Superiority of ivermectin 1% cream over metronidazole 0·75% cream in treating inflammatory lesions of rosacea: a randomized, investigator-blinded trial.

BACKGROUND: Few therapeutic alternatives currently exist in the treatment of papulopustular rosacea (PPR). OBJECTIVES: To demonstrate superiority of once-daily ivermectin 1% cream (IVM 1%) once daily vs. twice-daily metronidazole (MTZ 0·75%) cream, regarding percentage reduction of inflammatory lesions in subjects with moderate to severe PPR. METHODS: In this Phase 3, investigator-blinded, randomized, parallel-group study, subjects received IVM 1% once daily, or MTZ 0·75% twice daily over 16 weeks. Efficacy assessments were inflammatory lesion counts and Investigator's Global Assessment (IGA). Safety assessments included incidence of adverse events (AEs) and local tolerance parameters. Subjects evaluated their disease following a 5-grade scale and completed questionnaires. RESULTS: A total of 962 subjects were randomized to receive IVM 1% (n = 478) or MTZ 0·75% (n = 484). At week 16, IVM 1% was significantly superior to MTZ 0·75% in terms of reduction from baseline in inflammatory lesions (83·0% vs. 73·7%; P < 0.001), observed as early as week 3 (Last Observation Carried Forward, LOCF). IGA results (subjects 'clear' or 'almost clear') also favoured IVM 1%: 84·9% vs. 75·4%, respectively (P < 0.001). Incidence of AEs was comparable between groups and local tolerability was better for IVM 1%. More subjects receiving IVM rated their global improvement as 'excellent' or 'good.' CONCLUSIONS: Ivermectin 1% cream was significantly superior to MTZ 0·75% cream and achieved high patient satisfaction.

Dermoscopic features of congenital acral melanocytic naevi in children: a prospective comparative and follow-up study.

BACKGROUND: Acral naevi are a peculiar subtype of naevus with specific dermoscopic patterns. Little is known about congenital melanocytic naevi affecting acral volar skin in children. OBJECTIVES: To determine the dermoscopic features of acquired and congenital acral melanocytic naevi in children and to assess their key differences in this age group. METHODS: This was a prospective observational controlled study conducted in two outpatient dermatology university hospitals in Nice, France. We recruited 24 children with 24 congenital acral melanocytic naevi (CAMNs) and 26 children with 33 acquired acral melanocytic naevi (AAMNs), and determined the clinical and dermoscopic features of both. Images were evaluated and compared by two dermatologists. Fourteen patients with CAMN were followed up. RESULTS: CAMNs were larger, and more asymmetrical and comma shaped than AAMNs. The parallel furrow pattern was predominant in CAMN (75%) and AAMN (79%). Globules were more frequent in CAMN (88%) than in AAMN (61%) (P = 0·026), often with a 'pearl necklace' distribution along skin markings. Central blue-grey pigmentation was present in 50% of CAMNs vs. 9% of AAMNs (P = 0·001). A new dermoscopic feature of central enlarged pink ridges was observed in 54% of CAMNs vs. 6% of AAMNs (P < 0·001). The follow-up of CAMNs did not reveal the appearance of dermoscopic features of melanoma. CONCLUSIONS: CAMNs in children have specific features compared with AAMNs. Our results suggest that small CAMNs need not be excised, but should be followed up.

Evidence-based recommendations on the role of dermatologists in the diagnosis and management of psoriatic arthritis: systematic review and expert opinion.

BACKGROUND: Psoriatic arthritis (PsA) can develop at any time during the course of psoriasis. AIMS: The aims of these practical recommendations are to help dermatologists identify patients at risk of PsA, to diagnose PsA in collaboration with rheumatologists and to gain a better understanding of initial PsA management. MATERIALS AND METHODS: A scientific committee consisting of 10 dermatologists and a rheumatologist selected clinically relevant questions to be addressed by evidence-based recommendations using the DELPHI method. For each question, a systematic literature review was performed in Medline, Embase and the Cochrane Library databases. The levels of evidence of all selected and reviewed articles were appraised according to the Oxford levels of evidence. RESULTS: An expert board of 30 dermatologists reviewed and analysed the evidence and developed recommendations for the selected questions. Agreement among participants was assessed on a 10-point scale, and the potential impact of the recommendations on clinical practice was evaluated. Among the 6960 references identified, 190 relevant articles were included in the reviews. Three recommendations regarding risk factors for PsA and one regarding PsA prevalence were issued. The mean agreement score between participants varied from 7.8 to 9.6. Three recommendations on PsA screening tools that can be used by dermatologists were issued. The mean agreement score between participants varied from 7.7 to 9.4. Initial PsA treatment options according to published guidelines were critically appraised for axial and peripheral involvement and enthesitis/dactylitis. Three recommendations were issued. The mean agreement score between participants varied from 7.6 to 8.7. DISCUSSION: The systematic literature research and meta-analyses did not provide high-quality evidence to support recommendations regarding PsA screening. Conversely, PsA treatment options were supported by strong evidence. CONCLUSION: Cooperation between dermatologists and rheumatologists should be emphasized to better identify and manage PsA patients.

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.

Is there a psoriasis skin phenotype associated with psoriatic arthritis? Systematic literature review.

Psoriatic arthritis (PsA) is associated with psoriasis with a prevalence varying from 5.94% to 23.9%. The aim of this study was to assess if some psoriatic skin features are associated with a higher risk of PsA. A systematic literature search was carried out from 1980 to January 2013, in the Embase and Pubmed databases, using a combination of keywords including (Psoriasis) AND (PsA). Of the 2746 articles retrieved, 25 references were selected. Meta-analysis was performed when possible. Mean age at psoriasis onset appeared to be similar among patients with skin disease alone and in those with PsA. There was no clinical type of psoriasis specifically associated with PsA, including pustular psoriasis of palms and soles. Nonetheless specific psoriasis localizations were significantly associated with an increased risk of developing PsA in one cohort study: scalp lesions [Hazard Ratio (HR) 3.89 (95% confidence interval (CI):2.18-6.94)] and intergluteal/perianal lesions [HR 2.35 (95%CI:1.32-4.19)]. A similar association was found in two cross-sectional studies. Nail involvement was significantly associated with PsA in the meta-analysis [Odds Ratio (OR) 2.92 (95% CI 2.34-3.64)], particularly onycholysis [OR 2.38 (95% CI 1.74-3.26)]. Moreover, nail psoriasis was also associated with distal interphalangeal joint arthritis. The extent of psoriasis appeared to be associated with PsA in one cohort study [≥3 sites: HR 2.24 (95% CI 1.23-4.08)], one case-control study [body surface area >75%: OR 2.52 (95% CI 1.33-4.75)] and three cross-sectional studies. The meta-analysis suggested a trend for an association between high PASI and PsA risk [mean difference 3.39 (95% CI 0.94-5.83)]. Therefore, psoriasis patients with such clinical features may require a particular attention for early and close detection of PsA during the course of the cutaneous disease.

Symptoms dermatologists should look for in daily practice to improve detection of psoriatic arthritis in psoriasis patients: an expert group consensus.

BACKGROUND: Up to 29% of patients with psoriasis seen by dermatologists have undiagnosed psoriatic arthritis (PsA). As early detection of PsA may be associated with improved joint and skin outcomes, it is essential for dermatologists to improve their ability to diagnose PsA. Skin and nail features of psoriasis associated with PsA are well known to dermatologists but they may feel less confortable assessing other symptoms and they rarely use PsA screening questionnaires. OBJECTIVE: To develop a limited list of clinical signs and symptoms that a dermatologist should be looking for in a psoriasis patient in addition to specific skin features and nail involvement, to improve PsA detection. METHODS: A systematic search was performed in Pubmed, Cochrane and Embase databases to identify clinical key symptoms associated with PsA. It yielded 27 studies in which we extracted a list of clinical signs and symptoms observed in PsA and submitted it to a panel of dermatology experts through a DELPHI selection process. The experts had to determine which minimal set of signs and symptoms dermatologists should look for in daily practice to improve detection of PsA in patients with psoriasis. RESULTS: The four items that received a score higher than 90% in the DELPHI process were finally selected. Those items were as follows: peripheral inflammatory pain (100%), axial inflammatory pain (95.3%), dactylitis (93%), buttock and sciatic pain (90.7%). The remaining items: distal interphalangeal joints (DIPs) involvement (83.7%), Talalgia (79.1%), swollen Achille's tendon (41.9%), costo-chondral involvement (32.6%), uveitis (7%), mouth ulcerations (2.3%), were not retained. CONCLUSION: We propose a set of four items to screen psoriasis patients for psoriatic arthritis for routine clinical use by dermatologists.

Treatment (biotherapy excluded) of psoriatic arthritis: an appraisal of methodological quality of international guidelines.

BACKGROUND: Some international guidelines have been published to provide the best care for patients with psoriatic arthritis (PsA) but little is known about their quality. OBJECTIVE: The primary aim of this study was to examine the quality of guidelines that concern treatment (biotherapy exluded) of PsA. The secondary aim was to review studies published since the publication of the most recent guideline. METHODS: A systematic literature search was carried out from 2007 to February 2013, in the Embase, Medline and Cochrane Library databases, in English and French using a combination of keywords including 'Arthritis, Psoriatic/therapy' NOT 'Biological Therapy' OR 'Antibodies, Monoclonal' OR 'Recombinant Fusion Proteins' OR 'tumour necrosis factor-alpha'. The AGREE instrument (Appraisal of Guidelines Research and Evaluation) was used by four reviewers to evaluate the quality of selected guidelines according to the proposed methodology. RESULTS: Of the 518 identified references, six guidelines and two studies were selected. There was considerable variation in the quality of clinical guidelines across the AGREE domains. The least well-addressed domains were 'applicability', 'stakeholder involvement', 'scope and purpose' and 'quality of development', whereas 'editorial independence' and 'clarity and presentation' were less problematic. CONCLUSION: Although guidelines development was of good quality, many of the studies that they included are of poorer quality. This work indicates that the current guidelines can be improved, particularly the stakeholder domain and the applicability domain. The prospective use of the AGREE instrument should improve the guideline quality. More controlled trials should be required but are unlikely to be conducted, given the lack of interest in studying old drugs.

Laser-assisted depigmentation for resistant vitiligo: a retrospective case series with long-term follow-up.

BACKGROUND: Blanching creams are used to depigment and to achieve uniform skin tone in widespread vitiligo. Length of the treatment and side-effects strongly limit their use in common practice. OBJECTIVES: To assess the long-term efficacy and tolerance of Q-Switched (QS) lasers for depigmenting the remaining unaffected skin in vitiligo. METHODS: Retrospective study of vitiligo patients treated with QS lasers in the Department of Dermatology of the University Hospital of Nice, France, from 2002 to 2011. Localizations and the percentage of body surface area of treated lesions, the total number of sessions and the possible relapses and side-effects, were analysed. Global satisfaction of the patients was evaluated on a visual analogical scale. RESULTS: Sixteen areas of normally pigmented skin were treated in six patients. The median number of sessions to achieve a complete depigmentation was 2 (1-6). The mean duration of follow-up was 36 months (19-120). One third of the patients had no relapse. A complete repigmentation was observed after 21 months in one patient; a 50% repigmentation was noted in one patient, 7 months after the end of the treatment. Two patients showed a minimal repigmentation (<25%), 18 months and 9 years after the first laser treatments. The repigmentations were effectively treated with a maintenance session. The mean total number of sessions performed during this period was 3 (1-20). Side-effects were limited to transient purpura and crusts. The satisfaction of the patients was excellent (mean 9/10). conclusions: QS lasers appear as an efficient and safe modality for depigmenting normal skin in vitiligo.

Impact of systemic treatment of psoriasis on inflammatory parameters and markers of comorbidities and cardiovascular risk: results of a prospective longitudinal observational study.

BACKGROUND: Several markers of comorbidities and cardiovascular (CV) risk are disturbed in moderate to severe psoriasis (PsO). The effect of systemic treatments of psoriasis on these markers remains poorly understood. OBJECTIVES: To study the frequency of disturbance of inflammatory parameters and markers of comorbidities and CV risk associated with moderate to severe PsO and psoriatic arthritis (PsA), and to assess their evolution under systemic treatments. METHODS: Monocentric prospective study on patients with PsO and PsA starting a systemic treatment for their psoriasis. The following markers were evaluated at baseline (M0), 3 months (M3) and 6 months (M6); weight, fasting blood glucose, blood pressure, uric acid, hepatic steatosis, smoking, lipid, metabolic and inflammatory parameters. RESULTS: Forty-three patients, 31 PsO and 12 PsA, were included. Forty completed the study. Response to treatment was good, with 71% of the population obtaining a Psoriasis Area and Severity Index (PASI) of 75. All patients had at least one comorbidity, and 45% had two or more. A statistically significant decrease was observed only for inflammatory parameters (C-reactive protein [CRP], P = 0.004) and erythrocyte sedimentation rate (ESR, P = 0.002). We did not observe any correlation between the PASI and CRP (correlation coefficient 0.128, P = 0.438) or ESR (correlation coefficient 0.294, P = 0.069) for responding patients. CONCLUSIONS: We observed a high frequency of disturbance of inflammatory parameters and markers of comorbidities and CV risk in a population with moderate to severe PsO and PsA, most of which were not detected before. A significant decrease in inflammatory parameters was noted after the introduction of systemic therapy, while other parameters remained unaffected by the treatment, except the weight that increased under biologics therapies.

Psoriasis, cardiovascular events, cancer risk and alcohol use: evidence-based recommendations based on systematic review and expert opinion.

The relationship between psoriasis, chronic inflammation, cardiovascular risk and risk of cancer has long been debated. In addition, it has been suggested that alcohol consumption may be a risk factor for psoriasis onset and severity. The aim of this study was to develop evidence-based recommendations on the risk of comorbidities and its management for daily clinical use, focusing on cardiovascular risk, risk of cancer and alcohol use in psoriasis. A scientific committee identified and selected through the Delphi method clinically relevant questions about cardiovascular risk, risk of cancer and alcohol use in psoriasis. To address these questions, a systematic literature search was performed in Medline, Embase and the Cochrane Library databases. Systematic literature reviews including meta-analysis whenever possible were performed. Subsequently, an Expert board meeting involving 39 dermatologists took place to analyse the evidence and to elaborate recommendations on the selected questions. Recommendations were graded according to the Oxford level of evidence grading system. The degree of agreement of these recommendations was assessed on a 10-point scale, as well as their potential impact on daily clinical practice. A total of 3242 articles were identified through the systematic literature searches, among which 110 were included in the systematic reviews. Overall, 12 recommendations were elaborated regarding comorbidities management in psoriasis patients. A moderate increased risk of cardiovascular diseases (CVD), mainly myocardial infarction (MI) [meta-analysis of cohort studies: OR = 1.25 (95% CI 1.03-1.52) and of cross-sectional studies: OR = 1.57 (95% CI 1.08-2.27)], and coronary artery disease (CAD) [meta-analysis of cross-sectional: OR = 1.19 (95% CI 1.14-1.24), of cohort studies: OR = 1.20 (95% CI 1.13-1.27) and of case-control studies: OR = 1.84 (95% CI 1.09-3.09)] was acknowledged. This increased cardiovascular risk requires appropriate prevention measures. There was a lack of substantial evidence that conventional systemic treatment has any effect on cardiovascular risk although methotrexate might be cardioprotective. An increased risk of solid cancer potentially associated with smoking and alcohol use was identified. The role of systemic treatment on cancer risk could not be assessed thoroughly due to limited long-term follow-up data. A higher risk of non-melanoma skin cancers especially squamous cell carcinoma was shown, mainly due to previous exposure to oral 8-methoxypsoralen-ultraviolet-A (PUVA), ciclosporin and possibly methotrexate. No firm conclusion could be drawn regarding alcohol and psoriasis due to high variability in alcohol usage assessment in studies. Clinical experience suggests higher alcohol consumption among psoriasis patients compared to the general population. The mean expert participants' level of agreement on these recommendations varied from 6.8 to 9.4. These 12 recommendations are evidence based and supported by a panel of expert dermatologists. The next step is now to disseminate these recommendations to dermatologists who did not participate in the Expert board meeting and to assess their opinion about the recommendations.

Cardiovascular morbidity and mortality in psoriasis and psoriatic arthritis: a systematic literature review.

UNLABELLED: Previous epidemiological studies have demonstrated a high prevalence of cardiovascular (CV) risk factors in psoriasis patients, including metabolic syndrome, cigarette smoking, obesity, hypertension, diabetes mellitus, insulin resistance and dyslipidaemia. An increase in CV morbidity and mortality attributable to psoriasis is still under question. PRIMARY OBJECTIVE: to assess CV morbidity and mortality in psoriasis and psoriatic arthritis (PsA) including stroke, coronary artery disease, myocardial infarction (MI) and peripheral artery disease. SECONDARY OBJECTIVES: to assess if psoriasis per se is an independent CV risk factor and if psoriasis severity is a predictor of CV risk. We also evaluated the effect of conventional systemic treatments for psoriasis on CV mortality. A systematic literature search was carried out from 1980 to December 2011, in the Embase, Medline and Cochrane Library databases, in English and French using a combination of keywords including (Psoriasis) OR (Psoriatic arthritis) AND (Myocardial infarction) OR (Coronaropathy) OR (Stroke) OR (Cardiovascular) AND (Methotrexate) AND (Ciclosporin) AND (Retinoids). Of the 929 identified references, 33 observational studies evaluating the rates of cardiovascular events (CVE) in patients with psoriasis and PsA compared with controls were selected. Meta-analysis of both cohort and cross-sectional studies showed an increased risk of MI with Odds Ratio (OR) of 1.25 (95% CI 1.03-1.52) and 1.57 (95% CI 1.08-2.27) in psoriasis and PsA, respectively, compared with the general population. The risk of MI was more pronounced for patients having severe psoriasis and for patients with psoriasis of early onset. It remained significantly elevated after controlling for major CV risk factors. The meta-analysis identified a small, but significant association between psoriasis, PsA and coronary artery disease with an OR between 1.19 (95% CI 1.14-1.24) for cross-sectional studies, 1.20 (95% CI 1.13-1.27) for cohort studies and 1.84 (95% CI 1.09-3.09) for case-control studies. The risk of coronary artery disease seemed to be more pronounced in patients with severe psoriasis and in patients with psoriasis of early onset. The meta-analysis assessing the risk of stroke gave inconclusive results: analysis of cross-sectional studies suggested that psoriasis patients had a slightly higher risk of stroke with an OR of 1.14 (95% CI 1.08-1.99), whereas the meta-analysis of cohort studies failed to show an association. There was also an increased risk of peripheral artery disease in psoriasis. No significant increased risk of CV mortality could be shown for both psoriasis and PsA patients. The use of methotrexate was associated with a reduced incidence of cardiovascular disease in two studies. The use of etretinate was associated with a reduction of CV mortality in one study. Potential selection bias such as the 'healthy user effect' prevents from drawing definite conclusions. There may be a small, but significant increased risk of CVE, but not of CV mortality in psoriasis and PsA patients. The psoriasis attributable risk remains difficult to assess due to confounding factors. The moderate quality of CV risk factors reporting in studies should be acknowledged. In addition, heterogeneity in study design, outcome definition and assessment represent major limitations. Nevertheless, screening and management of CV risk factors are important in psoriasis.

Risk of cancer in psoriasis: a systematic review and meta-analysis of epidemiological studies.

The relationship between psoriasis and increased cancer risk is debated. The aim of this study was to evaluate if there is an increase in the background risk of cancer in psoriasis patients compared with the general population. A systematic literature search was performed on PubMed, Embase and Cochrane databases, using the keywords 'Psoriasis [Majr] AND Neoplasms', from 1980 to January 2012. Meta-analysis was performed based on observational studies showing consistency in cancer risk assessment methods. Of the 1080 articles retrieved, 37 references were selected. There may be an increased risk of some solid cancers in psoriasis: respiratory tract cancer [standardized incidence ratio (SIR) = 1.52, 95% confidence interval (CI) 1.35-1.71], upper aerodigestive tract cancer (SIR = 3.05, 95% CI 1.74-5.32), urinary tract cancer (SIR = 1.31, 95% CI 1.11-1.55) and liver cancer (SIR = 1.90, 95% CI 1.48-2.44). The risk of non-Hodgkin lymphoma appears slightly increased in psoriasis (SIR = 1.40, 95% CI 1.06-1.86). Psoriasis patients have an increased risk of squamous cell carcinoma (SIR = 5.3, 95% CI 2.63-10.71) and basal cell carcinoma (SIR = 2.00, 95% CI 1.83-2.20), whereas the risk of melanoma is not increased. There was a large heterogeneity in studies assessing cancer risk in psoriasis preventing from including all studies in meta-analysis. This systematic literature review shows a small increased risk of some solid cancers in psoriasis, especially those linked to alcohol drinking and cigarette smoking. A higher risk of non-melanoma skin cancers, especially squamous cell carcinoma, is shown, mainly due to previous exposure to 8-methoxypsoralen-ultraviolet-A (PUVA), ciclosporin and possibly methotrexate.

An observational cross-sectional survey of rosacea: clinical associations and progression between subtypes.

BACKGROUND: Few studies have evaluated differences between rosacea subtypes in epidemiological associations and clinical features. The natural history of rosacea is unknown and progression between subtypes has been implied but not formally evaluated. OBJECTIVES: To assess associations between the four rosacea subtypes [erythematotelangiectatic (ETR), papulopustular (PPR), phymatous (PHY) and ocular], including quantitative and qualitative details on primary and secondary features of rosacea. A secondary objective was to evaluate for the potential of progression between subtypes. METHODS: This cross-sectional study recruited subjects with rosacea from Northern Germany and comprised clinical evaluation by a dermatologist and a survey of demographics and onset of rosacea-associated signs and symptoms. RESULTS: A total of 135 subjects with rosacea were enrolled. PHY was more frequently associated with PPR than ETR (P < 0·001). Compared with ETR, PPR was significantly associated with facial burning/stinging (P = 0·001), phymas (P < 0·001) and oedema (P < 0·001); and during flushing episodes, was more frequently associated with burning (P = 0·018), skin tension (P = 0·005) and itching (P = 0·027). ETR was more frequently associated with dry facial skin (P < 0·001). Flushing was reported by 66% and the site most frequently involved was the cheeks (100%). Papulopustules were evanescent in 42% and the sites most frequently involved were the cheeks (80%) and nose (67%). Of those fulfilling criteria for at least two subtypes, 66% developed ETR before PPR; 92% developed ETR before PHY; 83% developed PPR before PHY; and the majority developed cutaneous rosacea-associated features before ocular signs/symptoms. CONCLUSIONS: Significant differences exist between ETR and PPR in rosacea-associated features and in subtype associations. A small proportion of subjects with rosacea may progress between subtypes.

A 24-week randomized clinical trial investigating the efficacy and safety of two doses of etanercept in nail psoriasis.

BACKGROUND: Nail psoriasis is common in patients with psoriasis and can seriously affect their quality of life. Current treatments are limited and there is no standard course of therapy. OBJECTIVES: To assess the efficacy and safety of etanercept (ETN) on nail psoriasis in patients with moderate-to-severe psoriasis. METHODS: Patients with moderate-to-severe plaque psoriasis, who had previously failed at least one form of systemic therapy for nail psoriasis, were randomized to receive open-label ETN 50 mg twice weekly (BIW) for 12 weeks followed by once weekly (QW) for 12 weeks (BIW/QW group) or ETN 50 mg QW for 24 weeks (QW/QW group). The primary endpoint was the mean improvement in the Nail Psoriasis Severity Index (NAPSI; score range 0-8) over 24 weeks in the target fingernail with the most severe abnormalities. RESULTS: Seventy-two patients received one or more doses of ETN (38 BIW/QW; 34 QW/QW) and 69 patients were included in the modified intent-to-treat population. At baseline, mean (standard error) target fingernail NAPSI score was 6.0 (0.3) in the BIW/QW group and 5.8 (0.3) in the QW/QW group. At week 24, mean target fingernail NAPSI score had decreased significantly by -4.3 [95% confidence interval (CI) -4.9 to -3.7; P < 0.0001] in the BIW/QW group and by -4.4 (95% CI -5.0 to -3.7; P < 0.0001) in the QW/QW group. Improvement in NAPSI showed significant correlation with Psoriasis Area and Severity Index improvement. ETN was well tolerated with no unexpected safety findings. CONCLUSIONS: Both ETN regimens were effective at treating nail psoriasis in this patient population.

[Normal and abnormal skin color]. / La couleur de la peau normale ou anormale.

The varieties of normal skin color in humans range from people of "no color" (pale white) to "people of color" (light brown, dark brown, and black). Skin color is a blend resulting from the skin chromophores red (oxyhaemoglobin), blue (deoxygenated haemoglobin), yellow-orange (carotene, an exogenous pigment), and brown (melanin). Melanin, however, is the major component of skin color ; it is the presence or absence of melanin in the melanosomes in melanocytes and melanin in keratinocytes that is responsible for epidermal pigmentation, and the presence of melanin in macrophages or melanocytes in the dermis that is responsible for dermal pigmentation. Two groups of pigmentary disorders are commonly distinguished: the disorders of the quantitative and qualitative distribution of normal pigment and the abnormal presence of exogenous or endogenous pigments in the skin. The first group includes hyperpigmentations, which clinically manifest by darkening of the skin color, and leukodermia, which is characterized by lightening of the skin. Hypermelanosis corresponds to an overload of melanin or an abnormal distribution of melanin in the skin. Depending on the color, melanodermia (brown/black) and ceruloderma (blue/grey) are distinguished. Melanodermia correspond to epidermal hypermelanocytosis (an increased number of melanocytes) or epidermal hypermelanosis (an increase in the quantity of melanin in the epidermis with no modification of the number of melanocytes). Ceruloderma correspond to dermal hypermelanocytosis (abnormal presence in the dermis of cells synthesizing melanins) ; leakage in the dermis of epidermal melanin also exists, a form of dermal hypermelanosis called pigmentary incontinence. Finally, dyschromia can be related to the abnormal presence in the skin of a pigment of exogenous or endogenous origin.

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.

Successful treatment of moderate to severe plaque psoriasis with the PEGylated Fab' certolizumab pegol: results of a phase II randomized, placebo-controlled trial with a re-treatment extension.

BACKGROUND: Certolizumab pegol (CZP) is a PEGylated antitumour necrosis factor agent. OBJECTIVES: To evaluate the efficacy and safety of CZP in patients with plaque psoriasis. METHODS: In a randomized, placebo-controlled, double-blind study, 176 patients with moderate to severe psoriasis received placebo or CZP 400 mg at week 0 followed by placebo or CZP (200 or 400 mg) every other week until week 10. Co-primary endpoints were ≥ 75% improvement from baseline in Psoriasis Area and Severity Index (PASI 75) and a Physician's Global Assessment (PGA) of clear-almost clear at week 12. A re-treatment extension study was conducted in 71 CZP PASI 75 responders who relapsed during a 12- to 24-week observation period without treatment. RESULTS: PASI 75 was achieved by 44/59 (75%), 48/58 (83%) and 4/59 (7%) patients in the CZP 200 mg, CZP 400 mg and placebo groups, respectively (P < 0·001 for both treatment arms vs. placebo). A PGA score of clear-almost clear was achieved by 53%, 72% and 2%, respectively (P < 0·001 for both treatment arms vs. placebo). In the re-treatment study median PASI scores were similar at week 12 in the first treatment and re-treatment periods for both CZP groups. Serious adverse events occurred in 3%, 5% and 2% of CZP 200 mg, CZP 400 mg and placebo patients, respectively. CONCLUSIONS: Treatment with CZP significantly improved psoriasis at week 12. Similar efficacy was observed at week 12 in patients receiving re-treatment for loss of response after drug withdrawal.