Although propranolol has become the first line therapy of infantile hemangiomas (IH), no study has yet investigated factors associated with the risk of relapse in children with IH treated with propranolol after treatment cessation.

To compare factors associated with the risk of relapse in children with IH treated with oral propranolol

We conducted a single-centre retrospective observational study. All files and photographs of patients with IH aged 5 months or less at the time of treatment initiation and who were seen between June 1^st 2008 and December 31^th 2011at the National Reference Center for rare skin diseases of Bordeaux were retrospectively reviewed.

A total of 158 children were included of whom 118 had not relapsed (R-) and 40 had relapsed (R+).52 patients were boys and 106 were girls (sex ratio M/F, 1:2), and 19 had a segmental IH (12%). When conducting multivariate analysis, only IH with a subcutaneous component and those with segmental distribution were independently associated with relapse.

Our study shows that segmental IH as well as hemangiomas with a deeper component are more at risk for relapse and should thus beneficiate of closer follow-up after treatment interruption and/or longer treatment.

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Multiphoton microscopy (MPM) is a novel imaging technology that has recently become applicable for diagnostic purposes. The use of (near) infrared light in MPM allows for deep tissue imaging. In addition, this modality exploits the autofluorescent nature of extracellular matrix fibres within the skin.

The aim of this study was to quantitate the structure and abundance of elastic fibres in human dermis in three dimensions utilising autofluorescent signals generated by MPM for the objective examination of elastin-related skin disorders.

Cross-sections of skin samples from elastin-related disorders were analysed by MPM and correlated to histopathological examination. In situ visualisation of elastic fibres by MPM was conducted by en face imaging of ex vivo skin samples through the intact epidermis. Image analysis software was used to quantify elastic fibres in three dimensions.

Based on the MPM-detected elastin-specific autofluorescence in skin sections, we developed the Dermal Elastin Morphology Index (DEMI), calculated as the ratio of elastic fibre surface area and volume. This enabled objective three-dimensional quantification of elastic fibres. Quantitative scoring of sun-damaged skin using the DEMI correlated with qualitative histopathological grading of the severity of solar elastosis. Furthermore, this approach was applied to changes in elastic fibre architecture in other elastin-related skin disorders, such as pseudoxanthoma elasticum (PXE), PXE-like syndrome, elastofibroma, focal dermal elastosis, anetoderma, mid-dermal elastolysis and striae distensae. We also imaged elastic fibres in intact ex vivo skin imaged en face through the epidermis, indicating that this approach could be used in patients in vivo.

MPM has the potential for non-invasive in vivo visualisation of elastic fibres in the dermis with near histological resolution. The DEMI is a novel approach to enable objective assessment of elastic fibres to support diagnosis as well as monitoring of disease progress or therapy of elastin-related skin disorders.

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Melanoma is responsible for almost 80% of the deaths attributed to skin cancer.

Stem cells, defined by CD133 expression, have been implicated in melanoma tumor growth, but their specific role is still uncertain.

We hypothesized that the phenotypic heterogeneity of human cutaneous melanomas is related to their content of CD133+ cells.

We compared the percentages of CD133+ cells in 29 tumors from four classic types of melanoma: lentigo maligna melanoma (LMM), superficial spreading melanoma, nodular melanoma, and acral lentiginous melanoma (ALM). Also, we compared the percentages of CD133+ cells in melanomas with different degrees of exposure to ultraviolet light: 16 melanomas from skin with chronic sun-induced damage and 13 melanomas from skin without such damage.

We found a statistically significant increase of CD133+ cells in three different contexts: in melanomas arising on skin with signs of chronic sun-induced damage versus non-exposed skin, in melanomas “in situ” versus invasive melanomas, and in LMM versus ALM. The proportions of CD133+ cells did not differ among samples of normal skin with different degrees of sun exposure. A distinct subpopulation of CD133+CXCR4+ cancer stem cells (CSCs) was identified and shown to be related with the invasive phenotype of the tumors.

Here, we provide evidences showing, for the first time, that an increase in the CD133+ cell content is associated both with melanomas arising on skin with signs of chronic sun-induced damage and in melanomas “in situ” with better prognostic. Moreover, our study further confirms the existence of a subpopulation of CD133+CXCR4+ CSCs in cutaneous melanomas with invasive phenotype and bad prognostic.

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Cadherin switch in melanoma, with loss of E-cadherin and up-regulation of N-cadherin, is believed to underlie melanoma cell detachment from the epidermis and promotion of dermal and vascular melanoma invasion. The tumour suppressor PTEN has been suggested as a potential regulator of this cadherin switch.

To study the biological and clinical implications of cadherin switch and PTEN expression in melanoma progression.

We constructed tissue microarrays from primary tumour samples from 393 formalin-fixed paraffin-embedded melanomas diagnosed between 2001 and 2006. Median follow-up was ten years. Tissue microarray sections were stained by immunohistochemistry for E-cadherin, N-cadherin, and PTEN, and expression was analysed semi-quantitatively.

Breslow thickness correlated strongly with reduced/absent PTEN expression (p<0.0001), low E-cadherin expression (p<0.0001), high N-cadherin expression (p<0.0001) and the combination of low E-cadherin and high N-cadherin expression (cadherin switch profile; p=0.001). There was a significant association between reduced/absent PTEN expression and the presence of the cadherin switch profile (p=0.03).

In univariate analyses, a low E-cadherin expression significantly predicted an adverse overall-relapse-free (p=0.04), melanoma-specific (p=0.03), and distant-metastasis-free (p=0.01) survival; reduced/absent PTEN predicted an adverse overall-relapse-free survival (p=0.006), and the cadherin switch profile predicted an adverse melanoma-specific (p=0.005), and distant-metastasis-free (p=0.01) survival.

In multivariate analysis, the cadherin switch profile was an independent prognostic marker of melanoma-specific (p=0.04) and distant-metastasis-free survival (p=0.02).

Cadherin switch and reduced/absent PTEN expression are associated in melanoma, and both factors may play important roles in the progression of melanoma.

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Anti-tumour necrosis factor (anti-TNF-α) agents can be used successfully to treat patients with psoriasis and other inflammatory diseases. However, very few studies have examined the relationship between TNF-α polymorphisms and the response to anti-TNF-α agents.

Single nucleotide polymorphisms (SNPs) for TNF-α promoter and IL12B/IL23R genes, and presence of HLA-Cw6 haplotype were genotyped for 109 patients. We studied the association between these SNPs and the efficacy of treatment at 3 and 6 months (PASI and BSA).

Patients with the TNF-α-238GG genotype more frequently achieved PASI75 at six months (82.5 vs. 58.8, p=0.049). At six months patients with the TNF-α-857CT/TT genotypes showed greater improvements in PASI and BSA (83.1 vs. 92.7, p=0.004; 82.7 vs. 92.6, p=0.009) and more frequently achieved PASI75 (71.4 vs. 96.3, p=0.006). More patients with the TNFα-1031TT genotype achieved PASI75 at three months (90.8 vs. 75.7, p=0.047) and six months (85.5 vs. 65.7, p=0.038) and demonstrated superior improvements in PASI at six months (89.9 vs. 78.7, p=0.041). Patients with the IL23R GG genotype (rs11209026) achieved PASI90 at six months (66.3 vs. 0, p=0.006) more frequently and the improvement of PASI was also greater (86.8 vs. 67.8, p=0.013). Patients with HLA-Cw6 haplotype showed poorer response than those without this haplotype.

This study identified a relationship between certain TNF-α and IL12B/IL23R polymorphisms and the short-term response to anti-TNF-α drugs. If these results are confirmed, this information will allow for stratified consent with more accurate prediction of response/personalized choice of treatment hierarchy for the patient.

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Propranolol is now widely used to treat severe infantile hemangiomas. Very few cases of propranolol-resistant infantile hemangiomas (PRIHs) are mentioned in the literature.

To describe the characteristics of PRIHs.

February 2011 to December 2011. All PRIH patients evaluated by the members of the “Groupe de Recherche Clinique en Dermatologie Pédiatrique” from 1 January 2007 to 1 December 2011 were eligible.

Among 1130 patients treated with propranolol for infantile hemangioma, 10 (0.9%) had PRIHs. Hemangioma propranolol-resistance was observed at all ages during early childhood and at any proliferation stage.

PRIH is a rare phenomenon that raises questions and merits further investigation.

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“Polysensitisation” (PS) is usually defined as contact sensitisation to 3 or more unrelated haptens of the baseline patch test series. Despite PS being an important clinical phenotype indicating increased susceptibility to contact allergy, statistical approaches to analyse PS have hitherto been preliminary.

To apply an appropriate regression model for count data, namely, negative binomial hurdle regression, to a large set of clinical patch test data with the aim of estimating PS risk in more detail than previously achieved.

The detailed information provided by the hurdle model includes a separate estimation of an ‘increment factor’ quantifying the likelihood of further positive reactions, i.e. PS. Clinical data of 126878 patients patch tested by departments comprising the IVDK network (www.ivdk.org) between 1995 and 2010 were included.

Regarding anatomical sites as exposure (surrogate), the axillae and the feet were found to be strong PS risk factors. Moreover, age was a strong PS risk factor, and less so, female sex. In comparison, atopic eczema and occupational dermatitis were less important risk factors. Single allergens contributed to PS to a varying extent.

The data presented point to some, very likely exposure–related, risk factors which need to be considered in future PS research, e.g., addressing the genetic basis for PS.

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Adherence is an overall marker of treatment success, and it depends on multiple factors including efficacy and safety. Despite the large use of TNF alpha blockers in the treatment of plaque-type psoriasis, only few data regarding treatment adherence in routine clinical practice are available.

To estimate the long-term survival rate of anti-TNF alpha therapy in a cohort of psoriatic patients in routine clinical practice; to evaluate the reasons responsible for and predictors of treatment discontinuation.

The OSCAR (Outcome and Survival rate Concerning Anti-tumor necrosis factor Routine treatment) study was based on a retrospective analysis to estimate the long-term survival rate of the first anti-TNF alpha treatment in patients with psoriasis, from three Italian academic referral centers. Adult patients (n=650) with plaque psoriasis treated with a first course of adalimumab, etanercept or infliximab for ≥ 3 months were included.

Global adherence to anti-TNF alpha 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) as compared to 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 (HR: 1.3), treatment with adalimumab or infliximab compared to 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).

Overall survival of anti-TNF alpha agents in psoriasis is elevated, with drug discontinuation mostly due to inefficacy. Etanercept showed a longer adherence compared to adalimumab and infliximab.

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Genital and anorectal mucosal melanomas (GAMM) are rare, compared to cutaneous melanoma (CM). Many epidemiological and genetic studies have been carried out in CM. In contrast, the genetic and environmental risk factors for GAMM have been poorly documented up to now.

The aim of the study was to compare the distribution of pigmentation and nevus phenotypes, sun exposure and family history of melanoma between GAMM and CM patients.

For that purpose, we compared two series of 81 GAMM and 293 CM patients.

GAMM and CM patients did not show significant differences for phenotypic risk factors. However, GAMM patients tend to display red hair (10.8% vs 5.5%, P = 0.08) and a poor tanning ability (22.2% vs 13.3%, P = 0.06) at a higher frequency than CM patients.A family history of melanoma was significantly more frequent in the GAMM than in the CM series (18.2% vs 7.5%, P = 0.005). Apart from the GAMM index case, affected relatives had CM except in one family. The frequency of multiple primary melanomas (MPM) was similar in GAMM and CM series (6.5% vs 5.3%, P=0.43). All GAMM patients with MPM had only one GAMM primary while the other primary was cutanaeous. No CDKN2A germline mutation was detected in GAMM patients.

This study shows that GAMM and CM may occur in the same patient and GAMM may develop in a familial setting. The association of both GAMM and CM in patients and families suggests shared genetic factors by these two types of melanoma.

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Knowledge about the development of untreated actinic keratosis (AK) and their risk of progression into squamous cell carcinoma (SCC) is important.

Synthesis of primary data on the natural history of AK.

Systematic literature search (Medline, Medline in Process, Embase, Cochrane) on studies (cohort studies/control arms from RCTs) on the natural course of AK (a) progression and regression rates per lesion-year, (b) changes in the total lesion counts over time, (c) spontaneous field regression and recurrence rates; taking into account: studies on participants without immunosuppression and history of skin cancer, immunosuppressed patients, participants with history of skin cancer and sunscreen use.

We indentified 24 eligible studies providing data on at least one of the outcomes. Progression rates of AKs to SCC ranged from 0% to 0.075%/lesion/year, with a risk of up to 0.53% per lesion when looking at participants with prior history of NMSC. Rates of regression of single lesions ranged between 15%-63% after one year. The data available on recurrence rates of single lesions one year after regression indicate a recurrence rate of between 15% and 53%. Data on the relative change of the total AK count over time are heterogeneous, with a 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 AKs developing into invasive carcinoma can be given, further studies are needed.

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Skin infections related to disrupted antimicrobial defence system in atopic dermatitis (AD) skin are a common problem in the control of AD. Altered levels of antimicrobial peptides, including human betadefensin-2 (hBD-2), have been reported in AD skin and a link to impaired barrier function has been suggested.

To study hBD-2 in relation to skin barrier function in AD-patients and controls, and to study hBD-2 in relation to disease severity in AD-patients.

25 AD-patients and 11 controls were enrolled. HBD-2 peptide concentration was determined by ELISA in stratum corneum samples collected by a minimally invasive tape-stripping method. Disease severity was assessed by SCORing Atopic Dermatitis (SCORAD), and skin barrier function was evaluated by measurement of trans-epidermal water loss (TEWL) and skin pH. AD-patients were characterized according to filaggrin mutations.

HBD-2 concentrations in stratum corneum were found to differ in lesional and non-lesional AD skin and healthy controls, with highest values in lesional skin of AD (p<0.001). SCORAD and TEWL were significantly increased in participants with measureable hBD-2 values as compared to those without (p< 0.018 and p<0.007, respectively), while no difference in skin pH values was found. Significant correlations between hBD-2 in lesional AD skin and TEWL, as well as SCORAD were observed (R=0.55 and R=0.44, respectively), while no correlation with skin pH was found. HBD-2 was not found to relate to filaggrin mutations.

A significant correlation was found between HBD-2 and disturbed skin barrier function and disease severity. The minimally invasive skin sample technique enables evaluation of stratum corneum and its proteins over time and provides the possibility of relating these findings to treatment, infections and physiological variations.

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Cutaneous melanoma tumour is classified into clinico-histopathological subtypes which may be associated with different genetic and host factors. Variation in the MC1R gene is one of the main factors of risk variation in sporadic melanoma. The relationship between MC1R variants and the risk of developing a specific subtype of melanoma has not been previously explored.

to analyze whether certain MC1R variants are associated with particular melanoma subtypes with specific clinico-histopathological features.

An association study between MC1R gene variants and clinico-pathological subtypes of primary melanoma derived from 1679 patients was performed.

We detected 53 MC1R variants (11 synonymous and 43 non-synonymous). Recurrent non-synonymous variants were p.V60L (29.9%), p.V92M (11.7%), p.D294H (9.4%), p.R151C (8.8%), p.R160W (6.2%), p.R163Q (4.2%) p.R142H (3.3%), p.I155T (3.8%), p.V122M (1.5%) and p.D84E (1%). Melanoma subtypes showed differences in total number of MC1R variants (P-value=0.028) and number of Red hair colour variants (P-value=0.035). Furthermore, an association between the p.R163Q variant and lentigo maligna melanoma subtype was detected under a dominant model of heritance (OR: 2.16 95% CI: 1.07-4.37; P-value=0.044). No association was found between p.R163Q and skin Fitzpatrick's phototype, eye colour or skin colour indicating that the association was independent of the role of MC1R in pigmentation. No association was observed between MC1R polymorphisms and other melanoma subtypes.

Our findings suggest that certain MC1R variants could increase melanoma risk due to their impact on pathways other than pigmentation and therefore be linked to specific melanoma subtypes.

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Dermatitis artefacta (DA) is a factitious skin disorder caused by the deliberate production of skin lesions by patients with a history of underlying psychological problems. The patient may not be fully aware of this, and the true extent of this disorder, especially in children, is currently unknownManagement of these patients is challenging as many fail to engage effectively with their dermatologist.

We aimed to explore the various clinical presentations and strategies employed to treat DA in our local population .Outcomes were also noted to evaluate effectiveness of our management.

A retrospective case note review was conducted of 28 patients attending the Regional Psychodermatology Clinic at the Royal London Hospital from January 2003 to December 2011.

Out of 28 patients identified with DA, the majority of patients were female, and the most frequent sites for skin lesions were the face and upper body. Anxiety, depression and personality disorders were common underlying psychiatric diagnoses. 93% of patients were successfully managed (i.e. the DA resolved or was in remission at the time of writing) in our combined psycho-dermatology clinic by a multi-disciplinary psychocutaneous medicine team (MDT). 32% of our cases were children (<16 years) and one of these was referred to local child protection services. 46% of patients had a concomitant mental health disease at the time of presentation with DA.

A multi-disciplinary psychocutaneous team is important in this condition particularly as the patient is likely to require psychological intervention (to facilitate the resolution of the precipitant) in addition to dermatological (to make the diagnosis and, importantly, to exclude organic disease) and psychiatric (to manage concomitant psychiatric disease) input.. Our findings indicate that our model of a psycho-dermatology MDT will achieve greater successful treatment of patients with DA and we are the first to describe this important service in the UK.

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Telangiectatic leg veins (TLV) represent a common cosmetic problem. Because of their deeper penetration of light into the dermis, near infrared lasers are widely used but with varying degrees of success, particularly in case of different vessel diameters. Indocyanine green (ICG)-augmented diode laser treatment (ICG+DL) may present an alternative treatment option.

This trial evaluates the efficacy of ICG+DL in the treatment of TLV and compares the safety and efficacy of ICG+DL therapy with the standard treatment, the long-pulsed Nd:YAG laser.

In a prospective randomized controlled clinical trial, 29 study participants with TLV were treated with a Nd:YAG laser (λ_em = 1064 nm, 160-240 J cm^-², 65 ms pulse duration, 5 mm spot size) and ICG+DL (λ_em = 810 nm, 60-110 J cm^-², 30-86 ms pulse duration, 6 mm spot size, total ICG dose: 4 mg kg⁻¹) in a side-by-side comparison in one single treatment setting that included histological examination (haematoxylin and eosin, CD31, ERG) in four participants. Two blinded investigators and the participants assessed clearance rate, cosmetic appearance and adverse events up to 3 months after the treatment.

According to both, the investigators’ and the participants assessment, clearance rates were significantly better after ICG+DL therapy than after Nd:YAG laser treatment (p<0.05). On a 10-point scale indicating pain during treatment, participants rated ICG+DL therapy to be more painful (6.1 ± 2.0) than Nd:YAG laser treatment (5.4 ± 2.0).

ICG+DL therapy represents a new and promising treatment modality for TLV with high clearance rates and a very good cosmetic outcome after one single treatment session.

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The systematic support of parents of children with eczema is essential to their effective management. The few existing support models have a limited evidence base. This paper reports the outcome-orientated service evaluation of an original, extensive social learning theory based, nurse-led Eczema Education Programme (EEP).

To evaluate the EEP using specified child and parental outcomes and service impact data.

From a sample of 257 parent-child dyads attending the EEP, a pretest-posttest design evaluated its child impact using health related quality of life measures (Infant's Dermatitis Quality of Life index, IDQOL, which includes a small dermatitis severity element; Children's Dermatology Life Quality Index, CDLQI), severity measures (Patient Orientated Eczema Measure, POEM), a new parental measure (Parental Self-Efficacy in Eczema Care Index, PASECI) and service impact data based on General Practice (GP) attendance patterns pre-post intervention.

Statistically significant impacts were observed, compared to baseline, on infant quality of life (p<0.001), child quality of life (p=0.027), disease severity (p<0.001) and parental self-efficacy (p<0.001). Improvements in child quality of life, parental efficacy and service impact were also evident from qualitative data. The cumulative total of all GP visits for selected participants post EEP reduced by 62%.

The EEP appears to be an effective model of delivering structured education to parents of children with eczema and one generalizable to other multi-ethnic metropolitan populations. As a non-controlled study, this rigorous service evaluation highlights the model's significance and the case for an evaluative multi-centre randomised controlled trial of this educational intervention to inform a nurse-led programme of care.

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Blastic plasmacytoid Dentritic Cell Neoplasm (BPDCN) is, as defined in the new 2008 World health Organized (WHO) classification of tumors of hematopoietic and lymphoid tissue, a rare disease characterized by malignant proliferation of a contingent blastic plasmacytoid dendritic cell. This rare entity is mostly revealed and diagnosed on cutaneous spreading associated d'emblée or not with a leukaemic component .The prognosis is very poor. We herein studied a large cohort of 90 patients with BPDCN and try to define additional clues to coin earlier the correct diagnosis and manage such patients accordingly.

We retrospectively reviewed BPDCN cases registered in the French Study Group on Cutaneous Lymphoma (GFELC) database from November 1995 to January 2012. Ninety patients were studied. Demographic data, clinical presentation, initial staging, and outcome were recorded.

The studied group contained 62 male and 28 female patients (sex ratio 2.2). Age ranged from 8 to 103 years at the time of diagnosis (mean age: 67.2 years).Three major different clinical presentations were identified: Sixty six patients (73.2%) presented with nodular lesions only, 11 patients with “bruise-like» patches (12.2%).The remaining 13 ones showed disseminated lesions (patches and nodules). Mucosal lesions were seen in five patients (5.6%) The median survival in patients with BPDCN was at 12 months .

We here distinct three different clinical presentation of BPDCN. Nodular pattern is actually a more common feature than the originally reported “bruise-like” pattern. Despite the fact that BPDCN may initially appear as a localized skin tumor an aggressive management including allogenic bone marrow transplantation should be considered d'emblée since it is so far the only one option associated with long term survival.

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Basal cell carcinoma (BCC) is the most common malignancy in Caucasians. It is an important driver of health care costs and causes significant morbidity. Topical imiquimod is a good non-invasive treatment alternative for surgical excision in superficial BCC (sBCC). However, there are currently no uniform histological definitions of sBCC. A definition based on tumour thickness might be a good alternative.

To determine whether tumour thickness in sBCC is a predictor of treatment failure.

We retrospectively examined 127 histological biopsy specimens of sBCC treated primarily with imiquimod 5 times a week for 6 weeks. Mean follow-up was 34 months (range 3-91). Recurrence was evaluated clinically with histological verification.

Among non-recurrent cases the median tumour thickness was 0.26 millimeters (0.09 – 0.61), while for recurrent cases the median tumour thickness was 0.57 millimeters (0.41 – 1.41, p<0.0001). Among lesions ≤ 0.40 millimeters in thickness, none recurred whereas for lesions > 0.40 millimeters the recurrence rate was 58% (p<0.0001).

We recommend the use of tumor thickness to define superficial pattern in pathology reports for BCC as this can help to determine treatment response of sBCC to imiquimod.

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Continuous maintenance therapy with infliximab 5 mg/kg every 8 weeks is effective for moderate-to-severe plaque-type psoriasis.

This study evaluated efficacy and safety of continuous versus intermittent infliximab maintenance therapy.

RESTORE2 was a long-term extension of RESTORE1. At baseline of RESTORE2, eligible patients who had received infliximab for 26 weeks and achieved Psoriasis Area and Severity Index (PASI) 75 in RESTORE1 were re-randomised 1:1 to continuous therapy (infliximab 5 mg/kg every 8 weeks) or intermittent therapy (no infliximab until >50% loss of PASI improvement). Safety and efficacy assessments occurred throughout the study.

222 patients were randomised to receive continuous therapy; 219 to intermittent therapy. Numerically more serious infusion-related reactions occurred with intermittent therapy (8/219 patients, 4%) than continuous therapy (1/222 patients, <1%), leading the sponsor to terminate the study. Mean duration of exposure to infliximab was 40.12 weeks (SD = 27.55,) with a mean of 5.8 infusions (range, 0–16) for continuous therapy and 22.78 weeks (SD = 22.98) with a mean of 3.4 infusions (range, 0–16) for intermittent therapy. Although no formal efficacy analyses were conducted, continuous therapy led to numerically greater PASI 75 at week 52 in the continuous group (81/101, 80%) than in the intermittent group (39/83, 47%); several other efficacy measures demonstrated similar patterns.

For patients with moderate-to-severe plaque-type psoriasis, continuous therapy with infliximab may be more effective than intermittent therapy. The incidence of serious infusion-related reactions in the intermittent group suggests that clinicians should avoid intermittent therapy in this population.

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Dyschromatosis symmetrica hereditaria (DSH) is characterized by the presence of hyperpigmented and hypopigmented macules mostly on the dorsal aspects of the extremities. Mutations in adenosine deaminase acting on RNA 1 (ADAR1) gene have been revealed to be the causation of DSH. ADAR1gene is known to give rise to two protein isoforms (p150 and p110) that differ by N-terminal 295 amino acids, but the specific roles of its two isoforms in pathogenesis of DSH are poorly understood.

A Chinese family with typical DSH was screened for mutation in ADAR1, and we aimed to investigate the functional significance of identified mutation.

All exons and adjacent exon-intron sequences were amplified and sequenced. The possible influence of identified mutation on functionality of p150 and p110 was analyzed using minigene strategy and dual-luciferase reporter assay, respectively.

We identified a novel 2-bp of AG deletion (c.271_272delAG) in exon 2 of ADAR1 gene. The AG deletion caused a frameshift mutation in the p150 isoform, the mutant p150 transcripts were subjected to nonsense-mediated mRNA decay (NMD), while the deletion mutation did not alter the encoded amino acid sequence of p110 protein due its position in the 5’-untranslated region (5’-UTR) of the p110 isoform, and had no influence on the expression of p110.

The results represent the first evidence that the ADAR1 p150 isoform is the determinant of DSH and may give insight into the yet unknown mechanisms involved in the development of DSH.

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Alopecia areata (AA) is a common auto-immune 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 it might have a beneficial role in hair growth.

To evaluate the efficacy and safety of PRP for the treatment of AA in a randomized, double-blinded, placebo and active-controlled, half-head, parallel group study.

Forty five AA patients 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. A total of three treatments were given for each patient, with an interval of one month from each other. The endpoints were hair regrowth, hair dystrophy as measured by dermoscopy, burning/itching sensation and cell prolifertation as measured by Ki-67 evaluation. Patients were followed for 1 year.

PRP was found to significantly increase hair regrowth and decrease hair dystrophy and burning/itching sensation when compared with TrA or placebo, and Ki-67 levels, which served as markers for cell proliferation, were significantly higher. No side effects were noted during treatment.

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.

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Alteration in T lymphocyte function and cytokines secreted by T cell subsets have been proposed in the immunopathogenesis of alopecia areata (AA). The role T helper and regulatory T cell cytokines in the pathogenesis of active AA has not been established.

The aim of this investigation was to assess the role of hallmark cytokines of T-helper (Th1, Th2, and Th17) and regulatory T cells (Tregs) in the pathogenesis of AA and its clinical correlation.

Fifty-one patients with AA and 45 age- and sex- matched healthy control subjects were included in the study. Serum IL-2, IFN-γ, IL-10, IL-13, IL-17A and TGF-β1 were measured by Enzyme linked immunosorbent assay in both the groups. Correlation of serum cytokine levels with age, sex, disease subtype and duration, number of patches on scalp, associated autoimmune disorder and atopy were studied.

The serum cytokine levels of IL-2, IFN-γ, IL-13, IL-17A were significantly increased and serum TGF-β1 levels were significantly decreased (P < 0.05) in patients with AA than in controls. Serum IL-2 levels were significantly different among AA subgroups (P < 0.05). Interleukin-2 levels were positively correlated with the total disease duration and number of patches on scalp.

The increased levels of serum IL-2, IFN-γ, IL-13, IL-17A suggested altered T helper (Th1, Th2 and Th17) cell function and reduced serum TGF-β1 levels suggested defect in Tregs function. Therefore, enhanced T cell mediated immunity and breakdown of immune tolerance due to deficiency in Tregs may facilitate the occurrence of alopecia areata.

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The traditional method of assessing Minimal Phototoxic Dose (MPD) prior to photochemotherapy (PUVA) is inconvenient; potential errors include UV source non-uniformity and exposure timing errors. A hand-held MED (UVB) tester can be modified by fitting a TL-10 UVA, compact fluorescence lamp (CFL). This lamp has a different output spectrum from PUVA treatment lamps. These MPD test results cannot directly determine PUVA start doses.

To determine if MPD testing is possible with a TL-10 UVA-CFL and to calculate a fixed-factor to convert observed-MPD with this device to a PUVA-equivalent MPD.

Patients had two sets of MPD tests performed on symmetrical, contra-lateral sites on the lower back. MPD test results from a panel of PUVA-lamps with a UV-opaque template and windows were compared to MPD from the modified hand-held MPD tester. Erythema was assessed at 96hours(bath PUVA). Additionally, a questionnaire survey was completed by 43 U.K phototherapy units, to assess routine practice concerning MPD-testing prior to commencing PUVA therapy.

37 psoriasis patients (17Females,20Males) aged 18-65years were recruited. Six had inconclusive MPD reactions and were excluded from the studies. Boston phototypes were: I-4; II-11; III-12; IV-4. The hand-held MPD results were linearly related to the PUVA-panel MPD results as follows: PUVA-MPD =0.48 x hand-held MPD +0.17J/cm². The measured PUVA-MPD was 0.48 of the hand-held MPD not 0.15 as predicted by the published PUVA action spectrum¹. Only 6/43 phototherapy units surveyed routinely performed MPD testing prior to PUVA therapy.

The modified MPD tester is a convenient and safe method for PUVA-MPD testing overcoming many problems of the “traditional method”. The difference in MPD between the PUVA lamps and the TL-10 lamp was lower than predicted from published PUVA action spectrum studies. This suggests that formal re-evaluation of the erythema action spectrum for PUVA is now needed.

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Basosquamous carcinoma (BSC) is a rare and potentially aggressive tumour, characterized by clinical and pathologic features of both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). It is reported to have a non-specific clinical presentation, which makes the naked-eye diagnosis a challenge.

To describe the dermoscopic patterns of BSC, which may facilitate early diagnosis and accurate management.

Retrospective evaluation of clinical and dermoscopic images of histopathologically proven BSC, collected from skin cancer centres in Australia (Perth), Greece (Thessaloniki) and Italy (Naples, Reggio Emilia).

Twenty-two tumours were included in the study. Our analysis revealed that the dermoscopic pattern of BSC comprises BCC-related criteria, as well as features that are known to characterize invasive SCC. The most frequently detected criteria were: unfocused (peripheral) arborizing vessels (72.7%), keratin masses (72.7%), white structureless areas (72.7%), superficial scale (68.2%), ulceration or blood crusts (68.2%), white structures (63.6%), blue-grey blotches (59.1%), and blood spots in keratin masses (54.6%). Notably, all but one of the tumours exhibited at least one BCC-related plus one SCC-related dermoscopic feature.

BSC appears to have overlapping dermoscopic features of BCC and invasive SCC and detection of at least one dermoscopic criterion of both BCC and SCC should raise suspicion for the tumour. Appreciation of the dermoscopic patterns of BSC might assist in the timely and accurate diagnosis and subsequent optimal management of this unusual and potentially metastatic skin tumour.

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Delusional infestation (DI) is the persistent belief of pathogenic infestation of the skin or body, without objective medical evidence. Treatment for symptoms of delusions can be particularly challenging, especially when patients are difficult to engage and adverse to the possibility of a non-skin disorder. To date there has been no study to evaluate patients’ adherence to DI treatment.

To assess the adherence of patients with DI to psychotropic and/or dermatological medication.

Sixty-nine consecutive DI patients receiving treatment from our psychodermatology clinic were identified from a departmental database. Patient adherence to treatment was assessed via medical records, patient letters and a telephone questionnaire.

18/69 patients were non-contactable, reducing the sample size to 51. 49/51 patients were receiving psychotropic medication (96%). Psychotropic agents included second generation antipsychotics and antidepressants. 29/49 patients were adherent to psychotropic medication. Secondary non-adherence was reported by 18/49 patients. Two patients were non-adherent to psychotropic medication. Adherence to dermatological medication was high (96%).

This is the first study to assess the adherence of patients with DI to treatment. The majority of patients on psychotropic medication were compliant. Secondary non-adherence was mainly due to drug side effects. The adherence to dermatological medications is high. Thorough counselling of patients with regards to indication, dosage and side effects of psychotropic agents can improve adherence to medication and is an essential part of the treatment process for DI.

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The objective of this systematic review was to report outcome measures used in clinically-based randomised controlled trials (RCTs) investigating therapeutic interventions in vulval disease.

The Medline, EMBASE and CENTRAL databases were searched to identify RCTs of vulval skin conditions written in English. Studies with laboratory tests or survival rates as the primary outcome, or those investigating, menopausal symptoms or infections, were excluded.

Twenty-eight published RCTs were included. The vulval conditions represented were vulvodynia (n=14), lichen sclerosus (n=9), vulval intraepithelial neoplasia (n=2), vulval pruritus (n=2) and lichen planus (n=1).

The 28 RCTs measured 25 different outcomes, using 49 different scales. The method of outcome assessment was lacking on nine occasions. Only 21% (6/28) of included trials had a clearly stated primary outcome. Patient-reported outcomes were more commonly reported than clinician-related outcome measures. The most commonly reported patient-rated outcome measure was a reduction in pain (measured 15 times) and an overall improvement in symptoms using a patient global assessment (measured 11 times). The most commonly reported clinician-rated outcome was an overall assessment of the appearance of affected sites (measured 13 times). There were no agreed standard scales used for the global assessments. Only nine of the recorded outcome measure tools were designed to assess vulval disease or sexual functioning, the remainder were general measures.

There is heterogeneity in the outcome measures used when reporting therapeutic interventions in vulval disease. This field of dermatology would benefit from development of a vulval-specific outcome measure and the establishment of a core outcome measure set.

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Sunbed use is considered carcinogenic in humans. Studies that examine behavioural patterns related to sunbed use over time are needed for developing skin cancer prevention strategies.

The objectives of this study were to explore age-related trends in the initiation age, to investigate individual histories of sunbed use and to identify characteristics associated with cessation.

We analysed cross-sectional data of 4,851 sunbed users and non-users from a representative sample of Germans, aged 14-45, interviewed in 2011/2012. Biographical data were reconstructed based on reported tanning frequency/duration and changes in sunbed use over time. We used survival analysis to model the initiation age and created birth cohorts to assess age-related trends. Characteristics associated with sunbed use cessation were identified using logistic regression.

Among sunbed users, median sunbed exposure was 180 minutes/year. Annual exposure remained constant in 85.6% of this subgroup with no changes over time during periods of sunbed use. Age at initiation decreased significantly across birth cohorts from 25 to 19 years (25th percentile; cohorts 1966-1975 to 1986-1993). Characteristics associated with sunbed use cessation included educational level (Odds ratio [OR] = 1.53 and 1.71 for medium and high education), greater awareness of skin cancer risk (OR = 2.41) and immigrant background (OR = 0.54; all P < 0.01).

Initiation of sunbed use at increasingly younger ages suggests the need for interventions targeted to young adults. Approaches that increase general skin cancer risk awareness and that are sensitive to participants’ educational level and immigrant background may also be helpful.

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HLA-B*58:01 is related with allopurinol induced severe cutaneous adverse drug reactions (sCADR) particularly in Han Chinese, but the risk in European populations has seldom been studied.

Study the association of HLA-B*58:01 with allopurinol induced sCADR in a Portuguese population.

We studied 25 patients (11M/14F, mean age 67.4y) with sCARD from allopurinol: 19 DRESS (drug reaction eosinophilia and systemic symptoms) and 6 Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).

HLA was genotyped by PCR-RSSO and results compared statistically with a control group of 23 allopurinol tolerant individuals and the control population.

HLA-B*58:01 was present in 16 patients with sCADR (64%), 12 DRESS (63.2%), 4 SJS/TEN (66.7%), in 1 allopurinol tolerant individual (4.3%) and 63 normal controls (1.96%) with a statistically significant difference between sCADR and the 2 control groups.

When compared to the normal population, HLA-B*58:01 was associated with a higher risk of sCADR, both DRESS (OR=85.36, 95% CI: 32.52-224.04) and SJS/TEN (OR=99.59, 95% CI: 17.91-553.72). There was no statistically different risk between these two patterns of CADR.

Portuguese patients with sCADR, both DRESS and SJS/TEN, have a high frequency of HLA-B*58:01, with an OR similar to European patients with SJS/TEN. This study also extends this association to DRESS in Europeans.

The recommendation to genotype systematically before therapy is controversial, particularly when HLA-B*58:01 prevalence in the normal population is low, as in Europe. However it could be an option for patients with other risks factors.

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Cutaneous squamous cell carcinoma (cSCC) is increasing in incidence but mortality rates are low. Identifying high-risk tumours is important when rationalising clinical review for patients with cSCC.

To assess accuracy of death certification in cases of reported fatal cSCC and identify risk factors for fatal cSCC.

A retrospective, observational study of cases of fatal cSCC over 11 years (1993-2004) in Leeds, identified in cancer registry and death certification data.

58 patients were recorded by the registry as having fatal cSCC in this period. Review of case notes and pathology specimens, where available (34 cases), confirmed that 21/34 patients had died of cSCC. 5 were on the ear, none on the lip. 4 patients had been treated for leukaemia/lymphoma and 1 was a renal transplant recipient. On pathology review 5 patients proved to have had malignant adnexal tumours rather than cSCC and one a melanoma. In addition 3 patients had disease of the ear canal or vulva.

A proportion of deaths were falsely attributed to cSCC as a result of inaccurate histological diagnosis. Some fatalities related to tumours in sites known to be at higher risk and a significant proportion was postulated to be related to immunosuppression. In those cases attributed to cSCC in which this could be assessed, the majority were AJCC stage 2 and only 24% were in high-risk sites.

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Up to now, there is no consensus conclusion about the association between psoriasis and HLA-B.

To clarify the association between psoriasis and HLA-B.

Articles were selected, following the predefined criteria, from the case-control studies on the association between psoriasis and HLA-B that were published from January 1, 1972 to November 11, 2012 and were included in PubMed and ISI Web of Knowledge databases.

Thirty-seven eligible articles covering 16,206 participants (14,644 Caucasian and 1,562 Asian) were included. Altogether sixty HLA-B alleles were reported, among which twenty-six were susceptible, twenty-four were protective, and ten were un-associated. For unspecific psoriasis (UPs), there were three strongly susceptible alleles (OR ≥ 3.0) in Caucasian and four in Asian, with HLA-B*57 and HLA-B*13 common to both races; there were four strongly protective (OR ≤ 0.3) alleles in Caucasian and seven in Asian, with HLA-B*07 common to both. For psoriasis vulgaris (PsV), nine alleles were strongly susceptible in Caucasian and five were in Asian, with HLA-Bw*37 and HLA-B*57 in both; three alleles were strongly protective in Caucasian, and one in Asian, with none in common. Psoriatic arthritis (PsA) and psoriasis guttate (PsG) cases were reported only in Caucasian, with eight and seven strongly susceptible alleles in each, as well as two and three strongly protective alleles in each. Analyses of onset age showed praecox patients with family history were significantly more susceptible to HLA-B*13 and HLA-B*57 alleles than tardive ones.

A significant association was identified between psoriasis and fifty HLA-B alleles. The association varied in terms of different races, clinical types and onset ages of psoriasis.

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Few studies have evaluated for 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.

This study assessed associations between the four rosacea subtypes (erythematotelangiectatic [ETR], papulopustular [PPR], phymatous [PHY], and ocular [OC]), 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.

This cross-sectional study recruited rosacea subjects from Northern Germany and comprised clinical evaluation by a dermatologist and a survey of demographics and onset of rosacea-associated signs and symptoms.

135 rosacea subjects were enrolled. PHY was more frequently associated with PPR than ETR (p < 0.000). Compared to ETR, PPR was significantly associated with facial burning/stinging (p = 0.001), phymas (p < 0.001) and edema (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 most frequent site involved was cheeks (100%). Papulopustules were evanescent in 42% and most frequent site involved was cheeks (80%) and nose (67%).

Of those fulfilling criteria for at least 2 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 sign/symptoms.

Significant differences exist between ETR and PPR in rosacea-associated features and in subtype associations. A small proportion of rosacea subjects may progress between subtypes.

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Paediatric cutaneous lupus erythematosus (LE) is uncommon and inadequately described in the literature. Similar to adults, children with cutaneous LE develop LE-specific and/or LE-nonspecific skin findings. Similarities and differences in demographics and clinical course between paediatric and adult cutaneous LE have not been sufficiently described.

The purpose of this study is to detail the demographic and clinical features of paediatric cutaneous LE and then compare these findings to those reported in the adult literature.

A retrospective chart review was performed of 53 children seen in a paediatric dermatology clinic with cutaneous manifestations of LE.

Patients presented with all five major subtypes of cutaneous LE, with some notable differences from adult cutaneous LE and previously published reports of paediatric cutaneous LE. Progression from discoid LE to systemic lupus erythematosus (SLE) did not occur in our cohort. Patients with subacute cutaneous LE were more likely than adults to have lesions below the waist as well as concomitant SLE. Sex distribution for cutaneous LE in our study was equal prior to puberty and female-predominant in post-pubertal patients.

Children with cutaneous LE have variable clinical presentations and progression to SLE that may be different from adult disease. Specifically, children with acute and subacute cutaneous LE may be more likely than adults to have systemic disease; therefore, patients with these subtypes should be monitored closely for evidence of SLE. Study limitations included small patient numbers that may limit ability to generalize this data and relatively short follow-up intervals.

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The increased susceptibility of atopic dermatitis (AD) patients to disseminated viral skin infections such as eczema herpeticum (ADEH+) is poorly understood.

The primary goal of the current study was to determine whether ADEH+ subjects have identifiable defects in cell-mediated immunity that reduce their ability to control viral infections.

In this study, we evaluated cytokine expression by various subsets of peripheral blood mononuclear cells from ADEH+ (n=24) as compared to AD without a history of viral infections (ADEH-) (n=20) before and after treatment with herpes simplex virus (HSV).

We found that IFNγ expression after HSV treatment was lower in the CD8+ T cells and monocytes from ADEH+ patients as compared to ADEH- or non-atopic (NA) patients. Given the induction of CD8+ T cells as the result of antigen presentation by HLA class I, consistent with the findings described above we also found that the HLA B7 allele was significantly associated with risk of the ADEH+ phenotype (OR = 1.91, P = 0.02, 125 ADEH+ and 161 ADEH- subjects).

These data suggest that defects in viral-induced IFNγ from CD8+ T cells contribute to the ADEH+ phenotype.

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MicroRNAs (miRNAs) are endogenous, non-protein-coding, regulatory RNAs with important roles in health and disease. MiRNAs are present in the circulation in a stable form and their levels are altered in diseases.

To determine whether anti-TNF-α therapy affects serum miRNA levels in psoriasis patients.

Serum samples were obtained from healthy donors and from patients with chronic plaque psoriasis before and 12 weeks after the initiation of treatment with the TNF-inhibitor etanercept or methotrexate. MiRNA expression profiling was utilized to identify miRNAs with altered serum level in psoriasis, as well as anti-TNF-α-regulated miRNAs in patients’ sera. The expression of five miRNAs regulated by etanercept was measured by qPCR in sera from patients and controls.

Etanercept significantly suppressed a panel of 38 miRNAs, which were found to be predominantly immune-cell derived and which have been implicated in inflammation and autoimmunity. Validation by qPCR showed that serum levels of miR-106b, miR-26b, miR-142-3p, miR-223 and miR-126 were significantly downregulated by etanercept in responders (PASI change > 50%). By contrast, methotrexate did not significantly affect the levels of these miRNAs. Serum levels of these miRNAs were not up-regulated in psoriasis patients compared to healthy controls. The level of four circulating miRNAs was significantly different (increased: miR-128a; decreased: let-7d, miR-142-3p, miR-181a) in psoriasis and healthy serum.

The level of circulating miRNAs is altered in psoriasis. Anti-TNF-α therapy has a profound effect on the serum level of miRNAs, However, these are not related to disease severity. Our results suggest that changes in the miRNA level may reflect a previously unknown effect of anti-TNF-α therapy. Our results suggest the involvement of miRNAs in pathways affected by anti-TNF-α therapy and warrant for further investigation of serum miRNAs as potential biomarkers for therapy response in psoriasis.

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The WHO classified the entire UV spectrum and artificial UV tanning devices as carcinogenic to humans. The Italian law has prohibited the use of tanning equipment by children under 18 years old and high risk populations.

The present large survey aimed to determine the prevalence of current sunbed use in Italy and to identify user characteristics. This study identifies starting points for future national interventions to reduce the health risks of exposure to artificial UV light.

In 2011 we conducted a survey of 4703 people in an area on the sunny Mediterranean coast in Italy. Through multivariate logistic models we investigated the associations of sunbed use with phenotypical factors.

Overall prevalence of sunbed use was 20%, higher among women (22% vs 16%; P<.0001), young (22% vs 17% for age<35; P<.0001) and high educated people (22% vs 14%; P<.0001). Subjects at high risk for melanoma used sunbeds significantly more: people with freckles (25% vs 18%; P<.0001), red hair (30% vs 19%; P=0.01), fair eyes (22% vs 19%; P=0.01). Associations were confirmed in multivariate models.

More skin cancer monitoring is needed at tanning centres and that educational campaigns should be promoted, especially for young women and subjects at high melanoma risk.

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To describe the long-term clinical response of DLE to hydroxychloroquine after 6 months of use.

A multi-centre retrospective cohort study was conducted in patients with DLE who had received treatment with hydroxychloroquine. All patients were recruited and interviewed by a single investigator and response to hydroxychloroquine assessed by the same individual through a retrospective review of casenotes using a specified protocol.

A total of 200 patients with DLE were recruited (F:M – 4:1) with a median age at diagnosis of 40 years (range 16-81) and median follow-up of 8 years (range 0.5-37). An adequate clinical response to hydroxychloroquine was recorded in 91 patients (45.5%) but non-response occurred in 85 patients (42.5%). The remainder of patients either had partial response or withdrew from therapy due to toxicity or were unclassifiable. Importantly, of those individuals that did respond to hydroxychloroquine within the first 6 months of use, almost 1 in 5 eventually lost their response, despite continued administration, after a median interval of 2 years. These patients often regained disease control if treated with a combination of hydroxychloroquine and mepacrine. Of those that did not respond to hydroxychloroquine within the first 6 months of use, almost 1 in 10 became eventual responders either after continued administration for upto 2 years or when rechallenged on hydroxchloroquine. The remaining non-responders relied frequently on oral corticosteroid.

In this cohort of patients with DLE, long-term clinical response to hydroxychloroquine occurred in less than 50% of patients. Non-responders to hydroxychloroquine frequently required oral steroid to achieve disease control. These findings merit further investigation through a multi-centre prospective study using a validated disease activity measure.

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Vitiligo is an autoimmune chronic depigmentation disorder caused by melanocyte loss. Previous studies found that CD4⁺CD25⁺ regulatory T cell (Treg) dysfunction was involved in the pathogenesis of vitiligo and that gene polymorphisms in FOXP3—a master regulator of Treg development and function—were associated with susceptibility to some autoimmune disorders. Therefore, we hypothesized that functional polymorphisms of the FOXP3 gene might be associated with vitiligo via dysregulation of Treg cells.

To evaluate whether FOXP3 polymorphisms are associated with vitiligo risk.

In this hospital-based case-control study of 682 vitiligo patients and 682 vitiligo-free age- and sex-matched controls, we genotyped 3 single nucleotide polymorphisms (SNPs) of the FOXP3 gene, that is, rs2232365, rs3761548, and rs5902434, by performing polymerase chain reaction with sequence-specific primers (PCR-SSP).

Significantly increased vitiligo risk was associated with the rs2232365 GG [odds ratio (OR) 1.68, 95% confidence interval (CI) 1.17–2.39, P = 0.004] and rs3761548 AA [OR 1.82, 95% CI 1.10–3.01, P = 0.033] genotypes compared to the rs2232365 AA and rs3761548 CC genotypes. On combined analysis of these 3 variant alleles, we found that individuals carrying 2–6 variant alleles had significantly increased vitiligo risk (OR 1.34, 95% CI 1.08–1.66). This risk was more pronounced in the following subgroups: age > 20 years, male gender, active vitiligo, nonsegmental vitiligo, and other accompanying autoimmune diseases.

FOXP3 gene polymorphisms contributed to vitiligo risk in a Han Chinese population.

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MicroRNA (miRNA) is an upcoming research area and quantitative reverse transcriptase in real-time (qPCR) is an important tool in the investigation. The small non-coding RNA candidates used for normalization in psoriatic skin biopsies have never been sufficiently validated.

To identify a reliable normalization method for miRNA analysis with qPCR in psoriatic skin.

5 miRNA candidates previously used for normalization in psoriatic skin were identified through search in the literature. 5 new candidates were uncovered using the NormFinder algorithm on miRNA microArray data. The candidates were validated in paired psoriatic biopsies, biopsies from patients during treatment and normal healthy skin with qPCR. The stability of the miRNAs was determined with NormFinder and geNorm. The dispersion of data was determined before and after use of different normalization approaches.

In lesional and nonlesional skin the two algorithms ranked the candidates similarly with an excellent correlation (R²=0.95). miR-26a had the best stability, whereas the commonly used RNU48 had less favourable stability. The same results were seen within the dispersion of the data, including biopsies from lesional, nonlesional, treated psoriatic skin and normal healthy skin.

This is the first study to validate the reliability of miRNA candidates for normalization by qPCR in psoriatic skin. From this study we conclude that miR-26a is the best candidates and better than those previously used. miR-26a can be used for miRNA normalization in future studies with psoriatic skin.

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Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy with a high mortality rate. Diagnosis is often delayed.

We set out to characterise the dermoscopic features of Merkel Cell Carcinoma.

Clinical and dermoscopic images of 12 biopsy proven MCCs were analysed in a retrospective manner with existing dermoscopic criteria being scored independently by three dermatologists.

The four most frequent clinical features were cherry red colour, shiny surface, sharp circumscription and nodular morphology. Significant dermoscopic features included linear irregular and polymorphous vessels, poorly focused vessels, milky pink areas, white areas and architectural disorder. Pigmented structures were absent for all lesions.

The dermoscopic features described herein help the clinician to distinguish MCC from other benign and malignant red nodules. Increasing recognition of the presenting features will facilitate earlier diagnosis of MCC and reduced mortality.

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To study the concordance of psoriasis in a population-based twin sample.

Data on psoriasis in 10,725 twin pairs, 20-71 years of age, from the Danish Twin Registry was collected via a questionnaire survey. The concordance and heritability of psoriasis were estimated.

In total, 4.1% of the men and 4.2% of the women had a lifetime history of psoriasis. The probandwise 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 non-shared environmental factors.

The results confirm that psoriasis is a complex multifactorial disease controlled by both exogenous and endogenous factors.

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Cutaneous squamous cell carcinoma (SCC) with no demonstrable point of epidermal origin is problematic as it raises consideration to metastatic SCC histologically. There are rare case reports and series of SCC arising from the wall of hair follicle structures. Such lesions have been termed follicular SCC (FSCC).

To investigate clinico-pathologic features of FSCC.

We prospectively collected cases of follicular SCC over a 5 year period. Follicular SCC is defined as a cutaneous SCC deriving from a pre-existing hair follicle structure. Lesions were considered to represent ‘hybrid’ SCC's if an interfollicular epidermal origin was also demonstrated; SCC's with greater than 50% of the origin from inter-follicular epidermis were excluded. Histologic features and clinical information were evaluated.

We identified 61 cases of follicular SCC arising in 60 patients from a database of 5212 cutaneous SCC's encountered over the same time period by the same authors.. There were 49 pure follicular SCC's and 12 hybrid lesions. The male to female ratio was 44:16; the mean age was 74 years (range from 44-93 yrs). Follicular SCC represents 1.2% of all primary SCC's. Biopsies of such lesions, if the appendage structure of origin is not represented, are histologically indistinguishable from metastatic SCC.

Recognition of this under-reported form of SCC is essential if an inappropriate diagnosis of metastatic SCC, with potentially harmful and inappropriate therapy and investigation, is to be avoided.

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Various psoriasis treatments are currently available: topical therapy, photo(chemo)therapy, oral agents, and biologicals. Little is known about patients’ satisfaction with these treatment options. Moreover, the few available studies show methodological shortcomings.

The present study aims to answer the following questions: 1a) How satisfied are psoriasis patients with their current treatment?; 1b) Does patients’ satisfaction significantly differ between treatment types when controlling for demographic and clinical factors?; 2a) How important are specific domains of satisfaction to patients?, and 2b) When taking perceived importance into account, which domains merit the most attention in improving quality of care?

Members of the two existing Dutch psoriasis patient associations were invited to complete a web-based survey, which included a study-specific satisfaction questionnaire.

1293 patients completed the survey (response rate 32%). Overall, patients were moderately satisfied with their current treatment. Patients receiving topical treatment were significantly least satisfied; patients receiving biological treatment were significantly most satisfied. Overall, patients rated ‘treatment effectiveness’ as most important, followed by ‘treatment safety’ and ‘doctor-patient communication’. Domains with the highest ‘room for improvement’ scores were: 1) effectiveness of topical therapy, phototherapy and oral agents, but not biological treatment, 2) convenience of topical treatment, and 3) safety of systemic treatments (both oral agents and biological).

From the patients’ perspective, biological treatment is promising. To further improve the quality of psoriasis care, the effectiveness and convenience of topical therapies, the safety of systemic therapies, and doctors’ communication skills need to be addressed.

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Onset of psoriasis may occur at any age. Early negative experiences often influence personality development, and may lead to physical disease, anxiety and depression in adulthood. Knowledge about onset of psoriasis and psychopathology is limited.

To examine whether patients with early onset psoriasis differ psychologically from patients with late onset, regarding personality traits, anxiety and depression.

A descriptive cross-sectional study was conducted among 101 consecutively recruited outpatients with psoriasis. A psychosocial interview was performed followed by self-assessment of validated questionnaires; Swedish universities Scales of Personality (SSP), Spielberger State-Trait Anxiety Inventory (STAI, Form-Y), and Beck Depression Inventory (BDI-II). Psoriasis severity was assessed by the Psoriasis Severity and Area Index (PASI).

Patients with early onset psoriasis (< age 20) were significantly more anxious and depressed than patients with late onset. In multiple linear regression models, younger age at onset of psoriasis was a significant determinant of higher scores of four personality traits, i.e. SSP-Embitterment, -Trait irritability, -Mistrust and -Verbal trait aggression.

Our results indicate that early detection of psychological vulnerability when treating children and adolescents with psoriasis seems to be of great importance. Traits of psychological vulnerability and pessimistic personality traits were found to be significantly associated with early onset of psoriasis, but not with disease duration in this study. These traits may be seen as a consequence of psoriasis, and / or as individual traits modulating and impairing clinical course and efforts to cope with psoriasis.

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Skin manifestations are the most characteristic finding of psoriasis. However, nail involvement is also a clinical feature of disease although it is often overlooked. The documented prevalence of nail psoriasis varies between 10.0 and 81.1%.

The aim of this investigation was to gain knowledge about the prevalence and clinical manifestations of nail psoriasis and patient experiences on treatment of nail psoriasis.

A structured self-administered questionnaire was distributed to all members (n=5400) of the Dutch Psoriasis Association. The questionnaire enquired about socio-demographic patient characteristics, disease-related data and treatment of nail psoriasis. Patients reported their nail manifestations after instruction with photographs. Patients with nail psoriasis were compared to patients without nail psoriasis.

A response rate of 27% was achieved. The prevalence of nail psoriasis was 66.0%. The most frequently observed psoriatic nail manifestation was pitting (65.4%), whereas red spots in the lunula were infrequently seen (6.5%). Patients with nail psoriasis more frequently stated psoriasis capitis (75.8 vs 65.7%), genital psoriasis (32.7 vs 20.3) and psoriatic arthritis (46.4 vs 30.6) compared to psoriatic patients without nail involvement. Only 16.0% of patients received treatment for nail psoriasis. Systemic therapies were most frequently stated as effective for nail lesions.

Nail manifestations seems to be more prevalent in psoriatic patients than previously thought. In addition, nail psoriasis shows to be associated with widespread and more severe forms of psoriasis and different treatment options are experienced as effective for nail psoriasis. Notwithstanding, nail psoriasis is still an often overlooked feature of the disease.

Psychological morbidity and reduced quality of life are common and linked with non-adherence to medication in psoriasis. Access to psychological therapy is often poor with long waiting times. Cognitive behavioural therapy (CBT) is a well accepted therapy for psychological disorders and is particularly effective when tailored to address condition-specific concerns.

To determine whether an electronic CBT intervention for Psoriasis (eTIPs) would reduce distress, improve quality of life and clinical severity in psoriasis patients.

A wait-list randomised trial of immediate intervention versus usual care. Self-assessed psoriasis severity (SAPASI), distress - Hospital Anxiety & Depression Scale (HADS) and quality of life - Dermatology Life Quality Index (DLQI) were measured before and after intervention. Analysis was based on complete cases and all cases using multiple imputation to substitute missing values

Anxiety scores between groups significantly reduced (p<0.05)for complete cases only: the mean and SD scores were, intervention 7.6(3.6) at baseline and at follow up 6.1(3.5) versus control at baseline: 8.3(3.5) and after intervention 8.1(4.4), p.004. Depression scores did not improve, the experimental group scores at baseline were 5.0(4.2) and after intervention 4.0(3.7) v control group at baseline 5.2(3.4) and after intervention 4.9(3.8). Psoriasis severity scores did not improve: baseline scores for the experimental group were 7.5(6.0) and after intervention 6.5(8.5) v the control group before 8.3(6.3) and after 7.6(6.1) p=ns. Quality of life scores improved in both analyses (p<0.05), the intervention group scores before were 6.6(4.2) and after intervention 5.0(5.1) v control before 7.4(4.4) and after intervention 7.7(4.5), p.042).

This first on-line CBT intervention for people with skin disease showed improvement in anxiety and quality of life in patients with psoriasis. The results are limited by the large number of missing data and at this stage on-line delivery cannot substitute for established methods of delivery for CBT.

Studies investigating systemic inflammation in psoriasis use different serum markers and report discrepant results.

To determine whether systemic inflammation is elevated in psoriasis patients compared to 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)1-beta, Il-6, Il-10, C-reactive-protein (CRP), Intracellular adhesion molecule-1 (ICAM-1), E-selectin or Tumor necrosis factor-alpha (TNFα) in psoriasis with healthy controls. Difference in serum marker levels between patients and controls were pooled as standardized mean differences (SMD) (Cohen's d) using random-effects model.

Seventy-eight studies were eligible. Of the 7852 individuals, 3085 had (severe plaque) psoriasis. The pooled SMDs were higher in psoriasis compared to healthy controls for Il-6 (d=1.32, 95%CI 0.83-1.81), CRP (d=1.83, 95%CI 0.76-2.90), TNFα (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 TNFα. For Il-6 the effect size was higher for plaque psoriasis studies (d=1.98). The effect size was not influenced by the PASI, measurement method or quality assessment.

The pooled analyses suggest modest, but significantly elevated levels of the pro-inflammatory cytokines in the serum of psoriasis patients 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.

Mutation of BRAF is a prevalent event in melanoma. Despite much attention to the role of BRAF mutation in melanoma, the status of BRAF protein expression and its significance in melanoma progression is unknown.

We investigated BRAF expression level in different stages of melanocytic lesions and evaluated its correlation with clinicopatholigical features and patient survival.

Using tissue microarray, BRAF expression and its correlation with patient outcome was evaluated in 49 nevi samples and 370 melanoma patients. We also evaluated the correlation of BRAF protein expression and V600E mutation using direct sequencing.

Compared with nevi samples, BRAF expression was remarkably increased in primary melanomas and further increased in metastatic melanomas (P=1.8×10^-11). High BRAF expression was significantly correlated with thicker tumors, ulceration and higher American Joint Committee on Cancer (AJCC) stages (P=1.5×10^-7, 1.5×10^-5, 3.6×10^-13, respectively). In primary melanoma cases, patients with high BRAF expression had significantly worse overall (P=0.009) and disease-specific five-year survival (P=0.007). While there was a trend for higher prevalence of BRAF-V600E mutation in patients with high BRAF protein expression, no significant correlation was observed between protein expression and BRAF mutation. Furthermore, univariate Cox-regression analysis confirmed high BRAF protein expression as a strong risk factor for poor patient survival in primary melanoma (HR2.08 overall survival; HR2.39 disease-specific survival).

Our data demonstrated that BRAF protein expression is significantly increased during melanoma progression. In addition, we revealed a novel prognostic value for BRAF protein expression in primary melanoma as it is significantly correlated with poor patient survival.

Solar ultraviolet (UV) radiation during the summer and vitamin D supplementation are two major sources of vitamin D for humans at northern latitudes. However, little is known about the relative efficiency of these two vitamin D sources.

The main goal of the present study was to compare the efficiency of high dose oral vitamin D₃ supplementation (2000 IU per day for 30 days) and simulated summer UV exposure (10 sunbed sessions to a total dose of 23.8 SED) to improve the vitamin D status.

Healthy volunteers were randomized into two groups: Group 1 received vitamin D supplementation followed by 10 whole body sunbed exposures. Group 2 started with 10 sunbed exposures followed by vitamin D supplementation.

The oral supplementation with vitamin D₃ resulted in an average serum 25-hydroxyvitamin (25(OH)D) increase of 25.3 nmol/L (SE ± 5.4 nmol/L). A similar increase (19.8 nmol/L, SE ± 5.4 nmol/L) was observed after simulated summer UV exposure. At the end of the study serum 25(OH)D concentrations were similar in both groups.

Two weekly whole body sunbed exposures to a total dose of 4.8 SED are equal to 2000 IU/d of oral vitamin D supplementation for 30 days and enough to achieve and maintain serum 25(OH)D concentrations above 75 nmol/L in ~ 55% of the cases. Based on our calculations, this dose corresponds to a cumulative weekly whole body exposure of 3.4 SED (~ 40 min) around midday during the summer at the latitude of Oslo

The burden of disease, describing loss of health and death due to a disease, has not been fully studied for melanoma in the general population over time.

Age- and gender-specific incidence data from all melanoma patients in the Netherlands between 1991 and 2010 were obtained from the Netherlands Cancer Registry. Melanoma-specific mortality and life expectancy data were obtained from Statistics Netherlands. Melanoma duration was calculated using the DISMOD software from the World Health Organisation. The Years of Life lived with Disability (YLD) and Years of Life Lost (YLL) due to melanoma were calculated using Dutch disability weights, incidence and mortality of melanoma and the life expectancy from the general population. The disability adjusted life years (DALY) was estimated by adding YLD and YLL.

The world standardised incidence rates of melanoma have more than doubled for both men (7.1 per 100,000 inhabitants in 1991 to 17.0 in 2010) and women (9.4 per 100,000 inhabitants in 1991 to 19.8 in 2010). Likewise, the burden of melanoma to society increased rapidly. The YLD for men increased from 4,795 (1991 to 1994) to 12,441 and for women from 7,513 (1991-1994) to 16,544 (2007-2010). In 2007-2010 the total YLL due to melanoma was 30,651 for men and 26,244 for women compared to 17,238 and 16,900 in 1991-1994. The DALYs increased with 96% for men from 22,033 (1991-1994) to 43,092 (2007-2010) and increased with 75% for women from 24,475 (1991-1994) to 42,788 (2007-2010).

Melanoma is becoming a great burden to Dutch society.

Despite the increasing use of medical photography by dermatologists, no study on patients’ perceptions of photography in Dermatology has been performed to date.

First, to evaluate patients’ perceptions of medical photography. Second, to assess whether perceptions differed between patients in our Adult Department and parents accompanying a child in our Pediatric Department,

An opinion survey was conducted in the Hospital of Tours (France) among adult patients (Adult Department) and accompanying parents (Pediatric Department) by completion of a questionnaire after any medical photography had been performed.

We collected 272 questionnaires regarding 158 adults and 114 children. A camera only used in the Department and storage of the images in the Department's records were the most accepted modalities (>90%), especially in the pediatric survey. Respondents agreed with the sharing of the images with other practitioners and in medical meetings (>85%) rather than distribution via publications (58.3%), e-mails (45.5%), health magazines (44.3%) and websites (32.0%). Most (78.8%) considered that the consent form should list all the possible uses of the images. Need for renewed consent for each use of the images was significantly more often expressed in the pediatric than the adult survey (44.5% vs 24.5%, p=0.001). More than 95% considered medical photography to be useful for improving diagnosis, monitoring of skin disease and aiding teaching.

These findings could be used to improve practice and to increase the acceptability of medical photography and for devising a standardized consent form for medical practitioners performing medical photography.

Several national prospective registries of psoriatic patients treated with systemic therapies are running, with the aim of describing the population treated, safety and effectiveness of these treatments, especially biologics. Psonet is an initiative to pool data from these registries.

To describe psoriasis therapy in Psonet countries, using baseline data of patients included in these registries.

We collected data from Psocare (Italy), Dermbio (Denmark), Biobadaderm (Spain), Clalit Health Services (Israel), Australasian Psoriasis Registry, Psobest (Germany), and AMC Medical Center Registry (Netherlands). We described previous use of drugs at the time that patients started a new classic systemic drug or any biologic drug.

Data from 20,232 patients was pooled in our analysis (9,668 treated with biologics, 10,564 with other systemic therapies). At a given time in the life course of psoriasis, we have shown large between country heterogeneity on the previous use of systemic drugs for psoriasis and relevant rates of use of biologic drugs in potentially off-label use (first line use and use in psoriasis forms different from plaque psoriasis). Variability in therapy is larger than variability in available patient characteristics likely to influence therapy.

We have shown the presence of large heterogeneity on the use of systemic drugs for psoriasis in participating countries, including differences in patient access to biologics amongst the participating countries. This might be an indicator of unwarranted clinical variation in some countries: a marker of inefficient or less safe use of systemic drugs for psoriasis, and requires further study.

A substantial proportion of psoriasis patients do not respond or lose initial response to tumour necrosis factor alpha antagonists. One possible mechanism relates to sub-therapeutic drug levels due to an immunogenic antibody response.

To investigate the association between serum adalimumab, etanercept levels, anti-drug antibody levels, and clinical response in a cohort of psoriasis patients using a commercially available enzyme-linked immunoassay.

In a single-centre cohort of 56 adults with chronic plaque psoriasis initiated on adalimumab or etanercept monotherapy between 2009 and 2011, drug and anti-drug antibody levels were measured at the patients’ routine clinic reviews (4, 12, 24 weeks of treatment and the last available observation). Patients’ responses at 6 months were stratified into responders (75% reduction in psoriasis area and severity index from baseline (PASI 75) or physician's global score of ‘clear’/’nearly clear’) and non-responders (failure to achieve PASI 50).

After 4 weeks, adalimumab levels were significantly higher in responders compared with non-responders (p=0.003) and these higher levels were sustained at 12 and 24 weeks. Anti-adalimumab antibodies were detected in 25% of non-responders (2/8 patients, average 22.5 weeks follow-up) and not in any responders (n=23, average 26.1 weeks follow-up). There was no significant association between etanercept levels and clinical response at 4 weeks (p=0.317) and no anti-etanercept antibodies were detected. Lack of serum trough levels may have underestimated the prevalence of anti-drug antibodies.

Early adalimumab drug level monitoring at 4 weeks may be useful in predicting treatment response and potentially reduce drug exposure (and associated cost) with earlier review of treatment in those with low levels. No conclusions about the value of etanercept drug monitoring can be made due to the paucity of data. Larger studies are now required to assess the clinical utility and cost effectiveness of these assays in personalising therapy in psoriasis.

Extracorporeal photochemotherapy has been used successfully to treat severe steroid-refractory acute and chronic GVHD since the late 1990s.

To retrospectively evaluate the efficacy and safety of extracorporeal photopheresis in patients with acute graft versus host disease. We also assess whether ECP may play a role in the prevention of cGVHD.

Nine consecutive allografted patients with acute GvHD grade II-III, as defined by consensus criteria, and refractory to steroids, were treated with ECP. ECP was started at a median interval of 46.3 days from onset of aGVHD (range 10-70). Patients were initially treated on two consecutive days (one cycle) at 1 week intervals until improvement and then every 2 weeks. Treatment was then tapered off individually. To evaluate statistical relationships with outcome after 30, 60 and 90 days of ECP, all clinical and historical variables of patients before treatment were analysed.

All patients survived and responded within 90 days. The average aGVHD score was 1.72 at onset of GVHD, 2.44 when ECP was started and then gradually declined to 0.44 on day 90. At the same time, the average dose of methylprednisolone declined from 2.22 mg/kg to 0.27 mg/kg (day 90), while the average dose of cyclosporine A declined from 2.46 to 0.77 mg/kg (day 90). Six out of 9 patients showed a complete skin response after 90 days of treatment. All patients with liver and gut involvement had complete responses after 90 days, apart one patient. All our patients developed cGVHD, 7/9 while still on maintenance regimen (6-13 months after SCT) and the other two patients after suspension of ECP (6 and 9 months after SCT).

ECP proves to be effective in patients with mild to moderate steroid-refractory aGVHD (grade II-III). On the other hand, ECP did not prevent the development of cGVHD in our patients.

There is no defined set of criteria for diagnosing erosive lichen planus affecting the vulva (ELPV) and there is geographical variation in management.

To reach consensus on clinico-pathological diagnostic criteria for ELPV.

This was a three-stage international electronic-Delphi exercise with a subsequent formal feedback process. In the first two rounds participants were asked to rate the importance of a list of clinicopathological criteria. Responses from Round One were summarised and presented in Round Two, along with additional criteria suggested by participants. In Round Three, participants were asked to rate the items that had reached consensus as ‘essential’ or ‘supportive’ features in diagnosing ELPV. Consensus was defined as being where 75% participants agreed on the importance of an item.

A total of 73 experts representing dermatology, gynaecology, histopathology and genitourinary medicine participated; 69 (95%) completed all three rounds. Consensus was achieved for the following ‘supportive’ diagnostic criteria: i)Scarring/loss of normal architecture; ii)presence of a hyperkeratotic border to lesions or Wickham's striae in surrounding skin; iii)involvement of other mucosal surfaces; iv)well-demarcated erosions/erythematous areas at the vaginal introitus; v)symptoms of pain/burning; vi)presence of vaginal inflammation; vii)presence of a well-defined inflammatory band involving the dermo-epidermo junction consisting viii)predominantly of lymphocytes and ix)signs of basal layer degeneration. It was suggested that at least three supportive features should be present to make a diagnosis of ELPV, although this number is subject to further discussion.

This study has identified a diagnostic dataset for ELPV that can be adopted into clinical practice and clinical trials.

Metastatic basal cell carcinoma (BCC) is a rare but life-threatening condition. Prior estimates of overall survival (OS) from time of diagnosis of distant metastasis to death are approximately 8-14 months. However, these estimates are based on analyses of case reports published prior to 1984.

To assess a more updated OS in metastatic BCC patients at a single academic institution.

Using patients from 1997 to 2011, a retrospective chart review was performed on biopsy-confirmed cases of distant metastatic BCC at Stanford University School of Medicine. Kaplan-Meier analysis was used to determine OS and progression free survival (PFS).

Ten consecutive cases of distant metastatic BCC were identified. Median OS was 7.3 (95% confidence interval, CI; 1.6, ∞) years; median PFS was 3.4 (95% CI; 1.1, 5.2) years.

Our findings suggest that OS in patients with distant metastaticBCC may be more favorable than previously reported.

Our understanding of the genetic bases of predisposition to psoriasis is increasing exponentially due to the progresses of genetics. 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 biologic therapy outcome.

Aim of our study was to analyze the presence of three different psoriasis susceptibility genetic variations (HLA-Cw6; TNFAIP3 rs610604 polymorphism; LCE3B/3C genes deletion) in a cohort of patients affected by moderate to severe psoriasis under ustekinumab treatment. Our primary endpoint was to evaluate the association between PASI 75 response at week 12 and HLA-Cw6 status.

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.

We observed increased response to ustekinumab in Cw6POS patients (PASI75 at week 12 96.4% in Cw6POS vs 65.2% in 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 (versus 60,9% of HLACw6NEG patients). 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 genes deletion did not show any significant association with response to ustekinumab.

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.

Vitiligo is an acquired disorder of pigmentation due to loss of epidermal melanocytes. Autologous noncultured epidermal cell suspension (NCES) and autologus noncultured extracted hair follicle outer root sheath cell suspension (NCORSHFS) are important surgical modalities for the treatment of stable vitiligo.

To compare NCES and NCORSHFS for producing repigmentation in stable vitiligo.

We randomized 30 patients with 47 stable vitiligo lesions into two groups. Patients in group 1 were treated with NCES, and those in group 2 with NCORSHFS. They were evaluated 16 weeks post surgery for the extent of repigmentation, colour match, change in Dermatology Life Quality Index (DLQI) score and patient satisfaction.

The extent of repigmentation was excellent (showing 90–100% repigmentation) in 83.3% of lesions in the NCES group and 65.2% of lesions in the NCORSHFS group (P = 0.154). Repigmentation > 75% (good repigmentation) was observed in 91.7% of lesions in the NCES group and 78.2% of lesions in the NCORSHFS group (P = 0.425). There was a significant decline in DLQI score in both the groups; the mean decline among groups do not differed significantly (P = 0.244). However, patients in NCES group were significantly more satisfied than the patients in NCORSHFS group. No significant difference was seen in colour match and pattern of repigmentation. Adverse effects were minimal.

Both NCES and NCORSHFS are safe and effective techniques with comparable efficacy. To best of our knowledge, this is the first study directly comparing two different cellular techniques.

Multiple congenital melanocytic naevi (CMN) in one individual are caused by somatic mosaicism for NRAS mutations, however the lineage of the mutated cells remains uncertain. This study was designed to test the hypothesis that CMN may be derived from cutaneous stem cells.

Sixty-six CMN samples from 44 patients were stained for immunohistochemical (IHC) markers of melanocytic differentiation (TYR, TRP1, TRP2, LEF1, MITF, cKit), pluripotency (Nestin, Fascin, CD133, CD20, CD34), monocyte/macrophage lineage (CD68, CD163, CD14), proliferation (Ki67), and MTOR/Wnt-signaling pathway activation (pS6, β-catenin). Semi-quantitative scoring compared samples with naevus cell nesting (group 1) to those with only diffuse dermal infiltration (group 2). Transmission electron microscopy (TEM) was performed on 10 samples.

A normal melanocyte population was seen overlying many dermal CMN. Group 1 samples were significantly more likely to express melanocytic differentiation markers than group 2, and expression decreased significantly with depth. Expression of these markers was significantly correlated with each other, and with nestin and fascin. CD20 staining was positive in a substantial proportion and stronger superficially. Expression of beta-catenin and pS6 was almost universal. Some samples expressed monocyte/macrophage markers. TEM revealed variable naevus cell morphology, striking macromelanosomes, double cilia and microvilli.

CMN development frequently co-exists with normal overlying melanocyte development, leading us to hypothesise that in these cases CMN are likely to develop from a cell present in the skin independent of, or remaining after, normal melanocytic migration. IHC and TEM findings are compatible with CMN cells being of cutaneous stem cell origin, capable of some degree of melanocytic differentiation superficially.

Dermatofibrosarcoma protuberans (DFSP) is a rare malignant cutaneous tumour of which diagnosis is often delayed because of the lack of early clinical clues.

To describe the main dermoscopic features of DFSP.

We performed dermoscopic examination in 15 unselected, consecutive cases of biopsy-proven DFSP. First, six dermoscopic features were identified collegially; then all cases were reviewed separately by 6 experimented dermoscopists. In a given lesion, only features recognised by all dermoscopists were taken into account.

The median number of dermoscopic features was 4 per lesion. The following dermoscopic features were found: delicate pigmented network (87%); vessels (80%); structureless light brown areas (73%); shiny white streaks (67%); pink background coloration (67%) and structureless hypo- or depigmented areas (60%). When detected, vessels were of arborizing type in 11 of 12 cases, and presented as either unfocused only, or both unfocused and focused.

this first approach to the dermoscopic spectrum of DFSP identifies 6 dermoscopic features (often associated in a multicomponent pattern) and a peculiar vascular pattern. Whether dermoscopy can help suspect DFSP remains to be established by further studies.

Integrin α6β4 is a transmembrane receptor and a key component of the hemidesmosome anchoring complex. It is involved in cell-matrix adhesion and signaling in various tissues. Mutations in the ITGA6 and ITGB4 genes coding for α6β4 integrin compromise dermal-epidermal adhesion and are associated with skin blistering and pyloric atresia, a disorder known as epidermolysis bullosa with pyloric atresia.

To elucidate the molecular pathology of skin fragility in eight cases, disclose the underlying ITGA6 and ITGB4 mutations and study genotype-phenotype correlations.

DNA was isolated from ethylenediamine tetraacetic acid-blood samples, and the coding exons and exon-intron boundaries of ITGA6 and ITGB4 were amplified by polymerase chain reaction, and directly sequenced. Skin samples were submitted to immunofluorescence mapping with antibodies to adhesion proteins of the dermal-epidermal junction. Primary keratinocytes were isolated, and used for RNA and protein extraction, RT-PCR and immunoblotting. Ultrastructural analysis of the skin was performed in one patient.

We disclosed ten novel mutations, one in ITGA6 and nine in ITGB4. Skin cleavage was either intraepidermal, or junctional. Lethal outcome and pyloric atresia correlated with loss of function mutations in two cases. Solely mild skin involvement was associated with deletion of the C-terminus of β4 integrin. Combinations of missense, nonsense or frameshift mutations caused severe urinary tract involvement in addition to skin fragility in five cases.

The present study reveals novel ITGA6 and ITGB4 gene mutations and supports previous reports showing that the phenotype may lack pylorus atresia and be limited to skin and nail involvement. In four out of six cases of EB-PA, life expectancy was not impaired. A high frequency of urinary tract involvement was found in this study, and represented the main cause of morbidity. Low levels of β4 integrin expression were compatible with hemidesmosomal integrity and a mild skin phenotype.

Cutaneous metastases of malignant melanoma (CMMM) can be confused with other skin lesions. Dermoscopy could be helpful in the differential diagnosis.

To describe distinctive dermoscopic patterns that are reproducible and accurate in the identification of CMMM

A retrospective study of 146 dermoscopic images of CMMM from 42 patients attending a Melanoma Unit between 2002 and 2009 was performed. Firstly, two investigators established six dermoscopic patterns for CMMM. The correlation of 73 dermoscopic images with their distinctive patterns was assessed by four independent dermatologists to evaluate the reproducibility in the identification of the patterns. Finally, 163 dermoscopic images, including CMMM and non-metastatic lesions, were evaluated by the same four dermatologists to calculate the accuracy of the patterns in the recognition of CMMM.

Five CMMM dermoscopic patterns had a good inter-observer agreement (blue nevus-like, nevus-like, angioma like, vascular and unspecific). When CMMM were classified according to these patterns, correlation between the investigators and the four dermatologists ranged from κ = 0.56 to 0.7. 71 CMMM, 16 angiomas, 22 blue nevus, 15 malignant melanoma, 11 seborrheic keratosis, 15 melanocytic nevus with globular pattern and 13 pink lesions with vascular pattern were evaluated according to the previously described CMMM dermoscopy patterns, showing an overall sensitivity of 68% (between 54.9-76%) and a specificity of 81% (between 68.6-93.5) for the diagnosis of CMMM.

Five dermoscopic patterns of CMMM with good inter-observer agreement obtained a high sensitivity and specificity in the diagnosis of metastasis, the accuracy varying according to the experience of the observer.

Genetic predisposition to psoriasis, an inflammatory skin disease affecting 0.2 – 4% of world populations, is well established. Thus far, 41 psoriasis susceptibility loci reach genome-wide significance (p ≤ 5 x 10^-8). Identification of genetic susceptibility loci in diverse populations will help understand the underlying biology of psoriasis susceptibility.

The primary objective of this study is to examine psoriasis susceptibility associations previously reported in Chinese and Caucasian populations in a Pakistani cohort.

Blood samples and phenotype data were collected from psoriasis cases and controls in Islamabad, Pakistan. DNA was isolated and genotypes of selected susceptibility markers were determined. The data were analyzed by chi square tests or logistic regression for psoriasis association.

HLA-Cw6 showed the strongest association (OR = 2.43, p = 2.3 x 10^-12). HLA-Cw1 showed marginally significant association (OR = 1.66, p = 0.049), suggesting that the HLA-Cw1-B46 risk haplotype may be present in the Pakistani population. Three other loci (IL4/IL13, NOS2, TRAF3IP2) showed nominally significant association (p < 0.05).

HLA-Cw6 is strongly associated with psoriasis susceptibility in the Pakistani population, as has been found in every other population studied. In addition, HLA-Cw1 showed marginal association, reflecting the relative geographic proximity and thus likely genetic relatedness to other populations in which HLA-Cw1–B46 haplotype is known to be associated. A larger cohort and a denser marker set will be required for further analysis of psoriasis associations in the South Asian population.

Self-administration of narrowband (TL-01) UVB phototherapy by patients at home is a safe and effective mode of treatment. Could selected patients self-administer phototherapy in hospital?

To assess the feasibility of outpatient self-administration of UVB phototherapy as a potential service development.

A total of 20 patients with psoriasis (n = 15) and eczema (n = 5), (13 females, mean age 32 years, range 17 to 56), were included in this pilot project. Patients underwent a training programme over two days, which included a Minimal Erythemal Dose (MED) test and supervised treatment, prior to commencing self-administration of phototherapy. Questionnaires were used to gather feedback from patients and staff.

Treatment data were collected for 18 (of 20) patients. The mean number of exposures was 25 (range 3 to 45), and the mean cumulative dose was 16 J/cm² (range 0.23 to 41.27). No unexpected adverse effects were noted. These results were similar to that of a sample group of outpatients who had nurse administered UVB phototherapy, for whom the mean number of exposures was 24 (range 4 to 49) and the mean cumulative dose was 17 J/cm² (range 0.53 to 71.16). Thirteen (of 20) patients completed the questionnaires. All concluded that the training programme sufficiently prepared them for self-administering phototherapy, and 12 reported that they would be happy to self-administer treatment in the future.

Self-administration of UVB phototherapy is practicable, safe and effective for most selected patients. This mode of treatment provides training and support for patients to gain more control over management of their skin disease, empowering them to take an active role in their treatment. Self-administration of UVB phototherapy by outpatients provides an intermediate level of care between nurse-administered hospital phototherapy and self-administered home phototherapy.

The collection of patient-reported outcomes (PROMs) within the national PROMs programme for elective procedures is now established mandatory practice in the NHS with high response rates and completion. This review examines the evidence of PROMs for people with skin cancer.

Comprehensive searches were conducted using several sources and databases, using a detailed search strategy developed by the University of Oxford's PROM Group. Articles were assessed for eligibility. Data were extracted per PROM for each measurement property and appraised using an appraisal framework.

A total of 3517 articles were identified in the searches, and 28 were included on the final review after assessment by two independent reviewers. Two generic instruments (SF-36 and Sickness Impact Profile) and nine condition–specific PROMs were identified.

Overall, there is a limited volume of published evidence for the application of generic PROMs in people with skin cancer. Evaluation of the EQ-5D may be particularly important given its widespread use in many other healthcare contexts in the UK.

The Skin Cancer Index could be considered for piloting in the NHS. For patients with NMSCs, the Skindex measures may also be considered. The SCQOLIT has some evidence of applicability across both skin cancer types but more evaluations are needed.

The FACT-M does have more promising characteristics for patients with malignant melanomas although no evidence of testing in the UK was found. The forthcoming EORTC-M may prove a useful measure given the expertise and track record of this European collaboration in cancer and quality of life.

Serration pattern analysis of direct immunofluorescence (DIF) allows differentiating epidermolysis bullosa acquisita (EBA) from other subtypes of pemphigoid. In daily practice its use is limited due to lack of experience and unfamiliarity.

To test the learnability of DIF serrated pattern recognition under groups with various a priori levels of competence.

An online nversusu-test (www.nversusu.umcg.nl) was created, which contained 26 DIF images of the epidermal basement membrane zone (BMZ), IgG stained, and photographed with a magnification of 40x and 63x. All images represented patients with a form of subepidermal autoimmune bullous disease. Thirteen DIF images were presented before and thirteen DIF images after an instruction video about n- and u-serrated patterns. There were three options to choose from: n-serrated, u-serrated or undetermined. The test was completed by three groups of professionals: i) dermatology residents in training at the University Medical Centre Groningen, ii) International experts on bullous diseases, iii) dermatologists and pathologists who participated in the Groningen Blistering Course in the last 10 years.

Overall the number of correct answers of serration patterns was significantly higher after instruction than before instruction (median 9.0 correct answers vs. 11.0 correct answers, P<.001). Participants showed a mean improvement after instruction of 15.4% in the UMCG group (66.7% vs. 82.1%), 16.2% in the International expert group (67.2% vs. 83.4%) and 12.1% in the Blistering Course group (60.7% vs. 72.8%). The u-serrated pattern was better recognized than the n-serrated.

Serattion pattern analysis by DIF can be learned irrespective of background of expertise.

Type VII collagen (coll VII) ELISA has been reported to have high sensitivity (>93%) and specificity (>96%) for diagnosing epidermolysis bullosa acquisita (EBA) patients who are sero-positive by indirect immunofluorescence on salt-split skin (SSS).

To investigate the added value of coll VII ELISA in the laboratory diagnosis of SSS-positive and SSS-negative EBA and to correlate the ELISA index with disease episode.

Coll VII ELISA was performed on banked sera of 28 EBA patients: 15 SSS-positive and 13 SSS-negative. Sera from healthy blood donors (n=17) and other autoimmune blistering diseases (n=29) served as controls. In four patients ELISA index was measured longitudinally. Serration pattern analysis by DIF was prospectively performed since 2000 and comprised 19 patients.

The sensitivity in the SSS-positive group was 80% whereas it was 23% in the SSS-negative group. In the prospective EBA subset it was 45%. The sensitivity of u-serration pattern analysis on skin biopsy was 89%. Ten (53%) of these cases were sero-negative by both ELISA and SSS, and would have been missed by serum analysis alone. Of the 46 control sera one serum tested positive (specificity 97.8%). The coll VII ELISA correlated with disease activity over time in individual patients.

Coll VII ELISA has limited added value in SSS-negative EBA cases. The ELISA test is very valuable in differentiating EBA from anti-laminin-332 MMP and anti-p200 pemphigoid and in its ability to serological monitor EBA patients. U-serration pattern analysis on IF skin biopsy is the golden standard for the diagnosis of EBA.

Malignant transformation of oral lichen planus (OLP) to oral squamous cell carcinoma (OSCC) is controversial. C-MYC is a proto-oncogene involved in various solid tumours, including OSCC.

To determine MYC status by florescence in situ hybridization (FISH) and immunohistochemistry (IHC) in OLP lesions from 10 patients with progression to OSCC (Group I) and to compare with OLP lesions from patients without progression to OSCC (Group II).

We constructed two tissue microarray with 11 OSCC samples (Group IA), 17 OLP samples from those patients (Group IB) and 13 OLP specimens from 12 control patients (Group II). FISH evaluation of the MYC gains was determined in 100 non-overlapping nuclei per sample. IHC evaluation was determined by calculating percentage C-MYC expression in the epithelial cells.

OSCC showed MYC copy number gains and C-MYC overexpression in 91% and 73% of cases, respectively. MYC gains were detected in 47% of samples from group IB and were absent in all samples from group II. C-MYC was overexpressed in 87% of cases from group IB and in only 44% of control specimens (group II). The differences in MYC status between group IB and II were statistically significant.

OLP lesions in patients with progression to OSCC show MYC gains and C-MYC overexpression. In patients with severe OLP determining MYC status may predict a subgroup of subjects with higher risk to progress to OSCC.

The estimation of body surface area involvement is an important tool. Hand or palm surface area (HSA/PSA) is commonly used for the estimate, with an assumption that HSA represents 1% of the total body surface area (TBSA).

To establish: (1) the most accurate value for mean HSA% and PSA% of TBSA; (2) the variability of these with patient variables.

PubMed, Embase and Cochrane databases were searched and 14 eligible studies were identified. Weighted means of HSA% and PSA% were produced. The meta-analysis examined systematic variation associated with gender, age (for children), BMI and ethnic group was investigated using random-effects models.

HSA% is 13% lower than the accepted 1% value for all adults (p = 0·004). PSA% is not significantly different from the accepted 0.5% value (p = 0·82). Men have a significantly higher HSA% than women (p < 0·0001).

Children have a significantly higher HSA% than adults (p < 0·0001). HSA% falls with increasing body mass index in adults (p < 0·0001). A comparison of European, Chinese and Indian sub-continent ethnic origin showed that each group was different from the others (p < 0·05).

The heterogeneity of the included studies and the lack of data for children are the major limitations of this study.

The use of HSA equating to 1% TBSA results in an over-estimate for adults (particularly women) and an under-estimate for children. PSA equating to 0·5% TBSA appears to be suitable for adults. Patient variables including gender and body mass index result in variation of HSA as%TBSA.

Punctate palmoplantar keratoderma (PPPK, OMIM 148600) is a rare hereditary disorder characterized by multiple punctate keratoses on the palms and soles. Recently, mutations in the alpha- and gamma-adaptin-binding protein p34 (AAGAB) and collagen, type XIV, alpha 1(COL14A1) PPPK have been reported to cause PPPK.

To identify mutations in the AAGAB and COL14A1 genes in three Chinese families with PPPK.

Genomic DNAs of the family members and 100 healthy individuals were isolated. Direct sequencing of all PCR products of the whole coding regions of AAGAB and COL14A1 genes was performed to identify the mutation.

A heterozygous nonsense mutation c.61C>T (Q21X) was identified in AAGAB gene in two Chinese families with PPPK. We failed to detect any mutations in the AAGAB or COL14A1 gene in Family 3.

A novel loss-of-function mutation within the AAGAB gene associated with PPPK was identified from 2 Chinese pedigrees.

Pathomechanisms of both psoriasis and atherosclerosis may involve platelet activation. Activated platelets show increased P-selectin; CD62 expression, and mean platelet volume (MPV). Impaired brachial artery flow mediated dilatation (FMD) is related to atherosclerosis.

to determine the presence of subclinical atherosclerosis in psoriasis patients (without overt cardiovascular complications or traditional cardiovascular disease risk factors), compared to controls.

In this case-control study, 25 psoriatic patients and 25 age- and gender- matched healthy individuals were subjected to assessment of MPV, CD62 expression using flow cytometry, and brachial artery FMD and transthoracic echocardiography by cardiac ultrasound scanner.

A statistically highly significant increased CD62 expression, but not MPV, was found in cases compared to controls, and in moderate/severe psoriatic patients compared to both mild cases and controls (p<0.001). CD62 expression was statistically significantly positively correlated with PASI score, base line brachial artery diameter (but not FMD), and aortic root diameter (ARD) (p<0.001, =0.03 and 0.03 respectively). ARD was statistically significantly higher in moderate/severe patients compared to controls (p-value = 0.017). Stepwise Simple Linear Regression analysis revealed that PASI score is the most important factor affecting CD62 expression (p<0.001).

Our study showed increased atherosclerosis risk in psoriatic patients; particularly those with moderate/severe disease, as evidenced by increased expression of platelet CD62 compared with healthy controls. Moreover, we found positive correlation between CD62 expression and ARD (another possible marker of atherosclerosis) with positive correlation to Psoriasis Area and Severity Index (PASI) score; the most important factor influencing CD62 expression. However, our data as regard MPV and FMD does not support using either to diagnose subclinical atherosclerosis in psoriatics, for further studies.

Skin exposure to water is considered to contribute to hand eczema. Knowledge about total water exposure during a day is scanty.

To investigate self-reported water exposure at work as well as throughout the day.

Skin exposure to water was assessed from two questionnaire-based health surveys: the nationwide Environmental Health Survey 2007 (EHS), which enquired about water exposure throughout the day, and the Stockholm Public Health Survey 2006 (PHS), which probed water exposure at work. Answers from 19 667 individuals (EHS) and 18 318 individuals (PHS) were available for analysis.

Twenty-two percent (women 30%, men 12%) reported skin exposure to water more than 20 times during an entire day (EHS) compared to 6% (women 8%, men 4%) at work (PHS). In a univariate analysis, using a merged file comprising data from the EHS and the PHS, water exposure more than 20 times/day, was more common in the EHS (PPR 3.570, 95% CI 3.353-3.802). In multivariate models the variables studied did not fulfill the criteria for being confounders. Water exposure at work declined with increasing age in both women and men (p<0.0001) as did water exposure during the entire day in men (p<0.0001). However, women were equally exposed during the entire day across age groups (p=0.205).

High water exposure over the entire day was found to be considerably more frequent than exposure at work. Thus, a significant proportion of water exposure seems to occur outside work. This should be considered when counselling hand eczema patients in clinical practice and in hand eczema prevention.

the chronic and relapsing nature of vulvar lichen sclerosus (VLS) represents a challenge for its long-term management after an effective treatment with topical corticosteroids.

to assess the effectiveness of proactive, twice-weekly application of mometasone furoate 0.1% ointment, compared with daily topical vitamin E or cold cream, in keeping VLS in remission and reducing the risk of relapse after a 3-month treatment with topical corticosteroid.

27 patients affected with VLS were enrolled into a 12-week active treatment phase (AP) with topical 0.1% mometasone furoate ointment once daily. Those who achieved disease remission entered a 52-week maintenance phase (MP) in which patients were randomized to apply either mometasone furoate 0.1% ointment twice weekly or a cold cream once daily or topical vitamin E once daily. The primary efficacy parameters were the relapse rate and the mean time of relapse.

25 patients considered to have been completely or almost completely healed after the AP entered the MP. By the end of the 52-week MP, 10 patients (40%) experienced a relapse: 5 in the vitamin E group (55.6%) and 5 in the cold cream group (62.5%), while no patient in the mometasone furoate 0.1% ointment group had a relapse. The occurrence of VLS relapse for patients in therapy with both vitamin E and cold cream was significantly higher than for those in proactive therapy with topical corticosteroid. The median time to relapse was the same (21.6 weeks) for the vitamin E and the emollient groups.

once VLS has been stabilized with topical corticosteroids, twice-weekly proactive application of 0.1% mometasone furoate ointment over 56 weeks was found to be an effective and safe therapy option in maintaining VLS remission and in preventing the occurrence of relapse.

mTOR (mammalian target of rapamycin) signalling integrates signals leading to cellular growth, proliferation and differentiation. Disturbance of this tightly regulated interplay leads to malignancies, as reflected by altered mTOR signalling in epidermal tumours. As psoriatic keratinocytes also show features of perturbed cell growth and differentiation, the question arises whether mTOR signalling also plays a role in the pathogenesis of psoriasis.

Investigation of the activation status of mTOR signalling components in psoriasis

Biopsies from lesional and non-lesional skin of psoriasis patients (n=10) as well as samples from healthy donors (n=3) were analysed by immunohistochemistry and Western blot, utilizing antibodies detecting phosphorylated mTOR (P-mTOR), P-S6K and P-S6 ribosomal protein.

We found mTOR and its downstream signalling molecule, the ribosomal protein S6 to be activated in lesional psoriatic skin. While mTOR is activated throughout the whole epidermis, with particularly strong activation in the basal layer, S6 is rather active in suprabasal layers of differentiating keratinocytes.

Altogether these results suggest a role for mTOR signalling in the epidermal changes leading to the psoriatic phenotype. mTOR inhibition might be a mode of action suitable to be explored for innovative anti-psoriatic drugs.

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.

This Phase 2a study aimed to assess the efficacy, systemic safety, local tolerability and systemic pharmacokinetics of topical tofacitinib in mild-to-moderate plaque psoriasis.

Two tofacitinib ointment formulations were evaluated in this multicentre, double-blind, vehicle–controlled trial (NCT01246583). Seventy-one patients were randomised 2:1:2:1 to 2% tofacitinib Ointment 1, Vehicle 1, 2% tofacitinib Ointment 2 and Vehicle 2, each administered twice daily for 4 weeks to a single fixed 300 cm2 treatment area containing a target plaque +/- one or more non-target plaques and normal skin.

The primary endpoint of percent change from baseline in Target Plaque Severity Score at Week 4 demonstrated statistically significant improvement for Ointment 1 (least squares mean [LSM] –54.4%) vs Vehicle 1 (LSM –41.5%), but not Ointment 2 (LSM –24.2%) vs Vehicle 2 (LSM –17.2%). Secondary endpoints (Target Plaque Area and Itch Severity Item) improved similarly for tofacitinib ointment vs corresponding vehicle. Adverse event (AE) occurrence was similar across treatment groups. All AEs were mild or moderate and none were serious or led to subject discontinuation. One application site AE (erythema) was reported. Tofacitinib mean systemic exposure was minimal and was greater for Ointment 1 than for Ointment 2.

Tofacitinib Ointment 1 was well tolerated and efficacious compared with vehicle for the treatment of plaque psoriasis. Further study of topical tofacitinib for psoriasis treatment is warranted.

Although sex and gender are increasingly perceived as important factors in medicine, there is only very little knowledge on these issues in chronic pruritus (CP) patients.

1037 patients (54.8% women) with CP (> 6 weeks of duration) were analysed concerning gender differences in multiple parameters, including quality of life, CP-underlying diseases, co-morbidities, and clinics. We used McNemar tests for dependent variables, and χ² tests and t-tests for independent variables, to evaluate gender-specific differences.

Men were significantly older (p < 0.001) than women and had significantly more often cardiovascular (p < 0.001) and urogenital (p < 0.0001) co-morbidities, a higher number of co-medications (p = 0.041), and more often dermatologic and systemic diseases leading to CP.

Women had more neuropathic and psychosomatic diseases underlying the CP. They significantly more often showed a worsening of the CP by emotional (p = 0.002) and psychosomatic factors (p = 0.046). Women reported more often on localised itching occurring in attacks, with stinging, warmth, and painful qualities (p < 0.05). Women significantly more often showed chronic scratch lesions and prurigo nodularis (p = 0.001), in contrast to men who significantly more frequently had CP on non-inflamed skin (p = 0.004). In addition, women obtained higher visual analogue scale scores (p = 0.031) and reported a higher impact on quality of life (p = 0.033) than men.

There are gender-specific differences not only in the quality, localisation, and triggering of CP but also in the underlying disease and scratching behaviour. These facts must be taken into account in the medical care of CP patients and when conducting any kind of clinical research on itch. Further research is needed to achieve a gender-specific and gender-adapted diagnostics and treatment of CP.

Hair and epithelial keratins constitute the major structural components of the skin and its appendages, including the hair fiber. While selected steroid hormones are appreciated to regulate specific keratins, little is known about the neuroendocrine control of human hair keratin expression. Preliminary evidence had suggested that thyrotropin-releasing hormone (TRH) may regulate keratin gene transcription.

We wanted to clarify whether TRH operates as a novel neuroendocrine regulator of human hair and epithelial keratin expression under physiologically relevant conditions in situ.

Microdissected human female scalp hair follicles (HFs) and female scalp skin were treated in serum-free organ culture for 12h – 6d with 100ng/ml TRH or vehicle. Both quantitative immunohistomorphometry and RT-qPCR were utilized to assess expression of selected keratins.

TRH significantly increased expression of the hair keratins K31 and K32, while that of K85 and K86, and of the epithelial keratins K14 and K17 was reduced. In the interfollicular epidermis, TRH stimulated expression of K6, K14 and K17, both at the mRNA and protein levels. Stimulation of the same keratins was also evident in the eccrine sweat and sebaceous glands.

Selected human hair and epithelial keratins are modulated in situ. This may be relevant to explain hair shaft growth-promoting effects of TRH. Our pilot study suggests that the neuroendocrine controls that regulate the expression of human keratins deserve more systematic exploration and that these may be harnessed therapeutically.

A series of studies have investigated epidemiological, clinical and genetic characteristics of multiple primary melanoma (MPM) patients. However, a comparison of the clinical and dermoscopic features of MPM within a given individual have been described only in case reports.

To describe the dermoscopic features of MPM for each given patient, and to evaluate the characteristics eventually associated with the similar or dissimilar appearance.

From the databases of three skin lesion clinics in US, Italy, and Spain we collected the dermoscopic images of melanomas in patients diagnosed with MPM.

Among 58 patients with MPM, we found 53.5% of patients having dermoscopically similar melanomas and 46.5% of patients having dermoscopically different melanomas. In older patients 59.1% of melanomas were dermoscopically similar vs 46.9% in younger patients (p=0.377). Similar thickness was associated with the occurrence of dermoscopically similar melanomas (19 cases; 63.3%) (p=0.039). Most (65.4%) of the synchronous lesions were similar, compared to 35.7% of non-synchronous lesions (p=0.029), and most (69%) of the melanomas on sun-damaged skin were similar, vs 36.7% of melanomas on non sun-damaged skin (p=0.015; OR=3.88; CI 95%, 1.11-13.98). The percentage of dermoscopically different melanomas was higher in patients with a family history of melanoma (66.7% vs 47.7%).

Thin and superficial spreading melanomas were predominant in our study population, this may have restricted variation in dermoscopic features according to tumour type.

Information about positive family history for melanoma and mutation in CDKN2A gene were only partially documented in our series.

MPM in a given patient have almost the same chance to look dermoscopically similar or different. However, a subset of elderly patients with sun-damaged skin may present multiple, similar, thin melanomas characterized by pigment network and regression structures.

Nodular lesions poses diagnostic challenge since nodular melanoma may simulate all kind of melanocytic and non-melanocytic lesions. Reflectance confocal microscopy is a novel technique that allows the visualization of skin at nearly histologic resolution although limited laser depth penetration hamper the visualization of deep dermis.

140 nodules were retrospectively evaluated by means of confocal microscopy in blind from histopathologic diagnosis. At the end of the study the patients’ codes were broken and the evaluations were matched with histopathologic diagnosis before performing statistical analysis.

We sought to assess whether the diagnostic accuracy of confocal microscopy compared to histopathology for the diagnosis of nodular lesions, and to identify possible limitations of this technique

The study consisted of 140 nodular lesions (23 “pure” nodular melanomas, 9 melanoma metastasis, 28 BCCs, 6 invasive SCC, 32 naevi, 14 Seborrheic keratosis, 17 dermatofibroma, 5 vascular lesions and 6 other lesions). Confocal microscopy correctly diagnosed 121 out of 140 lesions (86,4%); eight out of 140 (5,7%) lesions revealed discordance between histopathology and confocal microscopy. Eight out of 140 (5,7%) cases were not evaluable by means of confocal microscopy due to the presence of ulceration or hyperkeratosis and three cases showed a non specific pattern. Interestingly, confocal microscopy reached a 96.5% sensitivity and 94.1% specificity (AUC: 0.970) (CI95%: 0.924-1.015) (p<0.001) for the diagnosis of melanoma.

The study is retrospective and lesions were not included on the basis of their diagnostic difficulty

Despite the limited laser depth penetration of confocal microscopy, this imaging tool represents an effective instruments in diagnosing nodular lesions; however, fully ulcerated lesions or when a marked hyperkeratosis is present, biopsy should be always performed. Prospective studies on difficult to diagnose nodules should be performed to further analyze the pros and contra of RCM in skin cancer diagnosis.

Localised Scleroderma is a rare but potentially disfiguring and disabling condition. Systemic treatment should be started early in those with active disease in key functional and cosmetic sites but disease activity is difficult to determine clinically. Superficial blood flow has been shown to correlate with disease activity in localised scleroderma. This cohort study is the first to examine whether superficial blood flow measured by laser Doppler imaging (LDI) has the potential to predict disease progression and therefore select patients for early systemic treatment.

A group of 20 individuals had clinical assessment and scanning LDI blood flow measurements of 32 affected body sites. After a mean follow up of 8.7 months their clinical outcome was compared to the results of the initial LDI assessment.

11 out of 15 with active LDI assement had progressed clinically and 16 out of the 17 scans with inactive LDI assessment had not progressed giving a positive predictive value of 73% and a negative predictive value of 94%.

We believe that LD can be a useful tool in predicting disease progression in localised scleroderma and may help clinicians decide which patients to treat early.

There is indication of an increasing prevalence of psoriasis in some western populations. However, the results are not conclusive.

The objectives of this study were to analyse trends in psoriasis prevalence over the past 30 years separating age, birth-cohort and time period effects.

Five population-based surveys in North Norway, the Tromsø Study 2-6, collected in 1979-2008, 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 33,803 unique individuals born from 1915 to 1979. 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.

Self-reported lifetime prevalence of psoriasis increased from 4.8% in 1979-80 to 11.4% in 2007-08. Graphical plots showed an increasing prevalence of psoriasis by each consecutive survey in all examined age groups and birth-cohorts, leaving time period effects as explanatory for the increase. The odds for psoriasis in our cohort was 2.5 times higher in 2007-08 than in 1979-80 (adjusted odds ratio = 2.53, 95% confidence interval 2.11-3.03). The prevalence of persons reporting a doctor's diagnosis 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.

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.

Several recent studies have reported on the overexpression of human epidermal growth factor receptor 2 (HER2) in extramammary Paget disease (EMPD). However, there are only a few cases in which both overexpression and gene amplification of HER2 have been examined.

The aim was to evaluate the overexpression and gene amplification of HER2 by using standardized method with a large number of EMPD cases.

Immunohistochemically, the overexpression of HER2 protein was examined in 104 EMPDs including 31 intraepithelial cases and 73 invasive cases (35 superficially invasive EMPDs and 38 deeply invasive EMPDs). When HER2 protein was overexpressed or potentially overexpressed, further analysis of HER2 gene amplification with fluorescence in situ hybridization (FISH) was undertaken.

HER2 protein was overexpressed in 16 cases (15%) in total and 13 of 73 cases (18%) in invasive EMPD. HER2 gene was amplified in all HER2 score 3+ cases. HER2 score 3+, or score 2+ and HER2 gene amplification was significantly more frequent in the deeply invasive EMPDs than in the intraepithelial / the superficially invasive EMPDs (24% vs. 6% / 3%, p = 0.012) and was correlated with a larger number of lymph node metastasis (p = 0.047). By log-rank tests for survival curves showed that lymph node metastasis and HER2 gene amplification were significant prognostic factors (p = 0.0001 and 0.043, respectively). However, by a multivariate analysis, only lymph node status was a significant indicator of Paget disease specific survival (p = 0.0001).

A subset of EMPD, both intraepithelial and invasive, showed HER2 overexpression and gene amplification. These HER2 alterations were correlated with biologically aggressive EMPDs, i.e, those with deep invasion and lymph node metastasis. Clinical trials of HER2 targeted therapy are waited for the improvement of prognosis of patients with aggressive EMPD.

Lacrimal sac fistulae can arise after an episode of dacryocystitis, usually forming below the medial canthus. Preceding symptoms of a watery eye with mucous discharge and a history or signs of inflammation are typical.

To highlight the features of lacrimal sac fistulae and encourage readers to consider this in the differential diagnosis of apparently ulcerative medial canthal skin lesions.

We describe three patients with inferior-medial canthal ulcerative skin lesions, all referred to ophthalmic plastic surgeons either by dermatologists or plastic surgeons, presumed clinically to have basal cell carcinoma (BCC).

All three were in fact due to acquired lacrimal sac fistulae and syringing of the nasolacrimal system confirmed the presence of a fistula.

These cases illustrate the importance of questioning patients about their previous ocular symptoms when dealing with less familiar periocular lesions.

In the pathogenesis of psoriasis, pro-inflammatory T-cells are strongly involved in the inflammatory process, where regulatory T-cell (Treg) function is impaired.

As effective Treg function is associated with a numerical balance between Treg and effector T-cells, we wondered whether Treg/T-helper cell ratios may be associated with certain stages of the inflammatory process. We opted for the margin zone model as a dynamic approach.

From nine patients with chronic plaque psoriasis, 3 mm punch biopsies were obtained from the centre and margin of the lesion, perilesional skin, and distant uninvolved skin. Skin biopsies of ten healthy volunteers were included as control. Samples were analyzed by immunohistochemistry and immunefluorescence.

In the transition from symptomless to lesional skin, a significant increase for CD3+, CD4+, and Foxp3+ cells was found. In 7/9 patients the ratio Treg (Foxp3+) versus CD4+ T-cells was higher in the distant uninvolved skin than in the perilesional and lesional skin. Interestingly, the Foxp3/CD4 ratio in the distant uninvolved skin was even higher than in the skin of healthy controls. Notably, we found that the majority of IL-17 expression was not related to CD4+ cells, but to mast cells.

The relatively high Foxp3/CD4 ratio in symptomless skin of psoriatic patients suggests an active immune controlling mechanism distant from the psoriatic plaque. In the margin and center of the plaque the ratio appears skewed towards effector cells associated with inflammation. IL-17, an important driver of the psoriatic process, was mostly related to mast cells, and only sporadically to T-cells.

Hidradenitis suppurative (HS) is a chronic inflammatory and debilitating disease of the skin. No biomarkers for this disease exist.

We set out to test if Angiotensin Converting Enzyme (ACE), lysozyme, soluble interleukin (IL-)2 Receptor (sIL-2R) and S100A8/A9 (calprotectin) are elevated in patients suffering from HS.

Serum was collected from 29 HS patients suffering from different stages of the disease and from 51 controls. ACE, lysozyme, sIL-2R and S100A8/A9 were measured. Clinical observation of disease activity was scored according to the Hurley grading system and by a physician global disease score (PGS) of disease severity.

Serum levels of lysozyme and ACE were not increased above the normal reference values in controls or HS patients. sIL-2 and S100A8/A9 levels were significantly higher in HS patients than in controls (P < 0.001 for sIL-2 and S100A8/A9). Based on the receiver operating characteristic (ROC) curves, the optimum sIL-2R and S100A8/A9 cut-off values were 375 U/mL and 680 ng/mL respectively with a sensitivity of 0.79 and specificity of 0.78 for sIL-2R and 0.86 and 0.88 for S100A8/A9. No correlations with Hurley classification scores were found. However, when using PGS of disease activity to categorize patients, S100A/A9 but not sIL-2R levels tended to be higher in patients suffering from more active disease.

S100A8/A9 and sIL-2R but not ACE or lysozyme are elevated in serum of patients suffering from HS. However, there is no correlation between S100A8/A9 or sIL-2R levels and disease stage according to the Hurley classification system. Further research is needed to study the potential of S100A8/A9 to score disease activity in larger cohorts of patients and to predict disease flares.

The International Psoriasis Council in 2007 considered palmoplantar pustulosis (PPP) as a separate condition from psoriasis, despite the presence of certain phenotypes common in both diseases.

To describe and compare demographic and clinical characteristics among PPP and palmoplantar plaque psoriasis.

Retrospective case-series study from 2005 to 2010. The following data were obtained: age, sex, family history, smoking habits, nail involvement, joint involvement, disease duration, lesions morphology (plaque or pustular), histological diagnosis, co-morbidities, and PGA score for extra-palmoplantar lesions. Sample size calculation indicated that 80 patients, 40 patients for each group (palmoplantar plaque psoriasis and PPP) were needed to see clinically relevant differences between groups.

Ninety patients were selected: 51 had palmoplantar plaque psoriasis and 39 had PPP. No statistically significant differences were registered between patients affected by PPP and palmoplantar plaque psoriasis as regards age at the onset of the disease (48 vs. 44 years; p 0.4), disease duration (6 vs. 10 years; p 0.1), family history of psoriasis (28.2% vs. 33.3%; p 0.7), concomitant arthritis (25.6% vs. 25.5%; p 1.0), or smoking habits (54.1% vs. 41.2%; p 0.2). We observed a female predominance (p 0.01) and a lesser frequency of nail involvement (p 0.03) in patients affected by PPP.

Our data suggest a close relationship between PPP and psoriasis. The existing data concerning epidemiology, clinical presentation, genetics, histopathology and pathogenesis do not permit a clear distinction between these two entities, which seem to coincide in many aspects. PPP appears to have a marked predilection among female smokers.

The prevalence of onychomycosis has increased steadily in the last decade. An accurate diagnosis at the outset is important for successful and cost-effective treatment of patients. However, current diagnostic tests for onychomycosis are neither rapid nor sensitive nor specific.

Therefore, we developed a microsatellite-based PCR-ELISA (MS-ELISA) assay for the detection of Trichophyton rubrum, which is the most common etiologic agent of onychomycosis.

An archival set of 434 nail and skin specimens from 217 patients was included as the test sample in this study. We also compared MS-ELISA with an earlier published topoisomerase PCR-ELISA (TI-ELISA) assay using template DNA extracted by another method.

MS-ELISA detected highest number of positive samples (69%) followed by direct microscopy (56%), TI-ELISA (44%) and fungal culture (30%). When an identical DNA extraction method was applied to 120 specimens, MS-ELISA proved to be twice as sensitive as TI-ELISA.

In conclusion, we have optimized a target gene and DNA extraction method for rapid detection of T. rubrum onychomycosis.

Eczema is common in infancy; there is little evidence about its natural history to adulthood.

To study the natural history of eczema from birth to young adult life with particular reference to its relation to atopy.

A birth cohort of children with atopic family histories was followed up for 23 years. Clinical examinations were conducted to age seven, skin prick tests and serum total IgE recorded in infancy and ages seven and 23, and questionnaires about eczema symptoms completed at 15 and 23.

Information was obtained about 497 subjects at birth, 482 at one year, 440 at seven, 363 at 15 and 304 at 23. Eczema usually remitted from one to seven years but became more persistent from age 15, especially in those who were atopic. The prevalence of eczema rose in women from age 15 to 23 but declined in men. Adults with eczema had higher IgE than the others at three months (geometric means 3.0 and 1.7kU/l respectively; p=0.01), 7 years (107.9, 45.2kU/L; p=0.01) and 23 (123.4, 42.3kU/L; p=0.01), and were more likely to have had positive skin prick tests at one year. Current eczema was associated with raised IgE in infancy and adulthood but not in childhood.

Predisposed infants and children with eczema usually grow out of the disease, but in adolescence it is more likely to persist. Adult eczema is related to atopy from the age of three months.

Subungual haemorrhages are characterised by well-circumscribed dots or blotches with a red to red-black pigmentation, but some cases can be difficult to distinguish from subungual melanoma by the naked eye alone. Dermoscopy has proven to be a useful, noninvasive tool in the diagnosis of pigmented lesions in the nail; however, few dermoscopic studies for subungual haemorrhages have been reported.

The purpose of this study was to investigate characteristic dermoscopic patterns of subungual haemorrhage and to find distinctive features that can differentiate subungual haemorrhages from nail unit melanomas.

Patients with a confirmed diagnosis of either subungual haemorrhage or nail unit melanoma at a tertiary university hospital were included in the study. Clinical features and dermoscopic patterns were evaluated.

Sixty-four patients with a total of 90 lesions of subungual haemorrhage were enrolled in the study. The majority of cases (84.4%) showed a combination of more than 1 colour, while 15.6% had only 1 colour. The most common colour of the subungual haemorrhages was purple-black in 36.7% cases. A homogenous pattern was observed in 92.2% cases, globular patterns in 42.2%, and streaks in 38.9%. Peripheral fading and periungual haemorrhages were found in 54.4% and 22.3%, respectively. Destruction or dystrophy of the nail plate was observed in 15.6% cases. In the 16 cases with nail unit melanomas, Hutchinson sign, longitudinal irregular bands or lines, triangular shape of bands, vascular pattern, and ulcerations were found in 100%, 81.25%, 25%, 6.25%, and 81.25% cases, respectively. In contrast, these features were not found in subungual haemorrhages.

Dermoscopy provides valuable information for the diagnosis of subungual haemorrhage and aids in the differential diagnosis from nail unit melanoma.

Topical therapies are a mainstay of psoriasis treatment, but they vary substantially in terms of cost.

To determine the cost-effectiveness and optimal treatment sequence for psoriasis of the trunk, limbs and scalp.

Probabilities of response from a network meta-analysis were used to determine the short-term efficacy of topical therapies. Longer-term outcomes, including relapse, were informed by published evidence and clinical opinion. Benefits of treatment were measured as quality-adjusted life years (QALYs). Direct costs included topical agents, primary and secondary care visits and second-line therapies for treatment failures.

For the trunk and limbs, initial treatment with a two-compound formulation (TCF) product containing vitamin D and potent corticosteroid provided the most QALYs, followed by separate morning and evening application of vitamin D and potent corticosteroid [two-compound application, TCA (am/pm)], and then twice-daily potent corticosteroids. The use of twice-daily potent corticosteroids was the most cost-effective first-line strategy (incremental cost-effectiveness ratio £20 000 per QALY), followed by TCA (am/pm) (£22 658 per QALY) and TCF product (£179 439 per QALY). For scalp psoriasis, initial treatment with very potent corticosteroids generated the most QALYs, followed by TCF product and then potent corticosteroids. Very potent corticosteroids were the most cost-effective treatment but, if too aggressive, potent corticosteroids were optimal followed by TCF product (£219 846 per QALY). The cost-effectiveness of second- and third-line topical agents varied with the assumptions made.

Potent corticosteroids, used alone or in combination with vitamin D, are the most cost-effective treatment for patients with psoriasis of the trunk and limbs. Potent or very potent corticosteroids are the most cost-effective treatment for patients with scalp psoriasis.