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Background: Real-world data for guselkumab, the first interleukin-23 inhibitor approved to treat moderate-to-severe psoriasis, are scarce. This study represents the first 60-week, real-life, multicenter, retrospective experience to investigate the effectiveness, safety, tolerability, and drug retention of guselkumab in psoriatic patients., Research Design and Methods: Clinical information was collected at baseline and at weeks 12, 24, 36, 48, and 60., Results: The mean baseline Psoriasis Activity Severity Index (PASI) reduced from 14.2 to 3.1 at week 12 and decreased to around 0 at weeks 36, 48, and 60. PASI 75, PASI 90, and PASI 100 were 100%, 96.8%, and 83.9% at week 60, respectively. Multiple logistic regression analysis showed that neither body mass index >30, smoking, ≥3 comorbidities, difficult-to-treat areas, nor a failure to ≥2 prior biologic treatments significantly influenced PASI reduction (p > 0.05)., Conclusions: Our findings confirm guselkumab as an appropriate therapeutic option in routine clinical practice, especially when dealing with complex patients with comorbidities or previous failure to biologic treatments.

Atopic dermatitis is a common chronic-relapsing, inflammatory and itchy eczematous skin disorder which occurs in both children and adults. AD pathogenesis is complex and several factors are implicated. Pruritus plays a pivotal role in disease's burden, significantly worsening atopic patient quality of life by limiting productivity and daily activities. AD diagnosis relies still on the experience of the healthcare professional and there are several unmet needs as for the diagnostic criteria, the management and the recognition of the burden of the disease. In this paper we present an indeep focus on the main clinical features of AD and the major unmet needs that should be addressed in the next research.

Background: Apremilast ® (Amgen, Thousand Oaks, CA, USA) is the first small molecule approved for the treatment of moderate-to-severe psoriasis in adult patients; however, real-life data are still limited. We investigated the effectiveness and safety of this drug in a multicenter real-world setting., Methods: We retrospectively reviewed data from all psoriatic patients who received at least one dose of Apremilast ® (Amgen) and collected demographic data and medical history at baseline and periodically for 36 months., Results: A total of 111 patients entered in the study. The mean drug survival duration was 21.8±10.6 months; however, it was significantly shorter when comorbidities were ≥3 and if biologic drugs were previously administered. ΔPASI90 was achieved in 29% of patients and ΔPASI50 in 68% at T4; the rate of ΔPASI improvement increased progressively at T12, T24, T36 in patients who continued to receive Apremilast ® (Amgen). At the end of the study 50 patients discontinued the treatment because of adverse events (19.8%), primary failure (19%) or secondary failure (6.3%)., Conclusions: Apremilast ® (Amgen) proved to be an effective, safe, and manageable drug, showing effectiveness also in difficult-to-treat patients with psoriasis, with a favorable tolerability profile and a potentially valid weight loss effect. We believe that treating patients with few comorbidities who are naive to biological therapy may result in higher response rates and longer mean drug survival.

Competing Interests: A.C. served as advisory board member and consultant receiving fees and speaker's honoraria or has participated in clinical trials for AbbVie, Almirall, Biogen, Fresenius Kabi, Leo Pharma, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi Genzyme, and UCB Pharma. G.F. acted as speaker and consultant for AbbVie and Leo Pharma. G.G. has been principal investigator in clinical trials sponsored by and/or and has received personal fees from AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Bristol-Meyers Squibb, Celgene, Eli Lilly, Leo Pharma, Novartis, OM Pharma, Pfizer, Regeneron, Samsung, and Sandoz. A.O. has been a scientific consultant/speaker/clinical study investigator for AbbVie, Celgene, Janssen, Leo Pharma, Eli Lilly, MSD, Novartis, Pfizer, Sanofi, Alfasigma, and Almirall. M.T.R. has received personal fee for advisory board meeting from Sanofi, AbbVie, Novartis, and Cantabria. L.B. reports personal fees from speaker and as consultant for AbbVie, Novartis, Janssen-Cilag, Pfizer, UCB, and Leo Pharma, outside the submitted work. L.S. has been principal investigator in clinical trials sponsored by and/or received personal fees from AbbVie, Almirall, Celgene, Eli Lilly, Janssen, Novartis, and Sanofi-Genzyme. G.P. has been principal investigator in clinical trials sponsored by and/or received personal fees from AbbVie, Almirall, Eli Lilly, Leo Pharma, Novartis, and Sanofi. A.P. has served as a speaker and received honoraria from Sanofi-Genzyme for lectures, research grants, and as an advisory board member. C.F. has been speaker for Sanofi and AbbVie. M.C.F. has served on advisory boards, received honoraria for lectures, and research grants from Almirall, AbbVie, Galderma, Leo Pharma, Mylan, Medac Pharma, Celgene, Pierre Fabre, UCB, Eli Lilly, Pfizer, Janssen, Novartis, Sanofi Genzyme, Roche, Sun Pharma, and MSD. F.R. has served on advisory board, received honoraria for lectures and research grants from Novartis, AbbVie, Janssen-Cilag, Eli Lilly, Leo Pharma, and Sanofi-Genzyme. P.A. has received speaker honoraria from Sanofi, AbbVie, Janssen, Celgene, Novartis, and Sandoz. G.M. has been a scientific consultant/clinical study investigator for AbbVie, Eli Lilly, Janssen-Cilag, Leo Pharma, and Novartis. C.P. has been a consultant and held sponsored conferences for AbbVie, Novartis, Pfizer, and Sanofi. I.Z. has been a consultant and/or speaker for Novartis, Celgene, and Amgen. K.P. reports grants and personal fees for advisory board meeting from Almirall, AbbVie, Biogen, Lilly, Celgene, Galderma, Leo Pharma, Novartis, Pierre Fabre, Sanofi, Sandoz, Sun Pharma, and Janssen. S.F. has been principal investigator in clinical trials by AbbVie and Sanofi-Genzyme, has served on advisory board, received honoraria for lectures and research grants from Novartis, Menarini, and Almirall. The remaining authors have no funding or conflicts of interest to declare.

Soft tissues perineurioma is a rare nerve sheath tumor that affects most of all the subcutaneous tissue. Even if it could present as a large mass, it is a benign neoplasm for which a complete surgical excision represents the gold standard treatment. Considering that it usually affects acral sites of young people, it can be challenging to perform a reconstructive surgery that allows a full functional recovery. We report the case of a woman in her 20s presenting a perineurioma of the sole of the right foot, a nodule of about 2 cm of diameter that compromised the support of the foot on the ground. We performed a radical surgical excision with no recurrence after 3 years of follow up and we obtained a full functional recovery thanks to an autologous full-thickness skin graft., Competing Interests: Conflict of interest: The authors declare no potential conflict of interest., (©Copyright: the Author(s).)

Dimethyl fumarate (DMF) is a fumaric acid esters derivate approved for plaque psoriasis as first-line systemic therapy. It has been available in Italy since 2017 and an increasing number of patients are treated with this drug. To evaluate DMF effectiveness, side effects and drug survival in a dermatological real-life setting. We performed a retrospective multi-center study in five dermatologic clinics in Emilia-Romagna, Northern Italy, which included all consecutive patients affected by moderate-severe psoriasis treated with DMF. We assessed effectiveness (in terms of PASI50 and PASI75 in an intention to treat observation) and safety (occurrence of side effects) of DMF and their association with demographic and disease characteristics, mean daily dose taken and treatment discontinuation. We included 103 patients, 78 (75.72%) had at least one comorbidity including 19 (18.44%) with a history of cancer; the mean treatment duration was 23.61 ± 17.99 weeks (min 4, max 130) and the mean daily dose was 262.13 ± 190.94 mg. Twenty-four patients (23.30%) reached PASI75 at week 12, while a further 18 patients (17.47%) reached it at week 26. Side effects occurred in 63 patients (61.16%), the most frequent were diarrhea, epigastric discomfort, nausea, and flushing. Sixteen patients (15.53%) showed an alteration of laboratory tests. In some cases side effects were transitory, while in 53 patients (51.45%) they led to cessation of therapy. The median daily dose showed a direct association with PASI50 achievement and an indirect association with treatment discontinuation. Our study shows the peculiarities of DMF in a real-world setting: effectiveness is often reached after 12 weeks of treatment and side effects could limit the continuation of the therapy but, at the same time, DMF has no major contraindications and, due to the wide range of dosage, it can allow both to manage side effects and to personalize the prescription for each patient., (© 2021 The Authors. Dermatologic Therapy published by Wiley Periodicals LLC.)

Background/purpose: To assess efficacy, tolerability, adverse effects, recurrence, and aesthetic results of imiquimod 3.75% vs. photodynamic therapy with 5-aminolaevulinic acid (MAL-PDT) for actinic keratosis (AK)., Methods: A small randomized, intraindividual right-left pilot study for AK treatment of multiple scalp lesions was performed. Patients were treated with imiquimod and subsequently MAL-PDT (on opposite sides of the scalp) 14 days apart. Study end points were evaluated with clinical and dermoscopic examinations at 1, 3, 6, and 12 months., Results: Nine male bald patients were enrolled. Imiquimod achieved a slightly higher overall clearance rate than MAP-PDT (68.1% vs 56.5%). According to AK degree of severity, clearance rates were greater for degree I and III with imiquimod (68.8%, 64.5% and 75% with imiquimod vs. 48%, 69.8%, and 66.7% for MAL-PDT, respectively). At 12 months, a slightly higher total recurrence rate was noted for imiquimod compared with MAL-PDT (9.9% vs. 8.6%); new lesions were 2 degree I for imiquimod and 4 degree I for MAL-PDT. For both treatments, pain was moderate/strong (even if MAL-PDT seems to be less tolerable) adverse effects are common and transient; aesthetic results excellent., Conclusion: Both imiquimod and MAL-PDT were effective in the reduction in the number of AK. In the long-term, both present a good effectiveness maintained over time with excellent aesthetic results. A combination or sequential therapy could optimize the management of the cancerization field., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Psoriatic arthritis (PsA) patients are often treated by dermatology and rheumatology specialities and may receive different treatments. To evaluate the impact of dermatology/rheumatology specialist settings on diagnosis and therapeutic approach in PsA patients. This cross-sectional multicounty study in Italy involved twenty-eight rheumatology or dermatology clinics. Patients with suspected or confirmed PsA were examined by both a dermatologist and a rheumatologist. A total of 413 patients were enrolled and 347 (84%) were diagnosed with PsA. The majority of patients were enrolled from a rheumatology setting (N = 224, 64.6%). Patients with PsA in the dermatology settings had significantly higher disease activity, including skin involvement and musculoskeletal symptoms. Time from PsA onset to diagnosis was 22.3 ± 53.8 vs. 39.4 ± 77.5 months (p = 0.63) in rheumatology and dermatology settings; time from diagnosis to initiation of csDMARD was 7.3 ± 27.5 vs. 19.5 ± 50.6 months, respectively (p < 0.001). In contrast, time from diagnosis to bDMARD use was shorter in dermatology settings (54.9 ± 69 vs. 44.2 ± 65.6 months, p = 0.09, rheumatology vs. dermatology), similar to the time taken from first csDMARDs and bDMARDs (48.7 ± 67.9 vs. 35.3 ± 51.9 months, p = 0.34). The choice to visit a rheumatologist over a dermatologist was positively associated with female gender and swollen joints and negatively associated with delay in time from musculoskeletal symptom onset to PsA diagnosis. This study highlights a diagnostic delay emerging from both settings with significantly different therapeutic approaches. Our data reinforce the importance of implementing efficient strategies to improve early identification of PsA that can benefit from the integrated management of PsA patients. Key Points • A diagnostic delay was observed from both dermatology and rheumatology settings with significantly different therapeutic approaches. • Shared dermatology and rheumatology clinics offer the combined expertise to improve in the early identification and management of PsA.

Background: Few and small studies have described the management of immunomodulant/immunosuppressive therapies or phototherapy in atopic dermatitis (AD) patients during coronavirus disease 2019 (COVID-19) pandemic., Methods: A national registry, named DA-COVID-19 and involving 35 Italian dermatology units, was established in order to evaluate the impact of COVID-19 pandemic on the management of adult AD patients treated with systemic immunomodulant/immunosuppressive medications or phototherapy. Demographic and clinical data were obtained at different timepoints by teledermatology during COVID-19 pandemic, when regular visits were not allowed due to sanitary restrictions. Disease severity was assessed by both physician- and patient-reported assessment scores evaluating itch intensity, sleep disturbances, and AD severity., Results: A total of 1831 patients were included, with 1580/1831 (86.3%) continuing therapy during pandemic. Most patients were treated with dupilumab (86.1%, 1576/1831) that was interrupted in only 9.9% (156/1576) of cases, while systemic immunosuppressive compounds were more frequently withdrawn. Treatment interruption was due to decision of the patient, general practitioner, or dermatologist in 39.9% (114/286), 5.6% (16/286), and 30.1% (86/286) of cases, respectively. Fear of increased susceptibility to SARS-CoV-2 infection (24.8%, 71/286) was one of the main causes of interruption. Sixteen patients (0.9%) resulted positive to SARS-CoV-2 infection; 3 of them (0.2%) were hospitalized but no cases of COVID-related death occurred., Conclusions: Most AD patients continued systemic treatments during COVID pandemic and lockdown period, without high impact on disease control, particularly dupilumab-treated patients., (© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background : The susceptibility of patients with chronic plaque psoriasis and the risks or benefits related to the use of biological therapies for COVID-19 are unknown. Few data about prevalence, clinical course and outcomes of COVID-19 among psoriatic patients were reported. The aims of this study were 1) to assess the prevalence and severity of COVID-19 in psoriatic patients treated with biologic agents during the first phase of the emergency (22 February to 22 April 2020) in Italy, and 2) to report the clinical outcomes of patients who have been exposed to individuals with confirmed SARS-CoV-2 infection. Methods : Patients with moderate-to-severe chronic plaque psoriasis, aged ≥18 years and undergoing treatment with biologic agents as of 22 February 2020, were eligible to be included in PSO-BIO-COVID study. Demographic and clinical characteristics of patients using any biologic for psoriasis treatment between 22 February and 22 April 2020 were registered. Results : A total of 12,807 psoriatic patients were included in the PSO-BIO-COVID study. In this cohort 26 patients (0.2%) had a swab confirmation of SARS-CoV-2 infection. Eleven patients required hospitalization and two died. Conclusion : The incidence of COVID-19 observed in our cohort of psoriatic patients (0.2%) is similar to that seen in the general population (0.31%) in Italy. However, the course of the disease was mild in most patients. Biological therapies may likely lessen 'cytokine storm' of COVID-19, which sometimes lead to multiple organ failure, ARDS, and death.

Background: Advances in biologic treatments have led to a new therapeutic frontier for moderate-to-severe psoriasis. Nevertheless, the efficacy of anti-TNFα decreases with time, requiring adjustments to maintain valuable Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) responses., Objectives: To evaluate the efficacy and safety of adalimumab dose escalation (40 mg, subcutaneous, once a week for 24 weeks) in psoriatic adult patients with secondary loss of response (PASI ≥50 to ≤75 or PASI≥75 and DLQI ≥5)., Materials and Methods: A multicentre, observational study involving different Italian third-level referral centres for psoriasis enrolled a total of 64 adult patients with moderate-to-severe psoriasis who were treated with adalimumab and experienced a secondary loss of response. Primary end-points were PASI> 75 or PASI ≥50 to ≤ 75 with DLQI ≤ 5, and the secondary end-point was the ability to maintain a therapeutic response, resuming adalimumab every other week., Results: At Week 16 and Week 24, 29/64 (45.3%) and 35/64 (54.6%) responded based on PASI, and mean DLQI was 4.9 and 4.09, respectively. At Week 36 and Week 48, 45.3% and 28.1% patients achieved the second end-point, respectively. No adverse events were recorded except for one patient with recurrent tonsillitis., Conclusion: Adalimumab escalation could be considered in cases with loss of response before switching to alternative biologic therapy.

Aim: We collected 'real-life' data on the management of patients with mastocytosis in the Italian Mastocytosis Registry., Methods: Six hundred patients diagnosed with mastocytosis between 1974 and 2014 were included from 19 centers., Results: Among adults (n = 401); 156 (38.9%) patients were diagnosed with systemic mastocytosis. In 212 adults, no bone marrow studies were performed resulting in a provisional diagnosis of mastocytosis of the skin. This diagnosis was most frequently established in nonhematologic centers. In total, 182/184 pediatric patients had cutaneous mastocytosis. We confirmed that in the most patients with systemic mastocytosis, serum tryptase levels were >20 ng/ml and KIT D816V was detectable., Conclusion: The Italian Mastocytosis Registry revealed some center-specific approaches for diagnosis and therapy. Epidemiological evidence on this condition is provided.

PKCε is implicated in T cell activation and proliferation and is overexpressed in CD4 + -T cells from patients with autoimmune Hashimoto's thyroiditis. Although this might induce the suspicion that PKCε takes part in autoimmunity, its role in the molecular pathophysiology of immune-mediated disorders is still largely unknown. We studied PKCε expression in circulating CD4 + -T cells from patients with psoriasis, a skin disorder characterized by an increased amount of Th17 cells, a CD4 + subset that is critical in the development of autoimmunity. Although the mechanisms that underlie Th17 differentiation in humans are still unclear, we here show that: (i) PKCε is overexpressed in CD4 + -T cells from psoriatic patients, and its expression positively correlates with the severity of the disease, being reduced by effective phototherapy; (ii) PKCε interacts with Stat3 during Th17 differentiation and its overexpression results in an enhanced expression of Stat3 and pStat3(Ser727); iii) conversely, when PKCε is forcibly downregulated, CD4 + -T cells show lower levels of pStat3(Ser727) expression and defective in vitro expansion into the Th17-lineage. These data provide a novel insight into the molecular mechanisms of Th17 cell polarization that is known to play a crucial role in autoimmunity, pinpointing PKCε as a potential target in Th17-mediated diseases., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Evidence suggests a protective role for several nutrients and foods in the maintenance of skin function. Nevertheless, all the requests for authorization to use health claims under Article 13(5) in the framework of maintenance of skin function presented to the European Food Safety Authority (EFSA) have received a negative opinion. Reasons for such failures are mainly due to an insufficient substantiation of the claimed effects, including the choice of inappropriate outcome variables (OVs) and methods of measurement (MMs). The present paper reports the results of an investigation aimed at collecting, collating and critically analyzing the information with relation to claimed effects (CEs), OVs and MMs related to skin health compliance with Regulation 1924/2006. CEs, OVs and MMs were collected from both the EFSA Guidance document and from the authorization requests of health claims under Article 13(5). The critical analysis of OVs and MMs was based on a literature review, and was aimed at defining their appropriateness (alone or in combination with others) in the context of a specific CE. The results highlight the importance of an adequate choice of OVs and MMs for an effective substantiation of the claims., Competing Interests: The authors declare no conflict of interest.

Background: Notalgia paresthetica (NP) is a disorder characterized by pruritus localized to the patient's back. Little is known about predictors of severity, duration, side, and localization., Objective: To identify factors associated with perceived severity, duration, side, and localization of NP., Methods: In a cross-sectional study, disease severity, duration, side, and localization were compared among the considered variables. Multivariate analysis was used to assess each variable contribution in predicting disease severity and its duration., Results: Sixty-five patients were recruited. Disease involved more female than male patients (Female/Male: 1.6) and after adjusting for all potential confounders, it was perceived as more severe in females (OR = 7.3, 95% CI = 2-26.3, P < 0.01). NP was reported more frequently on the right side among patients sleeping on the left side and conversely (P < 0.05). A higher disease duration was significantly linked to a higher body mass index (OR = 4.8, 95% CI = 1.3-17.1, P < 0.05)., Conclusion: Our study linked female gender to worse disease severity, a higher body mass index to longer disease duration, and prevailing sleep position to NP side expression. The sleeping position should be considered a possible target for treating the disease., (© 2017 The International Society of Dermatology.)

Background: The majority of available systemic therapies have never been systematically investigated in moderate to severe childhood plaque psoriasis. For this reason, treatment preferences for moderate to severe psoriasis in childhood are still unknown. The aim of this study was to investigate the systemic treatment patterns of moderate to severe psoriasis in children and adolescents aged 18 or older in Italy. Additional secondary outcomes were duration of treatment and reasons for discontinuation., Methods: In order to define differences in treatment patterns, we performed a chart review of all consecutive patients treated with systemic drugs during an index period of 5 years. Consecutive sampling of all patients with psoriasis aged ≤18 years, who had been treated with at least one systemic drug over a 5-year period, was made., Results: The records of 58 consecutive patients, 27 males, 31 females. with moderate to severe psoriasis treated with at least one systemic therapy were reviewed. The median age (standard deviation) at the start of the first systemic treatment was 11.7±3.7 years. The most preferred first-line systemic treatment was cyclosporine, which was administered as first systemic treatment in 53.4% of patients, followed by acitretin in 22.4% of patients, etanercept and PUVA respectively in 8.6%, methotrexate in 6.8%. 48.2% of patients received a second systemic treatment due to inefficacy or side effects of the first-line therapy during the index period. Because of the small sample, and voluntary contribution, selection bias may have occurred., Conclusions: A considerable variation in the management of the first-line systemic therapy in children with moderate to severe psoriasis was observed. Cyclosporine was most commonly preferred as a first-line treatment. The availability of new therapeutic agents could change the scenario of treatment patterns in childhood psoriasis.

Chronic spontaneous urticaria (CSU) is perceived as a difficult to manage disease with negative impact on quality of life. The aim of this study was to highlight how to improve the care of people with CSU, using the methodology of narrative medicine. From June 2014 to March 2015, CSU-diagnosed patients and their physicians were asked to record their experiences of the condition in writing. Fourteen healthcare teams participated: 41% considered CSU as a challenge to overcome, while 22% experienced CSU as a big commitment. The number of professional involved was evaluated as insufficient in 11 hospitals. Seventy-five percent of the 190 Italian patients had visited 3 or more physicians before receiving a final diagnosis, with a perceived waste of time and resources. The therapeutic pathways were described as unsatisfactory in 83% of cases. As a result, anger and frustration were life-dominant emotions in 92% of patients. The critical points of the care pathway are related to organizational issues and lack of awareness.

Background: Acitretin is licensed for and is most commonly used to treat psoriasis. Little information exists about its efficacy and safety in childhood and adolescent psoriasis., Methods: Retrospective analysis of a group of children and adolescents (<17 years of age) with moderate to severe plaque psoriasis treated with acitretin between 2010 and 2014 at Italian dermatology clinics. Patients were identified through databases or registries., Results: The study population consisted of 18 patients with a median age of 9.5 years at the start of therapy. The median maintenance dosage per day was 0.41 mg/kg. Eight patients (44.4%) achieved complete clearance or good improvement of their psoriasis, defined as improvement from baseline of 75% or more on the Psoriasis Area and Severity Index at week 16. Three had three or more courses of treatment with short disease-free intervals. In three patients, acitretin treatment was ongoing at the time of data collection. The mean total duration of treatment in responders was 22.7 months. One patient discontinued treatment because of arthralgia. The remaining nine patients (50%) discontinued treatment because it was ineffective. Mucocutaneous adverse effects occurred in all patients, but did not affect therapy maintenance., Conclusions: In this retrospective case series, acitretin was a moderately effective, well-tolerated treatment in children with moderate to severe plaque psoriasis. Given the small number of patients, statements about long-term safety are not possible., (© 2016 Wiley Periodicals, Inc.)

Chronic activation of the inflammatory response, defined as inflammaging, is the key physio-pathological substrate for anabolic resistance, sarcopenia and frailty in older individuals. Nutrients can theoretically modulate this phenomenon. The underlying molecular mechanisms reducing the synthesis of pro-inflammatory mediators have been elucidated, particularly for vitamin D, n-3 polyunsaturated fatty acids (PUFA) and whey proteins. In this paper, we review the current evidence emerging from observational and intervention studies, performed in older individuals, either community-dwelling or hospitalized with acute disease, and evaluating the effects of intake of vitamin D, n-3 PUFA and whey proteins on inflammatory markers, such as C-Reactive Protein (CRP), interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α). After the analysis, we conclude that there is sufficient evidence for an anti-inflammatory effect in aging only for n-3 PUFA intake, while the few existing intervention studies do not support a similar activity for vitamin D and whey supplements. There is need in the future of large, high-quality studies testing the effects of combined dietary interventions including the above mentioned nutrients on inflammation and health-related outcomes.

This study aimed to evaluate the prevalence of sunbed use among teenagers and the association between familial behavior and the adoption of UV-protective practices in this age group. We also assessed the impact of an educational program on students' knowledge about the potential risks of sunbed use. The educational intervention focused on: (i) skin effects of UV radiation, (ii) photoaging and photocarcinogenesis, (iii) risk factors for skin cancer, (iv) indoor sun tanning and misleading concepts such as possible protective effect of sunbed use on skin cancer risk, (v) sun protection and relation with skin phototype, and (vi) early diagnosis of melanoma using the ABCDE check list and the ugly duckling sign. We carried out a survey of 3098 students and found a strong association between parental sunbed use and students' use of the same (P < 0.0001). Students who attended the educational intervention were more aware that sunbed use cannot prevent sunburns (P = 0.03) than those who did not attend, making adjustments for confounding variables. However, sunbed use by parents influenced the desire to use a sunbed more than participation in the educational intervention (P < 0.0001). In conclusion, although our results indicate that educational interventions can improve knowledge of the risk of sunbed use. They also reveal a strong correlation between sunbed use by teenagers and parental behavior that highlights the importance of educational interventions involving families.

Tumor necrosis factor-alpha (TNF-α) inhibitors represent an effective treatment for severe psoriasis in hepatitis C virus (HCV) patients. The literature reports mainly on short-term treatment in patients with chronic hepatitis with minimum-to-moderate activity with an acceptable safety profile. We report the first 2 cases of hepatocellular carcinoma (HCC) arising in HCV psoriatic patients with advanced liver disease during long-term treatment with etanercept. Our first patient, known to have had HCV infection for 41 years, developed an HCC after 21 months of therapy with etanercept (50 mg/week). The second patient, HCV+ for 20 years, was treated for 58 months with the same therapy, and despite no signs of liver function impairment was diagnosed with HCC. Both of them presented with cirrhosis, which was diagnosed 9 and 5 years earlier, respectively. It remains to be clarified whether there is any connection between psoriasis treatment with anti-TNF-α agents and the development of HCC in HCV-infected patients. Further long-term, follow-up studies and registries of HCV patients with mild/moderate activity may contribute to clarify this issue., (© 2015 S. Karger AG, Basel.)

Background: Photodynamic therapy with 5-methyl-aminolevulinate and photodynamic therapy with trichloroacetic acid 50% are the two techniques utilized in the management of actinic keratosis. This study was planned to compare the efficacy, adverse effects, recurrence and cosmetic outcome of these option therapies in patients with multiple actinic keratosis of the scalp., Methods: Thirteen patients with multiple actinic keratosis were treated with one of the two treatments on half of the scalp at baseline, while the other treatment was performed on the other half 15 days apart, randomly. Efficacy, adverse effects, cosmetic outcome and recurrence were recorded at follow-up visit at 1, 3, 6 and 12 months., Results: Photodynamic therapy with 5 methyl-aminolevulinate was more effective than trichloroacetic acid although less tolerated by patients as it was more painful. Early adverse effects were almost the same even if trichloroacetic acid leads also to crust formation and to a worse cosmetic outcome characterized by hypopigmentation. Recurrence was lower in the area treated with photodynamic therapy., Conclusion: Trichloroacetic acid 50% is less effective than photodynamic therapy with 5 methyl-aminolevulinate in the treatment of multiple actinic keratosis of the scalp although better tolerated by patients. As this technique is less painful and less expensive than photodynamic therapy, we hypothesize and suggest that more sequential treatments could lead to better results., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Bullous dermolysis of the newborn is a dominant or recessive inherited subtype of dystrophic epidermolysis bullosa characterized by the tendency to spontaneously stop blistering within the first months of life. Here we report two siblings with bullous dermolysis of the newborn who were born prematurely and have a novel recessive mutation, p.Pro2259Leu, in the triple helix domain of type VII collagen. We discuss the possible relationship between genotype and prematurity and clinical manifestations in these patients., (© 2015 Wiley Periodicals, Inc.)

Psoriasis is a common inflammatory dermatosis that may be seen in infants, children, and adolescents. The clinical presentation and course may be quite variable, and while patients with mild disease are often easily managed, those with recalcitrant or more severe disease often present a therapeutic dilemma given the number of therapies available and the relative lack of data on the efficacy and safety of use of these therapies in children. Diagnosis in children can be more difficult, but family history may be helpful. Moreover, sometimes clinical pattern of pediatric psoriasis is very different from its adult counterpart or it could manifests in association with atopic dermatitis, and for these reason it is possibly misdiagnosed and under recognized. We therefore focus on diagnostic patterns and effective treatments of this challenging disease.

Juvenile dermatomyositis (JDM) is a rare, severe, autoimmune disease characterized by a small-vessel vasculopathy that primarily affects skin and muscle, but also lung, joints, gut and heart. Nowadays prompt recognition of this entity and aggressive treatment, when needed, improves outcomes and has decreased mortality that, before corticosteroid became a mainstay in therapy, could reach 40%.

We have prospectively evaluated psoriatic arthritis (PsA) patients for (1) seropositivity for former viral infections and seroconversion and (2) efficacy of cyclosporine A (CsA) alone or in combination with other immunosuppressants in a time period of 12 months. Screening included HBV antibodies and antigens, HCV antibodies and RNA, HSV 1-2, HZV, EBV, and CMV IgG, and IgM, HHV-6 DNA, and HIV 1-2 antibodies. PsA was evaluated by the Psoriasis Area Severity Index (PASI), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and the Visual Analogue Scale (VAS). At baseline, 126 (56%) out of 225 evaluable patients had 2 or more seropositivities indicative of former infections, and 31 patients (13.8%) presented seropositivity for HCV, HBV, HSV-1 and -2, HHV-6, EBV, or parvovirus infection; one of them, positive for HBAg, was treated with lamivudine, while the remaining 30 received no specific treatment. None of the 31 patients developed virus reactivation. A reduction (P < 0.001) of PASI, BASDAI, and VAS scores was observed at 6 and 12 months. The treatment of PsA with CsA as monotherapy or in combination was safe and effective. In vitro experiments and clinical findings, including those from our study, suggest that CsA as monotherapy or in combination with biologics might be the treatment of choice in PsA HCV-positive patients.

Aim: The aim of this study was to provide practical recommendations for optimizing the use of conventional and biological systemic treatments for moderate-severe chronic plaque psoriasis, particularly in case of transitioning and switching., Methods: A total number of 147 dermatologists from 33 different countries including Italy achieved consensus in providing practical recommendations for the use of conventional and biological treatments for moderate to severe psoriasis based on systematic literature review and/or expert opinion., Results: In general, the continuous treatment regimen should be preferred in order to achieve a complete and long-term control of psoriasis. However, the treatment could be stopped or the dose reduced in case of complete disease clearance. A conventional drug could be associated to biological treatment in selected cases. Transitioning and/or switching could be considered in case of inefficacy or intolerance. A period of wash up is required if transitioning or switching is due to safety issues., Conclusion: This study provides practical suggestions for the optimal use of conventional and biological treatments for chronic plaque psoriasis.

Clinical evidence demonstrates that ubiquinol-10, the reduced active form of coenzyme Q10 (CoQ10H₂), improves endothelial function through its antioxidant and probably its anti-inflammatory properties. We previously reported that a biomarker combination including miR-146a, its target protein IL-1 receptor-associated kinase (IRAK-1), and released interleukin (IL)-6, here collectively designated as MIRAKIL, indicates senescence-associated secretory phenotype (SASP) acquisition by primary human umbilical vein endothelial cells (HUVECs). We explore the ability of short- and long-term CoQ10H₂ supplementation to affect MIRAKIL in HUVECs, used as a model of vascular aging, during replicative senescence in the absence/presence of lipopolysaccharide (LPS), a proinflammatory stimulus. Senescent HUVECs had the same ability as young cells to internalize CoQ10 and exhibit an improved oxidative status. LPS-induced NF-κB activation diminished after CoQ10H₂ pretreatment in both young and senescent cells. However, short-term CoQ10H₂ supplementation attenuated LPS-induced MIRAKIL changes in young cells; in senescent cells CoQ10H₂ supplementation significantly attenuated LPS-induced miR-146a and IRAK-1 modulation but failed to curb IL-6 release. Similar results were obtained with long-term CoQ10H₂ incubation. These findings provide new insights into the molecular mechanisms by which CoQ10H₂ stems endothelial cell inflammatory responses and delays SASP acquisition. These phenomena may play a role in preventing the endothelial dysfunction associated with major age-related diseases., (Copyright © 2013 Elsevier Inc. All rights reserved.)

In order to identify new markers of vascular cell senescence with potential in vivo implications, primary cultured endothelial cells, including human umbilical vein endothelial cells (HUVECs), human aortic endothelial cells (HAECs), human coronary artery endothelial cells (HCAECs) and ex vivo circulating angiogenic cells (CACs), were analysed for microRNA (miR) expression. Among the 367 profiled miRs in HUVECs, miR-146a, miR-9, miR-204 and miR-367 showed the highest up-regulation in senescent cells. Their predicted target genes belong to nine common pathways, including Toll-like receptor signalling (TLR) that plays a pivotal role in inflammatory response, a key feature of senescence (inflammaging). MiR-146a was the most up-regulated miR in the validation analysis (>10-fold). Mimic and antagomir transfection confirmed TLR's IL-1 receptor-associated kinase (IRAK1) protein modulation in both young and senescent cells. Significant correlations were observed among miR-146a expression and β-galactosidase expression, telomere length and telomerase activity. MiR-146a hyper-expression was also validated in senescent HAECs (>4-fold) and HCAECs (>30-fold). We recently showed that CACs from patients with chronic heart failure (CHF) presented a distinguishing feature of senescence. Therefore, we also included miR-146a expression determination in CACs from 37 CHF patients and 35 healthy control subjects (CTR) for this study. Interestingly, a 1,000-fold increased expression of miR-146a was observed in CACs of CHF patients compared to CTR, along with decreased expression of IRAK1 protein. Moreover, significant correlations among miR-146a expression, telomere length and telomerase activity were observed. Overall, our findings indicate that miR-146a is a marker of a senescence-associated pro-inflammatory status in vascular remodelling cells.

Treatment of patients with psoriasis and concomitant hepatitis-C virus (HCV) infection poses a therapeutic challenge because most systemic drugs are associated with potential hepatotoxicity, either due to direct liver damage or to immunosuppression. Among newly available drugs for the treatment of psoriasis and psoriatic arthritis, studies investigating the effect of anti-tumour necrosis factor-α in such patients are still limited. We describe three psoriatic patients with HCV, one with concomitant alcoholic hepatitis, who were treated with etanercept monotherapy for six months. We obtained good clinical responses for both psoriasis and arthritis in all three patients. While no significant changes in viral load and transaminases were observed in two patients, alanine aminotrasferase and gamma-glutamyltransferase levels were raised during treatment in the patient with concomitant alcoholic hepatitis. At baseline, one patient was negative and two were positive for mixed-type cryoglobulins. During treatment, none of the patients developed cryoglobulinemia-related clinical symptoms, and one of the two patients positive at baseline was negative for cryoglobulins at the end of follow-up. Our results add to accumulating data suggesting that etanercept represents a valuable therapeutic option for treatment of HCV-positive psoriatic patients, with an acceptable safety profile in the short-term. However, etanercept treatment of HCV cases with concomitant alcoholic hepatitis must be undertaken with caution.

T cells are present in normal adult human skin, but their occurrence in fetal skin is unknown. T cell and Langerhans cell (LC) populations were studied using single or double immunohistochemical staining on cryostat-section. Skin samples taken from different body regions of 17 fetuses ranging from 18 to 30 weeks estimated gestational-age (w-EGA), were examined. In all specimens but one, we did not find any epidermal T cell. In contrast, dermal CD3(+) T cells occurred at all w-EGA. The density of these cells increased with increasing age. Double staining showed that CD3(+) T cells were predominantly CD4(+)/CD45RA(+). On the other hand, LC, as assessed by CD1a expression, was evenly distributed within the interfollicular epidermis and papillary dermis at all gestational ages. Analysis of T cell and LC density in different body regions did not show significant topographic differences. We suggest that lack of epidermal T cells, although the LC network was fully represented, might reflect the scarce opportunity of fetal LC to contact foreign antigens in utero.

Bexarotene is approved for the treatment of cutaneous T cell lymphomas in patients refractory to at least one prior systemic therapy. Associated hypertriglyceridaemia requires monitoring, but can readily be managed with concomitant medication, such as fenofibrate. Here we report three cases of hypertriglyceridaemia secondary to bexarotene assumption, which was adequately managed with omega-3 fatty acids. If fenofibate-related side effects occur, or a statin is required to control low-density lipoprotein-cholesterol, omega-3 fatty acids should be considered as a good alternative therapy to lower lipid levels during bexarotene treatment.

Epidermal T cells, which are found in clinically normal human skin, show topographic differences in density and proportions; however, the mechanisms and the biological consequences of such differences are still unknown. In a previous work, we showed that epidermal T cells are altered in number and composition after a single exposure to solar-simulated radiation (SSR). The purposes of the present investigation were, first, to compare the density of epidermal T cells and the proportion of T cell subpopulations in habitually sun-exposed versus sun-protected sites; second, to determine the effects of repetitive exposures to SSR on the latter cell populations. Biopsies from habitually sun-exposed, sun-protected and solar-simulated-exposed skin of 28 healthy volunteers were taken and immunohistochemistry was performed on cryostat sections. Compared with sun-protected sites, epidermal CD3(+) T cell numbers of habitually sun-exposed sites were significantly lower. Double staining showed that the number of CD3(+)CD8(+) T cells was significantly lower in sun-exposed than in sun-protected skin, whereas the numbers of CD3(+)CD4(+) T cells were similar in both sites. Therefore, the CD4/CD8 ratio was markedly higher in sun-exposed compared to sun-protected sites. Moreover, repeated exposures of sun-protected skin to SSR induced a significant reduction in number of epidermal CD3(+) T cells. The mean number of epidermal CD3(+)CD8(+) double stained cells significantly decreased after such exposures, while the epidermal CD3(+)CD4(+) T cell subpopulation was not significantly changed. In conclusion, both chronically sun-exposed skin and repeatedly SSR-exposed skin show a decrease in density of epidermal CD3(+) and CD3(+)CD8(+) T cells. We hypothesize that such sun-induced changes may weaken the immunosurveillance capacity of the skin and therefore increase the occurrence of skin cancer.