Effectiveness and safety of apremilast in biologic-naïve patients with moderate psoriasis treated in routine clinical practice in Greece: the APRAISAL study.

BACKGROUND: Apremilast is an oral phosphodiesterase-4 inhibitor indicated for patients with moderate-to-severe chronic plaque psoriasis and active psoriatic arthritis. OBJECTIVES: To examine the effectiveness of apremilast on Dermatology Life Quality Index (DLQI), Psoriasis Area and Severity Index (PASI) and nail, scalp and palmoplantar involvement, when administered prior to biologics. METHODS: This 52-week real-world study included biologic-naive adults with moderate psoriasis (psoriasis-involved body surface area 10% to <20%, or PASI 10 to <20 and DLQI 10 to <20). Apremilast was initiated ≤7 days before enrolment. Data from the first 100 eligible patients who completed 24 weeks (W24) of observation (or were prematurely withdrawn) are presented in this interim analysis using the last-observation-carried-forward imputation method. RESULTS: Eligible patients (mean age: 49.9 years; 71.0% males; median disease duration: 8.0 years) were consecutively enrolled between April and October 2017, by 18 dermatology specialists practising in hospital outpatient settings in Greece. Baseline DLQI (median: 12.0) and PASI (median: 11.7) scores improved (P < 0.001) at all postbaseline timepoints (Weeks 6, 16 and 24; W24 median decreases: 9.0 and 9.4 points respectively). At W24, DLQI ≤5, DLQI 0 or 1, and PASI-75 response rates were 63.0%, 25.0% and 48.0% respectively. The Nail Psoriasis Severity Index score in patients with baseline nail involvement (n = 57) decreased at all postbaseline timepoints (P < 0.001; W24 median decrease: 20.0 points). At W24, 50.0% and 51.7% of patients with baseline scalp (n = 76) and palmoplantar (n = 29) involvement respectively achieved postbaseline Physician's Global Assessment (PGA) score of 0 or 1 if baseline score was ≥3, or 0 if baseline score was 1 or 2. The adverse drug reaction rate was 21.0% (serious: 2.0%). CONCLUSIONS: These interim results indicate that through 24 weeks, apremilast improved quality of life and reduced disease severity in biologic-naive patients with moderate plaque psoriasis, while demonstrating safety consistent with the known safety profile.

Long-term application potential of urban air mobility complementing public transport: an upper Bavaria example.

In this paper, the required models and methods to analyze and quantify the potential demand for urban air mobility (UAM) complementing public transport and possible impacts were defined and applied to the Munich Metropolitan region. An existing agent-based transport model of the study area were used and extended to cover socio-demographic changes up to the year 2030 and intermodal UAM services. An incremental logit model for UAM was derived to simulate demand for this new mode. An airport access model was developed as well. Three different UAM networks with different numbers of vertiports were defined. Sensitivity studies of ticket fare and structure, flying vehicle cruise speed, passenger process times at vertiports and different Urban Air Mobility networks sizes were performed. For the reference case, UAM accounts for a modal share of 0.5%. The absolute UAM demand is concentrated on very short routes; hence, UAM vehicle flight speed variation shows low UAM demand impacts. Kilometer-based fare, number of UAM vehicles per vertiport and passenger process times at vertiports show a significant impact on UAM demand.

Pilonidal sinus disease: an intergluteal localization of hidradenitis suppurativa/acne inversa: a cross-sectional study among 2465 patients.

BACKGROUND: Hidradenitis suppurativa (HS), also referred to as acne inversa, is a debilitating skin disease characterized by inflammatory nodules, chronic abscesses and tunnels (fistulae and sinuses). The association with pilonidal sinus disease (PSD) is frequently reported but not well documented. OBJECTIVES: To determine the prevalence and characteristics of inflammatory skin lesions located in the intergluteal fold (IGF) of patients with HS. METHODS: This was an international multicentre retrospective cross-sectional study based on data collection from a large cohort of patients with HS with and without histopathology. Results From a total of 2465 patients with HS included in the study, 661 (27%) reported lesions in the IGF. These patients were significantly more often smokers and had more severe HS. Of the 238 patients with an available clinical diagnosis, intergluteal-HS (IG-HS) was diagnosed in 52 patients (22%) and PSD was diagnosed in 186 patients (78%). IG-HS was associated with the localization of HS in the proximity of the IGF, including the buttocks, genitals and the anus. There was a possibility of misclassification bias in this study as a clinical/image-based diagnosis or histopathology of the IGF lesions was not always available. CONCLUSIONS: The high prevalence of PSD suggests a strong link between both entities. Therefore, it may be useful to identify common pathophysiological mechanisms and develop common therapeutic strategies. What's already known about this topic? The occurrence of pilonidal sinus disease has not been clearly reported among patients with hidradenitis suppurativa/acne inversa. What does this study add? This is the first study that investigated the prevalence of pilonidal sinus disease among a large cohort of patients and identified the patient characteristics. Risk factors that might help to improve the management of patients were identified.

Clinical and dermoscopic characteristics of congenital melanocytic naevi.

BACKGROUND: Prompted by the limited data, we conducted this study to gather more information on dermoscopic features of CN in children, in order to optimize clinical care and management. MATERIALS AND METHODS: All children with congenital nevi (CN) attending our Pediatric Pigmented Skin Lesion Unit during a 2-year period were included in the study. Clinical data were collected, and all children underwent clinical and dermoscopic examination. Dermoscopic patterns and specific features were recorded. RESULTS: Three hundred and thirty CN were examined in a population of 276 children, aged from 6 months to 14 years. The majority (85.14%) had only one congenital naevus, and 43.12% had a family history of congenital nevi. Children with multiple congenital nevi were more likely to have a positive family history of a CN (P = 0.012). Only, in 23 children, neurological/developmental abnormalities were reported. Small CN were the commonest in our cohort (167) followed by the medium-sized (160), whereas large CN (>20 cm) were only three. Thirty-eight CN were located on the volar skin. The globular was the commonest dermoscopic pattern, followed by the reticular, whereas the parallel furrow pattern was the commonest pattern on palms and soles. CN on the trunk were more likely to be globular on the limbs, and reticular and homogeneous on the head and neck (P < 0.001). The commonest dermoscopic findings were haloed and target globules, blotches and perifollicular hypopigmentation, whereas globules and dots around cristae on volar skin. CN located on the limbs were more likely to demonstrate an atypical network (P = 0.001) and a target network with globules (P = 0.020), whereas haloed and target globules (P < 0.001), blotches (P = 0.023) and dots (P = 0.004) were found with an increased frequency in CN on the trunk. CONCLUSIONS: Given that there is much controversy on the management and accurate classification of CN, our findings may provide useful information.

A multicenter, prospective, observational study examining the impact of risk factors, such as BMI and waist circumference, on quality of life improvement and clinical response in moderate-to-severe plaque-type psoriasis patients treated with infliximab in routine care settings of Greece.

BACKGROUND: Obesity has been associated with moderate-to-severe plaque psoriasis severity and PASI 75 response attainment of biologic therapies, but findings are inconsistent. OBJECTIVE: This study aimed to examine the association of body mass index (BMI) and waist circumference (WC) on disease severity, to identify potential patient characteristics associated with response attainment and to assess the impact of infliximab on the patients' health-related quality of life (HRQoL) among infliximab-treated patients in the routine care setting of Greece. METHODS: This was a multicenter, prospective, observational study of adult moderate-to-severe plaque psoriasis patients who had initiated treatment with originator infliximab within 2 weeks prior to enrolment. Postenrolment visits occurred at 14 ± 4, 30 ± 4 and 54 ± 4 weeks following treatment onset. RESULTS: Between October 2012 and June 2014, 136 eligible patients (62.5% males) with a median age of 48.6 years, BMI of 29.6 kg/m2 and WC of 107.0 cm at enrolment were recruited by 21 dermatology hospital/private offices. All patients had received prior psoriasis treatment(s); 62.5% were biologic-naïve. Mean baseline psoriasis area severity index (PASI) and Dermatology Quality of Life Index (DLQI) scores were 23.4 ± 13.6 and 15.0 ± 8.3, respectively. A low correlation was observed between WC at enrolment and baseline PASI [ρ = 0.324 (P < 0.001)]. Over a median 48.4 weeks of infliximab exposure, 89.3% of the per protocol set achieved a PASI 75 response. At 14, 30 and 54 weeks, the PASI 75 attainment rate was 66.4%, 74.8% and 76.6%, respectively; the clinically meaningful DLQI improvement (≥5 point decrease) rate was 68.9%, 75.7% and 69.8%, respectively. BMI category and abdominal obesity at enrolment did not impact PASI 75 or DLQI improvement rate attainment. CONCLUSION: In the routine care of Greece, infliximab reduced disease activity and improved the quality of life of moderate-to-severe psoriasis patients through 1 year of treatment, independent of their BMI and WC.

Low and high body mass index in hidradenitis suppurativa patients-different subtypes?

INTRODUCTION: Overweight is a well-established risk factor for hidradenitis suppurativa (HS). In this cross-sectional study, we compare HS patients with a high body mass index (BMI) with HS patients with a low BMI to investigate differences in disease characteristics. MATERIALS AND METHOD: Patients were recruited from 17 dermatological centres from four continents. A total of 246 patients with a BMI below 25 were compared to 205 patients with a BMI of above 35. RESULTS: Patients with a high BMI suffered more severe disease (Hurley, physician global assessment, number of areas affected and patient-reported severity (PRS), P < 0.001 for all). There was no difference in smoking (P = 0.783) nor in family history (P = 0.088). In both low and high BMI patients, early onset of HS was a predictor of positive family history (P < 0.001, for each). For low BMI patients, an increase in BMI significantly increased PRS (P < 0.001). For patients with a high BMI, number of pack-years significantly increased PRS (P = 0.001). Cluster analysis of eruption patterns was location specific for low BMI patients but severity specific for high BMI patients. DISCUSSION: Patients with a low and high BMI could represent two clinically different subtypes. We suggest a non-linear relationship between BMI and impact of HS. As patients go from a low BMI patient to a high BMI patient (or from high to low), eruption patterns and risk factors may change.

Quality of life and depression in chronic sexually transmitted infections in UK and Greece: The use of WHOQOL-HIV/STI BREF.

This is a comparative study aiming to investigate quality of life (QoL) and depression in individuals diagnosed either with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), or genital warts (GW) and genital herpes (GH), in two healthcare settings, in the United Kingdom (UK) or in Greece (Gr). Using a matched-pairs design, two equalized patient samples with sexually transmitted infections (STI) were recruited: from UK (n=43) and from Greece (n=43). QoL was assessed with WHOQOL-HIV BREF for HIV patients and WHOQOL-STI BREF -a newly adapted instrument- for genital warts and genital herpes patients. Depressive symptomatology was measured by the Centre for Epidemiological Studies- Depression Scale (CES-D) along with sociodemographic data. Results indicate that in both country- healthcare settings, a high percentage of individuals diagnosed with any type of STI, reported considerable depressive symptomatology: 35.7% for UK and 41.5% for Greek participants respectively. Regarding QoL, participants in the Greek healthcare settings reported significantly lower scores in the environment domain, and even lower scores were reported by the GW/GH group, in comparison to HIV. Specifically, these groups indicated significantly lower values in the following WHOQOL-BREF environment facets: (i) physical safety and security, (ii) participation in and opportunities for recreation/leisure activities, (iii) home environment, (iv) accessibility and quality in health and social care, and (v) transport facilities. Regarding correlation of QoL and depression, regression analysis provided significant evidence for depression having a differential effect on WHOQOL-BREF QoL domains. Evidence of increased depressive symptomatology in both STI patient- cohorts may shed light into unmet healthcare needs that should be addressed by healthcare providers in UK and Greece respectively. Furthermore, all types of Greek STI participants reported lower QoL, particularly the GW/GH group, indicating important unmet QoL needs in the environment domain, such as health and social care accessibility and quality, or environmental and social resources, all lowering everyday QoL. The present findings may provide guidelines for tailored mental health interventions alleviating depressive symptomatology in STI patients. Provision of targeted-interventions at healthcare and social-environmental levels will contribute to QoL/ health improvement in STI patients.

Are VNTRs co-localizing with breast cancer-associated SNPs?

PURPOSE: Several common genetic variants (single-nucleotide polymorphisms, SNPs) have been shown to be associated with breast cancer (BC) risk in the general population, and to modify BC risk for BRCA1 and BRCA2 mutation carriers. Co-localization of variable number of tandem repeats (VNTRs) with these BC-associated SNPS has not been comprehensively studied. METHODS: Cross referencing of genome-wide VNTRs with the known BC genome-wide association studies (GWAS) SNPs significantly associated with increased risk for developing breast cancer was carried out. Analysis was based on the overlap between the VNTRs and 10-kb windows around these BC-susceptibility SNPs. RESULTS: Cross referencing of the 1.2 million TR with the 161 known BC-associated SNPs in the general population led to 690 matches. Of those, in 17 VNTRs, the SNP was within the VNTR. Analysis restricted to loci known to modify BC penetrance in BRCA1 (n = 31) and BRCA2 (n = 33) mutation carriers led to 139 and 170 co-localization matches, respectively. For these, none of the SNPs were within the VNTR. The distances between the SNPs and the VNTRs were not significantly different from what was expected to occur by chance alone (p = 0.61; p = 0.44; p = 0.25, respectively). CONCLUSION: There is no evidence that VNTRs co-localize with currently reported SNP tagged BC GWAS loci.

Patients with Spitz naevi in the Greek population: Epidemiologic, Clinical and Histopathological characteristics.

BACKGROUND: Spitz naevi may present with clinical and histopathological atypical features that do not affect patient prognosis but may become worrisome for patients ≥40 years presenting with newly appearing SN. OBJECTIVE: Patient characteristics and sun behaviour patterns were investigated in correlation with age. SN characteristics and histopathological attributes were also investigated in correlation with age. METHODS: Patients with histopathologically confirmed diagnosis of SN were invited for a clinical examination. Data such as skin type, number of banal/atypical naevi, sun exposure patterns and personal/family history were collected. Histopathology preparations were re-examined by two different histopathologists, and characteristics were collected based on a prespecified checklist. Patients were afterwards followed up every 6 months. RESULTS: A total of 110 patients with SN were identified and assigned to three age groups. The most common area of presentation was the trunk, for the ≥40 years age group, and the limbs for the other age groups. Patients ≥40 years had a higher possibility of presenting with a naevus count ≥50 and at least one atypical naevus compared to the other age groups. Patients ≥40 years presented more commonly with a history of painful sunburn (100%) before the appearance of the SN, used less sunscreen, had higher sun exposure times and more clinical signs of solar skin damage compared to the other age groups. Finally, patients ≥40 years presented more commonly with signs of histopathological atypia such as the presence of mitoses, cellular atypia and prominent nucleolus. CONCLUSION: Patients ≥40 were more likely to report a history of longer sun exposure times, of never using a sunscreen and of having a history of painful sunburn. However, the importance of this observation remains to be elucidated as these patients also presented more commonly with lesions located on non-sun-exposed areas (trunk) and higher naevus/atypical naevus counts.

Global patterns of care in advanced stage mycosis fungoides/Sezary syndrome: a multicenter retrospective follow-up study from the Cutaneous Lymphoma International Consortium.

BACKGROUND: Advanced-stage mycosis fungoides (MF)/Sézary syndrome (SS) patients are weighted by an unfavorable prognosis and share an unmet clinical need of effective treatments. International guidelines are available detailing treatment options for the different stages but without recommending treatments in any particular order due to lack of comparative trials. The aims of this second CLIC study were to retrospectively analyze the pattern of care worldwide for advanced-stage MF/SS patients, the distribution of treatments according to geographical areas (USA versus non-USA), and whether the heterogeneity of approaches has potential impact on survival. PATIENTS AND METHODS: This study included 853 patients from 21 specialist centers (14 European, 4 USA, 1 each Australian, Brazilian, and Japanese). RESULTS: Heterogeneity of treatment approaches was found, with up to 24 different modalities or combinations used as first-line and 36% of patients receiving four or more treatments. Stage IIB disease was most frequently treated by total-skin-electron-beam radiotherapy, bexarotene and gemcitabine; erythrodermic and SS patients by extracorporeal photochemotherapy, and stage IVA2 by polychemotherapy. Significant differences were found between USA and non-USA centers, with bexarotene, photopheresis and histone deacetylase inhibitors most frequently prescribed for first-line treatment in USA while phototherapy, interferon, chlorambucil and gemcitabine in non-USA centers. These differences did not significantly impact on survival. However, when considering death and therapy change as competing risk events and the impact of first treatment line on both events, both monochemotherapy (SHR = 2.07) and polychemotherapy (SHR = 1.69) showed elevated relative risks. CONCLUSION: This large multicenter retrospective study shows that there exist a large treatment heterogeneity in advanced MF/SS and differences between USA and non-USA centers but these were not related to survival, while our data reveal that chemotherapy as first treatment is associated with a higher risk of death and/or change of therapy and thus other therapeutic options should be preferable as first treatment approach.

From basal cell carcinoma morphogenesis to the alopecia induced by hedgehog inhibitors: connecting the dots.

The deciphering of the hedgehog (Hh) signalling pathway implicated in the tumorigenesis of basal cell carcinoma (BCC) led to the development of targeted drug therapies, the Hh pathway inhibitors (HPIs) vismodegib and sonidegib. In the skin, physiological Hh signalling is activated in growing hair follicles (HFs), where it is required for proliferation of the epithelium of HFs during morphogenesis and for their postnatal growth. The effects of HPI treatment leading to the regression of BCC and the development of alopecia underpin the central role of the Hh pathway in BCC formation, as well as hair cycling. Given the fact that BCC is a follicular-driven tumour, it is a fine tuning of events that regulate hair cycling that may drive towards the formation of benign follicular hamartomas or malignant BCC neoplasms. Wnt/ß-catenin signalling interacts with the Hh signalling during HF morphogenesis, normal hair cycling and BCC development. The aim of this review is to present how key molecular events implicated in Hh pathway crosstalk in the HF are also involved in BCC pathogenesis and result in the alopecia developed by HPI treatment.

Psoriasis in patients with mycosis fungoides: a clinicopathological study of 25 patients.

BACKGROUND: It has been reported that patients with psoriasis are at increased risk for developing lymphoma including cutaneous T-cell lymphomas (CTCL). However, the comorbidity and the histopathologic correlation of psoriasis and mycosis fungoides (MF) have been less studied. OBJECTIVE: The objective of this study was to investigate the relation between MF and psoriasis. METHODS: We retrospectively reviewed and re-evaluated all MF cases diagnosed and followed in a 16-year period who carried both MF and psoriasis diagnoses. RESULTS: Forty-one of 321 MF patients was the rate of psoriasis' comorbidity according to medical records. Twenty-five patients (7.8%) finally met the inclusion criteria. The rest were excluded due to inadequate evidence. Twenty patients had psoriatic lesions at the time of MF diagnosis. In 23 patients, there was histological confirmation of both diseases. Six patients (24%) were diagnosed with folliculotropic MF, two were diagnosed with pustular psoriasis, and six patients were affected by palmoplantar and nail psoriasis. In four patients, there was a very short time interval between MF and psoriasis diagnosis. Fourteen patients with psoriasis had been previously treated with immunomodulatory regimens. Interestingly, in eight patients, typical histological findings of both diseases were detected in the same biopsy specimen. CONCLUSION: Our results support the opinion that the association between psoriasis and MF does exist. It is most possibly related to the chronic lymphocyte stimulation that occurs during psoriasis that eventually leads to a dominant clone and the evolution to CTCL. Our study suggests that apart from cases of early MF, which are being indeed misdiagnosed as psoriasis, there is another group of patients, where psoriasis truly coexists with - or even progresses to - MF.