and the cumulative treatment duration is preferably limited to 2 years or less.

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.