Showing papers in "British Journal of Dermatology in 2013"

Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction. Results from the prospective RegiSCAR study

Abstract: BackgroundCases of severe drug hypersensitivity, demonstrating a variable spectrum of cutaneous and systemic involvement, are reported under various names, especially drug reaction with eosinophilia and systemic symptoms (DRESS). Case definition and overlap with other severe cutaneous adverse reactions (SCAR) are debated. ObjectivesTo analyse the spectrum of signs and symptoms of DRESS and distribution of causative drugs in a large multicentre series. Patients and methodsRegiSCAR, a multinational registry of SCAR, prospectively enrolled 201 potential cases from 2003 to mid-2009. Using a standardized scoring system, 117 cases were validated as showing probable or definite DRESS. ResultsThe male/female ratio was 080; females were borderline significantly younger than males. Next to the ubiquitous exanthema, the main features were eosinophilia (95%), visceral involvement (91%), high fever (90%), atypical lymphocytes (67%), mild mucosal involvement (56%) and lymphadenopathy (54%). The reaction was protracted in all but two patients; two patients died during the acute phase. Drug causality was plausible in 88% of cases. Antiepileptic drugs were involved in 35%, allopurinol in 18%, antimicrobial sulfonamides and dapsone in 12% and other antibiotics in 11%. The median time interval after drug intake was 22days (interquartile range 17-31) for all drugs with (very) probable causality, with differences between drugs. ConclusionThis prospective observational study supports the hypothesis that DRESS is an original phenotype among SCAR in terms of clinical and biological characteristics, causative drugs, and time relation. The diversity of causative drugs was rather limited, and mortality was lower than that suggested by prior publications.

Epidemiology of acne vulgaris

Abstract: Summary Despite acne being an almost universal condition in younger people, relatively little is known about its epidemiology. We sought to review what is known about the distribution and causes of acne by conducting a systematic review of relevant epidemiological studies. We searched Medline and Embase to the end of November 2011. The role of Propionibacterium acnes in pathogenesis is unclear: antibiotics have a direct antimicrobial as well as an anti-inflammatory effect. Moderate-to-severe acne affects around 20% of young people and severity correlates with pubertal maturity. Acne may be presenting at a younger age because of earlier puberty. It is unclear if ethnicity is truly associated with acne. Black individuals are more prone to postinflammatory hyperpigmentation and specific subtypes such as ‘pomade acne’. Acne persists into the 20s and 30s in around 64% and 43% of individuals, respectively. The heritability of acne is almost 80% in first-degree relatives. Acne occurs earlier and is more severe in those with a positive family history. Suicidal ideation is more common in those with severe compared with mild acne. In the U.S.A., the cost of acne is over 3 billion dollars per year in terms of treatment and loss of productivity. A systematic review in 2005 found no clear evidence of dietary components increasing acne risk. One small randomized controlled trial showed that low glycaemic index (GI) diets can lower acne severity. A possible association between dairy food intake and acne requires closer scrutiny. Natural sunlight or poor hygiene are not associated. The association between smoking and acne is probably due to confounding. Validated core outcomes in future studies will help in combining future evidence.

Long-term safety of ustekinumab in patients with moderate-to-severe psoriasis: final results from 5 years of follow-up.

Abstract: Long-term safety evaluations of biologics are needed to inform patient management decisions.

Efficacy and safety of secukinumab in the treatment of moderate-to-severe plaque psoriasis: a randomized, double-blind, placebo-controlled phase II dose-ranging study

Abstract: Summary Background Conventional systemic therapies for plaque psoriasis have not fully met the needs of patients, and although current biologic treatments are generally well tolerated, concerns exist with respect to long-term safety. Interleukin (IL)-17A is believed to be an important effector cytokine in the pathogenesis of psoriasis and is produced by Th17 cells, a class of helper T cells that act outside the established Th1/Th2 paradigm for regulation of innate and adaptive immunity. Objectives To assess the efficacy and safety of different doses of secukinumab, a fully human anti-IL-17A IgG1κ monoclonal antibody, in patients with moderate-to-severe plaque psoriasis. Methods Patients (n = 125) were randomized 1 : 1 : 1 : 1 : 1 to receive subcutaneous doses of placebo (n = 22) or secukinumab [1 × 25 mg (n = 29), 3 × 25 mg (n = 26), 3 × 75 mg (n = 21) or 3 × 150 mg (n = 27)] at weeks 0, 4 and 8. After the 12-week treatment period, patients entered a follow-up period of 24 weeks. The primary efficacy outcome was at least 75% improvement from baseline in the Psoriasis Area and Severity Index score (PASI 75); secondary outcomes included the Investigator’s Global Assessment (IGA) and PASI 90 and 50 response rates. Results After 12 weeks of treatment, secukinumab 3 × 150 mg and 3 × 75 mg resulted in significantly higher PASI 75 response rates vs. placebo (82% and 57% vs. 9%; P < 0·001 and P = 0·002, respectively). Higher PASI 75 response rates compared with placebo were maintained throughout the follow-up period with these dosages [week 36, 26% (n = 7) and 19% (n = 4) vs. 4% (n = 1), respectively], with a gradual decline of PASI 75 response over time after the dosing period. IGA response rates were significantly higher in the 3 × 150 mg group vs. placebo at week 12 (48% vs. 9%; P = 0·005) and were consistently higher for the 3 × 150 mg and 3 × 75 mg groups vs. placebo at all time points from week 4 onward. The PASI 90 response rate was significantly higher in the 3 × 150 mg group vs. placebo (52% vs. 5%) at week 12 and remained higher during the follow-up period. Secukinumab was well tolerated. Two cases of neutropenia (≤ grade 2) were reported in the 3 × 150 mg cohort. Conclusions Treatment with subcutaneous secukinumab 3 × 75 mg and 3 × 150 mg met the primary outcome of PASI 75 response achievement after 12 weeks, demonstrating efficacy in moderate-to-severe psoriasis.

A multicentre study to determine the value and safety of drug patch tests for the three main classes of severe cutaneous adverse drug reactions

Abstract: Summary Background Drug patch tests (PTs) can reproduce delayed hypersensitivity to drugs and entail a moderate re-exposure of patients to offending drugs. Objectives To determine the value of PTs for identifying the responsible drug in severe cutaneous adverse drug reactions (SCARs) such as acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS) and Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Methods In a multicentre study, PTs were conducted on patients referred for DRESS, AGEP or SJS/TEN within 1 year of their SCAR. All drugs administered in the 2 months prior to and the week following the onset of the SCAR were tested. Results Among the 134 patients included (48 male, 86 female; mean age 51·7 years), positive drug PTs were obtained for 24 different drugs. These included positive tests for 64% (46/72) of patients with DRESS, 58% (26/45) of those with AGEP and 24% (4/17) of those with SJS/TEN, with only one relapse of AGEP. The value of PTs depended on the type of drug and the type of SCAR (e.g. carbamazepine was positive in 11/13 DRESS cases but none of the five SJS/TEN cases). PTs were frequently positive for beta lactams (22 cases), pristinamycin (11 cases) and in DRESS with pump proton inhibitors (five cases), but were usually negative for allopurinol and salazopyrin. Of 18 patients with DRESS, eight had virus reactivation and positive PTs. In DRESS, multiple drug reactivity was frequent (18% of cases), with patients remaining sensitized many years later. Conclusions PTs are useful and safe for identifying agents inducing SCAR.

Guidelines for the management of vitiligo: the European Dermatology Forum consensus

Abstract: The aetiopathogenic mechanisms of vitiligo are still poorly understood, and this has held back progress in diagnosis and treatment. Up until now, treatment guidelines have existed at national levels, but no common European viewpoint has emerged. This guideline for the treatment of segmental and nonsegmental vitiligo has been developed by the members of the Vitiligo European Task Force and other colleagues. It summarizes evidence-based and expert-based recommendations (S1 level).

The natural history of actinic keratosis: a systematic review

Abstract: Summary Knowledge about the development of untreated actinic keratosis (AK) and risk of progression into squamous cell carcinoma (SCC) is important. Therefore, we set out to synthesize primary data on the natural history of AK. We carried out a systematic literature search (Medline, Medline in Process, Embase, Cochrane) of studies on the natural course of AK, regarding (i) progression and regression rates per lesion-year, (ii) changes in total lesion counts over time, and (iii) spontaneous field regression and recurrence rates, taking into account studies on participants without immunosuppression and history of skin cancer, immunosuppressed patients and participants with a history of skin cancer and sunscreen use. Twenty-four eligible studies were identified providing data on at least one of the outcomes. Progression rates of AK to SCC ranged from 0% to 0·075% per lesion-year, with a risk of up to 0·53% per lesion in patients with prior history of nonmelanoma skin cancer. Rates of regression of single lesions ranged between 15% and 63% after 1 year. The data available on recurrence rates of single lesions 1 year after regression indicate a recurrence rate of 15–53%. Data on the relative change of total AK count over time are heterogeneous, and range from −53% to +99·1%. Spontaneous complete field regression rates range from 0% to 21%, with recurrences in 57%. In general, the available data are limited. Important methodological limitations apply. Currently, no reliable estimates concerning the frequency of AK developing into invasive carcinoma can be given, and further studies are needed.

A randomized, double-blind, placebo- and active-controlled, half-head study to evaluate the effects of platelet-rich plasma on alopecia areata

Abstract: Summary Background Alopecia areata (AA) is a common autoimmune condition, causing inflammation-induced hair loss. This disease has very limited treatment possibilities, and no treatment is either curative or preventive. Platelet-rich plasma (PRP) has emerged as a new treatment modality in dermatology, and preliminary evidence has suggested that it might have a beneficial role in hair growth. Objectives To evaluate the efficacy and safety of PRP for the treatment of AA in a randomized, double-blind, placebo- and active-controlled, half-head, parallelgroup study. Methods Forty-five patients with AA were randomized to receive intralesional injections of PRP, triamcinolone acetonide (TrA) or placebo on one half of their scalp. The other half was not treated. Three treatments were given for each patient, with intervals of 1 month. The endpoints were hair regrowth, hair dystrophy as measured by dermoscopy, burning or itching sensation, and cell proliferation as measured by Ki-67 evaluation. Patients were followed for 1 year. Results PRP was found to increase hair regrowth significantly and to decrease hair dystrophy and burning or itching sensation compared with TrA or placebo. Ki67 levels, which served as markers for cell proliferation, were significantly higher with PRP. No side-effects were noted during treatment. Conclusions This pilot study, which is the first to investigate the effects of PRP on AA, suggests that PRP may serve as a safe and effective treatment option in AA, and calls for more extensive controlled studies with this method.

Markers of systemic inflammation in psoriasis: A systematic review and meta-analysis

Abstract: Studies investigating systemic inflammation in psoriasis use different serum markers and report discrepant results. We set out to determine whether systemic inflammation is elevated in patients with psoriasis compared with healthy controls, and to measure the extent of this elevation, by summarizing available data on serum inflammatory markers. PubMed, Embase and Web of Science were searched from inception to March 2011. We included studies comparing the serum inflammatory markers interleukin (IL)-1β, IL-6, IL-10, C-reactive protein (CRP), intracellular adhesion molecule (ICAM)-1, E-selectin and tumour necrosis factor (TNF)-α in patients with psoriasis and healthy controls. Differences in serum marker levels between patients and controls were pooled as standardized mean differences (SMDs; Cohen's d) using a random-effects model. Seventy-eight studies were eligible. Of the 7852 individuals included, 3085 had (severe plaque) psoriasis. The pooled SMDs were higher in patients with psoriasis than in healthy controls for IL-6 [d = 1·32, 95% confidence interval (CI) 0·83-1·81], CRP (d = 1·83, 95% CI 0·76-2·90), TNF-α (d = 1·32, 95% CI 0·86-1·79), E-selectin (d = 1·78, 95% CI 1·32-2·25) and ICAM-1 (d = 1·77, 95% CI 1·15-2·39). The SMD between cases and controls for IL-1β and IL-10 was not significant. Age had a significant effect on the SMD for IL-6 and TNF-α. For IL-6 the effect size was higher for plaque psoriasis studies (d = 1·98). The effect size was not influenced by the Psoriasis Area and Severity Index, measurement method or quality assessment. The pooled analyses suggest modest but significantly elevated levels of the proinflammatory cytokines in the serum of patients with psoriasis with predominantly severe disease. To what extent this modest increment is clinically relevant could be investigated in a synthesis of all studies measuring inflammation before and after antipsoriatic therapy. What's already known about this topic? Psoriasis is an inflammatory disease affecting the skin. Many studies have investigated whether it can also be considered a systemic disease, by analysing serum levels of inflammatory cytokines in patients with psoriasis. What does this study add? This study systematically synthesizes the evidence on selected serum inflammatory markers to determine whether systemic inflammation is elevated in patients with psoriasis compared with healthy controls, and to measure the extent of this elevation.

Is the prevalence of psoriasis increasing? A 30 year follow-up of a population-based cohort

Abstract: Summary Background There is indication of an increasing prevalence of psoriasis in some western populations. However, the results are not conclusive. Objectives To analyse trends in the prevalence of psoriasis over the past 30 years, separating age, birth cohort and time period effects. Methods Five population-based surveys in North Norway, the Tromso Studies 2–6, collected between 1979 and 2008, were studied. Participants aged 20–79 years with self-reported psoriasis data in at least one of the surveys were included, yielding a total of 69 539 observations from 33 387 unique individuals born between 1915 and 1977. Trends in psoriasis prevalence were examined using cross-sectional, time lag and longitudinal designs of graphical plots. Observed trends were further evaluated in generalized linear-regression models. Results The self-reported lifetime prevalence of psoriasis increased from 4·8% in 1979–1980 to 11·4% in 2007–2008. Graphical plots showed an increasing prevalence of psoriasis with each consecutive survey in all examined age groups and birth cohorts, leaving time period effects as the explanation for the increase. The odds for psoriasis in the cohort were 2·5 times higher in 2007–2008 than in 1979–1980 (adjusted odds ratio 2·49, 95% confidence interval 2·08–2·99). The prevalence of persons reporting a doctor’s diagnosis of psoriasis was 9·9% in the last survey. In subgroups of the study population, psoriasis was associated with higher body mass index, lower physical activity during work and leisure time, lower educational level and smoking. Conclusions Our findings indicate an increasing prevalence of self-reported psoriasis. This could represent a true increase in prevalence, possibly due to changes in lifestyle and environmental factors, or an increased awareness of the disease.

A randomized phase 2a efficacy and safety trial of the topical Janus kinase inhibitor tofacitinib in the treatment of chronic plaque psoriasis.

Abstract: Background Tofacitinib (CP-690,550) is a novel Janus kinase inhibitor in development as an oral formulation for the treatment of several inflammatory diseases including psoriasis.

Translating Patient-Oriented Eczema Measure (POEM) scores into clinical practice by suggesting severity strata derived using anchor-based methods

Abstract: Background: The Patient-Oriented Eczema Measure (POEM) is a validated, patient-derived assessment measure for monitoring atopic eczema severity, although further information on how different POEM scores translate into disease severity categories is needed for clinical trials, epidemiological research and audit. Objectives: We sought to determine the relationship between Patient-Oriented Eczema Measure (POEM) scores (range 0–28) and two Global Questions (GQ1 and 2) concerning patients’/parents’ views of the overall severity of their/their child’s atopic eczema, in order to stratify POEM scores into five severity bands. Methods: POEM scores and GQs were completed by 300 patients from general practice and 700 patients from dermatology outpatient clinics, including 300 adults aged ≥ 16 years and 700 children. Results: The mean POEM score was 136 (range 0–28), and standard deviation (SD) was 72. Mean GQ1/GQ2 scores were 21/21, respectively (range 0–4 and SD 11 for both). The mean, mode and median of the GQ scores for each POEM score were used to devise possible POEM bandings. The proposed banding for POEM scores are: 0–2 (clear/almost clear); 3–7 (mild); 8–16 (moderate); 17–24 (severe); 25–28 (very severe), kappa coefficient 046. Conclusions: Severity banding of the POEM will allow more clinically meaningful use in everyday clinical practice and as a core outcome measure in future atopic eczema research.

Blastic plasmacytoid dendritic cell neoplasm: clinical features in 90 patients

Abstract: Summary Background Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare disease characterized by malignant proliferation of a contingent blastic plasmacytoid dendritic cell. This rare entity is recognized mostly by cutaneous spreading, or not having a leukaemic component. The prognosis is very poor. Objectives To study a large cohort of 90 patients with BPDCN, to define additional symptoms to form a correct diagnosis earlier, and to manage such patients accordingly. Methods We retrospectively reviewed BPDCN cases registered in the French Study Group on Cutaneous Lymphoma database between November 1995 and January 2012. Ninety patients were studied. Demographic data, clinical presentation, initial staging and outcome were recorded. Results The group contained 62 male and 28 female patients (sex ratio 2·2). Their ages ranged from 8 to 103 years at the time of diagnosis (mean 67·2 years). Three major different clinical presentations were identified. Sixty-six patients (73%) presented with nodular lesions only, 11 patients (12%) with ‘bruise-like’ patches and 13 (14%) with disseminated lesions (patches and nodules). Mucosal lesions were seen in five patients (6%). The median survival in patients with BPDCN was 12 months. Conclusions We here distinguish three different clinical presentations of BPDCN. A nodular pattern is a more common feature than the originally reported ‘bruise-like’ pattern. Despite the fact that BPDCN may initially appear as a localized skin tumour, aggressive management including allogeneic bone marrow transplantation should be considered immediately, as it is currently the only option associated with long-term survival.

Decreased risk of melanoma and nonmelanoma skin cancer in patients with vitiligo: a survey among 1307 patients and their partners

Abstract: Summary Background Vitiligo is a common skin disease characterized by autoimmune melanocyte destruction. Recent genetic studies suggest a lower susceptibility to melanoma in patients with vitiligo; however, lifetime melanoma prevalence in patients with vitiligo has not previously been studied. Nonmelanoma skin cancer (NMSC) prevalence has been studied, but only in small studies and with contradictory results. Objectives This retrospective, comparative cohort survey was designed to assess lifetime prevalences of melanoma and NMSC in patients with vitiligo compared with nonvitiligo controls. Methods Patients with nonsegmental vitiligo, who visited our clinic between January 1995 and September 2010, and were aged 50 years or older at the time of the study, were invited to participate in a postal survey. The questions regarded demographics, vitiligo characteristics, phototherapy history, skin cancer risk factors and the number of skin cancers experienced during the patient’s lifetime. Patients were asked to have their partner fill in a control questionnaire. All skin cancers were validated by a pathology report. In total 2635 invitations were sent and 1307 eligible questionnaires were returned (50%). Multivariate logistic regression models were used to quantify adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations between vitiligo and lifetime prevalences of melanoma and NMSC. Results Adjusted for confounders, patients with vitiligo had a threefold lower probability of developing melanoma (adjusted OR 0·32; 95% CI 0·12–0·88) and NMSC (adjusted OR 0·28; 95% CI 0·16–0·50). Subgroup analyses of patients treated with narrowband ultraviolet (UV) B, and psoralen and UVA did not show dose-related trends of increased age-adjusted lifetime prevalence of melanoma or NMSC. Conclusions Our findings suggest that patients with vitiligo have a decreased risk of both melanoma and NMSC.

Variations in skin colour and the biological consequences of ultraviolet radiation exposure.

Abstract: Summary Harmful consequences of sun exposure range from sunburn, photoageing and pigmentary disorders to skin cancer. The incidence and extent of these detrimental effects are largely due to the degree of constitutive pigmentation of the skin. The latter can be objectively classified according to the individual typology angle (°ITA) based on colorimetric parameters. The physiological relevance of the ITA colorimetric classification was assessed in 3500 women living in various geographical areas. Furthermore, in order to understand the relationship between constitutive pigmentation and ultraviolet radiation (UVR) sensitivity, we worked on ex vivo human skin samples of different colour exposed to increasing UVR doses. For each sample we defined the biologically efficient dose (BED), based on the induction of sunburn cells, and analysed UVR-induced DNA damage (cyclobutane thymine dimers, CPD). We found a significant correlation between ITA and BED. We also found a correlation between ITA and DNA damage. As the epidermal basal layer also hosts melanocytes and in order to analyse the relationship between skin colour and DNA damage occurring specifically within this cell type, we performed double staining for CPD and tyrosinase-related protein (TRP) 1, a key enzyme in melanin synthesis. We found that DNA damage within melanocytes depends on ITA. Taken together our results may explain the higher risk of lighter skin types developing skin cancers, including melanoma, as well as the development of pigmentary disorders in moderately pigmented skin. They show that skin classification based on ITA is physiologically relevant (as it correlates with constitutive pigmentation) and further support the concept of a more personalized approach to photoprotection that corresponds to a particular skin colour type's sensitivity to solar UVR.

Adherence to medication in patients with psoriasis: a systematic literature review.

Abstract: Psoriasis is associated with considerable physical and psychological morbidity. Optimal use of psoriasis treatments can limit the physical manifestations of psoriasis and help improve quality of life, but nonadherence is common. Smoking, obesity and excessive alcohol consumption are prevalent in this population. A systematic review of adherence to medication and recommendations for lifestyle change in psoriasis was undertaken, with a critical appraisal of the quality of the selected studies. Electronic searches from inception to March 2012 (PubMed, Web of Science and Embase) were conducted. Twenty-nine studies were included; however, none examined adherence to advice about lifestyle change. Studies using a dichotomous classification of adherence tended to report suboptimal adherence, with 21·6-66·6% of patients classed as adherent. No consistent pattern of results emerged for sociodemographical, disease and lifestyle factors as determinants of adherence. However, some treatment factors were associated with adherence. While mixed findings were reported for quality of life as a determinant of adherence, psychological factors (psychological distress and patient satisfaction with care and therapy) were associated with adherence. Only tentative conclusions can be made for determinants of adherence because the methodological quality of many of the included studies limits conclusions. There is a need for improved quality of research and reporting in this area, and this review provides a platform from which future research within this area should progress, along with suggested research recommendations.

Pharmacogenetics of psoriasis: HLA‐Cw6 but not LCE3B/3C deletion nor TNFAIP3 polymorphism predisposes to clinical response to interleukin 12/23 blocker ustekinumab

Abstract: SummaryBackground Our understanding of the genetic basis of predisposition to psoriasis is increasing exponentially due to the progress of genetic studies. However, so far little is known about genetic predisposition in relation to the response to psoriasis treatments. Recent data identified genetic predictors for the clinical outcome of conventional treatments such as methotrexate, acitretin and vitamin D derivatives, but few studies are available on genetic predictors of response to biologics. We hypothesized that genetic variations associated with increased risk of developing psoriasis may also act as predictors for the outcome of biologic therapy. Objectives The aim of our study was to analyse the presence of three different psoriasis susceptibility genetic variations (HLA-Cw6; TNFAIP3 rs610604 polymorphism; LCE3B/3C gene deletions) in a cohort of patients affected by moderate to severe psoriasis under ustekinumab treatment. Our primary endpoint was to evaluate the association between Psoriasis Area and Severity Index (PASI) 75 response at week 12 and HLA-Cw6 status. Methods Fifty-one patients were genotyped by standard methods and psoriasis severity (PASI score) was evaluated at day 0 and after 4, 12, 24 and 40 weeks of treatment. Results We observed increased response to ustekinumab in Cw6-positive (Cw6POS) patients [PASI 75 at week 12: 96·4% in Cw6POS vs. 65·2% in Cw6-negative (Cw6NEG) patients; P = 0·008]. In addition, we show that HLA-Cw6POS patients responded faster to ustekinumab, 89·3% of them reaching PASI 50 at week 4, after a single injection (vs. 60·9% of HLA-Cw6NEG patients). The superior response of HLA-Cw6POS patients was maintained throughout the study period, reaching the highest statistical significance for PASI 75 at week 28 (96·35% Cw6POS vs. 72·7% Cw6NEG; odds ratio 9·8). Analysis of TNFAIP3 rs610604 polymorphism and LCE3B/3C gene deletions did not show any significant association with response to ustekinumab. Conclusions Our observations underline the role of HLA-Cw6 not only as a psoriasis susceptibility gene, but also as a pharmacogenetic marker of response to ustekinumab in psoriasis.

Maintaining skin integrity in the aged: a systematic review

Abstract: Ageing is associated with structural and functional changes of the skin that result in increased vulnerability. The aim of this systematic review is to synthesize empirical evidence about the efficacy and effectiveness of basic skin care interventions for maintaining skin integrity in the aged. The databases Medline, EMBASE, CINAHL (1990-2012), Scopus, SCI (February 2013) and reference lists were searched. Inclusion criteria were primary intervention studies using skin care products in physiologically aged skin (lower age limit 50 years). Study and sample characteristics, interventions and outcomes were extracted. The methodological quality was assessed and a level of evidence was assigned. From 1535 screened articles 188 were read in full text. From these, 33 articles were included reporting results on treating dry skin conditions, and preventing incontinence-associated dermatitis and superficial ulcerations. Most studies had lower levels of evidence of 3 or 4. Skin-cleansing products containing syndets or amphoteric surfactants compared with standard soap and water washing improved skin dryness and demonstrated skin-protecting effects. Moisturizers containing humectants consistently showed statistically significant improvements in skin dryness. Skin barrier products containing occlusives reduced the occurrence of skin injuries compared with standard or no treatment. Owing to methodological limitations the current evidence base for basic skin care in the aged is weak. Using low-irritating cleansing products and humectant- or occlusive-containing moisturizers seems to be the best strategy for maintaining the skin barrier function and integrity. We know little about the effects of cleansing regimens and about the benefits of moisturizers when compared with each other.

Survival rate of antitumour necrosis factor-α treatments for psoriasis in routine dermatological practice: a multicentre observational study.

Abstract: Summary Background Adherence is an overall marker of treatment success, and it depends on multiple factors including efficacy and safety. Despite the wide use of tumour necrosis factor (TNF)-α blockers in the treatment of plaque-type psoriasis, few data regarding treatment adherence in routine clinical practice are available. Objectives To estimate the long-term survival rate of anti-TNF-α therapy in a cohort of patients with psoriasis in routine clinical practice; to evaluate the reasons for and predictors of treatment discontinuation. Methods The Outcome and Survival rate Concerning Anti-TNF Routine treatment (OSCAR) study was based on a retrospective analysis to estimate the long-term survival rate of the first anti-TNF-α treatment in patients with psoriasis, from three Italian academic referral centres. Adult patients (n = 650) with plaque psoriasis treated with a first course of adalimumab, etanercept or infliximab for ≥ 3 months were included. Results Global adherence to anti-TNF-α treatments after 28·9 ± 15·4 months (867 ± 462 days) of observation was 72·6%. Etanercept showed a longer survival (mean 51·4 months, 1565 days; P < 0·001) compared with infliximab (36·8 months, 1120 days) and adalimumab (34·7 months, 1056 days). Treatment discontinuation due to primary and secondary inefficacy was observed in 5·2% and 14·5% of patients, respectively, whereas discontinuation due to adverse events was reported in 29 subjects (4·5%). Independent predictors of treatment withdrawal were female gender [hazards ratio (HR) 1·3], treatment with adalimumab or infliximab compared with etanercept (HR 2·7 and 1·7, respectively), and the concomitant use of traditional systemic treatment, as a rescue therapy, compared with monotherapy (HR 1·9). Conclusions Overall survival of anti-TNF-α agents in psoriasis is elevated, with drug discontinuation mostly due to inefficacy. Etanercept showed a longer adherence compared with adalimumab and infliximab.

Heritability of psoriasis in a large twin sample

Abstract: Summary Background Previous twin studies have shown greater concordance rates for psoriasis in MZ than in DZ twins, and heritability estimates between 66% and 90%. This supports a genetic influence on psoriasis, but also highlights the fact that genes are not the only explanation for the disease. Objectives To study the concordance of psoriasis in a population-based twin sample. Methods Data on psoriasis in 10 725 twin pairs, aged 20–71 years, from the Danish Twin Registry was collected via a questionnaire survey. The concordance and heritability of psoriasis were estimated. Results In total, 4·1% of the men and 4·2% of the women had a lifetime history of psoriasis. The proband-wise concordance for psoriasis was larger in monozygotic than in dizygotic twins, 0·33 vs. 0·17. Genetic factors explained 68% (60–75%) of the variation in the susceptibility to psoriasis, whereas the rest of the variation was explained by nonshared environmental factors. Conclusion The results confirm that psoriasis is a complex multifactorial disease controlled by both exogenous and endogenous factors.

The association between psoriasis and dyslipidaemia: a systematic review.

Abstract: Psoriasis may be associated with dyslipidaemia, a known risk factor for cardiovascular disease. This systematic review aims to synthesize evidence for the association between psoriasis and dyslipidaemia. Through a systematic search using MEDLINE, Embase and the Cochrane Central Register, from 1 January 1980 to 1 January 2012, we identified 25 observational studies that met the inclusion criteria. These 25 studies included over 2·4 million participants, among whom 265,512 were patients with psoriasis. Twenty studies (80%) reported that psoriasis was significantly associated with dyslipidaemia, with odds ratios (ORs) for dyslipidaemia ranging from 1·04 to 5·55 in 238,385 patients with psoriasis, from a population of 2,340,605 participants. Specifically, four studies defining dyslipidaemia as triglyceride levels ≥ 150 mg dL reported significantly increased ORs of 1·20-4·98 for hypertriglyceridaemia in psoriasis. Three studies found that patients with psoriasis presented with significantly increased ORs (1·36-1·77) for high-density lipoprotein cholesterol levels < 40 mg dL , and two studies found hyperlipoproteinaemia to be significantly elevated in patients with psoriasis (ORs 1·55 and 2·09). One cohort study found a significantly higher incidence of hyperlipidaemia among patients with psoriasis (hazard ratio 1·17; 95% confidence interval 1·11-1·23). Among studies that assessed the severity of psoriasis, in 2662 patients with mild psoriasis and 810 patients with severe psoriasis, higher odds of dyslipidaemia were seen in patients with severe psoriasis. Five of the 25 studies (20%) in our review did not show any significant relationship between psoriasis and dyslipidaemia. This systematic review found that psoriasis was significantly associated with greater odds and incidence of dyslipidaemia. Greater psoriasis severity appeared to be associated with higher prevalence of dyslipidaemia.

Outdoor workers' sun-related knowledge, attitudes and protective behaviours: a systematic review of cross-sectional and interventional studies.

Abstract: Sun protection is a major concern for outdoor workers as they are particularly exposed to solar ultraviolet radiation and therefore at increased risk of developing some forms of skin cancer, cataract and ocular neoplasm. In order to provide an overview of outdoor workers' sun-related knowledge, attitudes and protective behaviours as reported in the literature and to evaluate the effectiveness of sun-safety education programmes in outdoor occupational settings, we conducted a systematic review of the literature by searching three electronic databases (PubMed, Embase, PsycINFO) from their inception up to 25 April 2012. An extensive hand search complemented the database searches. We identified 34 relevant articles on descriptive studies and 18 articles on interventional studies. Considerable numbers of outdoor workers were found to have sun-sensitive skin types; sunburn rates per season ranged from 50% to 80%. Data concerning outdoor workers' sun-related knowledge and attitudes were scarce and controversial. The reported sun-protective behaviours were largely inadequate, with many workers stating that they never or only rarely wore a long-sleeved shirt (50-80%), sun-protective headgear (30-80%) and sunscreen (30-100%) while working in the sun. However, there is growing evidence that occupational sun-safety education is effective in increasing outdoor workers' sun-protection habits and presumably in decreasing sunburn rates. Occupational sun-safety education programmes offer great potential for improving outdoor workers' largely insufficient sun-protective behaviours. It is hoped that, in the future, committed support from healthcare authorities, cancer foundations, employers and dermatologists will open the way for rapid and uncomplicated implementation of sun-safety education programmes.

Comparison of three screening tools to detect psoriatic arthritis in patients with psoriasis (CONTEST study).

Abstract: Summary Background Multiple questionnaires to screen for psoriatic arthritis (PsA) have been developed but the optimal screening questionnaire is unknown. Objectives To compare three PsA screening questionnaires in a head-to-head study using CASPAR (the Classification Criteria for Psoriatic Arthritis) as the gold standard. Methods This study recruited from 10 U.K. secondary care dermatology clinics. Patients with a diagnosis of psoriasis, not previously diagnosed with PsA, were given all three questionnaires. All patients who were positive on any questionnaire were invited for a rheumatological assessment. Receiver operating characteristic (ROC) curves were used to compare the sensitivity, specificity and area under the curve of the three questionnaires according to CASPAR criteria. Results In total, 938 patients with psoriasis were invited to participate and 657 (70%) patients returned the questionnaires. One or more questionnaires were positive in 314 patients (48%) and 195 (62%) of these patients attended for assessment. Of these, 47 patients (24%) were diagnosed with PsA according to the CASPAR criteria. The proportion of patients with PsA increased with the number of positive questionnaires (one questionnaire, 19·1%; two, 34·0%; three, 46·8%). Sensitivities and specificities for the three questionnaires, and areas under the ROC curve were, respectively: Psoriatic Arthritis Screening Evaluation (PASE), 74·5%, 38·5%, 0·594; Psoriasis Epidemiology Screening Tool (PEST), 76·6%, 37·2%, 0·610; Toronto Psoriatic Arthritis Screen (ToPAS), 76·6%, 29·7%, 0·554. The majority of patients with a false positive response had degenerative or osteoarthritis. Conclusion Although the PEST and ToPAS questionnaires performed slightly better than the PASE questionnaire at identifying PsA, there is little difference between these instruments. These screening tools identify many cases of musculoskeletal disease other than PsA.

Systemic involvement of acute generalized exanthematous pustulosis: a retrospective study on 58 patients

Abstract: Summary Background Acute generalized exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction characterized by rash with sterile pustules, high fever and elevated circulating neutrophil counts. Objectives To investigate the frequency and clinical features of AGEP systemic involvement. Methods This retrospective study included all patients hospitalized in our department between 2000 and 2010 with a discharge diagnosis of AGEP. Patients had to fulfil the following criteria: (i) a specific EuroSCAR score > 4 and (ii) biological and radiological work-up available. Results Among the 58 patients enrolled, 10 had at least one systemic involvement: hepatic function test results were abnormal for seven; six had renal insufficiency; two developed acute respiratory distress, with one patient's bronchoalveolar lavage fluid containing many neutrophils but no microorganisms; one was agranulocytotic. Mean peripheral neutrophil counts and mean C-reactive protein levels were elevated significantly in patients with systemic involvement. Amoxicillin rechallenge and hospitalization duration were associated with systemic involvement. AGEP systemic involvement was observed in 17% of cases studied, including liver, kidney, bone-marrow and lung involvement. Outcomes were favourable after drug withdrawal, and symptomatic and topical steroid treatments. Conclusions The neutrophil count–systemic involvement association may suggest a role for neutrophils in AGEP systemic involvement. Physicians should be aware of the possibility of systemic involvement in AGEP and should actively look for signs of extracutaneous reactions.

Pathogenesis of infantile haemangioma

Abstract: Hemangioma is a vascular tumor of infancy that is well-known for its rapid growth during the first weeks to months of a child’s life followed by a spontaneous but slow involution. During the proliferative phase, the vessels are disorganized and composed of immature endothelial cells but are not leaky 1, perhaps due to the abundance of α-smooth muscle actin (α-SMA)-positive perivascular that circumscribe the vessels (Figure 1). When the tumor involutes, the vessels mature and enlarge but are reduced in number. Fat, fibroblasts and connective tissue replace the vascular tissue, with few large feeding and draining vessels evident. Figure 1 α-Smooth muscle actin (α-SMA) highlights vessel maturation and regression during the life cycle of IH. Paraffin-embedded sections from proliferating, involuting and involuted phase IH were immunostained with anti-α-SMA, images ... Both angiogenesis 2 and vasculogenesis 3 have been proposed as mechanisms contributing to the neovascularization in hemangioma tumors. Angiogenesis is defined as the growth of new vessels from pre-existing vessels, requiring degradation of the basement membrane, migration of endothelial cells and tubulogenesis, followed by recruitment of perivascular cells. Vasculogenesis is the de novo formation of blood vessels from stem or progenitor cells. In recent years, several of the “building blocks”, the cells comprising the hemangioma, have been isolated. Among them are hemangioma progenitor/stem cells (HemSC), endothelial cells (HemEC) and pericytes (HemPericytes). This review will focus on these cell types, as well as molecular pathways within these cells that have been implicated in driving the pathogenesis of IH.

Elevated serum levels of endocan in patients with psoriasis vulgaris: correlations with cardiovascular risk and activity of disease

Abstract: SummaryBackground Psoriasis vulgaris is an inflammatory disease characterized by epidermal hyperproliferation, leucocyte adhesion molecule expression and leucocyte infiltration. Psoriasis is associated with an increased risk of cardiovascular disease. Endothelial dysfunction is widely regarded as being the initial process in the development of atherosclerosis. Human endothelial cell-specific molecule-1 (endocan) is a novel human endothelial cell-specific molecule. Previous studies suggested that endocan may be a novel endothelial dysfunction marker. Objectives To investigate the relationship between serum levels of endocan and both cardiovascular risk and disease activity in patients with psoriasis vulgaris. Methods A total of 29 patients with psoriasis vulgaris and 35 control subjects were included in the study. Endocan, high-sensitivity C-reactive protein (hsCRP) and carotid artery intima–media thickness (cIMT) were measured in all subjects. Results Serum endocan levels were significantly different between the two groups (P < 0·001). In patients with psoriasis, serum endocan levels correlated with Psoriasis Area and Severity Index, hsCRP and cIMT (r = 0·477, P = 0·009; r = 0·484, P = 0·008; r = 0·408, P = 0·02, respectively). Conclusions Circulating endocan may represent a new marker that correlates with cardiovascular risk as well as the severity of disease in patients with psoriasis vulgaris. Endocan may be a surrogate endothelial dysfunction marker and may have a functional role in endothelium-dependent pathological disorders. Whether endocan levels could become a treatment target merits further investigation.

Does early life exposure to antibiotics increase the risk of eczema? A systematic review

Abstract: Summary A number of studies have suggested that early life exposure to antibiotics can lead to an increased risk of developing eczema. This systematic review and meta-analysis of observational studies, involving children or young adults aged 0–25 years, assessed the impact of antibiotic exposure either in utero or during the first 12 months of life on subsequent eczema risk. Twenty studies examined the association between prenatal and/or postnatal exposure to antibiotics and development of eczema. The pooled odds ratio (OR) for the 17 studies examining postnatal antibiotic exposure was 1·41 [95% confidence interval (CI) 1·30–1·53]. The pooled OR for the 10 longitudinal studies was 1·40 (95% CI 1·19–1·64), compared with a pooled OR of 1·43 (95% CI 1·36–1·51) for the seven cross-sectional studies. There was a significant dose–response association, suggesting a 7% increase in the risk of eczema for each additional antibiotic course received during the first year of life [pooled OR 1·07 (95% CI 1·02–1·11)]. Finally, the pooled OR for the four studies relating to antenatal exposure was 1·30 (95% CI 0·86–1·95). We conclude that exposure to antibiotics in the first year of life, but not prenatally, is more common in children with eczema.

Psoriasis, psoriatic arthritis and type 2 diabetes mellitus: a systematic review and meta‐analysis

Abstract: Several observational studies have assessed the association between psoriasis, psoriatic arthritis (PsA) and type 2 diabetes mellitus, with inconclusive results. We set out to investigate the association between psoriasis, PsA and type 2 diabetes mellitus. Observational studies assessing the relationship between psoriasis or PsA and type 2 diabetes mellitus up to December 2012 were identified by electronic and hand searches in Medline, Embase, PubMed, the Cochrane Database of Systematic Reviews and Google Scholar. For each study we collected the first author's last name, publication year, country of origin, study design, characteristics of participants (sample size, age and sex), the variables incorporated into the multivariable analyses, and the odds ratios (ORs) of psoriasis associated with diabetes along with the corresponding 95% confidence intervals (CIs). From the data provided in each article, the crude OR was also calculated. Forty-four observational studies (in 37 articles) were identified for the final analysis. The pooled OR from random-effects analysis was determined to be 1·76 (95% CI 1·59-1·96). The highest risk was for patients suffering from PsA (OR 2·18, 95% CI 1·36-3·50). We also observed a dose effect in the risk of suffering from type 2 diabetes mellitus, as patients considered as having severe psoriasis had higher risk (OR 2·10, 95% CI 1·73-2·55) than the pooled OR. We perform meta-regression and sensitivity analyses to explore sources of heterogeneity among the studies and to determine how they would influence the estimates, and found no significant influence in the results of the meta-analyses. The findings support the association between psoriasis, PsA and type 2 diabetes mellitus. Some caution must be taken in the interpretation of these results because there may be heterogeneity between studies.

Efficacy and safety of 15(R/S)-methyl-lipoxin A(4) in topical treatment of infantile eczema.

Abstract: Summary Background Lipoxins are potential anti-inflammatory mediators and serve as an endogenous ‘braking signal’ in the inflammatory process. Accumulating evidence has indicated the efficacy of lipoxin A4 (LXA4) and its analogs in the treatment of many animal models of inflammatory diseases. Objectives This study investigates the efficacy and safety of 15(R/S)-methyl-lipoxin A4 in the topical treatment of infantile eczema. Patients and methods In this two-centre, double-blind, placebo-controlled, randomized, parallel-groups comparative study, 60 patients were randomly assigned to receive either the 15(R/S)-methyl-lipoxin A4 cream, mometasone furoate (Eloson, Schering-Plough, Shanghai, China) or placebo for 10 days. The efficacy was determined using the Severity Scale Score (SSS), Eczema Area and Severity Index (EASI) and the Infants’ Dermatitis Quality of Life Index (IDQOL). Safety was monitored by physical examination, laboratory investigation and documentation of clinical adverse events. Results The treatment of eczema with 15(R/S)-methyl-LXA4 cream significantly relieved the severity, induced a recovery, and improved the quality of life of the patients, as demonstrated by significantly reduced SSS, EASI and IDQOL, respectively, in a way similar to the efficacy of Eloson. All safety parameters remained within normal limits. No clinical adverse event was found in the three patient groups. Conclusions 15(R/S)-methyl-LXA4 was well tolerated, and significantly reduced the severity of eczema. The results of this small exploratory study suggest that 15(R/S)-methyl-LXA4 warrants further investigation in the treatment of eczema.

The safety profile of ustekinumab in the treatment of patients with psoriasis and concurrent hepatitis B or C.

Abstract: SummaryBackground Ustekinumab, an interleukin (IL)-12 and IL-23 blocker, has emerged as a new therapeutic option for patients with psoriasis. It is generally well tolerated but safety data on the use of ustekinumab in patients with viral hepatitis are limited. Objective To assess the safety profile of ustekinumab in the treatment of patients with psoriasis who have concomitant hepatitis B or hepatitis C. Methods This study included 18 patients with concurrent psoriasis and hepatitis B virus (HBV) infection (14 patients) or hepatitis C virus (HCV) infection (four patients) who were treated with at least two ustekinumab injections. Viral loads were measured at baseline and each time before the administration of ustekinumab. Relevant clinical data were recorded. Results Among 11 patients positive for hepatitis B surface antigen (HBsAg), two out of the seven (29%) patients who did not receive antiviral prophylaxis exhibited HBV reactivation during ustekinumab treatment. No viral reactivation was observed in the three occult HBV-infected patients (HBsAg-negative/hepatitis B core antibody-positive patients). One patient with HCV, liver cirrhosis and treated hepatocellular carcinoma (HCC) experienced HCV reactivation and recurrent HCC during the ustekinumab treatment. No significant increase in aminotransferase levels was observed in any patient. Conclusions Antiviral prophylaxis appears to minimize the risk of viral reactivation in patients with concurrent psoriasis and HBV infection. Without effective anti-viral prophylaxis, the risk/benefit of ustekinumab treatment should be carefully assessed in patients with psoriasis and HBV or HCV infection and/or HCC. Close monitoring for HBV and HCV viral load is recommended, particularly for patients with high-risk factors. Serum aminotransferase determination may not be useful for early detection of viral reactivation.