Psoriasis is now classified as an immune-mediated inflammatory disease (IMID) of the skin. It is being recognized that patients with various IMIDs, including psoriasis, are at higher risk of developing "systemic" co-morbidities, e.g., cardiovascular disease (CVD), metabolic syndrome, and overt diabetes. In non-psoriatic individuals, the pathophysiology of obesity, aberrant adipocyte metabolism, diabetes, and CVDs involves immune-mediated or inflammatory pathways. IMIDs may impact these co-morbid conditions through shared genetic risks, common environmental factors, or common inflammatory pathways that are co-expressed in IMIDs and target organs. Given that pathogenic immune pathways in psoriasis are now well worked out and a large number of inflammatory mediators have been identified in skin lesions, in this review we will consider possible mechanistic links between skin inflammation and increased risks of (1) obesity or metabolic alterations and (2) CVD. In particular, we will discuss how well-established risk factors for CVD can originate from inflammation in other tissues.

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Pustular psoriasis (PP) is a group of inflammatory skin conditions characterized by infiltration of neutrophil granulocytes in the epidermis to such an extent that clinically visible sterile pustules develop. Because of clinical co-incidence, PP is currently grouped with psoriasis vulgaris (PV). However, PP and PV are phenotypically different, respond differently to treatments and seem to be distinct on the genetic level. In contrast to PV, the phenotypes of Psoriasis Expert Network (ERASPEN) was founded to define consensus criteria for diagnosis, deeply phenotype large groups of PP patients, analyse the genetics and pathophysiology and prepare for prospective clinical trials. This work reviews historical aspects of these conditions, new genetic findings and presents our initial considerations on the phenotypes of PP and a consensus classification of clinical phenotypes that will be used as a baseline for further, prospective studies of PP. Generalized pustular psoriasis (GPP) is defined as primary, sterile, macroscopically visible pustules on non-acral skin (excluding cases where pustulation is restricted to psoriatic plaques). GPP can occur with or without systemic inflammation, with or without PV and can either be a relapsing (>1 episode) or persistent (>3 months) condition. Acrodermatitis continua of Hallopeau (ACH) is characterized by primary, persistent (>3 months), sterile, macroscopically visible pustules affecting the nail apparatus. Palmoplantar pustulosis (PPP) has primary, persistent (>3 months), sterile, macroscopically visible pustules on palms and/or soles and can occur with or without PV.

Direct invasion from proliferating basaloid atypical keratinocytes limited to the epidermal basal layer (AK I), known as the differentiated pathway, was the most common form of progression to cutaneous iSCC in our series. On the other hand, stepwise progression from AK I to AK II and AK III (classic pathway) was seen to be operative in a substantial proportion of iSCC cases. All AK lesions, irrespective of intraepidermal neoplasia thickness, are therefore potentially invasive and tumour advance along adnexal structures might facilitate iSCC development from AK I lesions.

Background There is limited information on systemic and biological treatment optimization and transitioning in routine

Two types of vulvar squamous cell carcinomas (VSCCs) are recognized according to their relationship to human papillomavirus (HPV). Basaloid or warty carcinomas are considered HPV-associated tumors, whereas differentiated keratinizing neoplasms are considered non-HPV-associated. Recently, immunohistochemical detection of p16 and p53 has been proposed to differentiate these 2 types of VSCCs. We conducted a histologic study with immunohistochemical evaluation of p16 and p53 and HPV detection and typing by polymerase chain reaction using 2 different sets of primers in 92 cases of VSCCs to evaluate the usefulness of immunohistochemistry in the classification of VSCCs and to describe the clinico-pathologic characteristics of both types of VSCCs. HPV was detected in 16/92 (17.4%) specimens, HPV16 being identified in 75% of positive cases. A significant number of discrepancies between histology and HPV detection were observed, with 37.5% of HPV-positive tumors being keratinizing and 9.2% of HPV-negative carcinomas showing basaloid or warty features. Diffuse positivity for p16 and p53 was observed in 100% and 6.2% of HPV-positive tumors and in 2.3% and 64.5% of HPV-negative neoplasms, respectively. The sensitivity and specificity of p16 immunostaining to detect HPV-associated carcinomas (100% and 98.7%, respectively) were better than those of histologic criteria (93.8% and 35.5%) and of p53 negative stain (62.5% and 93.4%). Vulvar intraepithelial neoplasia grade 3 of basaloid/warty type was identified in 53.8% HPV-positive tumors, including 3 keratinizing tumors. All these cases were p16 positive and p53 negative. Vulvar intraepithelial neoplasia grade 3 of differentiated type was observed in 45.6% of HPV-negative cases; 90.8% of them were positive for p53 but all were negative for p16. No differences in age, stage, or development of recurrence were observed between HPV-positive and negative tumors. In summary, the current morphologic criteria to discriminate HPV-positive and negative VSCCs have a significant overlap. Immunostaining for p16 is a reliable marker for HPV-positive VSSCs, which improves the results of histologic classification.

Patients with psoriasis, in particular those requiring systemic treatment, tend to be above normal weight. Obesity is associated with psoriasis and contributes significantly to the increased cardiovascular risk in these patients. Most biologics used to treat psoriasis in the European Union are fixed dosed treatments: etanercept, adalimumab and ustekinumab. Apart from infliximab, dosing regimens do not account for weight, with the exception of ustekinumab, the dose of which should be doubled in patients weighing more than 100 kg. The aim of this study was to review the available evidence on the association of obesity and psoriasis, and the effect of body weight or obesity on the efficacy of biologics as well as their practical implications in daily practice. A review was performed of the literature relating to obesity and psoriasis and weight effect, including subgroup analyses, on the efficacy of the biologicals available for treatment of psoriasis in the European Union, namely adalimumab, etanercept, infliximab and ustekinumab. Optimal responses with fixed dose biological agents are less frequent in patients with increasing weight, especially above 100 kg, who account for approximately 25% to 30% of patients in clinical trials. Body weight effect on drug clearance might partly account for this fact. The data are limited to subgroup analyses, often with no statistical significance reported. Further studies, including weight-based subanalysis of clinical trials and pharmacoeconomic evaluations, are required to assess the issue of body weight and response to therapy of the biologics. Infliximab response appears to be independent of body mass index. Possible weight-based dose adjustments and the impact of treatment on body weight changes also require additional study.

In a non-life-threatening disease such as psoriasis, treatment goals should be referred to the improvement in severity and extent of the disease and their impact on patients' perceived health-related quality of life (HRQoL), usually measured by the Dermatology Life Quality Index (DLQI). The ultimate goal of therapy is blanching, and an improvement of 90% or better (PASI90 response) with respect to baseline Psoriasis Area and Severity Index (PASI) is considered as treatment success by the European Medicines Agency. PASI75 response has become accepted as a less stringent reasonable therapeutic goal, but absolute PASI values might provide a better benchmark, irrespective of baseline PASI. Anyway, objective measures of psoriasis involvement are clinically meaningful only if they correlate with significant improvements in DLQI, and especially with the achievement of a DLQI = 0-1 status, corresponding to lack of effect of the disease on patient's HRQoL. Even though PASI75 response meets therapeutic expectations in most patients, PASI90 response or better has a significantly higher impact on DLQI improvement and is associated with significantly higher DLQI = 0-1 response rates. The introduction of anti-IL17 drugs in clinical practice bears the promise of achieving PASI90 response or better in the majority of patients, and initial data suggest that the PASI90 benchmark provides better discriminatory value as regards achievement of DLQI = 0-1 response. Further research is required to confirm the value of absolute PASI cut-offs as a measure of therapeutic success independent of baseline and duration of treatment, and to develop newer, more practical and more accurate measures of psoriasis severity.